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OBJECTIVE: To determine the safety and efficacy of the oral progesterone antagonist onapristone extended release (onapristone-XR) in patients with recurrent progesterone receptor (PR)-positive adult-type granulosa cell tumor (aGCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC). METHODS: This single-institution phase II study included patients with PR-positive aGCT, LGSOC, or EEC who received ≥1 prior line of chemotherapy. Patients were enrolled from 5/2019-5/2020. PR status was evaluated via immunohistochemistry. Eligible patients had PR expression ≥1% on tissue collected within 3 years of enrollment. Patients received 50 mg of onapristone-XR twice daily until disease progression or treatment discontinuation. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints were response duration, clinical benefit rate (CBR), and safety. RESULTS: Five patients with LGSOC and 1 with EEC enrolled, but both cohorts closed early due to slow accrual. Fourteen patients with aGCT enrolled and completed stage 1 accrual. No responses were observed. Four patients with LGSOC were evaluable, with median PFS of 4.4 months (range, 1.8-NE) and CBR of 50% (range, 6.8%-93.2%). All 14 patients with aGCT were evaluable, with median PFS of 2.8 months (range, 1.6-4.9), 6-month PFS rate of 21.4% (range, 5.2%-44.8%), 12-month PFS rate of 14.3% (range, 2.3%-36.6%), and a CBR of 35.7% (range, 12.8%-64.9%). CONCLUSIONS: The study did not meet its primary endpoint. While onapristone-XR was well tolerated in all 3 arms, no objective responses were observed.
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OBJECTIVE: To evaluate the feasibility and outcomes of performing procedural interventions, defined as surgical resection, tumor ablation, or targeted radiation therapy, for oligoprogressive disease among patients with gynecologic malignancies who are treated with immune checkpoint blockade. METHODS: Patients with gynecologic cancers treated with immune checkpoint blockade between January 2013 and October 2021 who underwent procedural interventions including surgical resection, interventional radiology ablation, or radiation therapy for oligoprogressive disease were identified. Procedures performed before immune checkpoint therapy initiation or ≥6 months after therapy completion were excluded. Long immunotherapy duration prior to intervention was defined as ≥6 months. Progression-free survival and overall survival were calculated from procedure date until disease progression or death, respectively. RESULTS: During the study period, 886 patients met inclusion criteria and received immune checkpoint blockade therapy. Of these, 34 patients underwent procedural interventions for oligoprogressive disease; 7 underwent surgical resection, 3 underwent interventional radiology ablation, and 24 underwent radiation therapy interventions. Primary disease sites included uterus (71%), ovary (24%), and cervix (6%). Sites of oligoprogression included abdomen/pelvis (26%), bone (21%), lung (18%), distant lymph node (18%), brain (9%), liver (6%), and vagina (3%). Most tumors (76%) did not exhibit microsatellite instability or mismatch repair deficiency. Approximately half (53%) of the patients had long immune checkpoint therapy duration prior to intervention. Median progression-free survival following the procedure was 5.3 months (95% CI, 3.1-9.9), and median overall survival was 21.7 months (95% CI, 14.9-not estimable). Long versus short immune checkpoint therapy duration prior to procedure and length of immune checkpoint therapy had no effect on progression-free or overall survival. CONCLUSIONS: Procedural interventions for patients with oligoprogression on immune checkpoint blockade therapy are feasible and demonstrate favorable outcomes. With expanding use of immune checkpoint therapy, it is important to investigate combined modalities to maximize therapeutic benefit for patients with gynecologic cancers.
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Neoplasias Encefálicas , Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/radioterapia , Inibidores de Checkpoint Imunológico , Terapia Combinada , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
OBJECTIVE: HER2 overexpression is associated with decreased overall survival in metastatic endometrial cancer. Trastuzumab with chemotherapy has demonstrated efficacy for first-line management of advanced HER2+ endometrial carcinoma, but HER2-directed therapy in the recurrent setting is limited. Zanidatamab (ZW25), a humanized, bispecific antibody that simultaneously binds the 2 distinct HER2 epitopes bound by trastuzumab and pertuzumab, has demonstrated safety and activity in HER2+ tumors. Here, we report the results of a phase 2, open-label study evaluating the efficacy and safety of zanidatamab in patients with HER2+ metastatic endometrial carcinoma/carcinosarcoma who received prior treatment. METHODS: We enrolled 16 patients with HER2+ endometrial carcinoma/carcinosarcoma after progression on ≤2 lines of therapy on a single-arm phase 2 study of zanidatamab. The primary endpoint was overall response rate (ORR; complete or partial response) by Response Evaluation Criteria in Solid Tumors version 1.1. HER2 immunohistochemistry and fluorescence in situ hybridization (FISH) were performed on pretreatment samples. Intratumor HER2 genetic heterogeneity was assessed. RESULTS: This study did not meet its primary efficacy endpoint. Although a clinical benefit rate of 37.5% was observed by 24 weeks, only 1 patient achieved a partial response (ORR, 6.2%). Eight patients had HER2 intratumor heterogeneity or lacked HER2 amplification by FISH. Decreased HER2 expression on repeat pretreatment samples was observed in 3 (75%) of 4 patients evaluated. CONCLUSIONS: We observed a low response rate to zanidatamab in recurrent HER2+ endometrial carcinoma/carcinosarcoma, which may be driven by downregulation of HER2 expression. Repeat HER2 testing should be considered prior to second-line HER2-directed therapy. CLINICALTRIALS: govidentifier: NCT04513665.
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Anticorpos Biespecíficos , Carcinossarcoma , Neoplasias do Endométrio , Feminino , Humanos , Receptor ErbB-2/metabolismo , Hibridização in Situ Fluorescente , Recidiva Local de Neoplasia/patologia , Trastuzumab , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Carcinossarcoma/tratamento farmacológico , Carcinossarcoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study.
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Laringoestenose , Humanos , Constrição Patológica , Estudos Prospectivos , Estudos Retrospectivos , Laringoestenose/cirurgia , Resultado do TratamentoRESUMO
This cross-sectional study evaluates the association of sociodemographic characteristics and care utilization with improved voice function among a large sample of older US adults.
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Distúrbios da Voz , Voz , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , AutorrelatoRESUMO
Interest in covalent enzyme inhibitors as therapeutic agents has seen a recent resurgence. Covalent enzyme inhibitors typically possess an organic functional group that reacts with a key feature of the target enzyme, often a nucleophilic cysteine residue. Herein, the application of small, modular ReV complexes as inorganic cysteine-targeting warheads is described. These metal complexes were found to react with cysteine residues rapidly and selectively. To demonstrate the utility of these ReV complexes, their reactivity with SARS-CoV-2-associated cysteine proteases is presented, including the SARS-CoV-2 main protease and papain-like protease and human enzymes cathepsin B and L. As all of these proteins are cysteine proteases, these enzymes were found to be inhibited by the ReV complexes through the formation of adducts. These findings suggest that these ReV complexes could be used as a new class of warheads for targeting surface accessible cysteine residues in disease-relevant target proteins.
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COVID-19 , Cisteína Proteases , Inibidores de Cisteína Proteinase , Cisteína , Rênio , SARS-CoV-2 , Humanos , Cisteína Proteases/metabolismo , Inibidores Enzimáticos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Inibidores de Cisteína Proteinase/química , Inibidores de Cisteína Proteinase/farmacologia , Inibidores de Cisteína Proteinase/uso terapêuticoRESUMO
INTRODUCTION: Our understanding of the biologic heterogeneity of endometrial cancer has improved, but which patients benefit from single-agent versus combination immune checkpoint blockade remains unclear. METHODS: We conducted a single-center, randomized, open-label, phase 2 study of durvalumab 1500 mg (Arm 1) versus durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks (Arm 2) in patients with endometrial carcinoma. The primary endpoints were overall response rate (ORR) and progression-free survival (PFS) at 24 weeks. Patients were stratified by mismatch repair (MMR) status and carcinosarcoma histology. Using a Simon two-stage minimax design, we determined 40 patients per arm would provide 90% power and Type 1 error of 10%. RESULTS: Eighty-two patients were enrolled; 77 were evaluable for toxicity (Arm 1: 38, Arm 2: 39) and 75 evaluable for efficacy (Arm 1: 37, Arm 2: 38). Patient were stratified by MMR status (Arm 1: 5, Arm 2: 4 were MMR-deficient). The ORR in Arm 1 was 10.8% (one-sided 90% CI: 4.8-100%); the ORR in Arm 2 was 5.3% (one-sided 90% CI: 1.4-100%). Since the primary endpoint of ORR was not met, 24-week PFS was not compared to historical controls per protocol specification. No new safety signals were identified. CONCLUSIONS: In these patients with predominantly MMR-proficient endometrial cancer, there was limited response with single-agent and combined immune checkpoint blockade. The pre-specified efficacy thresholds were not met for further evaluation. A deeper understanding of potential mechanisms of resistance to immunotherapy in MMR-proficient endometrial cancer is needed for the development of novel therapeutic approaches.
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Neoplasias do Endométrio , Inibidores de Checkpoint Imunológico , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológicoRESUMO
BACKGROUND: Preoperative dysphagia screening is rare. The purpose of this study was to assess the prevalence and potential risk factors of preoperative dysphagia risk in adults preparing for surgery. METHODS: The Eating Assessment Tool (EAT-10), Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF), and Sarcopenia Screening Tool (SARC-F) were self-administered in adults preparing for surgery to identify dysphagia, malnutrition, and sarcopenia risk, respectively. Other variables collected include clinical demographics, fall risk, and surgical history associated with increased dysphagia risk. Descriptive summary statistics, univariate analysis, and logistic regression were performed as appropriate. RESULTS: The median age was 69 years and preoperative dysphagia risk was 9.6%. Among 357 patients completing both EAT-10 and PG-SGA SF or SARC-F, 7.3% had preoperative dysphagia and malnutrition risk and 7.2% had preoperative dysphagia and sarcopenia risk. Preoperative dysphagia risk was 2.7 times greater in those with prior surgical history associated with increased risk of dysphagia, 2.2 times higher in women, and almost twice as high in Black patients and patients with fall risk. Logistic regression revealed significant odds ratios (ORs) for prior surgical history associated with increased risk of dysphagia (OR, 2.95; 95% CI, 1.62-5.40) and male sex (OR, 0.52; 95% CI, 0.29-0.94), and a significant relationship between preoperative dysphagia and malnutrition risk (OR, 4.56; 95% CI, 2.02-10.28) when controlling for clinical variables. CONCLUSION: The high prevalence of dysphagia risk alone and in combination with malnutrition and sarcopenia risk in community-dwelling adults underscores the need for standardized preoperative screening and optimization prior to surgery.
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Transtornos de Deglutição , Desnutrição , Sarcopenia , Humanos , Masculino , Feminino , Adulto , Idoso , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Vida Independente , Avaliação Nutricional , Sarcopenia/etiologia , Sarcopenia/complicações , Prevalência , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Fatores de RiscoRESUMO
BACKGROUND: This study evaluated the distribution of macrolide-resistant Mycoplasma genitalium in multiple urogenital specimens collected from women enrolled in a prospective multicenter US clinical study. METHODS: Four female urogenital specimens (vaginal swab, urine, endocervical swab, ectocervical brush/spatula) collected from each subject were tested using a transcription-mediated amplification (TMA) assay for M. genitalium. TMA-positive specimens were evaluated by reverse transcription-polymerase chain reaction and bidirectional Sanger sequencing of M. genitalium 23S rRNA to identify the presence of macrolide-resistance-mediating mutations (MRMs) at base positions 2058/2059. RESULTS: Of 140 women with ≥1 TMA-positive specimens, 128 (91.4%) yielded M. genitalium 23S rRNA sequence. MRMs were found in 52% of vaginal specimens, 46.3% of urine specimens, 37.8% of endocervical specimens, and 46% of ectocervical specimens. There were 44 unique specimen type/sequence phenotype combinations of M. genitalium infection. Most (81; 63.3%) women had single specimen-sequence phenotype (macrolide-susceptible, MRM, or both) infections, while 24 (18.8%) women had multiple specimen-sequence phenotype concordant infections, and 23 (17.9%) women had multiple specimen-sequence phenotype discordant infections. The sensitivity for any single specimen type to detect overall urogenital tract macrolide-resistant M. genitalium infection status was 96.3% for vaginal swab samples, 82.6% for urine samples, 70.8% for endocervical swab samples, and 82.1% for ectocervical brush/spatula liquid Pap samples. CONCLUSIONS: The distribution of M. genitalium infections in female urogenital tract specimens is highly complex, with multiple phenotypic combinations of the organism infecting a significant proportion of women at different anatomic specimen collection sites. Vaginal swab sampling yielded the highest sensitivity for identifying women with macrolide-resistant M. genitalium urogenital tract infections.
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Infecções por Mycoplasma , Mycoplasma genitalium , Feminino , Masculino , Humanos , Macrolídeos/farmacologia , Mycoplasma genitalium/genética , RNA Ribossômico 23S/genética , Estudos Prospectivos , Antibacterianos/farmacologia , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/diagnóstico , Farmacorresistência Bacteriana , PrevalênciaRESUMO
Isolation of Cokeromyces recurvatus, a dimorphic mucormycete fungus, from clinical specimens poses a diagnostic challenge to physicians and laboratorians as this organism may represent a rare colonizer or true pathogen. Here, we report a case of Cokeromyces recurvatus present in a circumferential duodenal lesion. The patient is a 64-year-old with no past medical history, admitted with a three-week history of left upper quadrant abdominal pain. Computerized tomography scan identified duodenitis with significant gastric outlet obstruction, confirmed by the presence of a partially obstructing non-bleeding duodenal ulcer on upper endoscopy. Histology showed variably sized spherical structures without nuclei, reproductive tracts, or alimentary tracts. Small, clustered spherules representing putative endospores were observed within the larger structures and in the exudate. Based on the histology, the differential included Coccidioides spp, Emmonsia spp, or Chrysosporium spp. Additionally, gastric biopsies revealed concurrent Helicobacter pylori gastritis. The fungus was identified as C. recurvatus by broad-range fungal polymerase chain reaction performed on formalin-fixed paraffin-embedded biopsy tissue, as well as morphology and DNA sequencing of the cultured isolate. The fungus had low MICs to all major antifungal classes; however, in the context of the Helicobacter pylori infection, the patient was only treated with amoxicillin and clarithromycin with improvement in his symptoms before hospital discharge. Only three cases of Cokeromyces recurvatus isolated from the GI tract have been reported; this case highlights a unique clinical presentation in the small bowel in a patient without underlying medical conditions.
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Obstrução da Saída Gástrica , Infecções por Helicobacter , Helicobacter pylori , Mucorales , Humanos , Pessoa de Meia-Idade , Obstrução da Saída Gástrica/diagnósticoRESUMO
PURPOSE: Tranexamic acid (TXA) is a potent pro-coagulation drug. Pre-operative, preventive TXA administration and TXA use for active bleeding are established treatments in many medical situations; yet, less is known about its use in otolaryngology head and neck surgery practice. The primary study goals were: MATERIALS AND METHODS: This is an international survey exploring TXA administration strategy. The electronic, anonymous, questionnaire was emailed to all registered Israeli and American Otolaryngology Head and Neck Surgery (OHNS) physicians, investigating TXA administration: RESULTS: Overall, 317 otolaryngologists participated in the study. TXA was administered to 40.5 % of the pediatric population and 50 % of the adult patients when needed. Epistaxis was the most common indication for TXA administration (48-55 %). A small number of otolaryngologists, 4-13 %, recommended preventive TXA for various operations. More surgeons include TXA in their practice and adjusted the dose according to renal function in academic compared to non-academic medical centers and among otolaryngologists practicing in Israel compared to the United States. CONCLUSIONS: TXA is provided by many otolaryngologists to treat active epistaxis but to a substantially lesser extent as a preventive measure. TXA is given to children and adults, some with substantial comorbidities. Treatment is more common among surgeons working in academic institutes and medical centers in Israel.
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Otolaringologia , Ácido Tranexâmico , Adulto , Criança , Epistaxe/tratamento farmacológico , Epistaxe/prevenção & controle , Humanos , Israel , Inquéritos e Questionários , Ácido Tranexâmico/uso terapêutico , Estados UnidosRESUMO
Portal vein thrombosis (PVT) is a partial or complete occlusion of the hepatic portal vein most frequently seen in patients with cirrhotic liver disease. Various non-cirrhotic conditions including inherited prothrombic blood disorders, neoplasms, and inflammatory diseases create hypercoagulable states that predispose individuals to blood clotting. Rarely does an exhaustive workup leave the etiology of a PVT unknown or unclear, and even more uncommon is a potential new etiology suspected. Our patient is a 34-year-old female, with no significant risk factors for pathologic clotting, who was diagnosed with an acute PVT several days after receiving the Moderna coronavirus disease 2019 (COVID-19) vaccine.
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There are limited treatment options for patients with advanced vulvar cancer. However, several immune checkpoint inhibitors (ICIs) are FDA-approved or NCCN-Compendia-listed for qualified patients with advanced disease. In this case report, we present a patient with metastatic vulvar squamous cell carcinoma who was treated with pembrolizumab in the setting of disease progression following prior treatment with radiation and chemotherapy. Best response to immunotherapy was an unconfirmed partial response. We summarize the current role of ICIs in treating advanced vulvar cancer, which is largely extrapolated from the squamous cell skin cancer and cervical cancer guidelines. Additionally, we emphasize the need for more inclusive clinical trials and a better understanding of vulvar cancer molecular biology, as well as the identification of biomarkers to predict response to targeted therapy in patients with advanced vulvar cancer.
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BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.
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COVID-19/complicações , COVID-19/mortalidade , Carcinoma/complicações , Carcinoma/mortalidade , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/mortalidade , Hospitalização/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/terapia , Carcinoma/terapia , Feminino , Neoplasias dos Genitais Femininos/terapia , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Gravidade do Paciente , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Uterine perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that occasionally shares morphologic and immunohistochemical overlap with low- and high-grade endometrial stromal sarcoma (LGESS and HGESS). In this study, we sought to characterize the clinical, morphologic, genetic, and epigenetic features of five uterine sarcomas that display histologic features of LGESS, HGESS, and PEComa. All tumors demonstrated epithelioid cells often associated with a low-grade spindled component resembling LGESS, with both regions expressing CD10, ER, PR, variable HMB45, and Melan-A immunoreactivity, and strong cathepsin K and pS6 expression. Targeted massively parallel sequencing analysis revealed the presence of somatic TSC2 mutations in all five cases, of which four harbored concurrent or consecutive JAZF1-SUZ12 gene fusions. Unsupervised hierarchical clustering analysis of methylation profiles of TSC2-mutant uterine sarcomas (n = 4), LGESS (n = 10), and HGESS (n = 12) demonstrated two clusters consisting of (1) all LGESS and TSC2-mutant uterine sarcomas and (2) all HGESS. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, calcium, and Rap1 signaling. TSC2-mutant uterine sarcomas were responsive to hormone suppression, and mTOR inhibition demonstrated clinical benefit in four patients with these neoplasms. Our results suggest that these tumors represent histologically distinctive LGESS with TSC2 mutations. TSC2 mutations and JAZF1-SUZ12 fusion may help diagnose these tumors and possibly direct effective treatment.
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Sarcoma/genética , Neoplasias Uterinas/genética , Idoso , Estudos de Coortes , Metilação de DNA , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Mutação , Sarcoma/patologia , Sarcoma/terapia , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapiaRESUMO
OBJECTIVE: The management of chronic rhinosinusitis (CRS) by a nonotolaryngologist prior to otolaryngology referral is an important component of the patient care pathway. The purpose of this study is to characterize CRS management during this period and to identify areas of quality improvement. STUDY DESIGN: Retrospective review of a national claims database. SETTING: Academic institution. METHODS: Data were analyzed from the IBM Health MarketScan Research Databases (2013-2017). Patients with 3-year enrollment data were identified who were initially diagnosed with CRS by a nonotolaryngologist and subsequently seen by an otolaryngologist. Management of CRS by the nonotolaryngologist was assessed in terms of duration, demographics, health care resource utilization, and health care expenditure. RESULTS: A total of 51,273 patients met inclusion criteria. The median length of the referral period was 142 days, with variations according to geography. Patients with a delayed referral period had higher health care resource utilization in terms of visits for CRS (mean, 1.8 vs 1.2), total visits (mean, 12.6 vs 3.9), and medication prescriptions (especially antibiotics; mean, 5.8 vs 2.1). Health care expenditure was almost twice as high for the delayed referral group (mean, $986 vs $571), mainly due to CRS-related medication costs (mean, $578 vs $214). CONCLUSION: Our findings suggest that there are wide variations in how CRS is managed prior to referral to an otolaryngologist. The dissemination of clinical practice guidelines to primary care providers may help to increase efficiency of CRS care and offers a unique opportunity for quality improvement that extends beyond the bounds of our own specialty.
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Otolaringologia , Rinite , Sinusite , Doença Crônica , Humanos , Melhoria de Qualidade , Encaminhamento e Consulta , Rinite/diagnóstico , Rinite/terapia , Sinusite/diagnóstico , Sinusite/terapiaRESUMO
BACKGROUND Richter transformation (RT) is an uncommon clinicopathological condition referring to the development of aggressive lymphoma from chronic lymphocytic lymphoma/small lymphocytic lymphoma (CLL/SLL) and characterized by sudden clinical deterioration with marked multifocal lymphadenopathy. Transformation of CLL/SLL to diffuse large B-cell lymphoma is the most common (2-9%), but T-cell and Hodgkin transformation (HL) (0.4%) occur, although less frequently. CASE REPORT A 68-year-old woman initially diagnosed with CLL/SLL presented to the hospital with fever, weakness, abdominal pain, and vomiting. The physical examination showed hepatosplenomegaly and extensive abdominal lymphadenopathy on radiological imaging. The laboratory work-up revealed pancytopenia and a markedly increased alkaline phosphatase. In the setting of extensive granulomatous hepatitis, the development of aggressive Hodgkin lymphoma Richter transformation with multi-organ involvement within a few months led to the patient's sudden death. Autopsy findings led to the post-mortem diagnosis of Richter's transformation of CLL. CONCLUSIONS Here, we describe a rare case of Hodgkin lymphoma RT from progressive CLL, with transformation occurring at approximately 12 years after initial diagnosis, despite treatment. Our case report underscores the diagnostic challenges and pitfalls associated with the granulomatous presentation masking RT transformation of CLL to Hodgkin lymphoma. The purpose of this report is to raise suspicion for the clinicopathological signs of Richter transformation in the presence of an atypical granulomatous presentation.
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Doença de Hodgkin , Leucemia Linfocítica Crônica de Células B , Linfoma Difuso de Grandes Células B , Idoso , Transformação Celular Neoplásica , Feminino , Hepatomegalia , Doença de Hodgkin/diagnóstico , Humanos , Linfoma Difuso de Grandes Células B/diagnósticoRESUMO
BACKGROUND: To assess variations in adherence to guideline-recommended processes of care for oral cavity cancer patients. METHODS: Retrospective study using a U.S. healthcare research database (MarketScan). Index diagnoses were considered from 2010 to 2012 with follow-up from 2013 to 2014. Diagnostic and procedure codes were utilized to identify oral cavity patients with a defined treatment modality. Compliance with guideline-recommended processes of care, which included pre-treatment imaging, thyroid-function testing (TFTs), multidisciplinary consultation and gastrostomy-tube insertion rates, were assessed. RESULTS: A total of 2752 patients were identified. Surgery alone was the most common treatment (60.8%), followed by surgery with adjuvant chemoradiotherapy (20.4%) and surgery with adjuvant radiotherapy (18.8%). Head/neck and chest imaging were obtained in 60% and 62.5% of patients respectively. Significant geographical differences in head and neck imaging were observed between North-central (64%), South (58.4%) and West (56.1%) regions (p = 0.026). Differences in chest imaging were also present between North-east (65%) and West (56.8%; p = 0.007). TFTs were obtained in 54.4% of the patients after radiation treatment, and 18.6% of patients had multidisciplinary consultation during the 6 months before and 3 months after initiation of treatment. During the year after treatment initiation, 21.2% of patients underwent G-tube placement, with significantly higher rates in patients receiving triple modality treatment (58%) when compared to surgery plus radiation (27%) and surgery alone (15%; p < 0.01). CONCLUSION: Adherence to evidence-based practices was low based on the database coding. These data suggest a potential to improve adherence and increase the routine use of practices delineated in national clinical practice guidelines. CLINICAL RELEVANCE: This study reflects a suboptimal adherence to guidelines based on the database employed. This study should be considered by healthcare providers and efforts should be maximized to follow the processes of care which have proven to impact on patient's outcomes.