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1.
Adv Skin Wound Care ; 33(4): 192-201, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31789623

ABSTRACT

OBJECTIVE: The purpose of this research was to build on previous work regarding predictive factors of acute skin failure (ASF) in the critically ill population. METHODS: Researchers conducted a retrospective case-control study with a main and validation analysis. Data were extracted from the New York Statewide Planning and Research Cooperative System. For the main analysis, there were 415 cases with a hospital-acquired pressure injury (HAPI) and 194,872 controls without. Researchers then randomly selected 100 cases with a HAPIs and 300 controls without for the validation analysis. A step-up logistic regression model was used. Researchers generated receiver operating characteristic curves for both the main and validation analyses, assessing the overall utility of the regression model. RESULTS: Eleven variables were significantly and independently related to ASF: renal failure (odds ratio [OR], 1.4, P = .003), respiratory failure (OR, 2.2; P = < .001), arterial disease (OR, 2.4; P = .001), impaired nutrition (OR, 2.3; P = < .001), sepsis (OR, 2.2; P = < .001), septic shock (OR, 2.3; P = < .001), mechanical ventilation (OR, 2.5; P = < .001), vascular surgery (OR, 2.2; P = .02), orthopedic surgery (OR, 3.4; P = < .001), peripheral necrosis (OR, 2.5; P = .003), and general surgery (OR, 3.8; P = < .001). The areas under the curve for the main and validation analyses were 0.864 and 0.861, respectively. CONCLUSIONS: The final model supports previous work and is consistent with the current definition of ASF in the setting of critical illness.


Subject(s)
Critical Care/methods , Critical Illness/nursing , Necrosis/diagnosis , Skin/pathology , Adult , Case-Control Studies , Female , Humans , Logistic Models , Male , Middle Aged , ROC Curve , Retrospective Studies
2.
Adv Skin Wound Care ; 32(11): 512-519, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31498171

ABSTRACT

OBJECTIVE: To replicate previous research that found four independent and significant predictors of heel pressure injuries (HPIs) in hospitalized patients using a larger and more diverse patient population. METHODS: Researchers conducted a retrospective, case-control study with a main and a validation analysis (N = 1,937). The main analysis had 1,697 patients: 323 patients who had HPIs and 1,374 who did not. The validation analysis had 240 patients: 80 patients who developed HPIs and 160 who did not. Researchers used a series of diagnosis codes to define variables associated with an HPI. Data were extracted from the New York Statewide Planning and Research Cooperative System for January 2014 to June 2015. Study authors conducted a series of forward stepwise logistic regression analyses for both samples to select the variables that were significantly and independently associated with the development of an HPI in a multivariable setting. Researchers generated a receiver operating characteristic curve using the final model to assess the regression model's ability to predict HPI development. RESULTS: Seven variables were significant and independent predictors associated with HPIs: diabetes mellitus, vascular disease, perfusion issues, impaired nutrition, age, mechanical ventilation, and surgery. The receiver operating characteristic curve demonstrated predictive accuracy of the model. CONCLUSIONS: Beyond a risk assessment scale, providers should consider other factors, such as comorbidities, which can predispose patients to HPI development.


Subject(s)
Comorbidity , Heel/physiopathology , Pressure Ulcer/epidemiology , Pressure Ulcer/prevention & control , Adult , Aged , Analysis of Variance , Case-Control Studies , Female , Hospitalization , Humans , Incidence , Length of Stay , Logistic Models , Male , Middle Aged , Predictive Value of Tests , Pressure Ulcer/physiopathology , Prognosis , ROC Curve , Reproducibility of Results , Retrospective Studies , Risk Factors
3.
Cancer ; 122(6): 859-67, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26938270

ABSTRACT

BACKGROUND: Widespread disparities in care have been documented in women with gynecologic cancer in the United States. This study was designed to determine whether structural barriers to optimal care were present during the preoperative period for patients with gynecologic cancer. METHODS: A retrospective review was conducted for patients undergoing surgery for a gynecologic malignancy at a public hospital or a private hospital staffed by the same team of gynecologic oncologists between July 1, 2013 and July 1, 2014. RESULTS: Two hundred fifty-seven cases were included for analysis (public hospital, 69; private hospital, 188). Patients treated at the private hospital were older (58 vs 52 years; P = .004) and had similar medical comorbidities (median Charlson comorbidity index at both hospitals, 6) but required fewer hospital visits in preparation for surgery (2 vs 4; P < .001). Public hospital patients had a longer wait time from the diagnosis of disease to surgery (63 vs 34 days; P < .001). According to a multiple linear regression model, the public hospital setting was associated with a longer interval from diagnosis to surgery with adjustments for the insurance status, age at diagnosis, cancer stage, and number of preoperative hospital visits (P < .001). CONCLUSIONS: Patients at the public hospital were subject to a greater number of preoperative visits and had to wait longer for surgery than patients at the private hospital. Attempts to reduce health care disparities should focus on improving efficiency in health care delivery systems once contact has been established.


Subject(s)
Genital Neoplasms, Female/surgery , Healthcare Disparities , Hospitals, Private , Hospitals, Public , Preoperative Period , Time-to-Treatment , Adult , Aged , Female , Genital Neoplasms, Female/diagnosis , Humans , Insurance, Health , Length of Stay , Middle Aged , Neoplasm Staging , Retrospective Studies
4.
Adv Skin Wound Care ; 28(11): 514-24; quiz 525-6, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26479695

ABSTRACT

PURPOSE: The purpose of this learning activity is to provide information regarding the differentiation between pressure ulcers and acute skin failure (ASF) in critically ill patients. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Describe the purpose, methodology and impact of this research.2. Differentiate the pathophysiology of pressure ulcers and ASF.3. Identify risk factors and diagnostic criteria for ASF. ABSTRACT: To develop a statistical model to predict the development of acute skin failure in patients admitted to the intensive care unit (ICU) and to validate this model.Retrospective case-control, logistic regression modeling552 ICU patientsIntensive care unit patients with and without pressure ulcers (PrUs) were studied and compared on key variables sorted into the following categories: (1) disease status, (2) physical conditions, and (3) conditions of hospitalization.The variables, peripheral arterial disease (odds ratio [OR], 3.8; P = .002), mechanical ventilation greater than 72 hours (OR, 3.0; P < .001), respiratory failure (OR, 3.2; P < .001), liver failure (OR, 2.9; P = .04), and severe sepsis/septic shock (OR, 1.9; P = .02), were found to be statistically significant and independent predictors of acute skin failure in ICU patients. These variables created a predictor model for acute skin failure in the ICU.Lack of objective criteria to define acute skin failure presents a clinical conundrum for practitioners-the acknowledgment that skin failure exists, but no clear-cut diagnostic criteria in which to support its existence as a result of a paucity of empirical evidence. In certain populations, such as the critically ill patient, the phenomenon of acute skin failure may be occurring, and with the current level of evidence, these ulcers may be incorrectly identified as PrUs. Accurately distinguishing risk factors that lead to a PrU from factors that result in a lesion due to acute skin failure is crucial in the quest to provide evidence-based practice to patients.


Subject(s)
Pressure Ulcer/diagnosis , Skin/pathology , Acute Disease , Adult , Aged , Aged, 80 and over , Critical Care , Diagnosis, Differential , Female , Humans , Logistic Models , Male , Middle Aged , Necrosis/diagnosis , Retrospective Studies , Young Adult
5.
Am J Cardiol ; 116(7): 1082-7, 2015 Oct 01.
Article in English | MEDLINE | ID: mdl-26251006

ABSTRACT

The aim of this study was to determine the diagnostic value of cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE), cine imaging, and resting first-pass perfusion (FPP) in the evaluation for ischemic (IC) versus nonischemic (NIC) cardiomyopathy in new-onset heart failure with reduced (≤40%) left ventricular ejection fraction (HFrEF). A retrospective chart review analysis identified 83 patients from January 2009 to June 2012 referred for CMR imaging evaluation for new-onset HFrEF with coronary angiography performed within 6 months of CMR. The diagnosis of IC was established using Felker criteria on coronary angiography. CMR sequences were evaluated for the presence of patterns suggestive of severe underlying coronary artery disease as the cause of HFrEF (subendocardial and/or transmural LGE, regional wall motion abnormality on cine, regional hypoperfusion defect on resting FPP). Discriminative power was assessed using receiver operator characteristics curve analysis. Coronary angiography identified 36 patients (43%) with IC. Presence of subendocardial and/or transmural LGE alone demonstrated good discriminative power (C-statistic 0.85, 95% confidence interval 0.76 to 0.94) for the diagnosis of IC. The presence of an ischemic pattern on both LGE and cine sequences resulted in a specificity of 87% for the diagnosis of IC, whereas the absence of an ischemic pattern on both LGE and cine sequences resulted in a specificity of 94% for the diagnosis of NIC. Addition of resting FPP on a subset of patients did not improve diagnostic values. In conclusion, CMR has potential value in the diagnostic evaluation of IC versus NIC.


Subject(s)
Heart Failure/diagnosis , Heart Ventricles/pathology , Magnetic Resonance Imaging, Cine/methods , Stroke Volume/physiology , Ventricular Dysfunction, Left/diagnosis , Ventricular Function, Left , Female , Follow-Up Studies , Heart Failure/complications , Heart Failure/physiopathology , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , ROC Curve , Reproducibility of Results , Retrospective Studies , Time Factors , Ventricular Dysfunction, Left/complications , Ventricular Dysfunction, Left/physiopathology
6.
Clin J Oncol Nurs ; 19(4): 451-5, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26207710

ABSTRACT

BACKGROUND: Women receiving radiation to the breast will likely be recommended to use a topical cream to minimize and delay the development of radiation dermatitis. Although many topical products are commercially available and have been tested for safety and efficacy, few studies have compared various products to one another for superiority and cost effectiveness. OBJECTIVES: The purpose of this pilot study was to compare three commonly used skin care products prospectively to one other in a homogenously controlled group of women undergoing whole breast irradiation to assess superiority in minimizing the common toxicity criteria grade of radiation dermatitis, effect on quality of life, and cost. METHODS: The authors conducted a systematic review to determine the three types of skin care products with the strongest evidence of minimizing radiation dermatitis. Patients were voluntarily enrolled and randomized to one of three possible skin care topical regimens. Patients completed a quality-of-life survey to assess their preference in topical skin care regimen. The cost of each arm's topical product was assessed at the completion of patient participation. FINDINGS: No statistical difference was noted in the severity or occurrence of radiation dermatitis among the groups. In addition, no statistical difference was found among the three treatment arms in quality-of-life score changes, and no patients required a treatment interruption in their radiation or in the skin care product during treatment. A cost difference among the treatment arms was noted.


Subject(s)
Breast Neoplasms/radiotherapy , Radiodermatitis/drug therapy , Administration, Topical , Humans , Pilot Projects
7.
Simul Healthc ; 10(4): 193-9; quiz 199-201, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25932707

ABSTRACT

INTRODUCTION: Goal-directed echocardiography (GDE) is used to answer specific clinical questions that provide invaluable information to physicians managing a hemodynamically unstable patient. We studied perception and ability of house staff previously trained in GDE to accurately diagnose common causes of cardiac arrest during simulated advanced cardiac life support (ACLS); we compared their results with those of expert echocardiographers. METHODS: Eleven pulmonary and critical care medicine fellows, 7 emergency medicine residents, and 5 cardiologists board certified in echocardiography were enrolled. Baseline ability to acquire 4 transthoracic echocardiography views was assessed, and participants were exposed to 6 simulated cardiac arrests and were asked to perform a GDE during ACLS. House staff performance was compared with the performance of 5 expert echocardiographers. RESULTS: Average baseline and scenario views by house staff were of good or excellent quality 89% and 83% of the time, respectively. Expert average baseline and scenario views were always of good or excellent quality. House staff and experts made the correct diagnosis in 68% and 77% of cases, respectively. On average, participants required 1.5 pulse checks to make the correct diagnosis. Of house staff, 94% perceived this study as an accurate assessment of ability. CONCLUSIONS: In an ACLS-compliant manner, house staff are capable of diagnosing management-altering pathologies the majority of the time, and they reach similar diagnostic conclusions in the same amount of time as expert echocardiographers in a simulated cardiac arrest scenario.


Subject(s)
Advanced Cardiac Life Support/education , Echocardiography/methods , Heart Arrest/diagnostic imaging , Heart Arrest/pathology , Internship and Residency/methods , Simulation Training/methods , Cardiology/education , Echocardiography/standards , Emergency Medicine/education , Humans , Internship and Residency/standards , Pilot Projects , Simulation Training/standards
8.
J Wound Ostomy Continence Nurs ; 42(3): 242-8; quiz E1-2, 2015.
Article in English | MEDLINE | ID: mdl-25945823

ABSTRACT

PURPOSE: To develop and validate a method of predicting whether patients will develop a heel pressure ulcer during their hospital stay. DESIGN: This retrospective case-control study used 2 separate data sets, one for an initial analysis followed by a second data set for validation analysis. SUBJECTS AND SETTING: From 2009 to 2011, medical records of discharged patients with a DRG code for heel pressure ulcers in our urban, tertiary medical center were retrospectively reviewed. Using age as the matching criterion, we then reviewed cases of patients without heel pressure ulcers. The initial analysis comprised 37 patients with hospital-acquired heel pressure ulcers and 300 without. The validation analysis included 12 patients with heel pressure ulcers and 68 without. METHOD: In order to develop this method of identifying patients with heel pressure ulcers, logistic regression modeling was used to select a set of patient characteristics and hospital conditions that, independently and in combination, predicted heel pressure ulcers. Logistic modeling produced adjusted and unadjusted odds ratios for each of the significant predictor variables. The validation analysis was employed to test the predictive accuracy of the final model. RESULTS: Initial analysis revealed 4 significant and independent predictors for heel pressure ulcer formation during hospitalization: diabetes mellitus, vascular disease, immobility, and an admission Braden Scale score of 18 or less. These findings were also supported in the validation analysis. CONCLUSION: Beyond a risk assessment scale, staff should consider other factors that can predispose a patient to heel pressure ulcer development during their hospital stay, such as comorbid conditions (diabetes mellitus and vascular disease) and immobility.


Subject(s)
Heel , Hospitalization , Pressure Ulcer/etiology , Aged , Aged, 80 and over , Female , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Risk Factors , Sensitivity and Specificity
9.
Pediatr Blood Cancer ; 61(9): 1644-52; quiz 1653-72, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24789527

ABSTRACT

BACKGROUND: Due to the devastating late effects associated with cranial irradiation in young children with central nervous system (CNS) tumors, treatment for these patients has evolved to include the use of intensive chemotherapy to either avoid or postpone irradiation. While survival outcomes have improved, late effects data in survivors treated on such regimens are needed. OBJECTIVE: This multi-institutional study comprehensively describes late effects in survivors treated on the Head Start I/II protocols. METHODS: Survivors of CNS tumors treated on Head Start I/II protocols were enrolled. Late effects data were collected using a validated parent-report questionnaire. Social, emotional, and behavioral functioning and quality of life were assessed using parent-report on the BASC-2 and CHQ-PF50 questionnaires. RESULTS: Twenty-one survivors (medulloblastoma = 13, sPNET = 4, ATRT = 1, ependymoma = 3) were enrolled. Ten (48%) were irradiation-free. Late effects (frequency; median time of onset since diagnosis) included ≥ grade III hearing loss (67%; 3.9 years), vision (67%; 4.1 years), hypothyroidism (33%; 4 years), growth hormone (GH) deficiency (48%; 4.7 years), dental (52%; 7.1 years), and no cases of secondary leukemia. Irradiation-free (vs. irradiated) survivors reported low rates of hypothyroidism (0/10 vs. 7/11; P = 0.004) and GH deficiency (2/10 vs. 8/11; P = 0.03). The BASC-2 and CHQPF-50 mean composite scores were within average ranges relative to healthy comparison norms. Neither age at diagnosis nor irradiation was associated with these scores. CONCLUSIONS: Irradiation-free Head Start survivors have lower risk of hypothyroidism and GH deficiency. Secondary leukemias are not reported. With extended follow-up, survivors demonstrate quality of life, social, emotional, and behavioral functioning within average ranges.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Central Nervous System Neoplasms/drug therapy , Growth Disorders/chemically induced , Hearing Loss/chemically induced , Hypothyroidism/chemically induced , Survivors , Vision Disorders/chemically induced , Adolescent , Adult , Central Nervous System Neoplasms/complications , Child , Child, Preschool , Female , Follow-Up Studies , Growth Disorders/diagnosis , Growth Disorders/mortality , Hearing Loss/diagnosis , Hearing Loss/mortality , Humans , Hypothyroidism/diagnosis , Hypothyroidism/mortality , Infant , Male , Prognosis , Surveys and Questionnaires , Survival Rate , Vision Disorders/diagnosis , Vision Disorders/mortality , Young Adult
10.
Clin Cancer Res ; 19(12): 3268-75, 2013 Jun 15.
Article in English | MEDLINE | ID: mdl-23637120

ABSTRACT

PURPOSE: Promoter hypermethylation has been recently proposed as a means for head and neck squamous cell carcinoma (HNSCC) detection in salivary rinses. In a prospective study of a high-risk population, we showed that endothelin receptor type B (EDNRB) promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy. EXPERIMENTAL DESIGN: Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was conducted and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by quantitative methylation-specific PCR. RESULTS: HOXA9, EDNRB, and deleted in colorectal cancer (DCC) methylation were associated (P = 0.012; P < 0.0001; P = 0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (P = 0.0003) or DCC (P = 0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC, and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (P = 0.008; P = 0.026; P = 0.046) and multivariate analysis (P = 0.012; P = 0.037; P = 0.047). CRC identified dysplasia/cancer with 56% of sensitivity and 66% of specificity with a similar area under curve [AUC; 0.61, 95% confidence interval (CI) = 0.60-0.81] when compared to EDNRB and DCC combined AUC (0.60, 95% CI = 0.51-0.69), sensitivity of 46% and specificity of 72%. A combination of EDNRB, DCC, and CRC was optimal AUC (0.67, 95% CI = 0.58-0.76). CONCLUSIONS: EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available.


Subject(s)
Diagnosis, Differential , Mouth Neoplasms/diagnosis , Neoplasms/diagnosis , Receptors, Cell Surface/biosynthesis , Receptors, Endothelin/biosynthesis , Tumor Suppressor Proteins/biosynthesis , Biomarkers, Tumor , DCC Receptor , DNA Methylation , Gene Expression Regulation, Neoplastic , Humans , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Neoplasms/genetics , Neoplasms/pathology , Promoter Regions, Genetic , Saliva/metabolism
12.
J Acquir Immune Defic Syndr ; 61(5): 535-44, 2012 Dec 15.
Article in English | MEDLINE | ID: mdl-22902724

ABSTRACT

OBJECTIVE: Myeloid dendritic cell (mDC) dysfunction during HIV infection may hinder the formation of both innate and adaptive immune responses and contribute to pathogenesis. Our objective was to determine whether circulating factors during chronic HIV infection impair mDC function with respect to secretion of IL-12, a pro-Th1 cytokine, and T-cell stimulatory capacity. Particular focus was placed on the effect of combination antiretroviral therapy (cART) and the role of HIV itself on mDC function. METHODS: Monocyte-derived DC (moDC) from uninfected donors were exposed to plasma from HIV-infected individuals before Toll-like receptor (TLR) stimulation. Cytokine secretion was measured via cytokine bead arrays, and T-cell proliferation and IFNγ secretion was evaluated after coculture with naive CD4 T cells. Expression of genes central to TLR-mediated signal transduction was analyzed via quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) arrays and western blot. RESULTS: Exposure of monocyte-derived DC to plasma from untreated HIV-infected donors suppressed secretion of IL-12, and impaired Th1-skewing of CD4 T cells. The suppressive effect was less by plasma donors receiving cART. Removal of virus from plasma did not relieve suppression nor was IL-12 secretion decreased on addition of HIV to control plasma. On a transcriptional level, decreased expression of IKKß, a key regulator in the TLR/NF-kappaB signaling pathway, corresponded to suppressed cytokine secretion. CONCLUSIONS: Plasma factors during chronic HIV infection impair mDC function in a manner that likely impacts the formation of immune responses to HIV, opportunistic pathogens, and vaccines. Despite partial alleviation by cART, this suppression was not directly mediated by HIV.


Subject(s)
Dendritic Cells/immunology , HIV Infections/blood , HIV Infections/immunology , HIV-1 , Interleukin-12/biosynthesis , Adult , CD4-Positive T-Lymphocytes/immunology , Coculture Techniques , Cross-Sectional Studies , Female , Gene Expression , HIV Infections/drug therapy , HIV Infections/genetics , HIV-1/immunology , Humans , I-kappa B Kinase/genetics , Immune Tolerance , Male , Middle Aged , Signal Transduction , Th1 Cells/immunology , Viral Load/immunology , Young Adult
13.
J Pediatr ; 161(6): 1160-5, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22727867

ABSTRACT

OBJECTIVE: To develop a reliable rating scale to assess functional capacity in children with familial dysautonomia, evaluate changes over time, and determine whether severity within a particular functional category at a young age affected survival. STUDY DESIGN: Ten functional categories were retrospectively assessed in 123 patients with familial dysautonomia at age 7 years ± 6 months. Each of the 10 Functional Severity Scale categories (motor development, cognitive ability, psychological status, expressive speech, balance, oral coordination, frequency of dysautonomic crisis, respiratory, cardiovascular, and nutritional status) were scored from 1 (worst or severely affected) to 5 (best or no impairment). Changes over time were analyzed further in 22 of the 123 patients who were also available at ages 17 and 27 years. RESULTS: Severely impaired cardiovascular function and high frequency of dysautonomic crisis negatively affected survival (P < .005 and P < .001, respectively). In the 22 individuals followed up to age 27 years, psychological status significantly worsened (P = .01), and expressive speech improved (P = .045). From age 17 to 27 years, balance worsened markedly (P = .048). CONCLUSION: The Functional Severity Scale is a reliable tool to measure functional capacity in patients with familial dysautonomia. The scale may prove useful in providing prognosis and as a complementary endpoint in clinical trials.


Subject(s)
Disease Progression , Dysautonomia, Familial/physiopathology , Severity of Illness Index , Adolescent , Adult , Age Factors , Child , Dysautonomia, Familial/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Observer Variation , Prognosis , Retrospective Studies , Survival Rate
14.
Mol Cancer Ther ; 10(10): 2000-7, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21835933

ABSTRACT

Epithelial ovarian cancer (EOC) patients with BRCA mutations (BRCA +) benefit from platinum-based treatment more than noncarriers. Impaired ability to repair DNA by homologous recombination increases their chemosensitivity. We investigated whether BRCA + predicts for improved outcome following pegylated liposomal doxorubicin (PLD) for recurrence. Recurrent EOC patients receiving second- or third-line PLD from 1998 to 2009 in 4 institutions (Tel Aviv, New York, Padua, and Jerusalem) were subjected to retrospective comparisons between 40 (25.8%) patients who were BRCA +, and 115 (74.2%) deemed nonhereditary (NH). Median age was 59 years (range 31-83); 111 (72%) had a platinum-free interval more than 6 months [PLD alone (n = 65) and PLD plus platinum (n = 90)]; 104 received PLD in second-line and 51 in third-line. BRCA + versus NH comparisons: median time to treatment failure (TTF) 15.8 months [95% confidence interval (CI): 11.4-21.6] versus 8.1 months (95% CI: 6.1-10.3; P = 0.009); overall survival (OS) 56.8 months (95% CI: 32.5-indeterminate) versus 22.6 months (95% CI: 17.0-34.1; P = 0.002). In multivariate Cox models BRCA status was significantly associated with TTF (HR = 1.66; 95% CI: 1.08-2.55; P = 0.02) and OS (adjusted HR 2.07; 95% CI: 1.18-3.60; P = 0.01). Adjusted HR relating platinum sensitivity to OS was 1.58 (95% CI: 0.93-2.68; P = 0.09); no significant association found with age at diagnosis, line of PLD or combinations, or institution. In this retrospective analysis, recurrent EOC BRCA mutation carriers treated with PLD had an improved outcome, and this result seemed to be independent of platinum sensitivity. Tumors arising in a background of defective BRCA function are more sensitive than other EOCs to DNA-damaging agents such as PLD, even after acquiring platinum resistance.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Doxorubicin/analogs & derivatives , Genes, BRCA1 , Genes, BRCA2 , Neoplasms, Glandular and Epithelial/drug therapy , Neoplasms, Glandular and Epithelial/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Polyethylene Glycols/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Carcinoma, Ovarian Epithelial , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Female , Germ-Line Mutation , Humans , Middle Aged , Organoplatinum Compounds/administration & dosage , Polyethylene Glycols/administration & dosage , Retrospective Studies , Treatment Outcome
15.
Cancer Cell ; 19(3): 333-46, 2011 Mar 08.
Article in English | MEDLINE | ID: mdl-21397857

ABSTRACT

Matrix metalloproteinase-2 (MMP-2) is a proteolytic enzyme degrading the extracellular matrix and overexpressed by many tumors. Here, we documented the presence of MMP-2-specific CD4(+) T cells in tumor-infiltrating lymphocytes (TILs) from melanoma patients. Strikingly, MMP-2-specific CD4(+) T cells displayed an inflammatory T(H)2 profile, i.e., mainly secreting TNF-α, IL-4, and IL-13 and expressing GATA-3. Furthermore, MMP-2-conditioned dendritic cells (DCs) primed naïve CD4(+) T cells to differentiate into an inflammatory T(H)2 phenotype through OX40L expression and inhibition of IL-12p70 production. MMP-2 degrades the type I IFN receptor, thereby preventing STAT1 phosphorylation, which is necessary for IL-12p35 production. Active MMP-2, therefore, acts as an endogenous type 2 "conditioner" and may play a role in the observed prevalence of detrimental type 2 responses in melanoma.


Subject(s)
Dendritic Cells/immunology , Interleukin-12/immunology , Matrix Metalloproteinase 2/immunology , OX40 Ligand/immunology , Signal Transduction/immunology , Th2 Cells/immunology , Blotting, Western , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Cell Differentiation/immunology , Dendritic Cells/metabolism , Enzyme-Linked Immunosorbent Assay , GATA3 Transcription Factor/immunology , GATA3 Transcription Factor/metabolism , Humans , Inflammation Mediators/immunology , Inflammation Mediators/metabolism , Interleukin-12/metabolism , Interleukin-13/immunology , Interleukin-13/metabolism , Interleukin-4/immunology , Interleukin-4/metabolism , Matrix Metalloproteinase 2/metabolism , Melanoma/immunology , Melanoma/metabolism , Melanoma/pathology , Models, Immunological , OX40 Ligand/metabolism , Th2 Cells/metabolism , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism
16.
J Clin Invest ; 121(3): 1088-101, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21339641

ABSTRACT

Plasmacytoid DCs (pDCs) are innate immune cells that are specialized to produce IFN-α and to activate adaptive immune responses. Although IFN-α inhibits HIV-1 replication in vitro, the production of IFN-α by HIV-activated pDCs in vivo may contribute more to HIV pathogenesis than to protection. We have now shown that HIV-stimulated human pDCs allow for persistent IFN-α production upon repeated stimulation, express low levels of maturation molecules, and stimulate weak T cell responses. Persistent IFN-α production by HIV-stimulated pDCs correlated with increased levels of IRF7 and was dependent upon the autocrine IFN-α/ß receptor feedback loop. Because it has been shown that early endosomal trafficking of TLR9 agonists causes strong activation of the IFN-α pathway but weak activation of the NF-κB pathway, we sought to investigate whether early endosomal trafficking of HIV, a TLR7 agonist, leads to the IFN-α-producing phenotype we observed. We demonstrated that HIV preferentially traffics to the early endosome in human pDCs and therefore skews pDCs toward a partially matured, persistently IFN-α-secreting phenotype.


Subject(s)
Dendritic Cells/virology , HIV Infections/metabolism , HIV/metabolism , Interferon-alpha/metabolism , NF-kappa B/metabolism , Toll-Like Receptor 9/agonists , Cytokines/metabolism , Humans , Immune System , Phenotype , RNA, Messenger/metabolism , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins/metabolism , Time Factors
17.
Fertil Steril ; 95(3): 1178-81, 2011 Mar 01.
Article in English | MEDLINE | ID: mdl-21047632

ABSTRACT

In this case-control study of euthyroid first-cycle IVF patients ≥ 38 years old with singleton baby, miscarriage, biochemical pregnancy, and no pregnancy outcomes from 2005-2008, we assayed frozen serum for autoimmune thyroid disease (AITD) and thyroid function at cycle start, trigger, and 4 and 5 weeks' gestation. AITD prevalence in older infertile women was similar across clinical outcomes, and although AITD was associated with a higher baseline TSH, TSH remained within acceptable ranges, suggesting that T(4) supplementation may not affect maternal outcomes in older euthyroid AITD patients through 5 weeks gestation.


Subject(s)
Fertilization in Vitro/statistics & numerical data , Infertility, Female/epidemiology , Pregnancy Outcome/epidemiology , Thyroid Gland/physiology , Thyroiditis, Autoimmune/epidemiology , Abortion, Spontaneous/epidemiology , Adult , Case-Control Studies , Female , Humans , Hypothyroidism/epidemiology , Infertility, Female/therapy , Maternal Age , Pregnancy , Prevalence
18.
Pacing Clin Electrophysiol ; 34(3): 269-77, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21070256

ABSTRACT

BACKGROUND: There are little data on the appropriate endpoint for slow pathway ablation that balances acceptable procedural times, recurrence rates, and complication rates. This study compared recurrence rates of three commonly utilized endpoints of slow pathway ablation for atrioventricular nodal reentrant tachycardia (AVNRT). METHODS: We performed a meta-analysis of AVNRT slow pathway ablation cohorts by searching electronic databases, the Internet, and conference proceedings. Inclusion criteria were age >18 years, >20 human subjects per study, primary AVNRT ablation, English language publication, and >1 month of follow-up. Data were analyzed with a fixed-effects model using Comprehensive Meta-Analysis software version 2.2.046 (Biostat, Englewood, NJ, USA). RESULTS: We included 10 studies encompassing 1,204 patients with a mean age of 41-53 years. Endpoints were complete slow pathway ablation, residual jump only, and single remaining echo beat. Pooled estimates revealed 28 of 641 patients (4.4%) with complete slow pathway ablation, 13 of 192 patients (6.8%) with a residual jump only, and 24 of 371 patients (6.5%) with one echo had recurrences. With uniform isoproterenol use after ablation, there was no significant difference in recurrence rates among the endpoints. However, when isoproterenol was utilized after ablation only if needed to induce AVNRT before ablation, a significantly higher recurrence rate occurred in patients with a residual jump (P = 0.002), a single echo (P = 0.003), or the combined group of a residual jump and/or one echo (P = 0.001). CONCLUSIONS: Isoproterenol should be used routinely after slow pathway modification, when a residual jump and/or single echo remain.


Subject(s)
Catheter Ablation/statistics & numerical data , Endpoint Determination/methods , Heart Conduction System/surgery , Outcome Assessment, Health Care/methods , Tachycardia, Atrioventricular Nodal Reentry/epidemiology , Tachycardia, Atrioventricular Nodal Reentry/surgery , Adult , Female , Humans , Male , Middle Aged , Prevalence , Risk Assessment , Risk Factors , Tachycardia, Atrioventricular Nodal Reentry/diagnosis , Treatment Outcome
19.
Am J Surg ; 200(4): 473-7, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20887840

ABSTRACT

BACKGROUND: The aim of this study was to calculate and analyze the cost of treatment for stage IV pressure ulcers. METHODS: A retrospective chart analysis of patients with stage IV pressure ulcers was conducted. Hospital records and treatment outcomes of these patients were followed up for a maximum of 29 months and analyzed. Costs directly related to the treatment of pressure ulcers and their associated complications were calculated. RESULTS: Nineteen patients with stage IV pressure ulcers (11 hospital-acquired and 8 community-acquired) were identified and their charts were reviewed. The average hospital treatment cost associated with stage IV pressure ulcers and related complications was $129,248 for hospital-acquired ulcers during 1 admission, and $124,327 for community-acquired ulcers over an average of 4 admissions. CONCLUSIONS: The costs incurred from stage IV pressure ulcers are much greater than previously estimated. Halting the progression of early stage pressure ulcers has the potential to eradicate enormous pain and suffering, save thousands of lives, and reduce health care expenditures by millions of dollars.


Subject(s)
Cost of Illness , Hospital Costs , Hospitals, University/economics , Length of Stay/economics , Pressure Ulcer/therapy , Humans , Pressure Ulcer/diagnosis , Pressure Ulcer/economics , Severity of Illness Index , United States
20.
Cancer Prev Res (Phila) ; 3(9): 1093-103, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20798208

ABSTRACT

Endothelin receptor type B (EDNRB) and kinesin family member 1A (KIF1A) are candidate tumor suppressor genes that are inactivated in cancers. In this study, we evaluated the promoter hypermethylation of EDNRB and KIF1A and their potential use for risk classification in prospectively collected salivary rinses from patients with premalignant/malignant oral cavity lesions. Quantitative methylation-specific PCR was performed to analyze the methylation status of EDNRB and KIF1A in salivary rinses of 191 patients. We proceeded to determine the association of methylation status with histologic diagnosis and estimate classification accuracy. On univariate analysis, diagnosis of dysplasia/cancer was associated with age and KIF1A or EDNRB methylation. Methylation of EDNRB highly correlated with that of KIF1A (P < 0.0001). On multivariable modeling, histologic diagnosis was independently associated with EDNRB (P = 0.0003) or KIF1A (P = 0.027) methylation. A subset of patients analyzed (n = 161) without prior biopsy-proven malignancy received clinical risk classification based on examination. On univariate analysis, EDNRB and risk classification were associated with diagnosis of dysplasia/cancer and remained significant on multivariate analysis (EDNRB: P = 0.047, risk classification: P = 0.008). Clinical risk classification identified dysplasia/cancer with a sensitivity of 71% and a specificity of 58%. The sensitivity of clinical risk classification combined with EDNRB methylation improved to 75%. EDNRB methylation in salivary rinses was independently associated with histologic diagnosis of premalignancy and malignancy and may have potential in classifying patients at risk for oral premalignant and malignant lesions in settings without access to a skilled dental practitioner. This may also potentially identify patients with premalignant and malignant lesions that do not meet the criteria for high clinical risk based on skilled dental examination.


Subject(s)
Carcinoma, Squamous Cell/genetics , DNA Methylation , Mouth Neoplasms/genetics , Precancerous Conditions/genetics , Promoter Regions, Genetic , Receptor, Endothelin B/genetics , Saliva/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , DNA Methylation/genetics , Female , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease/genetics , Humans , Kinesins/genetics , Kinesins/metabolism , Male , Middle Aged , Mouth/metabolism , Mouth/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Precancerous Conditions/metabolism , Precancerous Conditions/pathology , Receptor, Endothelin B/metabolism , Risk Factors , Young Adult
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