Abstract
Lamb–Shaffer Syndrome (LSS; OMIM #616803; ORPHA #313892; ORPHA #313884) is an infrequent genetic disorder that affects multiple aspects of human development especially those related to the ...development of the nervous system. LSS is caused by variants in the
SOX5
gene. At the molecular level,
SOX5
gene encodes for a transcription factor containing a High Mobility Group (HMG) DNA‐Binding domain with relevant functions in brain development in different vertebrate species. Clinical features of Lamb–Shaffer syndrome may include intellectual disability, delayed speech and language development, attention deficits, hyperactivity, autism spectrum disorder, visual problems and seizures. Additionally, patients with the syndrome may present distinct facial dimorphism such as a wide mouth with full lips, small chin, broad nasal bridge, and deep‐set eyes. Other physical features that have been reported in some patients include short stature, scoliosis, and joint hypermobility. Here, we report the clinical and molecular characterization of a Spanish LSS cohort of new 20 patients and review all the patients published so far which amount for 111 patients. The most frequent features included developmental delay, intellectual disability, visual problems, poor speech development and facial dysmorphic features. Strikingly, pain insensitivity and hypermetropia seems to be more frequent than previously reported, based on the frequency seen in the Spanish cohort. Eighty‐three variants have been reported so far, single nucleotide variants (SNV) and copy number variants represent 47% and 53%, respectively, from the total of variants reported. Similarly to previous reports, the majority of the SNVs variants of the novel patients reported herein fall in the HMG domain of the protein. However, new variants, affecting other functional domains, were also detected. In conclusion, LLS is a rare genetic disorder mostly characterized by a wide range of developmental and neurological symptoms. Early diagnosis would allow to start of care programs, clinical follow up, prospective studies and appropriate genetic counseling, to promote clinical and social improvement to have profound lifelong benefits for patients and their families. Further research is needed to better understand the underlying mechanisms of the syndrome related to
SOX5
haploinsufficiency.
OBJECTIVES:To determine the proportion of clinical errors by comparing clinical and pathological diagnoses, and to evaluate changes of errors over time.
DESIGN:We conducted a prospective study of all ...consecutive autopsies performed on patients who died in the intensive care unit of the Hospital Universitario de Getafe, Madrid, Spain, between January 1982 and December 2007. The diagnostic errors were classified in two categoriesclass I errors that were major misdiagnoses with direct impact on therapy, and class II diagnostic errors which comprised major unexpected findings that probably would not have changed therapy.
MAIN RESULTS:Of 2,857 deaths during the study period, autopsies were performed in 866 patients (30.3%). Autopsy reports were available in 834 patients, of whom 63 (7.5%) had class I errors and 95 (11.4%) had type II errors. The most frequently missed diagnoses were pulmonary embolism, pneumonia, secondary peritonitis, invasive aspergillosis, endocarditis and myocardial infarction. The autopsy did not determine the cause of death in 22 patients (2.6%). Our rate of diagnostic discrepancy remained relatively constant over time, and the conditions leading to discrepancies have slightly changed, with pneumonia showing a decline in diagnostic accuracy in the last years.
CONCLUSIONS:This study found significant discrepancies in 18.5% of patients who underwent autopsy, 7.5% of them were diagnoses with impact on therapy and outcome. This reinforces the importance of the postmortem examination in confirming diagnostic accuracy and improving the quality of care of critically ill patients.
Background
Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and ...undergoing invasive mechanical ventilation. We aimed to estimate 180-day mortality of patients with COVID-19 requiring invasive ventilation, and to develop a predictive model for long-term mortality.
Methods
Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes was 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model was developed to estimate the probability of 180-day mortality.
Results
868 patients were included (median age, 64 years interquartile range IQR, 56–71 years; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points IQR 50–63. Prior to intubation, 26% received some type of noninvasive respiratory support. The unadjusted overall 180-day survival rates was 59% (95% CI 56–62%). The predictive factors measured during ICU stay, and associated with 180-day mortality were: age Odds Ratio OR per 1-year increase 1.051, 95% CI 1.033–1.068)), SAPS3 (OR per 1-point increase 1.027, 95% CI 1.011–1.044), diabetes (OR 1.546, 95% CI 1.085–2.204), neutrophils to lymphocytes ratio (OR per 1-unit increase 1.008, 95% CI 1.001–1.016), failed attempt of noninvasive positive pressure ventilation prior to orotracheal intubation (OR 1.878 (95% CI 1.124–3.140), use of selective digestive decontamination strategy during ICU stay (OR 0.590 (95% CI 0.358–0.972) and administration of low dosage of corticosteroids (methylprednisolone 1 mg/kg) (OR 2.042 (95% CI 1.205–3.460).
Conclusion
The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments.
Trial registration
: ClinicalTrials.gov Identifier:
NCT04379258.
Registered 10 April 2020 (retrospectively registered)
Differences in the degree and severity of Acute Coronary Syndrome, associated to differences in the electrocardiogram, together with blood tests of biomarkers classify patients for diagnosis and ...treatment. Cases where the electrocardiogram and/or biomarkers are not conclusive still appear, and there is a need for complementary biomarkers for routine determinations. Metabolomics approaches with blind fingerprinting could reveal differences in metabolites, which must be confirmed by means of targeted determinations. CE‐MS and HILIC‐MS are well suited for the determination of highly polar compounds, like those from to the intermediate metabolism, altered due to acute stress induced by myocardial infarction. Serum from patients with ST‐elevated and non‐ST elevated myocardial infarction was collected at intensive care and emergency units, and fingerprinted with CE‐MS. Data pretreatment and analysis showed up carnitine‐related compounds and amino acids differentially present in both groups. Acylcarnitines and amino acids were then quantitatively measured with HILIC‐MS‐QqQ. The significance of the differences and the sensitivity/specificity of each compound were individually evaluated. The ratio of free carnitine to acylcarnitines, together with the ratios of acetylcarnitine to betaine, to threonine, and to citrulline, showed high significance and area under the curve in the respective receiver operating characteristic curves. This study opens new possibilities for defining new sets of biomarkers for refining the diagnosis of the patients with difficult classification.
Hemoptisis secundaria a vapeo Cano Aguirre, María del Puerto; Esperanza Barrios, Alba; Martínez Muñiz, Francisco ...
Archivos de bronconeumología,
July 2021, 2021-07-00, Letnik:
57, Številka:
7
Journal Article
Hemoptysis induced by vaping Cano Aguirre, María Del Puerto; Esperanza Barrios, Alba; Martínez Muñiz, Francisco ...
Archivos de bronconeumologia,
07/2021, Letnik:
57, Številka:
7
Report
Hemoptysis Induced by Vaping Cano Aguirre, María Del Puerto; Esperanza Barrios, Alba; Martínez Muñiz, Francisco ...
Archivos de bronconeumologia,
11/2020
Report
Background
Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause of SBI.
...Objectives
The aim of this study is to determine the prevalence of and risk factors for SBI in patients with AF and low-to-moderate embolic risk according to CHADS
2
and CHA
2
DS
2
VASc score.
Methods
Patients with a history of AF based on medical records who scored 0–1 in the CHADS
2
score were selected from the Seville urban area using the Andalusian electronic healthcare database (DIRAYA). Demographic and clinical data were collected and a 3T brain MRI was performed on patients older than 50 years and with absence of neurological symptoms.
Results
66 of the initial 443 patients (14.9%) and 41 of the 349 patients with low risk according to CHA
2
DS
2
VASc score (11.7%) presented at least 1 SBI. After adjusted multivariable analysis, an older age (OR 3.84, 95% CI 1.07–13.76) and left atrial (LA) enlargement (OR 3.13, 95% CI 1.15–8.55) were associated with SBI in the whole cohort, while only LA enlargement was associated with SBI in the low-risk cohort (OR 3.19, 95% CI 1.33–7.63).
Conclusions
LA enlargement on echocardiogram was associated with SBI in patients with AF and low or moderate embolic risk according to CHADS
2
and in the low-risk population according to CHA
2
DS
2
VASc. Although further studies are needed, a neuroimaging screening might be justified in these patients to guide medical therapies to improve stroke prevention.
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