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1.
BMC Nephrol ; 25(1): 200, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890600

RESUMO

Malakoplakia is a rare inflammatory disorder believed to result from a defect in macrophage phagocytic function triggering a granulomatous reaction. It can present with genitourinary, gastrointestinal, or cutaneous manifestations in immunocompromised or, less commonly, immunocompetent hosts. We describe a case of renal malakoplakia in a young, otherwise healthy patient presenting with nephromegaly and sepsis following an E. coli urinary tract infection. We discuss diagnosis and management, including antibiotic selection and the decision to pursue nephrectomy. This case highlights the potential for kidney recovery with prolonged antibiotic therapy in conjunction with adjunct immunomodulatory therapies and source control.


Assuntos
Infecções por Escherichia coli , Malacoplasia , Infecções Urinárias , Humanos , Malacoplasia/complicações , Malacoplasia/etiologia , Infecções Urinárias/complicações , Infecções Urinárias/tratamento farmacológico , Infecções por Escherichia coli/complicações , Masculino , Antibacterianos/uso terapêutico , Adulto , Feminino , Escherichia coli/isolamento & purificação
2.
Otol Neurotol ; 45(6): e460-e467, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38865720

RESUMO

OBJECTIVE: Misplacement of electrode arrays in the internal auditory canal (IAC) presents a unique clinical challenge. Speech recognition is limited for cochlear implant (CI) users with misplaced arrays, and there are risks with revision surgery including facial and/or cochlear nerve injury. DATABASES REVIEWED: PubMed, Embase, and Scopus. METHODS: A literature search was performed from inception to September 2023. The search terms were designed to capture articles on misplaced arrays and the management options. Articles written in English that described cases of array misplacement into the IAC for children and adults were included. The level of evidence was assessed using Oxford Center for Evidence Based Medicine guidelines. Descriptive statistical analyses were performed. RESULTS: Twenty-eight cases of arrays misplaced in the IAC were identified. Thirteen (46%) were patients with incomplete partition type 3 (IP3), and 7 (25%) were patients with common cavity (CC) malformations. Most misplaced arrays were identified postoperatively (19 cases; 68%). Of these cases, 11 (58%) were managed with array removal. No facial nerve injuries were reported with revision surgery. Eight cases (42%) were left in place. Several underwent mapping procedures in an attempt improve the sound quality with the CI. CONCLUSION: Electrode array misplacement in the IAC is a rare complication that reportedly occurs predominately in cases with IP3 and CC malformations. Removal of misplaced arrays from the IAC reportedly has not been associated with facial nerve injuries. Cases identified with IAC misplacement postoperatively can potentially be managed with modified mapping techniques before proceeding with revision surgery.


Assuntos
Implante Coclear , Implantes Cocleares , Orelha Interna , Humanos , Implantes Cocleares/efeitos adversos , Implante Coclear/efeitos adversos , Implante Coclear/métodos , Orelha Interna/cirurgia , Eletrodos Implantados/efeitos adversos , Reoperação/estatística & dados numéricos
3.
Nature ; 630(8015): 54-58, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38648852

RESUMO

Large-scale outflows driven by supermassive black holes are thought to have a fundamental role in suppressing star formation in massive galaxies. However, direct observational evidence for this hypothesis is still lacking, particularly in the young universe where star-formation quenching is remarkably rapid1-3, thus requiring effective removal of gas4 as opposed to slow gas heating5,6. Although outflows of ionized gas are frequently detected in massive distant galaxies7, the amount of ejected mass is too small to be able to suppress star formation8,9. Gas ejection is expected to be more efficient in the neutral and molecular phases10, but at high redshift these have only been observed in starbursts and quasars11,12. Here we report JWST spectroscopy of a massive galaxy experiencing rapid quenching at a redshift of 2.445. We detect a weak outflow of ionized gas and a powerful outflow of neutral gas, with a mass outflow rate that is sufficient to quench the star formation. Neither X-ray nor radio activity is detected; however, the presence of a supermassive black hole is suggested by the properties of the ionized gas emission lines. We thus conclude that supermassive black holes are able to rapidly suppress star formation in massive galaxies by efficiently ejecting neutral gas.

4.
Am J Surg ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38443270

RESUMO

BACKGROUND: The aim of this meta-analysis is to investigate the safety of outpatient thyroidectomy based on 24-h and same-day discharge criteria. METHODS: CENTRAL, Embase, PubMed, and Scopus were searched. A meta-analysis of selected studies was performed. The review was registered prospectively with PROSPERO (CRD42022361134). RESULTS: Thirty-one studies met the eligibility criteria, with a total of 74328 patients undergoing thyroidectomy in an outpatient setting based on 24-h discharge criteria. Overall postoperative complications after outpatient thyroidectomies were 5.7% (95%CI: 0.049-0.065; I2 â€‹= â€‹97.3%), consisting of hematoma (0.4%; 95%CI: 0.003-0.005; I2 â€‹= â€‹83.4%), recurrent laryngeal nerve injury (0.4%; 95%CI: 0.003-0.006; I2 â€‹= â€‹93.5%), and hypocalcemia (1.6%; 95%CI: 0.012-0.019; I2 â€‹= â€‹93.7%). The rate of readmission was 1.1% (95%CI: 0.007-0.015; I2 â€‹= â€‹95.4%). Results were similar for same-day criteria. CONCLUSIONS: Our analysis demonstrated that outpatient thyroidectomy is a safe procedure in the management of thyroid disease for selected patients.

5.
Am J Sports Med ; 52(5): 1357-1366, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37326248

RESUMO

BACKGROUND: Tibial spine fractures (TSFs) are uncommon injuries that may result in substantial morbidity in children. A variety of open and arthroscopic techniques are used to treat these fractures, but no single standardized operative method has been identified. PURPOSE: To systematically review the literature on pediatric TSFs to determine the current treatment approaches, outcomes, and complications. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: A systematic review of the literature was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines using PubMed, Embase, and Cochrane databases. Studies evaluating treatment and outcomes of patients <18 years old were included. Patient demographic characteristics, fracture characteristics, treatments, and outcomes were abstracted. Descriptive statistics were used to summarize categorical and quantitative variables, and a meta-analytic technique was used to compare observational studies with sufficient data. RESULTS: A total of 47 studies were included, totaling 1922 TSFs in patients (66.4% male) with a mean age of 12 years (range, 3-18 years). The operative approach was open reduction and internal fixation in 291 cases and arthroscopic reduction and internal fixation in 1236 cases; screw fixation was used in 411 cases and suture fixation, in 586 cases. A total of 13 nonunions were reported, occurring most frequently in Meyers and McKeever type III fractures (n = 6) and in fractures that were treated nonoperatively (n = 10). Arthrofibrosis rates were reported in 33 studies (n = 1700), and arthrofibrosis was present in 190 patients (11.2%). Range of motion loss occurred significantly more frequently in patients with type III and IV fractures (P < .001), and secondary anterior cruciate ligament (ACL) injury occurred most frequently in patients with type I and II fractures (P = .008). No statistically significant differences were found with regard to rates of nonunion, arthrofibrosis, range of motion loss, laxity, or secondary ACL injury between fixation methods (screw vs suture). CONCLUSION: Despite variation in TSF treatment, good overall outcomes have been reported with low complication rates in both open and arthroscopic treatment and with both screw and suture fixation. Arthrofibrosis remains a concern after surgical treatment for TSF, but no significant difference in incidence was found between the analysis groups. Larger studies are necessary to compare outcomes and form a consensus on how to treat and manage patients with TSFs.


Assuntos
Lesões do Ligamento Cruzado Anterior , Fraturas do Joelho , Fraturas da Tíbia , Humanos , Masculino , Adolescente , Criança , Feminino , Artroscopia/métodos , Técnicas de Sutura , Articulação do Joelho/cirurgia , Tíbia/cirurgia , Fraturas da Tíbia/etiologia , Fraturas da Tíbia/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Fixação Interna de Fraturas/métodos , Resultado do Tratamento
6.
Eur J Nucl Med Mol Imaging ; 51(4): 978-990, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38049658

RESUMO

PURPOSE: A same-day PET imaging agent capable of measuring PD-L1 status in tumors is an important tool for optimizing PD-1 and PD-L1 treatments. Herein we describe the discovery and evaluation of a novel, fluorine-18 labeled macrocyclic peptide-based PET ligand for imaging PD-L1. METHODS: [18F]BMS-986229 was synthesized via copper mediated click-chemistry to yield a PD-L1 PET ligand with picomolar affinity and was tested as an in-vivo tool for assessing PD-L1 expression. RESULTS: Autoradiography showed an 8:1 binding ratio in L2987 (PD-L1 (+)) vs. HT-29 (PD-L1 (-)) tumor tissues, with >90% specific binding. Specific radioligand binding (>90%) was observed in human non-small-cell lung cancer (NSCLC) and cynomolgus monkey spleen tissues. Images of PD-L1 (+) tissues in primates were characterized by high signal-to-noise, with low background signal in non-expressing tissues. PET imaging enabled clear visualization of PD-L1 expression in a murine model in vivo, with 5-fold higher uptake in L2987 (PD-L1 (+)) than in control HT-29 (PD-L1 (-)) tumors. Moreover, this imaging agent was used to measure target engagement of PD-L1 inhibitors (peptide or mAb), in PD-L1 (+) tumors as high as 97%. CONCLUSION: A novel 18F-labeled macrocyclic peptide radioligand was developed for PET imaging of PD-L1 expressing tissues that demonstrated several advantages within a nonhuman primate model when compared directly to adnectin- or mAb-based ligands. Clinical studies are currently evaluating [18F]BMS-986229 to measure PD-L1 expression in tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Domínio de Fibronectina Tipo III , Radioisótopos de Flúor , Neoplasias Pulmonares , Proteínas Recombinantes , Humanos , Camundongos , Animais , Antígeno B7-H1/metabolismo , Ligantes , Macaca fascicularis/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Peptídeos/química
7.
Cancer Res ; 84(1): 26-38, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-37874327

RESUMO

Clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (ENOC) are ovarian carcinoma histotypes, which are both thought to arise from ectopic endometrial (or endometrial-like) cells through an endometriosis intermediate. How the same cell type of origin gives rise to two morphologically and biologically different histotypes has been perplexing, particularly given that recurrent genetic mutations are common to both and present in nonmalignant precursors. We used RNA transcription analysis to show that the expression profiles of CCOC and ENOC resemble those of normal endometrium at secretory and proliferative phases of the menstrual cycle, respectively. DNA methylation at the promoter of the estrogen receptor (ER) gene (ESR1) was enriched in CCOC, which could potentially lock the cells in the secretory state. Compared with normal secretory-type endometrium, CCOC was further defined by increased expression of cysteine and glutathione synthesis pathway genes and downregulation of the iron antiporter, suggesting iron addiction and highlighting ferroptosis as a potential therapeutic target. Overall, these findings suggest that while CCOC and ENOC arise from the same cell type, these histotypes likely originate from different cell states. This "cell state of origin" model may help to explain the presence of histologic and molecular cancer subtypes arising in other organs. SIGNIFICANCE: Two cancer histotypes diverge from a common cell of origin epigenetically locked in different cell states, highlighting the importance of considering cell state to better understand the cell of origin of cancer.


Assuntos
Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Endometriose , Neoplasias Ovarianas , Feminino , Humanos , Endometriose/genética , Endometriose/metabolismo , Neoplasias Ovarianas/patologia , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Carcinoma Epitelial do Ovário , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Ferro
8.
Facial Plast Surg Aesthet Med ; 26(1): 41-46, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37751178

RESUMO

Background: Coronavirus disease 2019 (COVID-19) has been linked to Bell's palsy and facial paralysis. Studies have also shown increased risk of Bell's palsy in unvaccinated COVID-19 patients. Objective: To compare the relationship between Bell's palsy and COVID-19 infection and vaccination. Design: This is a retrospective longitudinal study. Methods: The COVID-19 research network was used to identify patients with facial palsy presenting to 70 health care organizations in the United States. The incidence of Bell's palsy was measured within an 8-week window after COVID-19 test or vaccination event in identified patients. Results: Incidence of facial palsy diagnosis (0.99%) was higher than the background rate within 2 months of COVID-19 infection. When compared with their negative counterparts, patients with COVID-19 infection had significantly higher risk of Bell's palsy (risk ratio [RR] = 1.77, p < 0.01) and facial weakness (RR = 2.28, p < 0.01). Risk ratio was also amplified when evaluating Bell's palsy (RR = 12.57, p < 0.01) and facial palsy (RR = 44.43; p < 0.01) in COVID-19-infected patients against patients who received COVID-19 vaccination. Conclusion: In our patient population, there is a higher risk of developing facial palsy within 2 months of COVID-19 infection versus vaccination. Vaccinated patients are not at higher risk of developing facial palsy.


Assuntos
Paralisia de Bell , COVID-19 , Paralisia Facial , Humanos , Estados Unidos/epidemiologia , Paralisia de Bell/epidemiologia , Paralisia de Bell/etiologia , Paralisia de Bell/diagnóstico , Paralisia Facial/etiologia , Paralisia Facial/complicações , Estudos Longitudinais , Estudos Retrospectivos , Vacinas contra COVID-19
9.
Am J Sports Med ; 51(14): 3749-3755, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37942655

RESUMO

BACKGROUND: Femoroacetabular impingement (FAI) has been described as repetitive and abnormal contact between a structurally abnormal proximal femur (cam) and/or acetabulum (pincer), occurring during the terminal range of motion of the hip. While cam and pincer lesions have traditionally been defined as osseous abnormalities, there may be a subset of adolescent patients whose impingement is primarily soft tissue (nonosseous). The existence of a nonosseous cam lesion in adolescents with FAI has not been well described. PURPOSE: To identify and characterize a series of adolescent patients with nonosseous (soft cam) FAI identified on magnetic resonance imaging (MRI) and compare these patients' clinical presentation and outcome with those of a cohort with primary osseous cam FAI in the same age group. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A prospective institutional registry of patients with symptomatic FAI was reviewed. Patients were included if they had an MRI scan and a lateral radiograph of the hip (45° Dunn or frog) at a baseline visit. On MRI, the anterolateral femoral head was evaluated using radial, coronal, sagittal, or axial oblique sequences. A soft cam lesion was identified by the presence of soft tissue thickening of ≥2 mm at the anterolateral femoral head-neck junction. An alpha angle was measured on MRI scans and radiographs when a lesion was identified. The cohort with soft cam lesions was reviewed and findings and outcomes were compared with those of a cohort with osseous cam lesions. Continuous variables were first examined for normality, and then nonparametric tests-such as the Kruskal-Wallis test-were considered. The change between pre- and postoperative patient-reported outcomes (PROs) was described by mean and standard deviation and evaluated with an independent-samples t test. RESULTS: A total of 31 (9.3%) of 332 hips (mean age, 16.4 years [range 13.1-19.6 years]; women, 83.9%) were identified with a soft tissue impingment lesion on MRI at the femoral head-neck junction between the 12 and 3 o'clock positions. These lesions demonstrated a thickened perichondral ring (71%), periosteal thickening (26%), or a cartilaginous epiphyseal extension (3%). The mean alpha angle on MRI was greater than on radiographs (63.5°± 7.9° vs 51.3°± 7.9°; P < .0001). A total of 22 patients (71%) with soft impingement underwent hip preservation surgery. When compared with patients in the osseous cohort who also underwent surgical management, both groups showed similar significant improvements from pre- to postoperatively (soft: modified Harris Hip Score [mHHS], 26.9 ± 18.2; Hip disability and Osteoarthritis Outcome Score [HOOS], 31.4 ± 22.9; osseous: mHHS, 22.8 ± 20.8; HOOS, 27.4 ± 20.1; P < .0001), with a mean follow-up of 3.4 years (range, 1-7 years) in the soft cam cohort and 3 years (1-10.1 years) in the osseous cam cohort. CONCLUSION: Clinicians should be aware of nonosseous or soft cam lesions that cause impingement in adolescent patients without an obvious osseous cam on radiographs. MRI is required to detect these soft cam lesions. When nonoperative treatment fails, the PROs in these patients after operative management are comparable with those in patients with osseous cam lesions. Further research is needed to determine whether the soft cam precedes an osseous cam or whether it is a separate entity.


Assuntos
Impacto Femoroacetabular , Articulação do Quadril , Humanos , Adolescente , Feminino , Adulto Jovem , Adulto , Estudos Prospectivos , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Quadril , Acetábulo , Impacto Femoroacetabular/diagnóstico por imagem , Impacto Femoroacetabular/cirurgia , Imageamento por Ressonância Magnética , Amplitude de Movimento Articular
10.
Sci Rep ; 13(1): 12424, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37528172

RESUMO

GBM (Glioblastoma) is the most lethal CNS (Central nervous system) tumor in adults, which inevitably develops resistance to standard treatments leading to recurrence and mortality. TRIB1 is a serine/threonine pseudokinase which functions as a scaffold platform that initiates degradation of its substrates like C/EBPα through the ubiquitin proteasome system and also activates MEK and Akt signaling. We found that increased TRIB1 gene expression associated with worse overall survival of GBM patients across multiple cohorts. Importantly, overexpression of TRIB1 decreased RT/TMZ (radiation therapy/temozolomide)-induced apoptosis in patient derived GBM cell lines in vitro. TRIB1 directly bound to MEK and Akt and increased ERK and Akt phosphorylation/activation. We also found that TRIB1 protein expression was maximal during G2/M transition of cell cycle in GBM cells. Furthermore, TRIB1 bound directly to HDAC1 and p53. Importantly, mice bearing TRIB1 overexpressing tumors had worse overall survival. Collectively, these data suggest that TRIB1 induces resistance of GBM cells to RT/TMZ treatments by activating the cell proliferation and survival pathways thus providing an opportunity for developing new targeted therapeutics.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Temozolomida/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Apoptose/genética , Quinases de Proteína Quinase Ativadas por Mitógeno , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia
11.
Am J Otolaryngol ; 44(6): 103987, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37579600

RESUMO

BACKGROUND: While the etiology of Bell's palsy (BP) is largely unknown, current evidence shows it may occur secondary to the immune response following a viral infection. Recently, BP has been reported as a clinical manifestation of coronavirus disease (COVID-19). OBJECTIVES: To investigate an association between COVID-19 infection and BP. Additionally, to evaluate the need for COVID-19 testing in patients who present with BP. METHODS: Hospital records of patients who presented to a single tertiary care center with BP in 2020 and 2021 were reviewed for presenting symptoms, demographics, COVID-19 infection and vaccination status. RESULTS: There was no statistically significant difference between patients with BP who had a positive or negative COVID test in terms of sex, BMI, age, race, smoking history or alcohol use. All 7 patients with BP and a positive COVID test were unvaccinated. Of the total cohort of 94 patients, 82 % were unvaccinated at the time of the study. None of the 17 patients who were vaccinated had a positive COVID test. A history of BP showed no statistical significance (10.3 % vs 14.3 %, p-value 0.73). CONCLUSION: We discovered a limited cohort of patients who underwent COVID-19 testing at the time of presentation for BP. Though there have been recent studies suggesting a COVID-19 and BP, we were unable to clearly identify a relationship between COVID-19 and BP. Interestingly, all patients with facial paralysis and COVID-19 were unvaccinated. To further study this relationship, we recommend consideration of a COVID-19 test for any patient that presents with facial paralysis.


Assuntos
Paralisia de Bell , COVID-19 , Paralisia Facial , Humanos , Paralisia de Bell/epidemiologia , Paralisia de Bell/etiologia , Paralisia de Bell/diagnóstico , Centros de Atenção Terciária , Teste para COVID-19 , COVID-19/complicações , COVID-19/epidemiologia
12.
Addict Behav ; 147: 107828, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37591107

RESUMO

AIMS: E-cigarette and tobacco-related content on social media continues to rise from lax restrictions on both personal and promotional posts. This content has been linked to various mechanisms of increased e-cigarette and tobacco use (i.e., lower risk perceptions and increased susceptibility). This study aimed to synthesis the association between exposure to e-cigarette and tobacco-related content and youth behaviours and attitudes. METHODS: A comprehensive search was conducted on PubMed, Scopus, PsycINFO and Web of Science. Studies published post-2004 reporting effect estimates for exposure or engagement with e-cigarette or tobacco content on social media and behaviour or attitude outcomes were included. RESULTS: Thirty-two studies (N = 274,283, aged 9 to 25 years) were included for synthesis. Meta-analyses revealed significant associations between engagement with tobacco content and use (OR 2.21; 95% CI = 1.27-3.82, p =.005; I2 = 96.4%), exposure to tobacco content and never users' lower risk perceptions (OR 0.68; 95% CI = 0.49-0.91; p =.011; I2 = 78.2%), and exposure to e-cigarette content and use (OR 1.37; 95% CI = 0.99-1.88; p = 0.058; I2 = 64.4%). There was no observed relationship between exposure to tobacco content and ever users' risk perceptions (OR 0.83; 95% CI = 0.61-1.13; p =.231; I2 = 83.5%). Qualitative synthesis found significant associations between tobacco exposure and increased current use and pro-tobacco attitudes; e-cigarette exposure and increased susceptibility and lower risk perceptions; tobacco engagement and increased susceptibility; e-cigarette engagement and increased use; dual exposure and increased susceptibility; and dual engagement and increased dual use. Mixed findings were identified for the influence of e-cigarette exposure on attitudes, tobacco exposure on susceptibility, dual exposure on dual use behaviours, and dual engagement on dual susceptibility. CONCLUSIONS: Findings suggest an association between exposure and engagement to e-cigarette or tobacco products on social media and use or pro-use attitudes among youth. Further substantive research in the area of youth-specific use and attitudes following exposure and engagement with e-cigarette and tobacco content is needed to quantify this association.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Mídias Sociais , Vaping , Adolescente , Humanos , Atitude
13.
Am J Sports Med ; 51(11): 2936-2944, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37565525

RESUMO

BACKGROUND: Preservation of articular cartilage in the setting of acute or chronic injury in the adolescent and young adult knee is paramount for long-term joint health. Achieving osseous union, minimizing implant-related injury, and eliminating the need for reoperation for traumatic chondral and osteochondral lesions (OCLs) and osteochondritis dissecans (OCD) remain a challenge for the orthopaedic surgeon. PURPOSE: To evaluate radiographic healing, patient-reported outcomes, and short-term complications after suture-bridge fixation of chondral fragments, osteochondral fractures, and OCD lesions in the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The study included consecutive patients (38 patients, 40 knees) treated within a single academic sports medicine institution who underwent suture-bridge fixation of an OCL or an OCD lesion of the knee from initiation of the technique in October 2019 through March 2021. The suture-bridge technique entailed bioabsorbable knotless anchors placed on the outside margins of the lesion with multiple strands of hand-tensioned absorbable (No. 0 or No. 1 Vicryl) or nonabsorbable (1.3-mm braided polyester tape) bridging suture. Healing was assessed by radiography and magnetic resonance imaging (MRI), with MRI scans obtained on all OCD lesions and any chondral-only lesions. MRI scans were available for 33 of 40 (82.5%) knees within 1 year of surgery and were evaluated for lesion healing. Complications and rates and timing of return to sport were evaluated. Patient-reported outcomes in the OCD cohort were evaluated with the Knee injury and Osteoarthritis Outcome Score (KOOS) to determine early pain and functional improvement. RESULTS: In total, 33 (82.5%) lesions demonstrated full union, and no lesions failed treatment. MRI assessment of healing (mean, 5.8 months; range, 3-12 months) demonstrated 9 (64.3%) OCD lesions with full union, 5 (35.7%) OCD lesions with stable union, and no OCD lesions with nonunion. Of the OCLs, 17 (89.5%) had full union, 2 (10.5%) had stable union, and none had nonunion. The 7 bony OCLs without an MRI scan demonstrated complete radiographic union. In 30 (75.0%) lesions, patients returned to sports at a mean of 6.5 months (range, 3.8-10.2 months). KOOS Activities of Daily Living, Pain, Quality of Life, and Symptoms scores demonstrated significant improvement from baseline at 6 months and at 1 year. There were 2 (5%) complications, consisting of reoperation for marginal chondroplasty on an otherwise stable lesion, and re-operation for intial un-treated patellar instability, with no reoperations for failure or revision of the suture-bridge construct. CONCLUSION: In this series of OCLs and OCD lesions of the knee, suture-bridge fixation demonstrated excellent rates of MRI and radiographic union and good early outcomes with minimal short-term complications. This technique may be used for lesion salvage as an alternative to metallic and nonmetallic screw/tack constructs in the treatment of these challenging lesions. Longer term follow-up and investigation are warranted.


Assuntos
Instabilidade Articular , Osteocondrite Dissecante , Articulação Patelofemoral , Adolescente , Adulto Jovem , Humanos , Osteocondrite Dissecante/diagnóstico por imagem , Osteocondrite Dissecante/cirurgia , Atividades Cotidianas , Qualidade de Vida , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Suturas , Dor , Resultado do Tratamento , Seguimentos
14.
bioRxiv ; 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37461447

RESUMO

Standard preclinical human tumor models lack a human tumor stroma. However, as stroma contributes to therapeutic resistance, the lack of human stroma may make current models less stringent for testing new therapies. To address this, using patient-derived tumor cells, patient derived cancer-associated mesenchymal stem/progenitor cells, and human endothelial cells, we created a Human Stroma-Patient Derived Xenograft (HS-PDX) tumor model. HS-PDX, compared to the standard PDX model, demonstrate greater resistance to targeted therapy and chemotherapy, and better reflect patient response to therapy. Furthermore, HS-PDX can be grown in mice with humanized bone marrow to create humanized immune stroma patient-derived xenograft (HIS-PDX) models. The HIS-PDX model contains human connective tissues, vascular and immune cell infiltrates. RNA sequencing analysis demonstrated a 94-96% correlation with primary human tumor. Using this model, we demonstrate the impact of human tumor stroma on response to CAR-T cell therapy and immune checkpoint inhibitor therapy. We show an immunosuppressive role for human tumor stroma and that this model can be used to identify immunotherapeutic combinations to overcome stromally mediated immunosuppression. Combined, our data confirm a critical role for human stoma in therapeutic response and indicate that HIS-PDX can be an important tool for preclinical drug testing. Statement of Significance: We developed a tumor model with human stromal, vascular, and immune cells. This model mirrors patient response to chemotherapy, targeted therapy, and immunotherapy, and can be used to study therapy resistance.

15.
J Trauma Acute Care Surg ; 95(6): 893-898, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37314426

RESUMO

BACKGROUND: Post-intensive care unit (ICU) syndrome (PICS) occurs at an exorbitant rate in surgical ICU (SICU) survivors. It remains unknown if critical illness due to trauma versus acute care surgery (ACS) may represent different pathophysiologic entities. In this longitudinal study, we determined if admission criteria in a cohort of trauma and ACS patients were associated with differences in the occurrence of PICS. METHODS: Patients were 18 years or older, admitted to a Level I trauma center to the trauma or ACS services, remained in the SICU for ≥72 hours, and were seen in an ICU Recovery Center at 2 weeks, 12 weeks, and 24 weeks after hospital discharge. Post-ICU syndrome sequelae were diagnosed by dedicated specialist staffing using clinical criteria and screening questionnaires. The PICS symptoms were distilled into physical, cognitive, and psychiatric categories. Preadmission histories, hospital courses, and recovery data were collected via retrospective chart review. RESULTS: One hundred twenty-six patients were included: 74 (57.3%) trauma patients and 55 (42.6%) ACS patients. Prehospital psychosocial histories were similar between groups. Acute care surgery patients had a significantly longer hospital course, higher APACHE II and III scores, were intubated for longer, and had higher rates of sepsis, acute renal failure, open abdomen, and hospital readmissions. At the 2-week follow-up visit, ACS patients had higher rates of PICS sequelae (ACS, 97.8% vs. trauma 85.3%; p = 0.03), particularly in the physical (ACS, 95.6% vs. trauma 82.0%, p = 0.04), and psychiatric domains (ACS, 55.6% vs. trauma 35.0%, p = 0.04). At the 12-week and 24-week visits, rates of PICS symptoms were comparable between groups. CONCLUSION: The occurrence of PICS is extraordinarily high in both trauma and ACS SICU survivors. Despite entering the SICU with similar psychosocial histories, the two cohorts have different pathophysiologic experiences, which are associated with a higher rate of impairment in the ACS patients during early follow-up. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.


Assuntos
Cuidados Críticos , Unidades de Terapia Intensiva , Humanos , Estudos Longitudinais , Estudos Retrospectivos , Progressão da Doença , Sobreviventes
16.
Addiction ; 118(8): 1430-1444, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37005862

RESUMO

BACKGROUND AND AIMS: Heated tobacco products (HTPs) are electronic devices that heat process tobacco to release an aerosol containing nicotine and other chemicals. Limited data exist on world-wide HTP use prevalence. This meta-analytic review estimated the prevalence of HTP use by country, World Health Organization (WHO) region, year, sex/gender and age. METHODS: Five databases (Web of Science, Scopus, Embase, PubMed and PsycINFO) were searched between January 2015 and May 2022. Included studies reported the prevalence of HTP use in nationally representative samples post-modern HTP device market entry (2015). A random-effects meta-analysis was used to estimate overall prevalence for life-time, current and daily HTP use. RESULTS: Forty-five studies (n = 1 096 076) from 42 countries/areas from the European Region (EUR), Western Pacific Region (WPR), Region of the Americas (AMR) and African Region (AFR) met inclusion criteria. Estimated pooled prevalence for life-time, current and daily HTP use was 4.87% [95% confidence interval (CI) = 4.16, 5.63], 1.53% (95% CI = 1.22, 1.87) and 0.79% (95% CI = 0.48, 1.18), respectively, across all years (2015-22). Life-time HTP use prevalence significantly increased by 3.39% for WPR [0.52% (95% CI = 0.25, 0.88) in 2015 to 3.91% (95% CI = 2.30, 5.92) in 2019] and 5.58% for EUR [1.13% (95% CI = 0.59, 1.97) in 2016 to 6.98% (95% CI = 5.69, 8.39) in 2020]. Current HTP use increased by 10.45% for WPR [0.12% (95% CI = 0, 0.37) in 2015 to 10.57% (95% CI = 5.59, 16.88) in 2020] and 1.15% for EUR [0% (95% CI = 0, 0.35) in 2016 to 1.15% (95% CI = 0.87, 1.47) in 2020]. Meta-regression revealed higher current HTP use in WPR [3.80% (95% CI = 2.88, 4.98)] compared with EUR [1.40% (95% CI = 1.09, 1.74)] and AMR [0.81% (95% CI = 0.46, 1.26)] and for males [3.45% (95% CI = 2.56, 4.47)] compared with females [1.82% (95% CI = 1.39, 2.29)]. Adolescents had higher life-time HTP use prevalence [5.25% (95% CI = 4.36, 6.21) than adults [2.45% (95% CI = 0.79, 4.97)]. Most studies scored a low risk of sampling bias due to their nationally representative sampling. CONCLUSION: The prevalence of HTPs use increased in the EUR and WPR between 2015 and 2020, with nearly 5% of the included populations having ever tried HTP and 1.5% identifying as current users during the study period.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Masculino , Adulto , Feminino , Adolescente , Humanos , Prevalência , Nicotina , Organização Mundial da Saúde , Uso de Tabaco
17.
Am J Sports Med ; 51(3): 687-693, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36856281

RESUMO

BACKGROUND: Femoroacetabular impingement (FAI) is a condition caused by repetitive abutment of a morphologically abnormal proximal femur and/or acetabulum that may result in chondral and labral pathology. An understanding of radiographic parameters associated with successful primary surgery has not been well established. PURPOSE: To determine preoperative radiographic parameters that predict reoperation for FAI and correlate radiographic measurements with outcomes in these patients. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A prospectively collected institutional registry of adolescent patients (age, <19 years) who underwent surgery for FAI (arthroscopic/open) was reviewed. Preoperative standing anteroposterior pelvic radiographs were analyzed for femoroepiphyseal acetabular roof (FEAR) index, as well as lateral center-edge angle (LCEA) and alpha, Tönnis, and Sharp angles. Patient-reported outcomes (PROs) (modified Harris Hip Score, Hip disability and Osteoarthritis Outcome Score) were analyzed preoperatively and at 1- and 2-year followup. Radiographic indication of risk for reoperation was evaluated using receiver operating characteristic (ROC) analysis. Spearman correlation was calculated between radiographic measurements and PROs at 2 years postoperatively. RESULTS: A total of 81 patients (91 hips) underwent primary surgery (57 surgical dislocations vs 34 arthroscopies) for FAI. The mean age at time of primary operation was 16.23 years (range, 10.4-19.6 years) (73.6% female). Eleven hips (12.1%) underwent reoperation at a mean of 20.6 months from primary surgery. The LCEA, FEAR index, Tönnis angle, and Sharp angle before index surgery were significantly different (P < .05) between patients who underwent reoperation and those who did not. ROC analysis indicated that LCEA <22°, FEAR index >-8.7°, Tönnis angle >6.0°, and Sharp angle >44° were predictors for increased risk of reoperation. Using the cutoff values from the ROC analysis in this series, 43% of patients with an LCEA ≤22° had a repeat procedure, while only 8% of those with an LCEA >22° had a repeat procedure. Similar trends were seen with the other aforementioned acetabular radiographic measurements (FEAR index, Tönnis angle, Sharp angle). Patients who did not require a reoperation demonstrated significant improvement in all PRO categories from their preoperative to 2-year postoperative visits (P < .0001). CONCLUSION: In patients undergoing treatment for FAI, a reoperation was associated with radiographic signs of hip dysplasia, indicating that patients with a shallower acetabulum are at risk for a repeat operation.


Assuntos
Impacto Femoroacetabular , Humanos , Adolescente , Feminino , Criança , Adulto Jovem , Adulto , Masculino , Reoperação , Impacto Femoroacetabular/diagnóstico por imagem , Impacto Femoroacetabular/cirurgia , Estudos de Casos e Controles , Cirurgia de Second-Look , Acetábulo
18.
Am J Otolaryngol ; 44(4): 103862, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37001394

RESUMO

Soft-tissue calcifications in the head and neck are relatively common and are the result of a wide variety of benign and malignant pathologies. They can present a diagnostic challenge given the broad range of underlying etiologies. Uremic tumoral calcinosis (UTC) is a rare complication of end-stage renal disease (ESRD) resulting from metastatic soft tissue calcification. Common sites include periarticular soft tissues of the shoulders, elbows, and hands (Pan and Chen, 2016). UTC can also affect the cervical spine and mimic osteosarcomas (Zhou et al., 2018). We present the case of a 71-year-old female with hypertension, left carotid artery stenosis, mitral valve prolapse, and ESRD secondary to diabetes mellitus type II (DMII) on peritoneal dialysis who was found to have large, heterogeneous, bilateral calcified neck masses. Given her clinical history, laboratory results, and imaging findings, she was diagnosed with UTC. In addition to this case, we provide an overview of tumoral calcinosis (TC) and a differential diagnosis for calcified lesions of the head and neck.


Assuntos
Calcinose , Falência Renal Crônica , Humanos , Feminino , Idoso , Calcinose/complicações , Calcinose/diagnóstico por imagem , Pescoço , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Vértebras Cervicais , Cabeça
19.
Updates Surg ; 75(7): 1979-1989, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36917365

RESUMO

Emergent ventral hernia repair (eVHR) is associated with significant morbidity, yet there is no consensus regarding optimal surgical approach. We hypothesized that eVHR with synthetic mesh would have a higher readmission rate compared to primary eVHR or biologic mesh repair. Retrospective analysis of the Nationwide Readmissions Database (NRD) was conducted for patient entries between 2016 and 2018. Adult patients who underwent eVHR were included. Patient demographics, comorbidities, and surgical techniques were compared between readmitted and non-readmitted patients. Predictors of readmission were assessed using multivariate analysis with propensity weighting for various eVHR techniques. Secondary outcomes included hospital length of stay and readmission diagnoses. 43,819 patients underwent eVHR; of the 22,732 with 6 months of follow-up, 6382 (28.1%) were readmitted. The majority of readmissions occurred within the first 30 days (51.8%). Over half of the readmissions were related to surgical complications (50.6%), the most common being superficial surgical site infection (30.1%) and bowel obstruction/ileus (12.2%). In the multivariate analysis, predictors of 30-day readmission included use of synthetic mesh (OR 1.07, 95% CI 1.00-1.14), biologic mesh (OR 1.26, 95% CI 1.06-1.49), and need for concomitant large bowel resection (OR 1.46, 95% CI 1.30-1.65). eVHR is associated with high rates of readmission. Primary repair had favorable odds for readmission and lower risk of surgical complications compared to synthetic and biologic mesh repairs. Synthetic repair had lower odds of readmission than biologic repair. Given the inherent limitations of the NRD, further institutional prospective studies are required to confirm these findings.


Assuntos
Produtos Biológicos , Hérnia Ventral , Hérnia Incisional , Adulto , Humanos , Estudos Retrospectivos , Readmissão do Paciente , Recidiva Local de Neoplasia/cirurgia , Hérnia Ventral/cirurgia , Hérnia Incisional/cirurgia , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Telas Cirúrgicas , Resultado do Tratamento , Recidiva
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