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1.
Artigo em Inglês | MEDLINE | ID: mdl-38858446

RESUMO

BACKGROUND: Multiparametric prostate MRI (mpMRI) is being increasingly adopted for work-up of prostate cancer. For patients selected to omit biopsy, we identified factors associated with repeat MRI, eventual prostate biopsy, and subsequent detection of clinically significant prostate cancer (csPCa, Grade Group ≥2). METHODS: We identified biopsy-naïve men presenting with PSA 2-20 ng/mL (March 2018-June 2021) undergoing initial mpMRI with PIRADS 1-3 lesions who were not selected for biopsy with ≥6 months follow-up. We examined factors associated with repeat mpMRI, progression to biopsy, and subsequent detection of csPCa with univariable and multivariable logistic regression. RESULTS: Of 1494 men, 31% (463/1494) did not pursue biopsy. PSA density (PSAD) ≤ 0.1, prostate health index (PHI) < 55, and PIRADS 1-2 were associated with omission of prostate biopsy. csPCa diagnosis-free survival was 97.6% (326/334) with median follow up of 23.1 months (IQR 15.1-34.6 months). Black race, PSA, PHI, PSA density, and PSA and PHI velocity were significant predictors of undergoing repeat mpMRI (15.6%, 52/334) and subsequent biopsy (8.4%, 28/334). 8 men were subsequently diagnosed with csPCa (N = 7 on prostate biopsy; N = 1 incidentally on holmium enucleation of prostate). All patients diagnosed with csPCa had PIRADS 4-5 on repeat mpMRI. CONCLUSIONS: The subsequent detection rate of csPCa among patients not initially biopsied after mpMRI was low at 2.4%. Decisions to omit biopsy after initial reassuring PHI, PSAD, and mpMRI appear safe with subsequent reassuring serum biomarkers and for cause mpMRI during follow-up.

3.
Orthop J Sports Med ; 12(5): 23259671241248589, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38745915

RESUMO

Background: Blood flow restriction training (BFRT) is a safe and potentially effective adjunctive therapeutic modality for postoperative rehabilitation related to various knee pathologies. However, there is a paucity of literature surrounding BFRT in high-performance athletes after anterior cruciate ligament reconstruction (ACLR). Purpose: To (1) compare the overall time to return to sports (RTS) in a cohort of National Collegiate Athletic Association (NCAA) Division I athletes who underwent a standardized rehabilitation program either with or without BFRT after ACLR and (2) identify a postoperative time interval for which BFRT has the maximum therapeutic benefit. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 55 student-athletes who underwent ACLR between 2000 and 2023 while participating in NCAA Division I sports at a single institution were included in this study. Athletes were allocated to 1 of 2 groups based on whether they participated in a standardized postoperative rehabilitation program augmented with BFRT (BFRT group; n = 22) or completed the standardized protocol alone (non-BFRT group [control]; n = 33). Our primary outcome measure was time to RTS. The secondary outcome measure was handheld dynamometry quadriceps strength testing at various postoperative time points, converted to a limb symmetry index (LSI). Quadriceps strength was not tested between the BFRT and non-BFRT groups because of the limited amount of data on the control group. Results: The mean age at the date of surgery was 18.59 ± 1.10 years for the BFRT group and 19.45 ± 1.30 years for the non-BFRT group (P = .011), and the mean RTS time was 409 ± 134 days from surgery for the BFRT group and 332 ± 100 days for the non-BFRT cohort (P = .047). For the BFRT group, the mean quadriceps strength LSI increased by 0.67% (95% CI, 0.53%-0.81%) for every week of rehabilitation, and there was a significantly positive rate of change in quadriceps strength in weeks 13-16 compared with weeks 9-12 (ΔLSI, 8.22%; P < .001). Conclusion: In elite NCAA Division I athletes, a statistically significant delay was observed in RTS with BFRT compared with standardized physical therapy alone after undergoing ACLR. There also appeared to be an early window during the rehabilitation period where BFRT had a beneficial impact on quadriceps strength.

4.
Eur Urol Oncol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38734544

RESUMO

The National Comprehensive Cancer Network (NCCN) very low risk (VLR) category for prostate cancer (PCa) represents clinically insignificant disease, and detection of VLR PCa contributes to overdiagnosis. Greater use of magnetic resonance imaging (MRI) and biomarkers before patient selection for prostate biopsy (PBx) reduces unnecessary biopsies and may reduce the diagnosis of clinically insignificant PCa. We tested a hypothesis that the proportion of VLR diagnoses has decreased with greater use of MRI-informed PBx using data from our 11-hospital system. From 2018 to 2023, 351/3197 (11%) men diagnosed with PCa met the NCCN VLR criteria. The proportion of VLR diagnoses did not change from 2018 to 2023 (p = 0.8) despite an increase in the use of MRI-informed PBx (from 49% to 82%; p < 0.001). Of patients who underwent combined systematic and targeted PBx and were diagnosed with VLR disease, cancer was found in systematic PBx regions in 79% of cases and in targeted PBx regions in 31% of cases. When performing both systematic and targeted PBx, prebiopsy MRI-based risk calculators could limit VLR diagnosis by 41% using a risk threshold of >5% for Gleason grade group ≥3 PCa to recommend biopsy; the reduction would be 77% if performing targeted PBx only. These findings suggest that VLR disease continues to account for a significant minority of PCa diagnoses and could be limited by targeted PBx and risk stratification calculators. PATIENT SUMMARY: We looked at recent trends for the diagnosis of very low-risk (VLR) prostate cancer. We found that VLR cancer still seems to be frequently diagnosed despite the use of MRI (magnetic resonance imaging) scans before biopsy. The use of risk calculators to identify men who could avoid biopsy and/or biopsy only for lesions that are visible on MRI could reduce the overdiagnosis of VLR prostate cancer.

5.
Breast Cancer Res ; 26(1): 69, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650031

RESUMO

BACKGROUND: We previously reported our phase Ib trial, testing the safety, tolerability, and efficacy of T-DM1 + neratinib in HER2-positive metastatic breast cancer patients. Patients with ERBB2 amplification in ctDNA had deeper and more durable responses. This study extends these observations with in-depth analysis of molecular markers and mechanisms of resistance in additional patients. METHODS: Forty-nine HER2-positive patients (determined locally) who progressed on-treatment with trastuzumab + pertuzumab were enrolled in this phase Ib/II study. Mutations and HER2 amplifications were assessed in ctDNA before (C1D1) and on-treatment (C2D1) with the Guardant360 assay. Archived tissue (TP0) and study entry biopsies (TP1) were assayed for whole transcriptome, HER2 copy number, and mutations, with Ampli-Seq, and centrally for HER2 with CLIA assays. Patient responses were assessed with RECIST v1.1, and Molecular Response with the Guardant360 Response algorithm. RESULTS: The ORR in phase II was 7/22 (32%), which included all patients who had at least one dose of study therapy. In phase I, the ORR was 12/19 (63%), which included only patients who were considered evaluable, having received their first scan at 6 weeks. Central confirmation of HER2-positivity was found in 83% (30/36) of the TP0 samples. HER2-amplified ctDNA was found at C1D1 in 48% (20/42) of samples. Patients with ctHER2-amp versus non-amplified HER2 ctDNA determined in C1D1 ctDNA had a longer median progression-free survival (PFS): 480 days versus 60 days (P = 0.015). Molecular Response scores were significantly associated with both PFS (HR 0.28, 0.09-0.90, P = 0.033) and best response (P = 0.037). All five of the patients with ctHER2-amp at C1D1 who had undetectable ctDNA after study therapy had an objective response. Patients whose ctHER2-amp decreased on-treatment had better outcomes than patients whose ctHER2-amp remained unchanged. HER2 RNA levels show a correlation to HER2 CLIA IHC status and were significantly higher in patients with clinically documented responses compared to patients with progressive disease (P = 0.03). CONCLUSIONS: The following biomarkers were associated with better outcomes for patients treated with T-DM1 + neratinib: (1) ctHER2-amp (C1D1) or in TP1; (2) Molecular Response scores; (3) loss of detectable ctDNA; (4) RNA levels of HER2; and (5) on-treatment loss of detectable ctHER2-amp. HER2 transcriptional and IHC/FISH status identify HER2-low cases (IHC 1+ or IHC 2+ and FISH negative) in these heavily anti-HER2 treated patients. Due to the small number of patients and samples in this study, the associations we have shown are for hypothesis generation only and remain to be validated in future studies. Clinical Trials registration NCT02236000.


Assuntos
Ado-Trastuzumab Emtansina , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Quinolinas , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Ado-Trastuzumab Emtansina/uso terapêutico , Pessoa de Meia-Idade , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Biomarcadores Tumorais/genética , Mutação , Idoso de 80 Anos ou mais , Trastuzumab/uso terapêutico , Trastuzumab/administração & dosagem , Resultado do Tratamento , Metástase Neoplásica
6.
J Am Acad Orthop Surg ; 32(12): 550-557, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38595147

RESUMO

BACKGROUND: The management of elderly acetabular fractures is complex, with high rates of conversion total hip arthroplasty (THA) after open reduction and internal fixation (ORIF), but potentially higher rates of complications after acute THA. METHODS: The California Office of Statewide Health Planning and Development database was queried between 2010 and 2017 for all patients aged 60 years or older who sustained a closed, isolated acetabular fracture and underwent ORIF, THA, or a combination. Chi-square tests and Student t tests were used to identify demographic differences between groups. Multivariate regression was used to evaluate predictors of 30-day readmission and 90-day complications. Kaplan-Meier (KM) survival analysis and Cox proportional hazards model were used to estimate the revision surgery-free survival (revision-free survival [RFS]), with revision surgery defined as conversion THA, revision ORIF, or revision THA. RESULTS: A total of 2,184 surgically managed acetabular fractures in elderly patients were identified, with 1,637 (75.0%) undergoing ORIF and 547 (25.0%) undergoing THA with or without ORIF. Median follow-up was 295 days (interquartile range, 13 to 1720 days). 99.4% of revisions following ORIF were for conversion arthroplasty. Unadjusted KM analysis showed no difference in RFS between ORIF and THA (log-rank test P = 0.27). RFS for ORIF patients was 95.1%, 85.8%, 78.3%, and 71.4% at 6, 12, 24 and 60 months, respectively. RFS for THA patients was 91.6%, 88.9%, 87.2%, and 78.8% at 6, 12, 24 and 60 months, respectively. Roughly 50% of revisions occurred within the first year postoperatively (49% for ORIF, 52% for THA). In propensity score-matched analysis, there was no difference between RFS on KM analysis ( P = 0.22). CONCLUSIONS: No difference was observed in medium-term RFS between acute THA and ORIF for elderly acetabular fractures in California. Revision surgeries for either conversion or revision THA were relatively common in both groups, with roughly half of all revisions occurring within the first year postoperatively. LEVEL OF EVIDENCE: III.


Assuntos
Acetábulo , Artroplastia de Quadril , Fixação Interna de Fraturas , Fraturas Ósseas , Redução Aberta , Reoperação , Humanos , Reoperação/estatística & dados numéricos , Idoso , Artroplastia de Quadril/efeitos adversos , Acetábulo/lesões , Acetábulo/cirurgia , Feminino , Masculino , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/efeitos adversos , Fraturas Ósseas/cirurgia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
7.
Acta Neuropathol ; 147(1): 37, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347231

RESUMO

There are several cellular and acellular structural barriers associated with the brain interfaces, which include the dura, the leptomeninges, the perivascular space and the choroid plexus epithelium. Each structure is enriched by distinct myeloid populations, which mainly originate from erythromyeloid precursors (EMP) in the embryonic yolk sac and seed the CNS during embryogenesis. However, depending on the precise microanatomical environment, resident myeloid cells differ in their marker profile, turnover and the extent to which they can be replenished by blood-derived cells. While some EMP-derived cells seed the parenchyma to become microglia, others engraft the meninges and become CNS-associated macrophages (CAMs), also referred to as border-associated macrophages (BAMs), e.g., leptomeningeal macrophages (MnMΦ). Recent data revealed that MnMΦ migrate into perivascular spaces postnatally where they differentiate into perivascular macrophages (PvMΦ). Under homeostatic conditions in pathogen-free mice, there is virtually no contribution of bone marrow-derived cells to MnMΦ and PvMΦ, but rather to macrophages of the choroid plexus and dura. In neuropathological conditions in which the blood-brain barrier is compromised, however, an influx of bone marrow-derived cells into the CNS can occur, potentially contributing to the pool of CNS myeloid cells. Simultaneously, resident CAMs may also proliferate and undergo transcriptional and proteomic changes, thereby, contributing to the disease outcome. Thus, both resident and infiltrating myeloid cells together act within their microenvironmental niche, but both populations play crucial roles in the overall disease course. Here, we summarize the current understanding of the sources and fates of resident CAMs in health and disease, and the role of the microenvironment in influencing their maintenance and function.


Assuntos
Macrófagos , Proteômica , Camundongos , Animais , Macrófagos/patologia , Sistema Nervoso Central/patologia , Microglia , Meninges
8.
Eur J Orthop Surg Traumatol ; 34(3): 1373-1379, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38175277

RESUMO

PURPOSE: Ankle arthrodesis is a mainstay of surgical management for ankle arthritis. Accurately risk-stratifying patients who undergo ankle arthrodesis would be of great utility. There is a paucity of accurate prediction models that can be used to pre-operatively risk-stratify patients for ankle arthrodesis. We aim to develop a predictive model for major perioperative complication or readmission after ankle arthrodesis. METHODS: This is a retrospective cohort study of adult patients who underwent ankle arthrodesis at any non-federal California hospital between 2015 and 2017. The primary outcome is readmission within 30 days or major perioperative complication. We build logistic regression and ML models spanning different classes of modeling approaches, assessing discrimination and calibration. We also rank the contribution of the included variables to model performance for prediction of adverse outcomes. RESULTS: A total of 1084 patients met inclusion criteria for this study. There were 131 patients with major complication or readmission (12.1%). The XGBoost algorithm demonstrates the highest discrimination with an area under the receiver operating characteristic curve of 0.707 and is well-calibrated. The features most important for prediction of adverse outcomes for the XGBoost model include: diabetes, peripheral vascular disease, teaching hospital status, morbid obesity, history of musculoskeletal infection, history of hip fracture, renal failure, implant complication, history of major fracture. CONCLUSION: We report a well-calibrated algorithm for prediction of major perioperative complications and 30-day readmission after ankle arthrodesis. This tool may help accurately risk-stratify patients and decrease likelihood of major complications.


Assuntos
Artroplastia de Substituição do Tornozelo , Fraturas Ósseas , Adulto , Humanos , Artroplastia de Substituição do Tornozelo/efeitos adversos , Articulação do Tornozelo/cirurgia , Readmissão do Paciente , Estudos Retrospectivos , Tornozelo/cirurgia , Artrodese/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fraturas Ósseas/cirurgia , Algoritmos , Resultado do Tratamento
9.
Adv Exp Med Biol ; 1423: 115-122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37525036

RESUMO

The genus Phyllanthus belongs to one of the largest plant families, the Phyllantaceae (L.). Phyllanthus niruri is an annual perennial herb that grows in tropical Asia, America, China, and the islands of the Indian Ocean. Numerous alkaloids, steroids, flavonoids, lignans, coumarins, polyphenols, and lipids are present in Phyllanthus. The effects of plants have been studied for a variety of purposes, including their antioxidant (Giribabu et al., Evid Based Complement Alternat Med, 2014), anti-inflammatory (Porto et al., Revista Brasileira de Pharmacognosy, 2013), antinociceptive (Sathisha et al., Indian Drugs, 2009), analgesic (Mostofa et al., BMC Complement Altern Med, 2017), antiulcer (Mali et al., Biomed Aging Pathol, 2011), antiarthritic (Obidike and Salawu, Planta Medica, 2010), antiplasmodial (Shilpa et al., Environ Dis, 2018), immunomodulatory (Manikkoth et al., Anticonvulsant activity of Phyllanthus amarus in experimental animal models), anticonvulsant (Wasnik et al., Int J Pharm Sci Rev Res, 2014), antidepressant (Venkateswaran et al., Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: In vitro and in vivo studies (antiviral agent/Marmota monax/DNA polymerase/hepatitis B surface antigen/woodchuck hepatitis surface antigen). In Hepatitis B and The Prevention of Primary Cancer of The Liver: Selected Publications of Baruch S Blumberg, pp 535-539), antiviral (Venkateswaran et al., Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: In vitro and in vivo studies (antiviral agent/Marmota monax/DNA polymerase/hepatitis B surface antigen/woodchuck hepatitis surface antigen). In Hepatitis B and The Prevention of Primary Cancer of The Liver: Selected Publications of Baruch S Blumberg, pp 535-539), antitumor (Sharma et al., Asian Pac J Cancer Prev, 2009), hyperlipidemia (Khanna et al., J Ethnopharmacol, 2002), and antifertility (Ezeonwu, Inquiries J, 2011). For additional docking investigations with distinct proteins, the leaf chemicals are assessed, that is, the crystal structure of serine protease hepsin in complex with inhibitor [PDB ID:5 CE1] for antiviral activity human topoisomerase II beta in complex with DNA and etoposide [PDB ID:3QX3] and crystal structure of E. coli GyraseB 24 kDa in complex with 4-(4-bromo-1H-pyrazol-1-yl)-6-[(ethylcarbamoyl)amino]-N-(pyridin-3-yl) pyridine-3-carboxamide [PDB ID: 6F86] for antibacterial activity and have been selected. To evaluate the in silico results and grading of virtual screening, or molecular docking, ritonavir antiviral activity and ampicillin for antibacterial activity were used as a benchmark.


Assuntos
Hepatite B , Neoplasias Hepáticas , Phyllanthus , Animais , Humanos , Extratos Vegetais/uso terapêutico , Antígenos de Superfície da Hepatite B , Marmota , Simulação de Acoplamento Molecular , Phyllanthus/química , Anticonvulsivantes/uso terapêutico , Escherichia coli , Hepatite B/tratamento farmacológico , Antibacterianos/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Folhas de Planta , DNA Polimerase Dirigida por DNA , Neoplasias Hepáticas/tratamento farmacológico , Antígenos de Superfície/uso terapêutico
10.
J Surg Case Rep ; 2023(6): rjad340, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37313431

RESUMO

Dermoid cysts of the head and neck region are very rare, with about 7% occurrence and parotid being an extremely rare location. In this case report, we presented a case of a 23-year-old man with a recurrent parotid dermoid cyst and the clinical presentation and diagnostic difficulties are discussed.

11.
Int J Biol Macromol ; 237: 123991, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36907293

RESUMO

Despite possessing a wide spectrum of biological activities, molecular targets of EGCG remain elusive and as a result, its precise mode of action is still unknown. Herein, we have developed a novel cell-permeable and Click-able bioorthogonal probe for EGCG, YnEGCG for in situ detection and identification of its interacting proteins. The strategic structural modification on YnEGCG allowed it to retain innate biological activities of EGCG (IC50 59.52 ± 1.14 µM and 9.07 ± 0.01 µM for cell viability and radical scavenging activity, respectively). Chemoproteomics profiling identified 160 direct EGCG targets, with H:L ratio ≥ 1.10 from the list of 207 proteins, including multiple new proteins that were previously unknown. The targets were broadly distributed in various subcellular compartments suggesting a polypharmacological mode of action of EGCG. GO analysis revealed that the primary targets belonged to the enzymes that regulate key metabolic processes including glycolysis and energy homeostasis, also the cytoplasm (36 %) and mitochondria (15.6 %) contain the majority of EGCG targets. Further, we validated that EGCG interactome was closely associated with apoptosis indicating its role in inducing toxicity in cancer cells. For the first time, this in situ chemoproteomics approach could identify a direct and specific EGCG interactome under physiological conditions in an unbiased manner.


Assuntos
Catequina , Catequina/farmacologia , Proteômica , Apoptose , Proteínas
12.
Prostate Cancer Prostatic Dis ; 26(3): 588-595, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36973367

RESUMO

PURPOSE: To develop nomograms that predict the detection of clinically significant prostate cancer (csPCa, defined as ≥GG2 [Grade Group 2]) at diagnostic biopsy based on multiparametric prostate MRI (mpMRI), serum biomarkers, and patient clinicodemographic features. MATERIALS AND METHODS: Nomograms were developed from a cohort of biopsy-naïve men presenting to our 11-hospital system with prostate specific antigen (PSA) of 2-20 ng/mL who underwent pre-biopsy mpMRI from March 2018-June 2021 (n = 1494). The outcomes were the presence of csPCa and high-grade prostate cancer (defined as ≥GG3 prostate cancer). Using significant variables on multivariable logistic regression, individual nomograms were developed for men with total PSA, % free PSA, or prostate health index (PHI) when available. The nomograms were both internally validated and evaluated in an independent cohort of 366 men presenting to our hospital system from July 2021-February 2022. RESULTS: 1031 of 1494 men (69%) underwent biopsy after initial evaluation with mpMRI, 493 (47.8%) of whom were found to have ≥GG2 PCa, and 271 (26.3%) were found to have ≥GG3 PCa. Age, race, highest PIRADS score, prostate health index when available, % free PSA when available, and PSA density were significant predictors of ≥GG2 and ≥GG3 PCa on multivariable analysis and were used for nomogram generation. Accuracy of nomograms in both the training cohort and independent cohort were high, with areas under the curves (AUC) of ≥0.885 in the training cohort and ≥0.896 in the independent validation cohort. In our independent validation cohort, our model for ≥GG2 prostate cancer with PHI saved 39.1% of biopsies (143/366) while only missing 0.8% of csPCa (1/124) with a biopsy threshold of 20% probability of csPCa. CONCLUSIONS: Here we developed nomograms combining serum testing and mpMRI to help clinicians risk stratify patients with elevated PSA of 2-20 ng/mL who are being considered for biopsy. Our nomograms are available at https://rossnm1.shinyapps.io/MynMRIskCalculator/ to aid with biopsy decisions.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Nomogramas , Antígeno Prostático Específico , Imageamento por Ressonância Magnética , Biópsia , Biópsia Guiada por Imagem
14.
Prostate ; 83(6): 516-523, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36591888

RESUMO

BACKGROUND: Genetic evaluation of men with advanced prostate cancer is recognized as imperative both to guide treatment decisions and to trigger cascade genetic testing of family members. Here we investigate utilization patterns of genetic testing among a contemporary cohort of men with advanced prostate cancer at our institution. METHODS: We queried the Northwestern Electronic Data Warehouse from January 2021 to present for all men diagnosed with National Comprehensive Cancer Network high-risk/very high-risk, regional, or metastatic prostate cancer. Patients were excluded from analyses if treated at an outside institution and/or presented for a second opinion evaluation. Statistics were performed using t-test, Chi-squared test, and univariable and multivariable logistic regression with significance defined as p < 0.05. RESULTS: Atotal of 320 men (52.5%) had local/regional disease and 290 (47.5%) had metastatic disease, 53 (18.3%) of whom had castrate resistant prostate cancer. Rates of germline genetic testing rate were low in patients with localized disease (9.4%) and metastatic disease (34.1%). Only 19 (35.8%) men diagnosed with metastatic castrate resistant prostate cancer underwent germline genetic evaluation. Germline testing was most frequently discussed or ordered by medical oncologists (52%) followed by urologists (20%). Men who underwent germline testing were younger (p < 0.001), more likely to have Medicaid or private insurance (p = 0.002), and more likely to have metastatic disease (p < 0.001). There were no statistically significant differences in baseline PSA, ethnicity, race, or castration sensitivity status. Age (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.91-0.97, p < 0.001) and metastatic disease (OR: 5.71, 95% CI: 3.63-9.22, p < 0.001) were significant independent predictors of genetic testing on multivariable logistic regression. CONCLUSIONS: Here we report that utilization of genetic testing is associated with metastatic disease and inversely associated with age. Overall, utilization rates of genetic testing remain low in all patient groups, including in the metastatic castrate resistant setting, where genetic testing can identify patients with homologous recombination repair deficiency who may benefit from use of targeted therapeutics such as PARP inhibitors. Genetic testing in men with aggressive prostate cancer is critical and barriers to routine implementation of testing require further study to develop strategies to improve utilization rates.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Testes Genéticos , Etnicidade
15.
Urology ; 172: 182-185, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36402274

RESUMO

We present a case of chemotherapy refractory spindle cell rhabdomyosarcoma of the lower urinary tract in a 15-month-old female that ultimately required consolidative surgery with cystectomy, urethrectomy, ovarian-sparing hysterectomy, bilateral salpingectomy, anterior vaginal wall resection, and bilateral pelvic lymph node dissection. Genitourinary reconstruction was performed by ileal conduit creation and vaginoplasty. After completion of her maintenance postoperative chemotherapy regimen, the patient has remained disease-free for approximately 27 months.


Assuntos
Rabdomiossarcoma , Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Feminino , Lactente , Bexiga Urinária/cirurgia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Cistectomia , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/cirurgia
16.
Am J Surg ; 224(5): 1308-1313, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35778232

RESUMO

BACKGROUND: This study aims to assess the impact of pre-injury anticoagulant use on outcomes of isolated blunt abdominal SOI patients who underwent NOM. METHODS: A 1-year(2017) analysis of the ACS-TQIP. We included all ≥18yrs trauma patients with isolated blunt abdominal-SOI who underwent NOM. Patients were stratified into two groups based on their history of pre-injury anticoagulant use. Propensity score matching was performed. RESULTS: A matched cohort of 2709 patients (AC, 903; No-AC,1806) was analyzed. Compared to the No-AC group, the AC group had higher rates of failure of NOM(2.6% vs. 4.5%, p = 0.03), cardiac arrest (1.2%vs. 3.1%, p = 0.02), acute kidney injury (2.4% vs. 4.2%, p < 0.01), myocardial infarction (0.6% vs. 1.4%,p = 0.03), and mortality (5.1%vs. 7.6%,p = 0.01), and longer hospital LOS (17[10-24]vs.17[12-26]days,p = 0.04) and ICU LOS (11[6-17]vs.11[7-18]days,p = 0.01). CONCLUSION: Among nonoperatively managed blunt abdominal SOI patients, preinjury use of anticoagulants negatively impacts outcomes. Extra surveillance is required while managing patients with blunt abdominal SOI on pre-injury anticoagulants. LEVEL OF EVIDENCE: Level III. STUDY TYPE: Therapeutic/care management.


Assuntos
Traumatismos Abdominais , Ferimentos não Penetrantes , Humanos , Baço/lesões , Traumatismos Abdominais/complicações , Traumatismos Abdominais/terapia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/terapia , Anticoagulantes/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Escala de Gravidade do Ferimento
17.
Cureus ; 14(5): e24951, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35706723

RESUMO

Characterized by intense, episodic lancinating pain within the distribution of the trigeminal nerve, trigeminal neuralgia (TN) is the most common craniofacial pain syndrome. Failure of medical management requires the consideration of interventional procedures. Stereotactic radiosurgery (SRS) is one of the more commonly used surgical options. Herein, we report the first published case of a patient with TN treated in the ZAP-X (San Carlos, CA: ZAP Surgical Systems, Inc.) gyroscopic radiosurgery system. This 59-year-old man with multiple sclerosis and recurrent intractable left idiopathic TN following previous SRS was retreated in the Zap-X system using 100 isocentric 5 mm beams to a dose of 7500 cGy. At a three-month follow-up, the patient reported a 45% decrease in his visual analogue scale (VAS) and a reduced need for medication. Albeit preliminary, this initial experience highlights the feasibility of a self-shielded, cobalt-free, device for radiosurgically treating TN.

18.
Curr Opin Oncol ; 34(3): 234-242, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35266906

RESUMO

PURPOSE OF REVIEW: The genomic and immunologic profiling of renal cell carcinoma (RCC) has provided the impetus for advancements in systemic treatments using combination therapy - either with immune check point inhibitor (ICI) + ICI or with ICI + targeted therapy. This approach has been examined in several landmark trials, treating both clear cell (ccRCC) and nonclear cell (nccRCC) histologies. In this review, we highlight systemic therapy advancements made in this new decade, the 2020s. RECENT FINDINGS: Targeting the programmed death receptor 1/PD-L1 pathway has created more tolerable and effective immunotherapy regimens, expanding the applications of ICIs. These new applications, paired with trial data, include ICI monotherapy in nccRCC and adjuvant pembrolizumab in resected, high-risk RCC. In addition, ICI + ICI and ICI + TKI combination therapy have demonstrated oncologic efficacy in advanced ccRCC and sarcomatoid RCC. Similar progress has been noted regarding new targeted therapies. Along the hypoxia inducible factor pathway, belzutifan has received FDA approval in von Hippel-Lindau-associated RCC. In addition, in papillary RCC, agents such as cabozantinib target the MET proto-oncogene pathway and have demonstrated impressive oncologic outcomes. SUMMARY: The 2020s utilize the molecular profiling of advanced RCC as a scaffold for recent trials in immunotherapy and targeted therapies. Going forward, emphasizing patient-reported outcomes and careful clinical trial construction remain critical to improve systemic therapy in RCC.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia
19.
Eur Spine J ; 31(8): 1952-1959, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34392418

RESUMO

PURPOSE: Posterior cervical fusion is associated with increased rates of complications and readmission when compared to anterior fusion. Machine learning (ML) models for risk stratification of patients undergoing posterior cervical fusion remain limited. We aim to develop a novel ensemble ML algorithm for prediction of major perioperative complications and readmission after posterior cervical fusion and identify factors important to model performance. METHODS: This is a retrospective cohort study of adults who underwent posterior cervical fusion at non-federal California hospitals between 2015 and 2017. The primary outcome was readmission or major complication. We developed an ensemble model predicting complication risk using an automated ML framework. We compared performance with standard ML models and logistic regression (LR), ranking contribution of included variables to model performance. RESULTS: Of the included 6822 patients, 18.8% suffered a major complication or readmission. The ensemble model demonstrated slightly superior predictive performance compared to LR and standard ML models. The most important features to performance include sex, malignancy, pneumonia, stroke, and teaching hospital status. Seven of the ten most important features for the ensemble model were markedly less important for LR. CONCLUSION: We report an ensemble ML model for prediction of major complications and readmission after posterior cervical fusion with a modest risk prediction advantage compared to LR and benchmark ML models. Notably, the features most important to the ensemble are markedly different from those for LR, suggesting that advanced ML methods may identify novel prognostic factors for adverse outcomes after posterior cervical fusion.


Assuntos
Doenças da Coluna Vertebral , Fusão Vertebral , Adulto , Vértebras Cervicais/cirurgia , Humanos , Aprendizado de Máquina , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos
20.
J Endourol ; 36(4): 528-534, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34731024

RESUMO

Objectives: To assess the accuracy, quality, and readability of online educational health information in English related to the most common benign prostatic hyperplasia (BPH) guideline-approved surgical treatments. Methods: The terms "benign prostatic hyperplasia," "BPH," and all eight guideline-approved treatment modalities studied, were searched to retrieve the first five relevant websites and first two paid advertised websites related to the surgical treatment options for BPH. These modalities included transurethral resection of the prostate (TURP), GreenLight photovaporization, endoscopic enucleation of the prostate, Rezum, Urolift, Aquablation, open simple prostatectomy, and robotic simple prostatectomy (RSP). All relevant websites were assessed for their accuracy, quality, and readability using standardized scoring systems. Results: The mean accuracy score for each of the treatment modalities were all indicative of good accuracy, with 76%-99% of the information presented as being accurate. The median quality score was statistically different across the eight treatment modalities (p = 0.015). The median readability grade level was statistically different across the eight treatment modalities (p = 0.009). Websites that described TURP (median readability grade level, 9.00 [interquartile range (IQR) 8.00-10.80]) were significantly easier to read than those related to RSP (median readability grade level, 14.35 [IQR, 11.08-16.50]) (p = 0.011). No other statistically significant differences were found within the other treatment modality websites. Conclusions: The majority of websites retrieved were found to be of high accuracy, good quality, and poor readability. Additionally, it was found that none of the retrieved websites included descriptions for all the other included treatment modalities. Given these findings, the authors recommend the development of centralized resources with all guideline-approved treatment modalities and accurate, readable, and high-quality information related to the surgical treatment of BPH.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Compreensão , Humanos , Internet , Masculino , Próstata/cirurgia , Prostatectomia , Hiperplasia Prostática/cirurgia
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