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1.
JAMA Netw Open ; 7(1): e2350903, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38194231

RESUMO

Importance: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment. Objective: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade. Design, Setting, and Participants: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023. Intervention: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP. Main Outcomes and Measures: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test. Results: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT. Trial Registration: ClinicalTrials.gov Identifier: NCT02008656.


Assuntos
Adenocarcinoma , Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Preservação de Órgãos , Neoplasias Retais/terapia , Adenocarcinoma/terapia
2.
Lung Cancer ; 181: 107250, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37196448

RESUMO

BACKGROUND: The epidermal growth factor receptor (EGFR)-K745_E746insIPVAIK and others with XPVAIK amino-acid insertions are exon 19 insertion mutations, which, at the structural modeling level, resemble EGFR tyrosine kinase inhibitor (TKI)-sensitizing mutants. An important unmet need is the characterization of therapeutic windows plus clinical outcomes of exon 19 XPVAIK amino-acid insertion mutations to available EGFR TKIs. METHODS: We used preclinical models of EGFR-K745_E746insIPVAIK and more typical EGFR mutations (exon 19 deletion, L858R, L861Q, G719S, A763_Y764insFQEA, other exon 20 insertion mutations) to probe representative 1st (erlotinib), 2nd (afatinib), 3rd generation (osimertinib), and EGFR exon 20 insertion active (mobocertinib) TKIs. We also compiled outcomes of EGFR exon 19 insertion mutated lung cancers-from our institution plus the literature-treated with EGFR TKIs. RESULTS: Exon 19 insertions represented 0.3-0.8% of all EGFR kinase domain mutation in two cohorts (n = 1772). Cells driven by EGFR-K745_E746insIPVAIK had sensitivity to all classes of approved EGFR TKIs when compared to cells driven by EGFR-WT in proliferation assays and at the protein level. However, the therapeutic window of EGFR-K745_E746insIPVAIK driven cells was most akin to those of cells driven by EGFR-L861Q and EGFR-A763_Y764insFQEA than the more sensitive patterns seen with cells driven by an EGFR exon 19 deletion or EGFR-L858R. The majority (69.2%, n = 26) of patients with lung cancers harboring EGFR-K745_E746insIPVAIK and other mutations with rare XPVAIK amino-acid insertions responded to clinically available EGFR TKIs (including icotinib, gefitinib, erlotinib, afatinib and osimertinib), with heterogeneous periods of progression-free survival. Mechanisms of acquired EGFR TKI resistance of this mutant remained underreported. CONCLUSIONS: This is the largest preclinical/clinical report to highlight that EGFR-K745_E746insIPVAIK and other mutations with exon 19 XPVAIK amino-acid insertions are rare but sensitive to clinically available 1st, 2nd, and 3rd generation as well as EGFR exon 20 active TKIs; in a pattern that mostly resembles the outcomes of models with EGFR-L861Q and EGFR-A763_Y764insFQEA mutations. These data may help with the off-label selection of EGFR TKIs and clinical expectations of outcomes when targeted therapy is deployed for these EGFR mutated lung cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Afatinib/uso terapêutico , Aminoácidos/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Éxons , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico
5.
J Clin Oncol ; 40(23): 2546-2556, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35483010

RESUMO

PURPOSE: Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS: In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS: Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION: Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.


Assuntos
Adenocarcinoma , Neoplasias Retais , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Quimiorradioterapia , Intervalo Livre de Doença , Fluoruracila , Humanos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Preservação de Órgãos , Oxaliplatina , Estudos Prospectivos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia
6.
Nephrol Dial Transplant ; 37(3): 507-514, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33355659

RESUMO

BACKGROUND: Our objective was to characterize the incidence, risk factors and clinical features of acute kidney injury (AKI) in patients receiving dabrafenib and trametinib. METHODS: We performed a retrospective cohort study examining the kidney outcomes of patients in a large healthcare system who received dabrafenib/trametinib between 2010 and 2019. The primary outcome was AKI, defined as a 1.5-fold increase in serum creatinine from baseline within a 12-month study period. AKI severity and etiology was determined for each case by chart review. Logistic regression was used to evaluate baseline predictors of AKI. RESULTS: A total of 199 patients who received dabrafenib in our healthcare system from 2010 to 2019 were included in the analysis. Forty-two patients (21%) experienced AKI within 12 months; 10 patients (5% of the total cohort, 24% of AKI patients) experienced AKI occurring during a dabrafenib/trametinib-induced febrile syndrome characterized by fever, chills, gastrointestinal symptoms and elevated liver enzymes. Preexisting liver disease was the only significant predictor of AKI in the cohort. One patient had biopsy-proven granulomatous acute interstitial nephritis that resolved with corticosteroids. CONCLUSIONS: Oncologists and nephrologists should be aware that AKI is common after dabrafenib/trametinib and a substantial number of cases occur in the setting of treatment-induced pyrexia.


Assuntos
Injúria Renal Aguda , Melanoma , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Imidazóis , Melanoma/tratamento farmacológico , Melanoma/etiologia , Mutação , Oximas , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/uso terapêutico , Piridonas , Pirimidinonas , Estudos Retrospectivos
7.
J Immunother Cancer ; 9(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34625513

RESUMO

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Idoso , Estudos de Coortes , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
Plast Reconstr Surg ; 148(5): 959-967, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34705770

RESUMO

BACKGROUND: The association between textured surface breast implants and breast implant-associated anaplastic large cell lymphoma has led to an increase in surgical procedures to exchange textured devices to smooth surface implants. Because patient satisfaction is an integral part of breast reconstruction, the purpose of this study was to compare patient-reported outcomes between smooth and textured implant recipients. METHODS: Patients aged 18 years or older who underwent implant-based postmastectomy breast reconstruction with either smooth or textured devices from 2009 to 2017 and completed the BREAST-Q patient-reported outcome measure following reconstruction were included in this analysis. The primary outcomes of interest were mean and median BREAST-Q scores and postoperative complications. RESULTS: Overall, 1077 patients were included-785 who underwent breast reconstruction with smooth implants and 292 who underwent breast reconstruction with textured implants. No statistical differences were observed between the textured and smooth implant groups for any of the BREAST-Q domain scores at any of the early (3-month) to late (2-year) postoperative time points. Smooth implant recipients reported significantly more rippling (p = 0.003) than textured implant recipients. In contrast, textured implant recipients had a higher rate of cellulitis than smooth implant recipients (p = 0.016). CONCLUSIONS: These data suggest that postoperative satisfaction with breasts or health-related quality of life following immediate postmastectomy implant-based breast reconstruction is likely independent of implant surface type. However, smooth breast implants may result in more rippling. The authors' findings represent an important aid in counseling patients who have questions about the risks and benefits of replacing their textured implants with smooth surface devices. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Implante Mamário/efeitos adversos , Implantes de Mama/efeitos adversos , Celulite (Flegmão)/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias/epidemiologia , Adulto , Implante Mamário/instrumentação , Neoplasias da Mama/cirurgia , Celulite (Flegmão)/etiologia , Celulite (Flegmão)/prevenção & controle , Feminino , Humanos , Mastectomia/efeitos adversos , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Propriedades de Superfície , Inquéritos e Questionários/estatística & dados numéricos , Resultado do Tratamento
9.
Biology (Basel) ; 10(9)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34571811

RESUMO

Recent studies suggest that Th2 cells play a key role in the pathology of secondary lymphedema by elaborating cytokines such as IL4 and IL13. The aim of this study was to test the efficacy of QBX258, a monoclonal IL4/IL13 neutralizing antibody, in women with breast cancer-related lymphedema (BCRL). We enrolled nine women with unilateral stage I/II BCRL and treated them once monthly with intravenous infusions of QBX258 for 4 months. We measured limb volumes, bioimpedance, and skin tonometry, and analyzed the quality of life (QOL) using a validated lymphedema questionnaire (Upper Limb Lymphedema 27, ULL-27) before treatment, immediately after treatment, and 4 months following treatment withdrawal. We also obtained 5 mm skin biopsies from the normal and lymphedematous limbs before and after treatment. Treatment was well-tolerated; however, one patient with a history of cellulitis developed cellulitis during the trial and was excluded from further analysis. We found no differences in limb volumes or bioimpedance measurements after drug treatment. However, QBX258 treatment improved skin stiffness (p < 0.001) and improved QOL measurements (Physical p < 0.05, Social p = 0.01). These improvements returned to baseline after treatment withdrawal. Histologically, treatment decreased epidermal thickness, the number of proliferating keratinocytes, type III collagen deposition, infiltration of mast cells, and the expression of Th2-inducing cytokines in the lymphedematous skin. Our limited study suggests that immunotherapy against Th2 cytokines may improve skin changes and QOL of women with BCRL. This treatment appears to be less effective for decreasing limb volumes; however, additional studies are needed.

10.
Eur J Cancer ; 157: 50-58, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34482189

RESUMO

BACKGROUND: In patients with genitourinary cancers, the effect of immune checkpoint inhibitors (ICIs) on kidney function is unknown. PATIENTS AND METHODS: This is a retrospective cohort study of patients with renal cell carcinoma (RCC) and urothelial carcinoma who received ICIs at two major cancer centers between 2012 and 2018. Cumulative incidence and Fine and Gray subdistribution hazard models were performed to determine predictors of the co-primary outcomes, (1) acute kidney injury (AKI) and (2) sustained estimated glomerular filtration rate (eGFR) loss, defined as a >20% decline in eGFR sustained ≥90 days. We also determined the association between immune-related adverse events (irAE) and adverse kidney outcomes among patients surviving ≥1 year. RESULTS: 637 patients were included; 320 (50%) patients had RCC and 317 (50%) patients had urothelial carcinoma. Half of the cohort had eGFR<60 mL/min/1.73 m2 at baseline. irAEs, AKI, and sustained eGFR loss were common, occurring in 33%, 25% and 16%, respectively. Compared to patients with urothelial carcinoma, patients with RCC were more likely to develop irAEs (aHR 1.61, 95% CI 1.20-2.18) and sustained eGFR loss (aHR 1.97, 95% CI 1.24-3.12), but not AKI (aHR 1.53, 95% CI 0.97-2.41). Among patients surviving ≥1 years, experiencing a non-renal irAE was associated with a significantly higher risk of sustained eGFR loss (aHR 1.71, 95% CI 1.14-2.57). CONCLUSION: AKI and sustained eGFR loss are common in patients with genitourinary cancers receiving ICIs. irAEs may be a novel risk factor for kidney function decline among patients receiving ICIs.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Carcinoma de Células Renais/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/fisiopatologia , Feminino , Humanos , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/fisiopatologia
11.
J Immunother Cancer ; 9(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33849926

RESUMO

BACKGROUND: Current guidelines for treatment of immune checkpoint inhibitor (ICI)-induced nephritis are not evidence based and may lead to excess corticosteroid exposure. We aimed to compare a rapid corticosteroid taper to standard of care. METHODS: Retrospective cohort study in patients with ICI-induced nephritis comparing a rapid taper beginning with 60 mg/day prednisone and tapered to 10 mg within 3 weeks to a historical control group that began 60 mg/day tapered to 10 mg within 6 weeks (standard of care). Renal recovery was defined as creatinine returning to within 1.5-fold baseline. The log-rank test compared the differences in time to renal recovery between the groups. We report rates of renal recovery at 30, 60 and 90 days, and timing and outcomes of ICI rechallenge. RESULTS: Thirteen patients received rapid corticosteroid taper and 14 patients received standard of care. Baseline characteristics were similar between groups. The median time to ≤10 mg/day prednisone was 20 days (IQR 15-25) in the rapid-taper group compared with 38 days (IQR 30-58) in the standard-of-care group. There was no significant difference in the time to renal recovery between the groups, though numerically higher numbers of patients recovered by 30 days, 11 (85%) in the rapid-taper arm versus 6 (46%) in the standard of care arm. Exposure to other nephritis-causing medications (proton pump inhibitor or trimethoprim-sulfamethoxazole) during the corticosteroid taper was more common in the standard of care group, 9 (64%) versus rapid-taper group, 2 (15%), and was associated with longer time to renal recovery, 20 days (IQR 14-101) versus 13 days (IQR 7-34) in those that discontinued nephritis-causing medications. Fifteen (56%) of patients were rechallenged with ICIs, and only two (13%) developed recurrent nephritis. CONCLUSIONS: Patients with ICI-induced nephritis have excellent kidney outcomes when treated with corticosteroids that are tapered over 3 weeks.


Assuntos
Corticosteroides/administração & dosagem , Redução da Medicação , Inibidores de Checkpoint Imunológico/efeitos adversos , Nefrite/tratamento farmacológico , Prednisona/administração & dosagem , Corticosteroides/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Boston , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite/induzido quimicamente , Nefrite/imunologia , Prednisona/efeitos adversos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
12.
Nephrol Dial Transplant ; 36(12): 2241-2247, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33374011

RESUMO

BACKGROUND: Hyponatremia due to endocrinopathies such as adrenal insufficiency and hypothyroidism has been reported in patients receiving immune checkpoint inhibitors (ICIs). We determined the risk and predictors of hyponatremia and other electrolyte abnormalities in a 'real-world' sample of patients receiving ICIs to treat advanced malignancies. METHODS: This was a retrospective observational study of all patients who received ICIs from a single cancer center between 2011 and 2018. Patients were followed for 12 months after initiation of ICIs or until death. Common Terminology for Cancer Adverse Events version 5.0 criteria were used to grade the severity of hyponatremia and other electrolyte abnormalities. The predictors of severe (Grade 3 or 4) hyponatremia were determined using a multivariable logistic regression model. The etiology of Grade 3 or 4 hyponatremia was determined by chart review. RESULTS: A total of 2458 patients were included. Their average age was 64 years [standard deviation (SD) 13], 58% were male and 90% were white. In the first year after starting ICIs, 62% experienced hyponatremia (sodium <134 mEq/L) and 136 (6%) experienced severe hyponatremia (<124 mEq/L). Severe hyponatremia occurred on average 164 days (SD 100) after drug initiation. Only nine cases of severe hyponatremia were due to endocrinopathies (0.3% overall incidence). Risk factors for severe hyponatremia included ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor) use, diuretic use and non-White race. Other severe electrolyte abnormalities were also commonly observed: severe hypokalemia (potassium <3.0 mEq/L) occurred in 6%, severe hyperkalemia (potassium ≥6.1 mEq/L) occurred in 0.6%, severe hypophosphatemia (phosphorus <2 mg/dL) occurred in 17% and severe hypocalcemia (corrected calcium <7.0 mg/dL) occurred in 0.2%. CONCLUSIONS: Hyponatremia is common in cancer patients receiving ICIs. However, endocrinopathies are an uncommon cause of severe hyponatremia.


Assuntos
Hipopotassemia , Hiponatremia , Eletrólitos , Humanos , Hiponatremia/induzido quimicamente , Hiponatremia/epidemiologia , Inibidores de Checkpoint Imunológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sódio
13.
Adv Chronic Kidney Dis ; 28(5): 469-476.e1, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-35190113

RESUMO

As breakthroughs in cancer care are leading to improved long-term outcomes in a subset of advanced cancers, there is a growing population of long-term cancer survivors that are at risk of long-term complications. In this review, we summarize what is known about chronic kidney disease in cancer survivors, focusing on the following high-risk groups: survivors of childhood cancers, stem cell transplant recipients, patients with renal cell carcinoma, patients exposed to cisplatin and other nephrotoxic chemotherapies, and patients receiving immunotherapy for cancer. As new anticancer therapies are developed, more research is needed to understand the long-term risks of kidney function decline and to devise methods to prevent chronic kidney disease.


Assuntos
Sobreviventes de Câncer , Neoplasias , Insuficiência Renal Crônica , Cisplatino/efeitos adversos , Humanos , Neoplasias/complicações , Neoplasias/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Sobreviventes
15.
Ann Surg ; 272(3): 403-409, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32694446

RESUMO

OBJECTIVE: This study sought to estimate the incidence and incidence rate of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) at a high-volume single institution, which enables vigorous long-term follow-up and implant tracking for more accurate estimates. SUMMARY BACKGROUND DATA: The reported incidence of BIA-ALCL is highly variable, ranging from 1 in 355 to 1 in 30,000 patients, demonstrating a need for more accurate estimates. METHODS: All patients who underwent implant-based breast reconstruction from 1991 to 2017 were retrospectively identified. The incidence and incidence rate of BIA-ALCL were estimated per patient and per implant. A time-to-event analysis was performed using the Kaplan-Meier estimator and life table. RESULTS: During the 26-year study period, 9373 patients underwent reconstruction with 16,065 implants, of which 9589 (59.7%) were textured. Eleven patients were diagnosed with BIA-ALCL, all of whom had a history of textured implants. The overall incidence of BIA-ALCL was 1.79 per 1000 patients (1 in 559) with textured implants and 1.15 per 1000 textured implants (1 in 871), with a median time to diagnosis of 10.3 years (range, 6.4-15.5 yrs). Time-to-event analysis demonstrated a BIA-ALCL cumulative incidence of 0 at up to 6 years, increasing to 4.4 per 1000 patients at 10 to 12 years and 9.4 per 1000 patients at 14 to 16 years, although a sensitivity analysis showed loss to follow-up may have skewed these estimates. CONCLUSIONS: BIA-ALCL incidence and incidence rates may be higher than previous epidemiological estimates, with incidence increasing over time, particularly in patients exposed to textured implants for longer than 10 years.


Assuntos
Neoplasias da Mama/cirurgia , Previsões , Linfoma Anaplásico de Células Grandes/epidemiologia , Mamoplastia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Medição de Risco/métodos , Implantes de Mama/efeitos adversos , Feminino , Seguimentos , Humanos , Incidência , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/etiologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologia
16.
Am J Kidney Dis ; 76(2): 299-302, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32417401
18.
J Clin Virol ; 91: 79-83, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28434810

RESUMO

BACKGROUND: The Centers for Disease Control and Prevention (CDC) published updated guidelines in 2014 for the laboratory diagnosis of HIV in the United States, which recommend use of a supplemental immunoassay (IA) that differentiates HIV-1 from HIV-2 after a repeatedly reactive HIV-1/2 antigen/antibody "Combo" screening test. In October 2014, Bio-Rad Laboratories introduced the FDA-cleared Geenius HIV-1/HIV-2 Supplemental assay and in July 2016, it replaced the Multispot HIV-1/HIV-2 differentiation rapid test as the second test in the HIV diagnostic algorithm. OBJECTIVE: To compare performance of the new FDA-cleared Bio-Rad Geenius HIV-1/HIV-2 Supplemental assay and the Bio-Rad Multispot HIV-1/HIV-2 differentiation assay for use as the primary supplemental test in the 2014 CDC/APHL HIV Diagnostic Algorithm. STUDY DESIGN: Two sets of specimens were used to assess the performance of Geenius; 340 select retrospective specimens, obtained through routine clinical submissions from individuals seeking HIV serostatus determinations and 10 known HIV-2 antibody reactive specimens provided by Bio-Rad Laboratories. Panels were created and characterized solely by in-house laboratory results. The panels consisted of: algorithm-defined "established HIV-1 infections" (n=250), "acute HIV-1 infections" (n=20), "early HIV-1 infections" (n=10) and "false positive Combo specimens" (n=60). RESULTS: CONCLUSIONS: The Geenius assay provides significant advantages over Multispot as an appropriate replacement for the primary supplemental test in the HIV Diagnostic Algorithm. In this retrospective study, Geenius was highly concordant with Multispot, reclassified some acute and early algorithm-defined HIV-1 positive specimens and demonstrated a potential decrease in the number HIV-1 RNA nucleic acid amplification tests needed to complete the diagnostic algorithm.


Assuntos
Sorodiagnóstico da AIDS , Testes Diagnósticos de Rotina/métodos , Imunoensaio , Saúde Pública , Algoritmos , Centers for Disease Control and Prevention, U.S. , Testes Diagnósticos de Rotina/instrumentação , Feminino , Florida , Anticorpos Anti-HIV/sangue , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , HIV-1/genética , HIV-1/imunologia , HIV-1/isolamento & purificação , HIV-2/genética , HIV-2/imunologia , HIV-2/isolamento & purificação , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Masculino , Programas de Rastreamento , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Técnicas de Amplificação de Ácido Nucleico/métodos , Kit de Reagentes para Diagnóstico , Estudos Retrospectivos , Estados Unidos
19.
Plast Reconstr Surg ; 138(6): 1312-1320, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27879602

RESUMO

BACKGROUND: Improved understanding and management of health-related quality of life represents one of the greatest unmet needs for patients with head and neck malignancies. The purpose of this study was to prospectively measure health-related quality of life associated with different anatomical (head and neck) surgical resections. METHODS: A prospective analysis of health-related quality of life was performed in patients undergoing surgical resection with flap reconstruction for stage II or III head and neck malignancies. Patients completed the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire-30 and the European Organization for Research and Treatment of Cancer Head and Neck Cancer Module-35 preoperatively, and at set postoperative time points. Scores were compared with a paired t test. RESULTS: Seventy-five patients were analyzed. The proportion of the cohort not alive at 2 years was 53 percent. Physical, role, and social functioning scores at 3 months were significantly lower than preoperative values (p < 0.05). At 12 months postoperatively, none of the function or global quality-of-life scores differed from preoperative levels, whereas five of the symptom scales remained below baseline. At 1 year postoperatively, maxillectomy, partial glossectomy, and oral lining defects had better function and fewer symptoms than mandibulectomy, laryngectomy, and total glossectomy. From 6 to 12 months postoperatively, partial glossectomy and oral lining defects had greater global quality of life than laryngectomies (p < 0.05). CONCLUSIONS: Postoperative health-related quality of life is associated with the anatomical location of the head and neck surgical resection. Preoperative teaching should be targeted for common ablative defects, with postoperative expectations adjusted appropriately. Because surgery negatively impacts health-related quality of life in the immediate postoperative period, the limited survivorship should be reviewed with patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Indicadores Básicos de Saúde , Procedimentos de Cirurgia Plástica , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Resultado do Tratamento
20.
J Womens Health (Larchmt) ; 21(9): 942-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22747330

RESUMO

BACKGROUND: We conducted a qualitative study to examine acute, situational factors and chronic stressors that triggered severe intimate partner violence (IPV) in women. METHODS: Our sample consisted of 17 heterosexual couples, where the male was in detention for IPV and made telephone calls to his female victim. We used up to 4 hours of telephone conversational data for each couple to examine the couple's understanding of (1) acute triggers for the violent event and (2) chronic stressors that created the underlying context for violence. Grounded theory guided our robust, iterative data analysis involving audiotape review, narrative summation, and thematic organization. RESULTS: Consistently across couples, violence was acutely triggered by accusations of infidelity, typically within the context of alcohol or drug use. Victims sustained significant injury, including severe head trauma (some resulting in hospitalization/surgery), bite wounds, strangulation complications, and lost pregnancy. Chronic relationship stressors evident across couples included ongoing anxiety about infidelity, preoccupation with heterosexual gender roles and religious expectations, drug and alcohol use, and mental health concerns (depression, anxiety, and suicide ideation/attempts). CONCLUSIONS: Disseminated models feature jealousy as a strategy used by perpetrators to control IPV victims and as a red flag for homicidal behavior. Our findings significantly extend this notion by indicating that infidelity concerns, a specific form of jealousy, were the immediate trigger for both the acute violent episode and resulting injuries to victims and were persistently raised by both perpetrators and victims as an ongoing relationship stressor.


Assuntos
Enganação , Ciúme , Maus-Tratos Conjugais/psicologia , Cônjuges/psicologia , Confiança , Adolescente , Adulto , Ira , Feminino , Humanos , Relações Interpessoais , Entrevistas como Assunto , Masculino , Casamento , Saúde Mental , Prisioneiros , Pesquisa Qualitativa , Gravação em Fita , Telefone , Washington
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