RESUMO
PURPOSE: A systematic review was conducted to investigate differences in incidence and primary origin of synchronous brain metastasis (sBM) in varying racial groups with different primary cancers. METHODS: Adhering to PRISMA 2020 guidelines a search was conducted using PubMed and Ovid databases for publications from January 2000 to January 2023, with search terms including combinations of "brain metastasis," "race," "ethnicity," and "incidence." Three independent reviewers screened for inclusion criteria encompassing studies clearly reporting primary cancer sites, patient demographics including race, and synchronous BM (sBM) incidence. RESULTS: Of 806 articles, 10 studies comprised of mainly adult patients from the United States met final inclusion for data analysis. Higher sBM incidence proportions were observed in American Indian/Alaska native patients for primary breast (p < 0.001), colorectal (p = 0.015), and esophageal cancers (p = 0.024) as well as in Asian or Pacific islanders for primary stomach (p < 0.001), thyroid (p = 0.006), and lung/bronchus cancers (p < 0.001) yet higher proportions in White patients for malignant melanoma (p < 0.001). Compared to White patients, Black patients had higher sBM incidence likelihood in breast cancer (OR = 1.27, p = 0.01) but lower likelihood in renal (OR = 0.46, p < 0.001) and esophageal cancers (OR = 0.31, p = 0.005). American Indian/Alaska native patients had a higher sBM likelihood (OR = 3.78, p = 0.004) relative to White patients in esophageal cancer. CONCLUSIONS: These findings reveal several comparative racial differences in sBM incidence arising from different primary cancer origins, underscoring a need for further research to explain these variations. Identifying the factors contributing to these disparities holds the potential to promote greater equity in oncological care according to cancer type.
Assuntos
Neoplasias Encefálicas , Humanos , Incidência , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/epidemiologia , Grupos Raciais/estatística & dados numéricos , Neoplasias/patologia , Neoplasias/epidemiologiaRESUMO
BACKGROUND: For the vast majority of displaced femoral neck fractures in older patients, cemented femoral fixation is indicated because it is associated with a lower risk of periprosthetic fracture than cementless fixation. Nevertheless, cementless fixation continues to be utilized with high frequency for hip fractures in the United States. It is therefore helpful to understand the performance of individual cementless brands and models. Although prior studies have compared femoral stems by design type or stem geometry, there may still be a difference in revision risk according to femoral stem brand given the potential differences within design groupings with regard to manufacturing, implantation systems, and implant design nuances among vendors. QUESTIONS/PURPOSES: (1) Is there a difference in aseptic revision risk among femoral stem brands in patients ≥ 60 years of age who have displaced femoral neck fractures treated with cementless hemiarthroplasty? (2) Is there a difference in revision for periprosthetic fracture among femoral stem brands in patients ≥ 60 years of age with displaced femoral neck fractures treated with cementless hemiarthroplasty? METHODS: A retrospective, comparative, large-database cohort study was conducted using data from Kaiser Permanente's Hip Fracture Registry. This integrated healthcare system covers more than 12 million members throughout eight regions in the United States; membership has been found to be representative of the general population in the areas served. The Hip Fracture Registry collects details on all patients who undergo hip fracture repair within the organization. These patients are then longitudinally monitored for outcomes after their repair, and all identified outcomes are manually validated through chart review. Patients ages ≥ 60 years who underwent unilateral hemiarthroplasty treatment of a displaced femoral neck fracture from 2009 to 2021 were identified (n = 22,248). Hemiarthroplasties for polytrauma, pathologic or open fractures, or patients who had additional surgeries at other body sites during the same stay, as well as those with prior procedures in the same hip, were excluded (21.4% [4768]). Cemented procedures and those with missing or inconsistent implant information (for example, cement used but cementless implant recorded) were further excluded (47.1% [10,485]). To allow for enough events for evaluation, the study sample was restricted to seven stems for which there were at least 300 hemiarthroplasties performed, including four models from DePuy Synthes (Corail®, Summit®, Summit Basic, and Tri-Lock®) and three from Zimmer Biomet (Medial-Lateral [M/L] Taper®, Trabecular Metal®, and Versys® Low Demand Fracture [LD/FX]). The final sample included 5676 cementless hemiarthroplasties: 653 Corail, 402 M/L Taper, 1699 Summit, 1590 Summit Basic, 384 Tri-Lock, 637 Trabecular Metal, and 311 Versys LD/FX. Procedures were performed by 396 surgeons at 35 hospitals. The mean age and BMI for the cohort was 81 years and 24 kg/m2, respectively; most were women (66% [3733 of 5676]) and White (79% [4488 of 5676]). Based on standardized mean differences, we controlled for age, race/ethnicity, American Society of Anesthesiologist (ASA) classification, anesthesia technique, operative year, average annual surgeon hemiarthroplasty volume, and operative year across the seven stem groups. Of the 5676 patients, 7% (378 of 5676) were lost to follow-up through membership termination at a median time of 1.6 years, and 56% (3194 of 5676) of the patients died during study follow-up. A multivariable cause-specific Cox proportional hazards regression model was used to evaluate the risk for aseptic revision with adjustment for age, gender, ASA classification, depression, operating surgeon, deficiency anemias, time from admission to surgery, and average annual surgeon hemiarthroplasty volume. A random intercept was included to address effects from hemiarthroplasties performed by the same surgeon. Risk for revision for periprosthetic fracture was also evaluated as a secondary outcome. RESULTS: In the adjusted analysis, the Summit Basic (HR 1.91 [95% confidence interval 1.34 to 2.72]; p < 0.001), the M/L Taper (HR 1.91 [95% CI 1.15 to 3.15]; p = 0.01), and the Versys LD/FX (HR 2.12 [95% CI 1.25 to 3.61]; p = 0.005) had higher aseptic revision risks during follow-up when compared with the Summit. No differences were observed for the Corail (HR 0.57 [95% CI 0.29 to 1.10]; p = 0.09), the Tri-Lock (HR 1.13 [95% CI 0.62 to 2.07]; p = 0.68), or the Trabecular Metal (HR 1.14 [95% CI 0.69 to 1.89]; p = 0.61) compared with the Summit. A higher risk for revision because of periprosthetic fracture was observed with the M/L Taper (HR 2.43 [95% CI 1.29 to 4.58]; p = 0.006) and the Summit Basic (within 3 months of follow-up: HR 1.16 [95% CI 0.60 to 2.25]; p = 0.66; after 3 months of follow-up: HR 2.84 [95% CI 1.36 to 5.94]; p = 0.006) stems when compared with the Summit. CONCLUSION: In a cohort of 5676 cementless hemiarthroplasties, we found differences in revision risks among different femoral stem brands. Based on our findings, we recommend against utilization of the Zimmer M/L Taper, DePuy Summit Basic, and Zimmer Versys LD/FX in the treatment of displaced geriatric femoral neck fractures with cementless hemiarthroplasty. Future large registry studies are needed to further elucidate differences in aseptic revision risk among higher performing cementless femoral stems. Although cemented fixation remains the recommended approach based on the best available evidence in hemiarthroplasty treatment of hip fractures, our findings may help to mitigate aseptic revision risk should cementless fixation be chosen. LEVEL OF EVIDENCE: Level III, therapeutic study.
RESUMO
PURPOSE: The purpose of this study was to determine the rates of compartment syndrome and other early complications following outpatient open reduction and internal fixation (ORIF) of tibial plateau fractures. METHODS: This was a retrospective cohort at a single US level I academic trauma centre of patients with tibial plateau fractures managed operatively. Inpatients received their definitive ORIF during their index hospital stay and were admitted post-operatively following ORIF. Outpatients were scheduled for ambulatory surgery during definitive ORIF. Exclusion criteria for outpatient surgery included compartment syndrome, polytrauma, open types IIIb/IIIc, and patients who received any internal fixation during index presentation. The primary outcome measure was post-operative compartment syndrome. Secondary outcomes were return to the 90-day return to the ED, 90-day readmission, surgical wound infection, thromboembolism, and 90-day mortality. An intention-to-treat (ITT) and as-treated (AT) analyses were performed. RESULTS: Totally, 71 inpatients and 47 outpatients were included. There were no cases of post-operative compartment syndrome. In the ITT analysis, there were no differences for inpatients vs outpatients for 90-day re-admission (22.5% vs 12.8%, p = 0.275), 90-day return to the ED (35.2% vs 17.0%, p = 0.052), infection (12.7% vs 2.1%, p = 0.094), DVT (7% vs 4.3%, p = 0.819), or PE 1.4% vs 0.0%, p = 1.000). The AT analysis showed a significantly higher 90-day re-admission (26.9% vs 2.5%, p = 0.003) and 90-day ED visit (38.5% vs 7.5%, p = 0.001) rate in the inpatient group. CONCLUSIONS: Appropriately selected patients with isolated tibial plateau fractures can have non-inferior rates of compartment syndrome and post-operative complications when compared to inpatients.
RESUMO
BACKGROUND: With the advancement in device technology, the use of durable left ventricular assist devices (LVADs) has increased significantly in recent years. However, there is a dearth of evidence to conclude whether patients who undergo LVAD implantation at high-volume centers have better clinical outcomes than those receiving care at low- or medium-volume centers. METHODS: We analyzed the hospitalizations using the Nationwide Readmission Database for the year 2019 for new LVAD implantation. Baseline comorbidities and hospital characteristics were compared among low- (1-5 procedures/year), medium- (6-16 procedures/year) and high-volume (17-72 procedures/year) hospitals. The volume/outcome relationship was analyzed using the annualized hospital volume as a categorical variable (tertiles) as well as a continuous variable. Multilevel mixed-effect logistic regression and negative binomial regression models were used to determine the association of hospital volume and outcomes, with tertile 1 (low-volume hospitals) as the reference category. RESULTS: A total of 1533 new LVAD procedures were included in the analysis. The inpatient mortality rate was lower in the high-volume centers compared with the low-volume centers (9.04% vs 18.49%, aOR 0.41, CI0.21-0.80; Pâ¯=â¯0.009). There was a trend toward lower mortality rates in medium-volume centers compared with low-volume centers; however, it did not reach statistical significance (13.27% vs 18.49%, aOR 0.57, CI0.27-1.23; Pâ¯=â¯0.153). Similar results were seen for major adverse events (composite of stroke/transient ischemic attack and in-hospital mortality). There was no significant difference in bleeding/transfusion, acute kidney injury, vascular complications, pericardial effusion/hemopericardium/tamponade, length of stay, cost, or 30-day readmission rates between medium- and high-volume centers compared to low-volume centers. CONCLUSION: Our findings indicate lower inpatient mortality rates in high-volume LVAD implantation centers and a trend toward lower mortality rates in medium-volume LVAD implantation centers compared to lower-volume centers.
Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Humanos , Coração Auxiliar/efeitos adversos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/etiologia , Hospitalização , Hospitais , Mortalidade Hospitalar , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Point-of-care cardiac ultrasound (cardiac POCUS) has potential to become a useful tool for improving cardiovascular care in Tanzania. We conducted a pilot program to train clinicians at peripheral health centers to obtain and interpret focused cardiac POCUS examinations using a hand-held portable device. METHODS: Over a 5-day period, didactic and experiential methods were used to train clinicians to conduct a pre-specified scanning protocol and recognize key pathologies. Pre- and post-training knowledge and post-training image acquisition competency were assessed. In their usual clinical practices, trainees then scanned patients with cardiovascular signs/symptoms, recorded a pre-specified set of images for each scan, and documented their interpretation as to presence or absence of key pathologies on a case report form. A cardiologist subsequently reviewed all images, graded them for image quality, and then documented their interpretation of key pathologies in a blinded fashion; the cardiologist interpretation was considered the gold standard. RESULTS: 8 trainees (6 Clinical Officers, 1 Assistant Medical Officer, and 1 Medical Doctor) initiated and completed the training. Trainees subsequently performed a total of 429 cardiac POCUS examinations in their clinical practices over a 9 week period. Stratified by trainee, the median percent of images that were of sufficient quality to be interpretable was 76.7% (range 18.0-94.2%). For five of eight trainees, 75% or more of images were interpretable. For detection of pre-specified key pathologies, kappa statistics for agreement between trainee and cardiologist ranged from - 0.03 (no agreement) for detection of pericardial effusion to 0.42 (moderate agreement) for detection of tricuspid valve regurgitation. Mean kappa values across the key pathologies varied by trainee from 0 (no agreement) to 0.32 (fair agreement). CONCLUSIONS: The 5-day training program was sufficient to train most clinicians to obtain basic cardiac images but not to accurately interpret them. Proficiency in image interpretation may require a more intensive training program.
Assuntos
Ecocardiografia , Educação Médica Continuada , Cardiopatias/diagnóstico por imagem , Capacitação em Serviço , Testes Imediatos , Adulto , Competência Clínica , Estudos de Viabilidade , Feminino , Humanos , Aprendizagem , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Avaliação de Programas e Projetos de Saúde , Reprodutibilidade dos Testes , TanzâniaRESUMO
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and the most common symptoms include fever, dry cough, dyspnea, fatigue, anorexia, ageusia, and anosmia. Cutaneous manifestations are less common and we share our experience with an otherwise healthy and asymptomatic young man. The patient presented with painless acrocynosis of the left toes which progressed to desquamation by day 16 of disease onset. Disease progression is documented via multiple photographs that portray progression of disease and subsequent resolution over approximately six weeks. Symptomatic treatment included non-steroidal anti-inflammatory medications, leg elevation, and warm compresses.
Assuntos
COVID-19/complicações , Pérnio/etiologia , Dermatoses do Pé/etiologia , Humanos , Masculino , Adulto JovemRESUMO
RDH1 is one of the several enzymes that catalyze the first of the two reactions to convert retinol into all-trans-retinoic acid (atRA). Here, we show that Rdh1-null mice fed a low-fat diet gain more weight as adiposity (17% males, 13% females) than wild-type mice by 20 weeks old, despite neither consuming more calories nor decreasing activity. Glucose intolerance and insulin resistance develop following increased adiposity. Despite the increase in white fat pads, epididymal white adipose does not express Rdh1, nor does muscle. Brown adipose tissue (BAT) and liver express Rdh1 at relatively high levels compared to other tissues. Rdh1 ablation lowered body temperatures during ambient conditions. Given the decreased body temperature, we focused on BAT. A lack of differences in BAT adipogenic gene expression between Rdh1-null mice and wild-type mice, including Pparg, Prdm16, Zfp516 and Zfp521, indicated that the phenotype was not driven by brown adipose hyperplasia. Rather, Rdh1 ablation eliminated the increase in BAT atRA that occurs after re-feeding. This disruption of atRA homeostasis increased fatty acid uptake, but attenuated lipolysis in primary brown adipocytes, resulting in increased lipid content and larger lipid droplets. Rdh1 ablation also decreased mitochondrial proteins, including CYCS and UCP1, the mitochondria oxygen consumption rate, and disrupted the mitochondria membrane potential, further reflecting impaired BAT function, resulting in both BAT and white adipose hypertrophy. RNAseq revealed dysregulation of 424 BAT genes in null mice, which segregated predominantly into differences after fasting vs after re-feeding. Exceptions were Rbp4 and Gbp2b, which increased during both dietary conditions. Rbp4 encodes the serum retinol-binding protein-an insulin desensitizer. Gbp2b encodes a GTPase. Because Gbp2b increased several hundred-fold, we overexpressed it in brown adipocytes. This caused a shift to larger lipid droplets, suggesting that GBP2b affects signaling downstream of the ß-adrenergic receptor during basal thermogenesis. Thus, Rdh1-generated atRA in BAT regulates multiple genes that promote BAT adaptation to whole-body energy status, such as fasting and re-feeding. These gene expression changes promote optimum mitochondria function and thermogenesis, limiting adiposity. Attenuation of adiposity and insulin resistance suggests that RDH1 mitigates metabolic syndrome.
Assuntos
Tecido Adiposo Marrom/fisiologia , Adiposidade , Jejum , Hidroxiesteroide Desidrogenases/metabolismo , Tretinoína/metabolismo , Animais , Dieta com Restrição de Gorduras , Ingestão de Alimentos , Metabolismo Energético , Feminino , Deleção de Genes , Intolerância à Glucose/genética , Intolerância à Glucose/metabolismo , Hidroxiesteroide Desidrogenases/genética , Resistência à Insulina , Metabolismo dos Lipídeos , Masculino , Camundongos Endogâmicos C57BL , Termogênese , Vitamina A/metabolismoRESUMO
PURPOSE: This study aimed to evaluate facet joint parameters and osteoarthritis grades, and segmental angular and translational motions among different grades of L5/S1 intervertebral disc (IVD) degeneration. METHODS: This retrospective study analysed kinematic magnetic resonance imaging (kMRI) images of the lumbar spine of 214 patients with low back pain. Degenerations of the L5/S1 IVDs and facet joints osteoarthritis were assessed using the Pfirrmann and Pathria grading scales, respectively. Facet joint parameters included facet joint angle and facet joint space width. Angular and translation segmental motions were measured using MRI Analyzer software. RESULTS: The mean age of the studied patients was 44.1 ± 13.9 years. Patients with L5/S1 disc degeneration were associated with higher odds of facet joint osteoarthritis (odds ratio = 2.28, 95% confidence interval = 1.23-4.23, P = 0.008). There was a positive correlation between L5/S1 disc degeneration grade and the facet joint grade (r = 0.365, P > 0.001). Grade IV facet joint osteoarthritis did not appear in grades I or II disc degeneration (P > 0.001). The average facet joint width decreased significantly with increasing Pfirrmann grading (P = 0.017). The difference in facet joint angle between groups was not statistically significant (P = 0.532). The differences in the angular and translational motions were not statistically significant (P = 0.530, and 0.510, respectively). CONCLUSION: A positive correlation exists between L5/S1 disc degeneration and facet joint osteoarthritis grades. The facet joint space width decreases significantly with increasing grade of disc degeneration.
Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Articulação Zigapofisária , Adulto , Fenômenos Biomecânicos , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Retrospectivos , Articulação Zigapofisária/diagnóstico por imagemAssuntos
Contusão Encefálica , Lesões Encefálicas Traumáticas , Hipertensão Intracraniana , Humanos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/cirurgia , Encéfalo , Contusão Encefálica/cirurgia , Lobo Temporal/cirurgia , Pressão Intracraniana , Monitorização FisiológicaRESUMO
The effect of percent relative humidity (16-84% RH), moisture content (4.2-6.5% w/w MC), and compression force (4.9-44.1 kN CF) on the light-induced fluorescence (LIF) response of 10% w/w active pharmaceutical ingredient (API) compacts is reported. The fluorescent response was evaluated using two separate central composite designs of experiments. The effect of % RH and CF on the LIF signal was highly significant with an adjusted R (2) = 0.9436 and p < 0.0001. Percent relative humidity (p = 0.0022), CF (p < 0.0001), and % RH(2) (p = 0.0237) were statistically significant factors affecting the LIF response. The effects of MC and CF on LIF response were also statistically significant with a p value <0.0001 and adjusted R (2) value of 0.9874. The LIF response was highly impacted by MC (p < 0.0001), CF (p < 0.0001), and MC(2) (p = 0022). At 10% w/w API, increased % RH, MC, and CF led to a nonlinear decrease in LIF response. The derived quadratic model equations explained more than 94% of the data. Awareness of these effects on LIF response is critical when implementing LIF as a process analytical tool.
Assuntos
Fluorescência , Umidade , Pressão , Tecnologia Farmacêutica/métodos , Química Farmacêutica/métodos , Luz , Fenômenos Mecânicos , Modelos TeóricosRESUMO
Determining the individual roles of the two dopamine D1-like receptors (D1R and D5R) on sodium transport in the human renal proximal tubule has been complicated by their structural and functional similarity. Here we used a novel D5R-selective antagonist (LE-PM436) and D1R- or D5R-specific gene silencing to determine second messenger coupling pathways and heterologous receptor interaction between the two receptors. D1R and D5R colocalize in renal proximal tubule cells and physically interact, as determined by co-immunoprecipitation and fluorescent resonance energy transfer microscopy. Stimulation of renal proximal tubule cells with fenoldopam (D1R/D5R agonist) led to both adenylyl cyclase and phospholipase C (PLC) activation using real-time fluorescent resonance energy transfer biosensors ICUE3 and CYPHR, respectively. Fenoldopam increased cAMP accumulation and PLC activity and inhibited both NHE3 and NaKATPase activities. LE-PM436 and D5R siRNA blocked the fenoldopam-stimulated PLC pathway but not cAMP accumulation, whereas D1R siRNA blocked both fenoldopam-stimulated cAMP accumulation and PLC signaling. Either D1R or D5R siRNA, or LE-PM436 blocked the fenoldopam-dependent inhibition of sodium transport. Further studies using the cAMP-selective D1R/D5R agonist SKF83822 and PLC-selective D1R/D5R agonist SKF83959 confirmed the cooperative influence of the two pathways on sodium transport. Thus, D1R and D5R interact in the inhibition of NHE3 and NaKATPase activity, the D1R primarily by cAMP, whereas the D1R/D5R heteromer modulates the D1R effect through a PLC pathway.
Assuntos
Túbulos Renais Proximais/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D5/metabolismo , Sódio/metabolismo , Benzazepinas/farmacologia , Transporte Biológico Ativo/efeitos dos fármacos , Células Cultivadas , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Fenoldopam/farmacologia , Transferência Ressonante de Energia de Fluorescência , Células HEK293 , Humanos , Túbulos Renais Proximais/efeitos dos fármacos , Modelos Biológicos , RNA Interferente Pequeno/genética , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de Dopamina D5/agonistas , Receptores de Dopamina D5/antagonistas & inibidores , Sistemas do Segundo MensageiroRESUMO
BACKGROUND: The optimal treatment for multivessel coronary artery disease in patients with end-stage renal disease (ESRD) is unresolved. AIM OF STUDY: Compare clinical adverse events after percutaneous intervention with drug-eluting stents (DESs) and coronary artery bypass grafting (CABG) in patients with ESRD. METHODS: MEDLINE, Web of Science, and Scopus were searched for appropriate studies published in the English language (between January 2000 and August 2013). The pooled odds ratio (OR) was estimated by the Peto method with a random effect model. Data are presented with 95% confidence interval; p<0.05 is significant. RESULTS: Five observational studies (12,035 DES patients; 6317 CABG) with a follow-up period of 27.4 ± 6.3 months were included. Early mortality (CABG 8% and DES 2.6%) was less in the DES cohort (OR 0.29 [0.14-0.59]; p=0.0006; I(2)=18%). Repeat intervention (DES 29% and CABG 12%) was more likely in the DES cohort (OR 3.72 [2.24-6.18]: p<0.0001). Late mortality (27.4 ± 7.3 months) was comparable in both cohorts (OR 0.72 [0.40-1.29]; p=0.27). While DES cohort (32%) patients suffered a slightly higher incidence of major adverse cardiac and cerebrovascular events (MACCE) as compared to CABG (25%), this was not significant (1.35 [0.72-2.53]; p=0.35; I(2)=30%). CONCLUSION: Data regarding this topic are limited to small retrospective studies. Early mortality is lower with DESs compared with coronary artery bypass in patients with ESRD. Rate of reintervention is significantly higher in the DES cohort. At a mean pooled follow-up of two years, both mortality and MACCE are comparable in both cohorts.
Assuntos
Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Falência Renal Crônica/complicações , Intervenção Coronária Percutânea/efeitos adversos , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/etiologia , Estudos de Coortes , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/complicações , Feminino , Seguimentos , Humanos , Incidência , Falência Renal Crônica/terapia , MEDLINE , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/mortalidade , Terapia de Substituição Renal , Estudos Retrospectivos , Fatores de TempoRESUMO
CONTEXT: This study presents novel nanostructured oil-in-water (o/w) mists based on self-nanoemulsifying (SNE) mixtures capable of delivering poorly water-soluble drugs into the lungs. OBJECTIVE: Formulation development of an o/w nanoemulsion (NE) capable of being nebulized for pulmonary delivery of poorly water-soluble drugs. MATERIALS AND METHODS: SNE mixtures were prepared and evaluated using Tween 80 and Cremophor RH 40 as surfactants; Transcutol P, Capryol 90 and PEG 400 as cosurfactants; and Labrafac Lipophile Wl 1349 (a medium-chain triglyceride) as an oil. Liquid NEs were analyzed by light scattering, zeta potential, transmission electron microscopy (TEM) and in vitro drug release studies. The aqueous NE was nebulized and assessed by light scattering and TEM. The formulation was aseptically filtered and the sterility validated. In vitro cytotoxicity of the formulations was tested in NIH 3T3 cells. The capability of the formulation to deliver a poorly water-soluble drug was determined using ibuprofen. RESULTS: Ibuprofen was found to be stable in the NEs. The formulations were neutrally charged with a droplet size of about 20 nm. TEM images displayed 100 nm oil droplets. The aseptic filtration method produced sterile NE. The nebulized mist revealed properties ideal for pulmonary delivery. The biocompatible aerosol has a nanostructure consisting of several oil nanodroplets enclosed within each water drop. Solubility and in vitro drug release studies showed successful incorporation and release of ibuprofen. CONCLUSION: The developed formulation could be used as an inhalation for delivering material possessing poor water solubility into the lungs.
Assuntos
Emulsões/administração & dosagem , Emulsões/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Animais , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Pulmão/metabolismo , Camundongos , Células NIH 3T3 , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Óleos/química , Tamanho da Partícula , Solubilidade , Tensoativos/química , Água/químicaRESUMO
INTRODUCTION: Data regarding the long-term clinical effects of a continuous flow left ventricular assist device (CF-LVAD) on hepato-renal function is limited. Hence our aim was to assess changes in hepato-renal function over a one-year period in patients supported on a CF-LVAD. METHODS: During the study period 126 patients underwent CF-LVAD implant. Changes in hepato-renal laboratory parameters were studied in 61/126 patients successfully supported on a CF-LVAD for period of one year. A separate cohort of a high-risk group (HCrB) of patients (56/126) with a serum creat>1.9 mg/dL (168 µmol/L) (75th percentile) or a serum bil>1.5 mg/dL (25.65 µmol/L) (75th percentile) was created. Changes in serum creatinine and bilirubin were analysed at regular intervals for this group along with the need for renal replacement therapy. RESULTS: Baseline creatinine and blood urea nitrogen (BUN) for the entire cohort was 1.4[1.2,1.9 mg/dL] [123.7(106,168) µmol/L) and 27[20,39.5 mg/dL] [9.6(7.1,14.1) mmol/L] respectively. After an initial reduction at the end of one month [1(0.8,1.2) mg/dL; 88(70,105) µmol/L] (p<0.0001), a gradual increase was noted over the study period to reach (1.25[1.1,1.5] mg/dL; 106(97.2,132.6) µmol/L] (p=0.0003). The serum bilirubin normalised from a [1(0.7,1.55) mg/dL] [17(18.8,25.7) µmol/L) to 0.9(0.6,1.2)mg/dL [15.4(10.2,20.5) µmol/L] (p=0.0005) and continued to decline over one year. Improvement in the synthetic function of the liver was demonstrated by a rise in the serum albumin levels to reach 4.3[4.1,4.5] [43(41,45) gm/L] at the end of one year (p<0.0001). The baseline serum creatinine and bilirubin for the high-risk cohort (HCrB) was 1.9(1.3,2.4) mg/dL [168(115,212) µmol/L] and 1.7(1.00,2.4) mg/dL [29(17.1,68.4) µmol/L] respectively. The high-risk cohort (HCrB) demonstrated a trend towards higher 30-day mortality (p=0.06). While the need for temporary renal replacement therapy was higher in this cohort (16% vs. 4%; p=0.03), only 3% need it permanently. A significant reduction in creatinine was apparent at the end of one month [1.1(0.8,1.4) mg/dL; 97(70.7,123.7) µmol/L] (p<0.0001) and then remained stable at [1.3(1.1,1.5) mg/dL; 115(97,132.6) µmol/L]. Bilirubin demonstrated a 30% decline over one month and then remained low at [0.7(0.5,0.8) mg/dL; 62(44,70) µmol/L] p=0.0005 compared to the pre-operative baseline. CONCLUSION: Hepato-renal function demonstrates early improvement and then remains stable in the majority of patients on continuous flow left ventricular assist device support for one year. High-risk patients demonstrate a higher 30-day mortality and temporary need for renal replacement therapy. Yet even in this cohort, improvement is present over a period of one year on the device, with a minimal need for permanent haemodialysis.
Assuntos
Bilirrubina/sangue , Creatinina/sangue , Coração Auxiliar , Rim , Fígado , Ureia/sangue , Idoso , Humanos , Rim/metabolismo , Rim/fisiopatologia , Testes de Função Renal , Fígado/metabolismo , Fígado/fisiopatologia , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION: Cardiac transplantation is an effective surgical therapy for end-stage heart failure. Patients (pts) may need to be bridged with a continuous flow left ventricular assist device (CF-LVAD) while on the transplant list as logistic factors like organ availability are unknown. Cardiac transplantation post-LVAD can be a surgically challenging procedure and outcome in these pts is perceived to be poorer based on experience with earlier generation pulsatile flow pumps. Data from a single institution comparing these pts with those undergoing direct transplantation in the present era of continuous flow device therapy are limited. AIM: Evaluate results of cardiac transplantation in pts bridged with a CF-LVAD (BTx) and compare outcomes with pts undergoing direct transplantation (Tx) in a single institution. RESULTS: From June 2007 till January 2012, 106 pts underwent cardiac transplantation. Among these, 37 (35%) pts (51±11 years; 85% male) were bridged with a CF-LVAD (BTx), while 70 (65%) comprised the Tx group (53±12 years; 72% males). The median duration of LVAD support was 227 (153,327) days. During the period of LVAD support, 10/37 (27%) pts were upgraded to status 1A and all were successfully transplanted. Median hospital stay in the BTx (14 days) was slightly longer than the Tx group (12 days) but not statistically significant (p=0.21). In-hospital mortality in the BTx (5%) and Tx (1%) were comparable (p=0.25). Estimated late survival in the BTx cohort was 94±7, 90±10 and 83±16% at the end of one, two and three years, respectively which was comparable to 97±4%, 93±6% and 89±9% for the Tx group (p=0.50). CONCLUSION: Cardiac transplantation after LVAD implant can be performed with excellent results. Patients can be supported on the left ventricular assist device even for periods close to a year with good outcome after cardiac transplantation.
Assuntos
Cardiomiopatias , Transplante de Coração/métodos , Coração Auxiliar , Adulto , Idoso , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Cardiomiopatias/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoRESUMO
INTRODUCTION: External fixation of unstable ankle injuries is commonly done by orthopaedic surgeons. An improper technique can negate the benefits of the procedure and necessitate revision. This study sought to determine the risk factors for revision of external fixation of unstable ankle injuries. METHODS: Retrospective cohort at a level I academic trauma center of 120 consecutive patients underwent external fixation of an unstable ankle injury. Exclusion criteria included external fixation for reason other than fracture, inadequate intraoperative imaging, skeletal immaturity, and follow-up less than 30 days. Primary outcome measurement was revision of external fixation within 30 days. RESULTS: Ninety-seven patients met inclusion criteria. Eighteen (18.6%) underwent revision within 30 days of whom 5 (28%, P < 0.001) had a poor reduction intraoperatively. No patients with a good reduction required revision. Revised patients had a significantly higher talar tilt (P < 0.001) and were more likely to lack a first metatarsal pin (P = 0.018). Multivariate analysis revealed talar tilt >0.5° (odds ratio, 22.62; 95% confidence interval, 6.52 to 50.63) as an independent risk factor for revision. DISCUSSION: For external fixation of unstable ankle injuries, poor reduction quality is a risk factor for need for revision surgery. Orthopaedic surgeons should be critical of their final intraoperative assessment to prevent revision.
Assuntos
Traumatismos do Tornozelo , Fixação de Fratura , Humanos , Estudos Retrospectivos , Fixação de Fratura/métodos , Fixadores Externos , Traumatismos do Tornozelo/diagnóstico por imagem , Traumatismos do Tornozelo/cirurgia , Fatores de RiscoRESUMO
INTRODUCTION: Distal femur fractures are difficult to successfully treat due to high rates of nonunion. Obesity is an independent prognostic risk factor for nonunion. Advances in finite element analyses (FEAs) have allowed researchers to better understand the performance and behavior of constructs at the bone-implant interface under a variety of conditions. The purpose of this study is to determine the impact of body weight on fracture strain in a lateral locking plate construct for supracondylar femur fractures and whether additional construct rigidity is beneficial to optimize fracture strain in high body mass patients. HYPOTHESIS: We hypothesized that increased loads would produce a higher interfragmentary strain (IFS), which could be decreased by shortening the working length of the construct. MATERIALS AND METHODS: A 3D finite element analysis was performed on two separate femur models with a comminuted supracondylar distal femur fracture fixed with a lateral distal femoral locking plate in bridging mode with Ansys software. Axial forces were varied to recreate the effect of load from normal and high body mass patients. Working length and screw density of the construct were varied for each condition. Measurements of interfragmentary strain and shear motion (SM) were compared. RESULTS: Doubling the axial load from 70kg (control) to 140kg (high body mass) increased the interfragmentary strain by an average of 76% for the three working lengths (3.38%±1.67% to 4.37%±0.88% at the baseline working length (BWL), 1.42%±1.00% to 2.87%±2.02% at the intermediate working length (IWL) and 0.62%±0.22% to 1.22%±0.42% at the short working length (SWL)). On average, decreasing the working length in the 140kg load reduced the mean IFS to within 15% of the mean IFS of the 70kg load at the longer working length (2.87%±2.02% at IWL 140kg versus 3.38%±1.67% at BWL 70kg and 1.22%±0.45% SWL 140kg versus 1.42±1.00% IWL 70kg). DISCUSSION: Increased axial load increases interfragmentary strain in an AO/OTA 33A distal femur fracture fixed with a lateral distal femoral locking plate. Decreasing the working length of the fixation construct in the high body mass model decreased interfragmentary strain. Higher loading conditions reflective of high body mass patients should be considered in studies investigating optimization of fracture strain. LEVEL OF PROOF: V; Finite Element Analysis (FEA).
RESUMO
OBJECTIVE: The local effects of an intracerebral hemorrhage (ICH) on surrounding brain tissue can be detected bedside using multimodal brain monitoring techniques. The aim of this study is to design a gradient boosting regression model using the R package boostmtree with the ability to predict lactate-pyruvate ratio measurements in ICH. METHODS: We performed a retrospective analysis of 6 spontaneous ICH and 6 traumatic ICH patients who underwent surgical removal of the clot with microdialysis catheters placed in the perihematomal zone. Predictors of glucose, lactate, pyruvate, age, sex, diagnosis, and operation status were used to design our model. RESULTS: In a holdout analysis, the model forecasted lactate-pyruvate ratio trends in a representative in-sample testing set. We anticipate that boostmtree could be applied to designs of similar regression models to analyze trends in other multimodal monitoring features across other types of acute brain injury. CONCLUSIONS: The model successfully predicted hourly lactate-pyruvate ratios in spontaneous ICH and traumatic ICH cases after the hemorrhage evacuation and displayed significantly better performance than linear models. Our results suggest that boostmtree may be a powerful tool in developing more advanced mathematical models to assess other multimodal monitoring parameters for cases in which the perihematomal environment is monitored.
Assuntos
Hemorragia Cerebral , Ácido Láctico , Ácido Pirúvico , Humanos , Hemorragia Cerebral/diagnóstico , Estudos Retrospectivos , Ácido Láctico/metabolismo , Masculino , Feminino , Ácido Pirúvico/metabolismo , Pessoa de Meia-Idade , Idoso , Algoritmos , Microdiálise/métodos , Microdiálise/tendências , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Risk assessment is critically important in elective and high-risk interventions, particularly spine surgery. This narrative review describes the evolution of risk assessment from the earliest instruments focused on general surgical risk stratification, to more accurate and spine-specific risk calculators that quantified risk, to the current era of big data. METHODS: The PubMed and SCOPUS databases were queried on October 11, 2023 using search terms to identify risk assessment tools (RATs) in spine surgery. A total of 108 manuscripts were included after screening with full-text review using the following inclusion criteria: 1) study population of adult spine surgical patients, 2) studies describing validation and subsequent performance of preoperative RATs, and 3) studies published in English. RESULTS: Early RATs provided stratified patients into broad categories and allowed for improved communication between physicians. Subsequent risk calculators attempted to quantify risk by estimating general outcomes such as mortality, but then evolved to estimate spine-specific surgical complications. The integration of novel concepts such as invasiveness, frailty, genetic biomarkers, and sarcopenia led to the development of more sophisticated predictive models that estimate the risk of spine-specific complications and long-term outcomes. CONCLUSIONS: RATs have undergone a transformative shift from generalized risk stratification to quantitative predictive models. The next generation of tools will likely involve integration of radiographic and genetic biomarkers, machine learning, and artificial intelligence to improve the accuracy of these models and better inform patients, surgeons, and payers.
Assuntos
Complicações Pós-Operatórias , Humanos , Medição de Risco/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Coluna Vertebral/cirurgia , Procedimentos Neurocirúrgicos , Doenças da Coluna Vertebral/cirurgiaRESUMO
OBJECTIVE: According to the 2017 World Health Organization classification of neuro-endocrine tumors, pituitary adenomas (PAs) are classified according to immunoexpression of the pituitary-specific transcription factors (TFs). A small subset of PAs exhibit multiple TF staining on immunohistochemistry and we present a series of 27 pathologically-confirmed cases of dual TF staining PAs (dsTF-PAs), and report clinically relevant implications. METHODS: A retrospective chart review of a multi-institutional database of patients with PAs surgically resected between 2008-2021 was performed. PAs expressing immunopositivity 2+ TFs. Patient demographics, neuro-imaging characteristics, histopathologic findings, and clinical data were collected. RESULTS: Twenty-seven patients had pathologically verified dsTF-PAs, of whom 17 were female (63%), with ages ranging from 20-84 years. Twenty-three (85.2%) patients harbored functional PAs, with acromegaly being the most common functional subtype (86.4%). The most common combination of TFs within a single tumor was PIT-1/SF-1 (85.2%). Six PAs exhibited Knosp cavernous sinus invasion grades of 3 or 4 and the Ki-67 labeling index was ≥3% in 6 patients (24.0%) and all stained for PIT-1/SF-1. Hormonal remission was achieved in 78% of functional dsTF-PAs. No PAs showed evidence of recurrence or progression over the mean follow-up period of 28.5 months. CONCLUSIONS: PAs exhibiting dsTF-PAs represent a small but clinically relevant diagnostic subset of PAs according to the 2021 World Health Organization criteria, as a majority are GH-producing. Precise classification using TF staining plays a key role in understanding the biology of these tumors. Favorable outcomes can be achieved in this subset of PAs with evolving TF classification.