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1.
Genet Med ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35567594

RESUMO

PURPOSE: SRRM2 encodes the SRm300 protein, a splicing factor of the SR-related protein family characterized by its serine- and arginine-enriched domains. It promotes interactions between messenger RNA and the spliceosome catalytic machinery. This gene, predicted to be highly intolerant to loss of function (LoF) and very conserved through evolution, has not been previously reported in constitutive human disease. METHODS: Among the 1000 probands studied with developmental delay and intellectual disability in our database, we found 2 patients with de novo LoF variants in SRRM2. Additional families were identified through GeneMatcher. RESULTS: Here, we report on 22 patients with LoF variants in SRRM2 and provide a description of the phenotype. Molecular analysis identified 12 frameshift variants, 8 nonsense variants, and 2 microdeletions of 66 kb and 270 kb. The patients presented with a mild developmental delay, predominant speech delay, autistic or attention-deficit/hyperactivity disorder features, overfriendliness, generalized hypotonia, overweight, and dysmorphic facial features. Intellectual disability was variable and mild when present. CONCLUSION: We established SRRM2 as a gene responsible for a rare neurodevelopmental disease.

2.
Am Surg ; : 31348221087901, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35465680

RESUMO

INTRODUCTION: Short bowel syndrome (SBS) is a debilitating condition associated with significant morbidity and mortality. Historically, SBS patients require indefinite parenteral nutrition (PN) and endure lifelong nutritional challenges. The purpose of this study was to review the outcomes, specifically nutritional independence, of a multidisciplinary nutrition service. METHODS: A retrospective analysis of SBS patients followed by our surgical nutrition service was performed. Patients without 1-year follow-up were excluded. Demographics and nutritional parameters were collected at 4 intervals: initial presentation, 1-year, 2-year, and 5-year follow-up. Short bowel syndrome anatomical subtypes identified through operative reports were characterized as end jejunostomy, jejunocolonic, or jejuno-ileocolonic with ileo-cecal valve intact. Intestinal failure was defined by the requirement of PN, while intestinal insufficiency was defined by enteral support requirement. Clinical outcomes examined included mortality, fistula closure, and nutritional independence. RESULTS: The study cohort comprised 89 patients, 50 of whom had ≤ 100 cm intestinal length. Mean age was 57 ± 17y, 55 (62%) were female, and median initial intestinal length was 77 [60-120] cm. Short bowel syndrome was complicated by fistulas in 47 (53%) of patients. Overall mortality was 13%, and 67 (75%) were liberated from PN. A total of 58 (65%) underwent operative intervention and fistula closure was achieved in 37 of 47 (79%) patients. CONCLUSIONS: Short bowel syndrome patients can experience significant benefit under treatment by a multidisciplinary nutrition service. By incorporating surgical intervention, the majority of patients previously relegated to lifelong PN have the opportunity to become nutritionally independent within 5 years.

3.
Am Surg ; 88(5): 953-958, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35275764

RESUMO

BACKGROUND: The American Association for the Surgery of Trauma (AAST) has developed a grading system for emergency general surgery (EGS) conditions. We sought to validate the AAST EGS grades for patients undergoing urgent/emergent colorectal resection. METHODS: Patients enrolled in the "Eastern Association for the Surgery of Trauma Multicenter Colorectal Resection in EGS-to anastomose or not to anastomose" study undergoing urgent/emergent surgery for obstruction, ischemia, or diverticulitis were included. Baseline demographics, comorbidity severity as defined by Charlson comorbidity index (CCI), procedure type, and AAST grade were prospectively collected. Outcomes included length of stay (LOS) in-hospital mortality, and surgical complications (superficial/deep/organ-space surgical site infection, anastomotic leak, stoma complication, fascial dehiscence, and need for further intervention). Multivariable logistic regression models were used to describe outcomes and risk factors for surgical complication or mortality. RESULTS: There were 367 patients, with a mean (± SD) age of 62 ± 15 years. 39% were women. The median interquartile range (IQR) CCI was 4 (2-6). Overall, the pathologies encompassed the following AAST EGS grades: I (17, 5%), II (54, 15%), III (115, 31%), IV (95, 26%), and V (86, 23%). Management included laparoscopic (24, 7%), open (319, 87%), and laparoscopy converted to laparotomy (24, 6%). Higher AAST grade was associated with laparotomy (P = .01). The median LOS was 13 days (8-22). At least 1 surgical complication occurred in 33% of patients and the mortality rate was 14%. Development of at least 1 surgical complication, need for unplanned intervention, mortality, and increased LOS were associated with increasing AAST severity grade. On multivariable analysis, factors predictive of in-hospital mortality included AAST organ grade, CCI, and preoperative vasopressor use (odds ratio (OR) 1.9, 1.6, 3.1, respectively). The American Association for the Surgery of Trauma emergency general surgery grade was also associated with the development of at least 1 surgical complication (OR 2.5), while CCI, preoperative vasopressor use, respiratory failure, and pneumoperitoneum were not. CONCLUSION: The American Association for the Surgery of Trauma emergency general surgery grading systems display construct validity for mortality and surgical complications after urgent/emergent colorectal resection. These results support incorporation of AAST EGS grades for quality benchmarking and surgical outcomes research.


Assuntos
Neoplasias Colorretais , Cirurgia Geral , Laparoscopia , Idoso , Feminino , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos
4.
J Trauma Acute Care Surg ; 92(6): 1031-1038, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35195095

RESUMO

BACKGROUND: Controversy exists about the preferred initial treatment of appendicitis. We sought to compare the two treatments for initial management of simple appendicitis. METHODS: In this post hoc analysis of the Multicenter Study for the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous database, subjects were divided into appendectomy or nonoperative management (NOM; antibiotics only or percutaneous drainage) cohorts. A novel topic-specific hierarchical ordinal scale was created with eight mutually exclusive categories: mortality, reoperation, other secondary interventions, readmission, emergency department visit, wound complication, surgical site infection, and no complication. Pairwise comparisons of American Association for the Surgery of Trauma Imaging Severity Grade 1 (simple appendicitis) patients were compared using win-lose-tie scoring and the sums of appendectomy/NOM groups were compared. RESULTS: A total 3,591 subjects were included: 3,262 appendectomy and 329 NOM, with significant differences in baseline characteristics between groups. Across 28 sites, the rate of NOM ranged from 0% to 48%, and the loss to follow-up rate was significantly higher for NOM compared with appendectomy (16.5% vs. 8.7%, p = 0.024). In the simple appendicitis hierarchical ordinal scale analysis, 2,319 subjects resulted in 8,714,304 pairwise comparisons; 75% of comparisons resulted in ties. The median (interquartile range) sums for the two groups are as follows: surgical, 400 (400-400), and NOM, 400 (-2,427 to 400) (p < 0.001). A larger proportion of appendectomy subjects (88.1%) had an outcome that was equivalent (or better) than at least half of the subjects compared with NOM subjects (NOM, 70.5%; OR [95% confidence interval], 0.3 [0.2-0.4]). CONCLUSION: In contemporary American practice, appendectomy (compared with NOM) for simple appendicitis is associated with lower odds of developing clinically important unfavorable outcomes in the first year after illness. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.


Assuntos
Apendicectomia , Apendicite , Antibacterianos/uso terapêutico , Apendicectomia/métodos , Apendicite/tratamento farmacológico , Apendicite/cirurgia , Drenagem , Humanos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Resultado do Tratamento
5.
J Trauma Acute Care Surg ; 92(3): 481-488, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34882598

RESUMO

BACKGROUND: The Trauma and Injury Severity Score (TRISS) uses anatomical and physiologic variables to predict mortality. Elderly (65 years or older) trauma patients have increased mortality and morbidity for a given TRISS, in part because of functional status and comorbidities. These factors are incorporated into the American Society of Anesthesiologists Physical Status (ASA-PS) and National Surgical Quality Improvement Program Surgical Risk Calculator (NSQIP-SRC). We hypothesized scoring tools using comorbidities and functional status to be superior at predicting mortality, hospital length of stay (LOS), and complications in elderly trauma patients undergoing operation. METHODS: Four level I trauma centers prospectively collected data on elderly trauma patients undergoing surgery within 24 hours of admission. Using logistic regression, five scoring models were compared: ASA-PS, NSQIP-SRC, TRISS, TRISS-ASA-PS, and TRISS-NSQIP-SRC.Brier scores and area under the receiver operator characteristics curve were calculated to compare mortality prediction. Adjusted R2 and root mean squared error were used to compare LOS and predictive ability for number of complications. RESULTS: From 122 subjects, 9 (7.4%) died, and the average LOS was 12.9 days (range, 1-110 days). National Surgical Quality Improvement Program Surgical Risk Calculator was superior to ASA-PS and TRISS at predicting mortality (area under the receiver operator characteristics curve, 0.978 vs. 0.768 vs. 0.903; p = 0.007). Furthermore, NSQIP-SRC was more accurate predicting LOS (R2, 25.9% vs. 13.3% vs. 20.5%) and complications (R2, 34.0% vs. 22.6% vs. 29.4%) compared with TRISS and ASA-PS. Adding TRISS to NSQIP-SRC improved predictive ability compared with NSQIP-SRC alone for complications (R2, 35.5% vs. 34.0%; p = 0.046). However, adding ASA-PS or TRISS to NSQIP-SRC did not improve the predictive ability for mortality or LOS. CONCLUSION: The NSQIP-SRC, which includes comorbidities and functional status, had superior ability to predict mortality, LOS, and complications compared with TRISS alone in elderly trauma patients undergoing surgery. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.


Assuntos
Melhoria de Qualidade , Medição de Risco/métodos , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/cirurgia , Idoso , Comorbidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Complicações Pós-Operatórias/mortalidade , Valor Preditivo dos Testes , Estudos Prospectivos , Centros de Traumatologia , Estados Unidos
6.
Hum Mol Genet ; 31(3): 440-454, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34505148

RESUMO

Recently, others and we identified de novo FBXO11 (F-Box only protein 11) variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data, our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs.


Assuntos
Proteínas F-Box , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Proteínas F-Box/genética , Células HEK293 , Células HeLa , Humanos , Deficiência Intelectual/genética , Mutação de Sentido Incorreto/genética , Transtornos do Neurodesenvolvimento/genética , Proteína-Arginina N-Metiltransferases/genética
7.
J Surg Res ; 269: 69-75, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520984

RESUMO

BACKGROUND: There are significant practice variations in antibiotic treatment for appendicitis, ranging from short-course narrow spectrum to long-course broad-spectrum. We sought to describe the modern microbial epidemiology of acute and perforated appendicitis in adults to help inform appropriate empiric coverage and support antibiotic stewardship initiatives. METHODS: This is a post-hoc secondary analysis of the Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous (MUSTANG) which prospectively enrolled adult patients (age ≥ 18 years) diagnosed with appendicitis between January 2017 and June 2018 across 28 centers in the United States. We included all subjects with positive microbiologic cultures during primary or secondary (rescue after medical failure) appendectomy or percutaneous drainage. Culture yield was compared between low- and high-grade appendicitis as per the AAST classification. RESULTS: A total of 3,471 patients were included: 230 (7%) had cultures performed, and 179/230 (78%) had positive results. Cultures were less likely to be positive in grade 1 compared to grades 3, 4, or 5 appendicitis with 2/18 (11%) vs 61/70 (87%) (p < .001). Only 1 subject had grade 2 appendicitis and culture results were negative. E. coli was the most common pathogen and cultured in 29 (46%) of primary appendectomy samples, 16 (50%) of secondary, and 44 (52%) of percutaneous drainage samples. CONCLUSION: Culturing low-grade appendicitis is low yield. E. coli is the most commonly cultured microbe in acute and perforated appendicitis. This data helps inform empiric coverage for both antibiotics alone and as an adjunct to operative or percutaneous intervention.


Assuntos
Gestão de Antimicrobianos , Apendicite , Adolescente , Adulto , Antibacterianos/uso terapêutico , Apendicectomia/métodos , Apendicite/complicações , Apendicite/epidemiologia , Apendicite/cirurgia , Drenagem/métodos , Escherichia coli , Humanos , Estudos Retrospectivos , Estados Unidos
8.
Am J Med Genet A ; 188(1): 292-297, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34533271

RESUMO

Cohen-Gibson syndrome is a rare genetic disorder, characterized by fetal or early childhood overgrowth and mild to severe intellectual disability. It is caused by heterozygous aberrations in EED, which encodes an evolutionary conserved polycomb group (PcG) protein that forms the polycomb repressive complex-2 (PRC2) together with EZH2, SUZ12, and RBBP7/4. In total, 11 affected individuals with heterozygous pathogenic variants in EED were reported, so far. All variants affect a few key residues within the EED WD40 repeat domain. By trio exome sequencing, we identified the heterozygous missense variant c.581A > G, p.(Asn194Ser) in exon 6 of the EED-gene in an individual with moderate intellectual disability, overgrowth, and epilepsy. The same pathogenic variant was detected in 2 of the 11 previously reported cases. Epilepsy, however, was only diagnosed in one other individual with Cohen-Gibson syndrome before. Our findings further confirm that the WD40 repeat domain represents a mutational hotspot; they also expand the clinical spectrum of Cohen-Gibson syndrome and highlight the clinical variability even in individuals with the same pathogenic variant. Furthermore, they indicate a possible association between Cohen-Gibson syndrome and epilepsy.


Assuntos
Epilepsia , Deficiência Intelectual , Pré-Escolar , Epilepsia/genética , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Mutação , Complexo Repressor Polycomb 2/genética , Sequenciamento Completo do Exoma
9.
J Clin Endocrinol Metab ; 106(12): 3413-3427, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34383079

RESUMO

CONTEXT: CPE encodes carboxypeptidase E, an enzyme that converts proneuropeptides and propeptide hormones to bioactive forms. It is widely expressed in the endocrine and central nervous system. To date, 4 individuals from 2 families with core clinical features including morbid obesity, neurodevelopmental delay, and hypogonadotropic hypogonadism, harboring biallelic loss-of-function (LoF) CPE variants, have been reported. OBJECTIVE: We describe 4 affected individuals from 3 unrelated consanguineous families, 2 siblings of Syrian, 1 of Egyptian, and 1 of Pakistani descent, all harboring novel homozygous CPE LoF variants. METHODS: After excluding Prader-Willi syndrome (PWS), exome sequencing was performed in both Syrian siblings. The variants identified in the other 2 individuals were reported as research variants in a large-scale exome study and in the ClinVar database. Computational modeling of all possible missense alterations allowed assessing CPE tolerance to missense variants. RESULTS: All affected individuals were severely obese with neurodevelopmental delay and other endocrine anomalies. Three individuals from 2 families shared the same CPE homozygous truncating variant c.361C > T, p.(Arg121*), while the fourth carried the c.994del, p.(Ser333Alafs*22) variant. Comparison of clinical features with previously described cases and standardization according to the Human Phenotype Ontology terms indicated a recognizable clinical phenotype, which we termed Blakemore-Durmaz-Vasileiou (BDV) syndrome. Computational analysis indicated high conservation of CPE domains and intolerance to missense changes. CONCLUSION: Biallelic truncating CPE variants are associated with BDV syndrome, a clinically recognizable monogenic recessive syndrome with childhood-onset obesity, neurodevelopmental delay, hypogonadotropic hypogonadism, and hypothyroidism. BDV syndrome resembles PWS. Our findings suggest missense variants may also be clinically relevant.


Assuntos
Carboxipeptidase H/genética , Hipogonadismo/patologia , Hipotireoidismo/patologia , Mutação com Perda de Função , Transtornos do Neurodesenvolvimento/patologia , Obesidade/patologia , Síndrome de Prader-Willi/diagnóstico , Adolescente , Alelos , Criança , Feminino , Humanos , Hipogonadismo/genética , Hipotireoidismo/genética , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/genética , Obesidade/genética , Linhagem , Prognóstico , Síndrome
10.
Clin Genet ; 100(4): 412-429, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34216016

RESUMO

ZMYND11 is the critical gene in chromosome 10p15.3 microdeletion syndrome, a syndromic cause of intellectual disability. The phenotype of ZMYND11 variants has recently been extended to autism and seizures. We expand on the epilepsy phenotype of 20 individuals with pathogenic variants in ZMYND11. We obtained clinical descriptions of 16 new and nine published individuals, plus detailed case history of two children. New individuals were identified through GeneMatcher, ClinVar and the European Network for Therapies in Rare Epilepsy (NETRE). Genetic evaluation was performed using gene panels or exome sequencing; variants were classified using American College of Medical Genetics (ACMG) criteria. Individuals with ZMYND11 associated epilepsy fell into three groups: (i) atypical benign partial epilepsy or idiopathic focal epilepsy (n = 8); (ii) generalised epilepsies/infantile epileptic encephalopathy (n = 4); (iii) unclassified (n = 8). Seizure prognosis ranged from spontaneous remission to drug resistant. Neurodevelopmental deficits were invariable. Dysmorphic features were variable. Variants were distributed across the gene and mostly de novo with no precise genotype-phenotype correlation. ZMYND11 is one of a small group of chromatin reader genes associated in the pathogenesis of epilepsy, and specifically ABPE. More detailed epilepsy descriptions of larger cohorts and functional studies might reveal genotype-phenotype correlation. The epileptogenic mechanism may be linked to interaction with histone H3.3.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas Correpressoras/genética , Proteínas de Ligação a DNA/genética , Epilepsia/diagnóstico , Epilepsia/genética , Variação Genética , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Fenótipo , Adolescente , Adulto , Alelos , Substituição de Aminoácidos , Criança , Pré-Escolar , Bases de Dados Factuais , Eletroencefalografia , Epilepsia/terapia , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem
11.
Surg Infect (Larchmt) ; 22(8): 780-786, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33877912

RESUMO

Background: We sought to assess the efficacy of prophylactic abdominal drainage to prevent complications after appendectomy for perforated appendicitis. Methods: In this post hoc analysis of a prospective multi-center study of appendicitis in adults (≥ 18 years), we included patients with perforated appendicitis diagnosed intra-operatively. The 634 subjects were divided into groups on the basis of receipt of prophylactic drains. The demographics and outcomes analyzed were surgical site infection (SSI), intra-abdominal abscess (IAA), Clavien-Dindo complications, secondary interventions, and hospital length of stay (LOS). Multivariable logistic regression for the cumulative 30-day incidence of IAA was performed controlling for age, Charlson Comorbidity Index (CCI), antibiotic duration, presence of drains, and Operative American Association for the Surgery of Trauma (AAST) Grade. Results: In comparing the Drain (n = 159) versus No-Drain (n = 475) groups, there was no difference in the frequency of male gender (61% versus 55%; p = 0.168), weight (87.9 ± 27.9 versus 83.8 ± 23.4 kg; p = 0.071), Alvarado score (7 [6-8] versus 7 [6-8]; p = 0.591), white blood cell (WBC) count (14.8 ± 4.8 versus 14.9 ± 4.5; p = 0.867), or CCI (1 [0-3] versus 1 [0-2]; p = 0.113). The Drain group was significantly older (51 ± 16 versus 48 ± 17 years; p = 0.017). Drain use increased as AAST EGS Appendicitis Operative Severity Grade increased: Grade 3 (62/311; 20%), Grade 4 (46/168; 27%), and Grade 5 (51/155; 33%); p = 0.007. For index hospitalization, the Drain group had a higher complication rate (43% versus 28%; p = 0.001) and longer LOS (4 [3-7] versus 3 [1-5] days; p < 0.001). We could not detect a difference between the groups in the incidence of SSI, IAA, or secondary interventions. There was no difference in 30-day emergency department visits, re-admissions, or secondary interventions. Multi-variable logistic regression showed that only AAST Grade (odds ratio 2.7; 95% confidence interval7 1.5-4.7; p = 0.001) was predictive of the cumulative 30-day incidence of IAA. Conclusions: Prophylactic drainage after appendectomy for perforated appendicitis in adults is not associated with fewer intra-abdominal abscesses but is associated with longer hospital LOS. Increasing AAST EGS Appendicitis Operative Grade is a strong predictor of intra-abdominal abscess.


Assuntos
Abscesso Abdominal , Apendicite , Abscesso Abdominal/epidemiologia , Abscesso Abdominal/prevenção & controle , Adulto , Apendicectomia/efeitos adversos , Apendicite/cirurgia , Drenagem , Humanos , Tempo de Internação , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos
12.
J Trauma Acute Care Surg ; 90(3): 557-564, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507026

RESUMO

BACKGROUND: The Emergency Surgery Score (ESS) was recently validated as an accurate mortality risk calculator for emergency general surgery. We sought to prospectively evaluate whether ESS can predict the need for respiratory and/or renal support (RRS) at discharge after emergent laparotomies (EL). METHODS: This is a post hoc analysis of a 19-center prospective observational study. Between April 2018 and June 2019, all adult patients undergoing EL were enrolled. Preoperative, intraoperative, and postoperative variables were systematically collected. In this analysis, patients were excluded if they died during the index hospitalization, were discharged to hospice, or transferred to other hospitals. A composite variable, the need for RRS, was defined as the need for one or more of the following at hospital discharge: tracheostomy, ventilator dependence, or dialysis. Emergency Surgery Score was calculated for all patients, and the correlation between ESS and RRS was examined using the c-statistics method. RESULTS: From a total of 1,649 patients, 1,347 were included. Median age was 60 years, 49.4% were men, and 70.9% were White. The most common diagnoses were hollow viscus organ perforation (28.1%) and small bowel obstruction (24.5%); 87 patients (6.5%) had a need for RRS (4.7% tracheostomy, 2.7% dialysis, and 1.3% ventilator dependence). Emergency Surgery Score predicted the need for RRS in a stepwise fashion; for example, 0.7%, 26.2%, and 85.7% of patients required RRS at an ESS of 2, 12, and 16, respectively. The c-statistics for the need for RRS, the need for tracheostomy, ventilator dependence, or dialysis at discharge were 0.84, 0.82, 0.79, and 0.88, respectively. CONCLUSION: Emergency Surgery Score accurately predicts the need for RRS at discharge in EL patients and could be used for preoperative patient counseling and for quality of care benchmarking. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.


Assuntos
Serviço Hospitalar de Emergência , Hospitalização , Laparotomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Diálise Renal , Respiração Artificial , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Complicações Pós-Operatórias/terapia , Valor Preditivo dos Testes , Medição de Risco
13.
Am J Surg ; 221(5): 1069-1075, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32917366

RESUMO

INTRODUCTION: We sought to evaluate whether the Emergency Surgery Score (ESS) can accurately predict outcomes in elderly patients undergoing emergent laparotomy (EL). METHODS: This is a post-hoc analysis of an EAST multicenter study. Between April 2018 and June 2019, all adult patients undergoing EL in 19 participating hospitals were prospectively enrolled, and ESS was calculated for each patient. Using the c-statistic, the correlation between ESS and mortality, morbidity, and need for ICU admission was assessed in three patient age cohorts (65-74, 75-84, ≥85 years old). RESULTS: 715 patients were included, of which 52% were 65-74, 34% were 75-84, and 14% were ≥85 years old; 51% were female, and 77% were white. ESS strongly correlated with postoperative mortality (c-statistic:0.81). Mortality gradually increased from 0% to 20%-60% at ESS of 2, 10 and 16 points, respectively. ESS predicted mortality, morbidity, and need for ICU best in patients 65-74 years old (c-statistic:0.81, 0.75, 0.83 respectively), but its performance significantly decreased in patients ≥85 years (c-statistic:0.72, 0.64, 0.67 respectively). CONCLUSION: ESS is an accurate predictor of outcome in the elderly EL patient 65-85 years old, but its performance decreases for patients ≥85. Consideration should be given to modify ESS to better predict outcomes in the very elderly patient population.


Assuntos
Tratamento de Emergência/estatística & dados numéricos , Laparotomia/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Tratamento de Emergência/efeitos adversos , Tratamento de Emergência/mortalidade , Feminino , Humanos , Laparotomia/efeitos adversos , Laparotomia/mortalidade , Masculino , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos
14.
Surg Infect (Larchmt) ; 22(5): 504-508, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32897168

RESUMO

Background: The post-operative management of simple (acute) appendicitis differs throughout the United States. Guidelines regarding post-operative antibiotic usage remain unclear, and treatment generally is dictated by surgeon preference. We hypothesize that post-operative antibiotic use for simple appendicitis is not associated with lower post-operative complication rates. Methods: In a post-hoc analysis in a large multi-center observational study, only patients with an intra-operative diagnosis of AAST EGS Grade I were included. Subjects were classified into those receiving post-operative antibiotics (POST) and those given pre-operative antibiotics only (NONE). Clinical outcomes examined were length of stay (LOS), 30-day emergency department (ED) visits and hospital re-admissions, secondary interventions, surgical site infection (SSI), and intra-abdominal abscess (IAA). Results: A total of 2,191 subjects were included, of whom 612 (28%) received post-operative antibiotics. Compared with the NONE group, POST patients were older (age 37 [range 26-50] versus 33 [26-46] years; p < 0.001), weighed more (82 [70-96] versus 79 [68-93] kg (p = 0.038), and had higher white blood cell counts (13.5 ± 4.2 versus 13.1 ± 4.4/103/mcL (p = 0.046), Alvarado Scores (6 [5-7] versus 6 [5-7]; p < 0.001), and Charlson Comorbidity Indices (median score 0 in both cohorts; p < 0.001). The POST patients had a longer LOS (1 [1-2] versus 1 [1-1] days; p < 0.001). There were no differences in the number who had ED visits within 30 days (9% versus 8%; p = 0.435), hospital re-admission (4% versus 2%; p = 0.165), an index hospitalization SSI (0.2% for both cohorts; p = 0.69), an SSI within 30 days (4% versus 2%; p = 0.165), index hospitalization IAA rate (0.3% versus 0.1%; p = 0.190), 30-day IAA (2% versus 1%; p = 0.71), index hospitalization interventions (0.5% versus 0.1%; p = 0.137) or 30-day secondary interventions (2% versus 1%; p = 0.155). Conclusions: Post-operative antibiotic use after appendectomy for simple appendicitis is not associated with better post-operative clinical outcomes at index hospitalization or at 30 days after discharge.


Assuntos
Abscesso Abdominal , Apendicite , Adulto , Antibacterianos/uso terapêutico , Apendicectomia , Apendicite/tratamento farmacológico , Apendicite/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do Tratamento
15.
J Trauma Acute Care Surg ; 89(6): 1023-1031, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32890337

RESUMO

OBJECTIVE: Evidence comparing stoma creation (STM) versus anastomosis after urgent or emergent colorectal resection is limited. This study examined outcomes after colorectal resection in emergency general surgery patients. METHODS: This was an Eastern Association for the Surgery of Trauma-sponsored prospective observational multicenter study of patients undergoing urgent/emergent colorectal resection. Twenty-one centers enrolled patients for 11 months. Preoperative, intraoperative, and postoperative variables were recorded. χ, Mann-Whitney U test, and multivariable logistic regression models were used to describe outcomes and risk factors for surgical complication/mortality. RESULTS: A total of 439 patients were enrolled (ANST, 184; STM, 255). The median (interquartile range) age was 62 (53-71) years, and the median Charlson Comorbidity Index (CCI) was 4 (1-6). The most common indication for surgery was diverticulitis (28%). Stoma group was older (64 vs. 58 years, p < 0.001), had a higher CCI, and were more likely to be immunosuppressed. Preoperatively, STM patients were more likely to be intubated (57 vs. 15, p < 0.001), on vasopressors (61 vs. 13, p < 0.001), have pneumoperitoneum (131 vs. 41, p < 0.001) or fecal contamination (114 vs. 33, p < 0.001), and had a higher incidence of elevated lactate (149 vs. 67, p < 0.001). Overall mortality was 13%, which was higher in STM patients (18% vs. 8%, p = 0.02). Surgical complications were more common in STM patients (35% vs. 25%, p = 0.02). On multivariable analysis, management with an open abdomen, intraoperative blood transfusion, and larger hospital size were associated with development of a surgical complication, while CCI, preoperative vasopressor use, steroid use, open abdomen, and intraoperative blood transfusion were independently associated with mortality. CONCLUSION: This study highlights a tendency to perform fecal diversion in patients who are acutely ill at presentation. There is a higher morbidity and mortality rate in STM patients. Independent predictors of mortality include CCI, preoperative vasopressor use, steroid use, open abdomen, and intraoperative blood transfusion. Following adjustment by clinical factors, method of colon management was not associated with surgical complications or mortality. LEVEL OF EVIDENCE: Therapeutic study, level IV.


Assuntos
Colectomia/métodos , Cirurgia Colorretal/educação , Doença Diverticular do Colo/cirurgia , Cirurgia Geral/educação , Idoso , Anastomose Cirúrgica , Colectomia/educação , Colectomia/estatística & dados numéricos , Emergências , Feminino , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Padrões de Prática Médica/estatística & dados numéricos , Estudos Prospectivos , Resultado do Tratamento , Estados Unidos
16.
Surgery ; 168(4): 701-706, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32739139

RESUMO

BACKGROUND: The incidence of underlying malignancy in appendicitis ranges between 0.5% and 1.7%. We sought to identify the subset of patients with appendicitis who are at increased risk of appendiceal malignancy. METHODS: Using the Eastern Association for the Surgery of Trauma Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous database, we included all patients from 28 centers undergoing immediate, delayed, or interval appendectomy between 2017 and 2018. Univariate then multivariable analyses were performed to compare patients with and without malignancy and to identify independent demographic, clinical, laboratory, and/or radiological predictors of malignancy. Akaike information criteria for regression models were used to evaluate goodness of fit. RESULTS: A total of 3,293 patients were included. The median age was 38 (27-53) years, and 46.5% were female patients. On pathology, 48 (1.5%) had an underlying malignancy (adenocarcinoma [60.4%], neuroendocrine [37.5%], and lymphoma [2.1%]). Patients with malignancy were older (56 [34.5-67] vs 37 [27-52] years, P < .001), had longer duration of symptoms before presentation (36-41 vs 18-23 hours, P = .03), and were more likely to have a phlegmon on imaging (6.3% vs 1.3%, P = .03). Multivariable analyses showed that an enlarged appendiceal diameter was independently associated with malignancy (odds ratio = 1.06, 95% confidence interval = 1.01-1.12; P = .01). The incidence of malignancy in patients >40 years with an appendiceal diameter >10 mm on computed tomography was 2.95% compared with 0.97% in patients ≤40 years old with appendiceal diameter ≤10 mm. The corresponding risk ratio for that population was 3.03 (95% confidence interval: 1.24-7.42; P = .02). CONCLUSION: The combination of age >40 and an appendiceal diameter >10 mm is associated with a greater than 3-fold increased risk of malignancy in patients presenting with appendicitis.


Assuntos
Neoplasias do Apêndice/diagnóstico por imagem , Apendicite/patologia , Apêndice/patologia , Adulto , Fatores Etários , Apendicectomia , Apendicite/diagnóstico por imagem , Apendicite/cirurgia , Apêndice/diagnóstico por imagem , Apêndice/cirurgia , Celulite (Flegmão)/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tomografia Computadorizada por Raios X
17.
Mod Pathol ; 33(11): 2341-2353, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32612247

RESUMO

Uterine leiomyomas (ULs) constitute a considerable health burden in the general female population. The fumarate hydratase (FH) deficient subtype is found in up to 1.6% and can occur in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. We sequenced 13 FH deficient ULs from a previous immunohistochemical screen using a targeted panel and identified biallelic FH variants in all. In eight, we found an FH point mutation (two truncating, six missense) with evidence for loss of the second allele. Variant allele-frequencies in all cases with a point mutation pointed to somatic variants. Spatial clustering of the identified missense variants in the lyase domain indicated altered fumarase oligomerization with subsequent degradation as explanation for the observed FH deficiency. Biallelic FH deletions in five tumors confirm the importance of copy number loss as mutational mechanism. By curating all pathogenic FH variants and calculating their population frequency, we estimate a carrier frequency of up to 1/2,563. Comparing with the prevalence of FH deficient ULs, we conclude that most are sporadic and estimate 2.7-13.9% of females with an FH deficient UL to carry a germline FH variant. Further prospective tumor/normal sequencing studies are needed to develop a reliable screening strategy for HLRCC in women with ULs.


Assuntos
Fumarato Hidratase/genética , Leiomioma/genética , Neoplasias Uterinas/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Fumarato Hidratase/metabolismo , Mutação em Linhagem Germinativa , Humanos , Leiomioma/metabolismo , Leiomioma/patologia , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
18.
BMC Med Imaging ; 20(1): 86, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727387

RESUMO

BACKGROUND: BRCA1/2 deleterious variants account for most of the hereditary breast and ovarian cancer cases. Prediction models and guidelines for the assessment of genetic risk rely heavily on criteria with high variability such as family cancer history. Here we investigated the efficacy of MRI (magnetic resonance imaging) texture features as a predictor for BRCA mutation status. METHODS: A total of 41 female breast cancer individuals at high genetic risk, sixteen with a BRCA1/2 pathogenic variant and twenty five controls were included. From each MRI 4225 computer-extracted voxels were analyzed. Non-imaging features including clinical, family cancer history variables and triple negative receptor status (TNBC) were complementarily used. Lasso-principal component regression (L-PCR) analysis was implemented to compare the predictive performance, assessed as area under the curve (AUC), when imaging features were used, and lasso logistic regression or conventional logistic regression for the remaining analyses. RESULTS: Lasso-selected imaging principal components showed the highest predictive value (AUC 0.86), surpassing family cancer history. Clinical variables comprising age at disease onset and bilateral breast cancer yielded a relatively poor AUC (~ 0.56). Combination of imaging with the non-imaging variables led to an improvement of predictive performance in all analyses, with TNBC along with the imaging components yielding the highest AUC (0.94). Replacing family history variables with imaging components yielded an improvement of classification performance of ~ 4%, suggesting that imaging compensates the predictive information arising from family cancer structure. CONCLUSIONS: The L-PCR model uncovered evidence for the utility of MRI texture features in distinguishing between BRCA1/2 positive and negative high-risk breast cancer individuals, which may suggest value to diagnostic routine. Integration of computer-extracted texture analysis from MRI modalities in prediction models and inclusion criteria might play a role in reducing false positives or missed cases especially when established risk variables such as family history are missing.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Feminino , Variação Genética , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Análise de Regressão , Medição de Risco , Neoplasias de Mama Triplo Negativas/genética
19.
J Surg Res ; 254: 217-222, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32474194

RESUMO

BACKGROUND: We sought to compare the effectiveness of narrow- versus broad-spectrum antibiotics (abx) in preventing infectious complications in adults with acute appendicitis treated with appendectomy. METHODS: In this post hoc analysis of a prospective multicenter observational study of appendicitis in adults (≥18 y) conducted from January 2017 to June 2018, we included only patients with simple appendicitis. Subjects were grouped based on receipt of broad-spectrum or narrow-spectrum abx before and/or after appendectomy. Outcomes compared were surgical site infection, intra-abdominal abscess, secondary interventions (percutaneous drainage or operation), emergency department (ED) visits, 30-d readmission, and hospital length of stay. RESULTS: A total of 2336 subjects were analyzed. In comparing narrow (n = 778) versus broad (n = 1558) groups, there were no differences in male sex (53% versus 54%, P = 0.704), white blood cell (13.0 ± 3.9 versus 13.4 ± 4.5, P = 0.05), Alvarado score (6 [5-7] versus 6 [5-7], P = 0.25), or Charlson comorbidity index (0 [0-1] versus 0 [0-1], P = 0.09). A total of 688 (29%) received postoperative abx, [184 (24%) narrow and 504 (32%) broad, P < 0.001] for a median 5 [2-7] d [42 (23%) narrow and 235 (47%) broad, P < 0.001]. There were no significant differences between narrow and broad groups in surgical site infection, intra-abdominal abscess, secondary interventions, ED visits, or hospital readmissions. CONCLUSIONS: Significant practice variation in duration and spectrum of antibiotic adjunct for surgical treatment of simple acute appendicitis treatment is evident, and broad-spectrum abx did not offer clinical advantages over narrow-spectrum abx. Restriction of antibiotic spectrum should be considered, although randomized trials are required to overcome selection bias.


Assuntos
Antibacterianos/uso terapêutico , Apendicite/tratamento farmacológico , Adulto , Apendicectomia , Apendicite/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Artigo em Inglês | MEDLINE | ID: mdl-32562287

RESUMO

BACKGROUND: Classic experiments demonstrating hypermetabolism after major trauma were performed in a different era of critical care. We aim to describe the modern posttraumatic metabolic response in the trauma intensive care unit (TICU). METHODS: This prospective observational study enrolled TICU mechanically ventilated adults (aged ≥18) from 3/2018-2/2019. Multiple, daily resting energy expenditure (REE) measurements were recorded. Basal energy expenditure (BEE) was calculated by the Harris-Benedict equation. Hypometabolism was defined as average daily REE < 0.85*BEE and hypermetabolism defined as average daily REE > 1.15*BEE. Demographics, interventions, and clinical outcomes were abstracted. Descriptive statistics and multivariable logistical regression models evaluating demographics with the outcome variable of hypermetabolism for the first 3 days ("sustained hypermetabolism") were performed, along with group-based trajectory modeling (GBTM). RESULTS: Fifty-five patients were analyzed: median age was 38 (28-56) years; 38 (69%) were male; body mass index (kg/m2 ) was 28 (26-32); and Injury Severity Score was 27 (19-34), with (38 [71%] blunt, 8 [15%] penetrating, 7 [13%] burn) injury mechanism. Overall, 19 (35%) had hypermetabolism on day 1 ("immediate hypermetabolism"), and 11 (21%) had sustained hypermetabolism for the first 3 days. Logistic regression analysis identified penetrating mechanism (adjusted odds ratio [AOR], 16.4; 95% CI, 1.9-199.6; p = .015), burn mechanism (AOR, 11.1; 95% CI, 1.3-116.8; p =.029), and maximum temperature (AOR, 4.2; 95% CI, 1.3-20.3; p= .041) as independent predictors of sustained hypermetabolism. GBTM identified 4 nutrition phenotypes, with 2 hyperconsumptive phenotypes associated with increased risk of malnutrition at discharge. CONCLUSION: Only a minority of injured patients is hypermetabolic in the first week after injury. Elevated temperature, penetrating mechanism, and burn mechanism are independently associated with sustained hypermetabolism. Hyperconsumptive phenotype patients are more likely to develop malnutrition during hospitalization.

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