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Background: Despite the need for specific weaning strategies in neurological patients, evidence is generally insufficient or lacking. We aimed to describe the evolution over time of weaning and extubation practices in patients with acute brain injury compared with patients who are mechanically ventilated (MV) due to other reasons. Methods: We performed a secondary analysis of three prospective, observational, multicenter international studies conducted in 2004, 2010, and 2016 in adults who had need of invasive MV for more than 12 h. We collected data on baseline characteristics, variables related to management ventilator settings, and complications while patients were ventilated or until day 28. Results: Among the 20,929 patients enrolled, we included 12,618 (60%) who started the weaning from MV, of whom 1722 (14%) were patients with acute brain injury. In the acutely brain-injured cohort, 538 patients (31%) did not undergo planned extubation, defined as the need for a tracheostomy without an attempt of extubation, accidental extubation, and death. Among the 1184 planned extubated patients with acute brain injury, 202 required reintubation (17%). Patients with acute brain injury had a higher odds for unplanned extubation (odds ratio [OR] 1.35, confidence interval for 95% [CI 95%] 1.19–1.54; p < 0.001), a higher odds of failure after the first attempt of weaning (spontaneous breathing trial or gradual reduction of ventilatory support; OR 1.14 [CI 95% 1.01–1.30; p = 0.03]), and a higher odds for reintubation (OR 1.41 [CI 95% 1.20–1.66; p < 0.001]) than patients without brain injury. Patients with hemorrhagic stroke had the highest odds for unplanned extubation (OR 1.47 [CI 95% 1.22–1.77; p < 0.001]), of failed extubation after the first attempt of weaning (OR 1.28 [CI 95% 1.06–1.55; p = 0.009]), and for reintubation (OR 1.49 [CI 95% 1.17–1.88; p < 0.001]). In relation to weaning evolution over time in patients with acute brain injury, the risk for unplanned extubation showed a downward trend; the risk for reintubation was not associated to time; and there was a significant increase in the percentage of patients who underwent extubation after the first attempt of weaning from MV. Conclusions: Patients with acute brain injury, compared with patients without brain injury, present higher odds of undergoing unplanned extubated after weaning was started, lower odds of being extubated after the first attempt, and a higher risk of reintubation. [ABSTRACT FROM AUTHOR]

Purpose: To synthesise the evidence on the prevalence of associated intraarticular lesions in subjects with acute acromioclavicular joint (ACJ) dislocations.Methods: A search in two electronic databases (PUMBMED and EMBASE) was performed from 1985 to 2019. Two independent reviewers selected studies that complied with the following inclusion criteria: (1) the study included data on surgically treated ACJ dislocation grade III-V in the Rockwood classification, (2) the ACJ injuries were acute (the surgery was performed less than 6 weeks after injury), (3) an arthroscopic evaluation of the glenohumeral joint was performed during surgery. The quality of the studies included was assessed using the tool of the Joanna Briggs Institute.Results: A total of 47 studies with acute ACJ injuries met the initial inclusion criteria. Of these, 21 studies (9 retrospective case series, 9 prospective case series and 3 retrospective cohort studies) presented data on associated intraarticular lesions amenable for use in the meta-analysis. The meta-analysed studies included a total of 860 subjects with acute ACJ dislocations with a male/female ratio of 6.5 and a mean age of 32 years. The meta-analysis showed a prevalence of associated intraarticular lesions in subjects with acute ACJ of 19.9% (95% confidence interval [CI] 14.0-26.4%; 21 studies, 860 analysed participants; P = 0.000; I2: 74.5% random-effects model; low risk of bias).Conclusion: One in five subjects with surgically treated acute ACJ dislocations will have an associated intraarticular lesion that requires further intervention. The case for a customary arthroscopic evaluation of the joint, even when an open procedure is performed to deal with the ACJ dislocation, is strong. Level of evidence IV Trial registry Systematic review registration number: PROSPERO CRD42018090609. [ABSTRACT FROM AUTHOR]

Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing–remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82–15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). This shows that low baseline sNfL values identify MS patients with higher probability of optimal response to DMF and of a reduction in effector immune cells. [ABSTRACT FROM AUTHOR]

Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. We evaluated the mortality, the risk of need for mechanical ventilation (MV), or death and the risk of developing a severe acute respiratory distress syndrome (ARDS) between high (HD) and standard doses (SD) among patients with a severe COVID-19. All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an ARDS. Patients were allocated to the HD (≥ 250 mg/day of methylprednisolone) of corticosteroids or the SD (≤ 1.5 mg/kg/day of methylprednisolone) at discretion of treating physician. Five hundred seventy-three patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54–73) years. In the HD group, a worse baseline respiratory situation was observed and male gender, older age, and comorbidities were significantly more common. After adjusting by baseline characteristics, HDs were associated with a higher mortality than SD (adjusted OR 2.46, 95% CI 1.59–3.81, p < 0.001) and with an increased risk of needing MV or death (adjusted OR 2.35, p = 0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly patients. Our real-world experience advises against exceeding 1–1.5 mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients. [ABSTRACT FROM AUTHOR]

Immunosuppressed patients are at higher risk for developing herpes zoster (HZ), and neurological complications are frequent in them. However, the influence of immunosuppression (IS) on the severity and prognosis of neurological complications of varicella-zoster virus (VZV) reactivation is unknown. We studied retrospectively patients with neurological complications due to VZV reactivation who attended our hospital between 2004 and 2019. We aimed to assess the clinical spectrum, potential prognostic factors, and the influence of the immune status on the severity of neurological symptoms. A total of 98 patients were included (40% had IS). Fifty-five patients (56%) had cranial neuropathies which included Ramsay-Hunt syndrome (36 patients) and cranial multineuritis (23 patients). Twenty-one patients developed encephalitis (21%). Other diagnosis included radiculopathies, meningitis, vasculitis, or myelitis (15, 10, 6, and 4 patients, respectively). Mortality was low (3%). At follow-up, 24% of patients had persistent symptoms although these were usually mild. IS was associated with severity (defined as a modified Rankin scale greater than 2) (odds ratio, 4.23; 95% confidence interval, 1.74–10.27), but not with prognosis. Shorter latency between HZ and neurologic symptoms was the only factor associated with an unfavorable course (death or sequelae) (odds ratio, 0.82; 95% confidence interval, 0.71–0.95). In conclusion, the clinical spectrum of neurological complications in VZV reactivation is wide. Mortality was low and sequelae were mild. The presence of IS may play a role on the severity of neurological symptoms, and a shorter time between HZ and the onset of neurological symptoms appears to be a negative prognostic factor. [ABSTRACT FROM AUTHOR]

Purpose: Variations in clinical characteristics and management and in the mortality of mechanically ventilated patients have not been sufficiently evaluated. We hypothesized that mortality shows a variability associated with country after adjustment for clinical characteristics and management.Methods: Analysis of four studies carried out at 6-year intervals over an 18-year period. The studies included 26,024 patients (5183 in 1998, 4968 in 2004, 8108 in 2010, and 7765 in 2016) admitted to 1253 units from 38 countries. The primary outcome was 28-day mortality. We performed analyses using multilevel logistic modeling with mixed-random effects, including country as a random variable. To evaluate the effect of management strategies on mortality, a mediation analysis was performed.Results: Adjusted 28-day mortality decreased significantly over time (first study as reference): 2004: odds ratio 0.82 (95% confidence interval [CI] 0.72-0.93); 2010: 0.63 (95% CI 0.53-0.75); 2016: 0.49 (95% CI 0.39-0.61). A protective ventilatory strategy and the use of continuous sedation mediated a moderate fraction of the effect of time on mortality in patients with moderate hypoxemia and without hypoxemia, respectively. Logistic multilevel modeling showed a significant effect of country on mortality: median odds ratio (MOR) in 1998: 2.02 (95% CI 1.57-2.48); in 2004: 1.76 (95% CI 1.47-2.06); in 2010: 1.55 (95% CI 1.37-1.74), and in 2016: 1.39 (95% CI 1.25-1.54).Conclusions: These findings suggest that country could contribute, independently of confounder variables, to outcome. The magnitude of the effect of country decreased over time. Clinical trials registered with http://www.clinicaltrials.gov (NCT02731898). [ABSTRACT FROM AUTHOR]

Purpose: To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS).Patients and Methods: We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality.Main Outcomes: We included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48 h and mortality suggests higher mortality at or above PaCO2 of ≥50 mmHg. Patients with severe hypercapnia (PaCO2 ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04-2.41; p = 0.032).Conclusions: Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.Trial Registration: Clinicaltrials.gov identifier, NCT01093482. [ABSTRACT FROM AUTHOR]

Purpose: There are limited data available about the role of sedation and analgesia during noninvasive positive pressure ventilation (NPPV). The objective of study was to estimate the effect of analgesic or sedative drugs on the failure of NPPV. Methods: We studied patients who received at least 2 h of NPPV as first-line therapy in a prospective observational study carried out in 322 intensive care units from 30 countries. A marginal structural model (MSM) was used to analyze the association between the use of analgesic or sedative drugs and NPPV failure (defined as need for invasive mechanical ventilation). Results: 842 patients were included in the analysis. Of these, 165 patients (19.6 %) received analgesic or sedative drugs at some time during NPPV; 33 of them received both. In the adjusted analysis, the use of analgesics (odds ratio 1.8, 95 % confidence interval 0.6-5.4) or sedatives (odds ratio 2.8, 95 % CI 0.85-9.4) alone was not associated with NPPV failure, but their combined use was associated with failure (odds ratio 5.7, 95 % CI 1.8-18.4). Conclusions: Slightly less than 20 % of patients received analgesic or sedative drugs during NPPV, with no apparent effect on outcome when used alone. However, the simultaneous use of analgesics and sedatives may be associated with failure of NPPV. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to assess the association between severe disc degeneration (DD) and low back pain (LBP). Methods: A case-control study was conducted with 304 subjects, aged 35-50, recruited in routine clinical practice across six hospitals; 240 cases (chronic LBP patients with a median pain duration of 46 months) and 64 controls (asymptomatic subjects without any lifetime history of significant LBP). The following variables were assessed once, using previously validated methods: gender, age, body mass index (BMI), lifetime smoking exposure, degree of physical activity, severity of LBP, disability, and findings on magnetic resonance (MRI) (disc degeneration, Modic changes (MC), disc protrusion/hernia, annular tears, spinal stenosis, and spondylolisthesis). Radiologists who interpreted MRI were blinded to the subjects' characteristics. A multivariate logistic regression model assessed the association between severe DD and chronic LBP, adjusting for gender, age, BMI, physical activity, MC, disc protrusion/hernia, and spinal stenosis. Results: Severe DD at ≥1 level was found in 46.9 % of the controls and 65.8 % of the cases. Crude odds ratio (95 % CI), for suffering chronic LBP when having severe DD, was 2.06 (1.05; 4.06). After adjusting for 'MC' and 'disc protrusion/hernia,' it was 1.81 (0.81; 4.05). Conclusions: The association between severe DD and LBP ceases to be significant when adjusted for MC and disc protrusion/hernia. These results do not support that DD as a major cause of chronic LBP. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting additional lesions and contralateral cancer not identified using conventional imaging in primary breast cancer.Methods: We have conducted a systematic review and meta-analyses to estimate diagnostic accuracy indices and the impact of MRI on surgical management.Results: Fifty articles were included (n = 10,811 women). MRI detected additional disease in 20% of women and in the contralateral breast in 5.5%. The summary PPV of ipsilateral additional disease was 67% (95% CI 59-74%). For contralateral breast, the PPV was 37% (95% CI 27-47%). For ipsilateral lesions, MRI devices ≥1.5 Tesla (T) had higher PPV (75%, 95% CI 64-83%) than MRI with <1.5 T (59%, 95% CI 53-71%). Similar results were found for contralateral cancer, PPV 40% (95% CI 29-53%) and 19% (95% CI 8-39%) for high- and low-field equipments, respectively. True positive MRI findings prompted conversion from wide local excision (WLE) to more extensive surgery in 12.8% of women while in 6.3% this conversion was inappropriate.Conclusions: MRI shows high diagnostic accuracy, but MRI findings should be pathologically verified because of the high FP rate. Future research on this emerging technology should focus on patient outcome as the primary end-point. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Immunomodulators are used as maintenance treatment of inflammatory bowel disease (IBD). Data regarding their possible effects in the course of pregnancy when the father is exposed at the time of conception are limited.METHODS:To evaluate the outcomes of pregnancies of which the fathers were exposed to thiopurines at the time of conception. A series of male patients followed in seven IBD clinics in Madrid, Spain, was studied. Any exposure to thiopurines during the 3 months preceding conception was considered significant. Controls were pregnancies fathered by patients who either had never been treated with thiopurines or had interrupted them >3 months before conception. Statistical comparisons and multivariate analysis were carried out with the generalized estimating equations model.RESULTS:There were 46 conceptions in the exposed group (mercaptopurine 9, azathioprine 37) and 84 in the control group. In the exposed group, there were more Crohn's patients (82.6% vs. 53.6%), the duration of the disease was longer (median: 8 vs. 5 years), fathers were slightly older (mean: 34.2 vs. 32.7 years), and there were fewer patients on mesalamine (15.2% vs. 47.6%). Otherwise, baseline characteristics were similar in both groups. There were no significant differences regarding unsuccessful pregnancies—namely, spontaneous abortions, ectopic pregnancies, anembryonic pregnancies, or fetal deaths (10.9% exposed group vs. 13.1% control group; odds ratio (OR): 0.79, confidence interval (CI): 0.22–2.85), preterm births (4.3% vs. 2.4%; OR: 1.3, CI: 0.22–7.61), low birth weight (6.5% vs. 6%; OR: 1.06, CI: 0.25–4.54), or congenital malformations (2.2% vs. 2.4%; OR: 0.82, CI: 0.08–9). No infant neoplasms were detected. The proportion of conceptions that needed >1 year to be achieved was higher in the exposed group, but this was not statistically significant (15.2% vs. 8.3%; OR: 1.92, CI: 0.54–6.88). Multivariate analysis was carried out for unsuccessful pregnancies and fertility impairment, and it showed that, although mesalamine exposure confounded the effect of the exposure to thiopurines on these outcomes, this effect was still nonsignificant (respectively, OR: 0.49, CI: 0.17–1.44; OR: 2.82, CI: 0.7–11.38).CONCLUSIONS:Our data do not support the practice of routinely recommending to male patients that they interrupt thiopurines when wanting to conceive. [ABSTRACT FROM AUTHOR]