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1.
BMC Palliat Care ; 23(1): 103, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38637806

BACKGROUND: Chronic lung disease affects nearly 37 million Americans and often results in significant quality of life impairment and healthcare burden. Despite guidelines calling for palliative care (PC) integration into pulmonary care as a vital part of chronic lung disease management, existing PC models have limited access and lack scalability. Use of telehealth to provide PC offers a potential solution to these barriers. This study explored perceptions of patients with chronic lung disease regarding a telehealth integrated palliative care (TIPC) model, with plans to use findings to inform development of an intervention protocol for future testing. METHODS: For this qualitative study, we conducted semi-structured interviews between June 2021- December 2021 with patients with advanced chronic lung disease. Interviews explored experiences with chronic lung disease, understanding of PC, and perceived acceptability of the proposed model along with anticipated facilitators and barriers of the TIPC model. We analyzed findings with a content analysis approach. RESULTS: We completed 20 interviews, with two that included both a patient and caregiver together due to patient preference. Perceptions were primarily related to three categories: burden of chronic lung disease, pre-conceived understanding of PC, and perspective on the proposed TIPC model. Analysis revealed a high level of disease burden related to chronic lung disease and its impact on day-to-day functioning. Although PC was not well understood, the TIPC model using a shared care planning approach via telehealth was seen by most as an acceptable addition to their chronic lung disease care. CONCLUSIONS: These findings emphasize the need for a patient-centered, shared care planning approach in chronic lung disease. The TIPC model may be one option that may be acceptable to individuals with chronic lung disease. Future work includes using findings to refine our TIPC model and conducting pilot testing to assess acceptability and utility of the model.


Hospice and Palliative Care Nursing , Lung Diseases , Telemedicine , Humans , Palliative Care/methods , Quality of Life , Telemedicine/methods , Lung Diseases/therapy
2.
Ann Am Thorac Soc ; 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38507646

RATIONALE: Hospital-free days (HFDs), a measure of the number of days alive spent outside the hospital, is increasingly used as an endpoint in studies of patients with acute respiratory failure (ARF) or other critical and serious illnesses. Current approaches to measuring HFDs do not account for decrements in functional status or quality of life that ARF survivors and family members value. OBJECTIVES: To develop an acceptable approach to measure quality-weighted HFDs using patient-reported outcomes. METHODS: We conducted a 4-round modified Delphi among ARF experts - those with lived or professional experience. Experts rated survivorship domains, instrument and data collection characteristics, and methods to translate responses into quality-weighted HFDs. The consensus threshold was that >70% of respondents rated an item "Totally Acceptable" or "Acceptable" and <15% of respondents rated the item "Totally Unacceptable", "Unacceptable", or "Slightly Unacceptable." RESULTS: Fifty-seven experts participated in Round 1. Response rates were 82-93% for subsequent rounds. Priority survivorship domains were physical function and health-related quality of life. Participants reached consensus that data collection during ARF recovery should take fewer than 15 minutes per assessment, allow for surrogate completion when patients are unable, and continue for at least 24 months of follow-up. Using the EuroQol-5 Dimensions (EQ-5D) to quality-weight HFDs met consensus criteria for acceptability. A majority of panelists preferred quality-weighted HFDs to unweighted HFDs or survival for use in future ARF studies. CONCLUSIONS: Quality-weighting HFDs using patient and/or surrogate responses to the EQ-5D captured stakeholder priorities and was acceptable to this Delphi panel.

3.
BMC Health Serv Res ; 23(1): 1232, 2023 Nov 09.
Article En | MEDLINE | ID: mdl-37946170

BACKGROUND: Refugee and immigrant populations have diverse cultural factors that affect their access to health care and must be considered when building a new clinical space. Health design thinking can help a clinical team evaluate and consolidate these factors while maintaining close contact with architects, patients' community leaders, and hospital or institutional leadership. A diverse group of clinicians, medical students, community leaders and architects planned a clinic devoted to refugee and immigrant health, a first-of-its-kind for South Philadelphia. METHODS: The planning process and concept design of this wellness center is presented as a design case study to demonstrate how principles and methods of human-centered design were used to create a community clinic. Design thinking begins with empathizing with the end users' experiences before moving to ideation and prototyping of a solution. These steps were accomplished through focus groups, a design workshop, and iterations of the center's plan. RESULTS: Focus groups were thematically analyzed and generated two themes of access and resources and seven subthemes that informed the design workshop. A final floor plan of the wellness center was selected, incorporating priorities of all stakeholders and addressing issues of disease prevention, social determinants of health, and lifestyle-related illness that were relevant to the patient population. CONCLUSIONS: Design thinking methods are useful for health care organizations that must adapt to the needs of diverse stakeholders and especially populations that are underserved or displaced. While much has been written on the theory and stages of design thinking, this study is novel in describing this methodology from the beginning to the end of the process of planning a clinical space with input from the patient population. This study thus serves as a proof of concept of the application of design thinking in planning clinical spaces.


Fitness Centers , Refugees , Humans , Health Facilities , Delivery of Health Care , Focus Groups
4.
Diabetes Spectr ; 35(2): 216-222, 2022.
Article En | MEDLINE | ID: mdl-35668887

Objective: People with type 2 diabetes are likely to experience shame or guilt as they navigate through their disease. Previous research has shown that feelings of shame and guilt often exist within the clinician-patient relationship, often as a result of the complex care regimen required to achieve treatment goals. The purpose of this qualitative study was to explore patients' experiences of shame and guilt in type 2 diabetes management and the impact their clinicians have on these experiences. Methods: Semistructured interviews were used to explore patients' experiences with shame and guilt. Interviews were audio-recorded, transcribed, and coded using directed content analysis. Demographic data were also obtained. Results: We completed 20 interviews with people with type 2 diabetes (65% Black, 70% female). Participants exhibited feelings more consistent with guilt than with shame. All participants discussed how their clinicians affected these feelings. Patients who expressed feelings of guilt were able to recognize opportunities for behavior change without experiencing global devaluation, in which they linked their actions to an unchangeable aspect of their identity or personality, often describing their guilt as motivating of change. Unlike guilt, when patients experienced shame, they often exhibited global devaluation, in which they blamed their personality, experienced hopelessness, and increased maladaptive behaviors. Conclusion: Our findings highlight a notable difference between shame and guilt in the context of type 2 diabetes management. We believe that incorporation of an understanding of these nuances, along with ideal responses to both shame and guilt, will enhance clinicians' ability to provide high-quality patient-centered care to people with diabetes.

5.
Female Pelvic Med Reconstr Surg ; 28(4): 240-243, 2022 04 01.
Article En | MEDLINE | ID: mdl-34628445

OBJECTIVE: The aim of the study was to evaluate the quality of patient-focused websites addressing postpartum pelvic floor health. METHODS: The Google search engine was used to perform a search of the following 3 terms: (1) "postpartum pelvic floor (PPF)," (2) "postpartum leaking urine (PLU)," and (3) "postpartum leaking stool (PLS)." The top 20 results from each search term were evaluated using the DISCERN quality appraisal tool and Journal of the American Medical Association (JAMA) benchmark criteria by 2 independent researchers. Websites were also categorized by type. Cohen κ was performed to determine interrater reliability between reviewers. The Kruskal-Wallis test was used to evaluate the differences in DISCERN and JAMA criteria scores. RESULTS: The weighted mean κ between the investigators for each search term was κ = 0.47 (range = 0.163 [PPF] to 0.759 [PLU]), suggesting moderate agreement between reviewers. There was a significant difference in mean DISCERN scores between the terms, with "postpartum leaking urine" yielding the highest mean score. When comparing DISCERN scores by category, society- and government-sponsored websites (mean = 55 ± 13) scored significantly higher than other categories. Using JAMA criteria, mean scores ranged between 1.83 and 2.83/4, but there were no significant differences between websites. CONCLUSIONS: The overall quality of health information available on the internet regarding postpartum pelvic health is low. Higher-quality search results are found within society- and government-sponsored websites as well as under the search term "postpartum leaking urine." It is important for health care providers to guide their patients to websites with reliable information about postpartum pelvic floor recovery.


Consumer Health Information , Pelvic Floor , Female , Humans , Internet , Postpartum Period , Reproducibility of Results , Search Engine
6.
PLoS One ; 16(12): e0260852, 2021.
Article En | MEDLINE | ID: mdl-34855882

Establishing a universally applicable protocol to assess the impact of BRCA1 variants of uncertain significance (VUS) expression is a problem which has yet to be resolved despite major progresses have been made. The numerous difficulties which must be overcome include the choices of cellular models and functional assays. We hypothesised that the use of induced pluripotent stem (iPS) cells might facilitate the standardisation of protocols for classification, and could better model the disease process. We generated eight iPS cell lines from patient samples expressing either BRCA1 pathogenic variants, non-pathogenic variants, or BRCA1 VUSs. The impact of these variants on DNA damage repair was examined using a ɣH2AX foci formation assay, a Homologous Repair (HR) reporter assay, and a chromosome abnormality assay. Finally, all lines were tested for their ability to differentiate into mammary lineages in vitro. While the results obtained from the two BRCA1 pathogenic variants were consistent with published data, some other variants exhibited differences. The most striking of these was the BRCA1 variant Y856H (classified as benign), which was unexpectedly found to present a faulty HR repair pathway, a finding linked to the presence of an additional variant in the ATM gene. Finally, all lines were able to differentiate first into mammospheres, and then into more advanced mammary lineages expressing luminal- or basal-specific markers. This study stresses that BRCA1 genetic analysis alone is insufficient to establish a reliable and functional classification for assessment of clinical risk, and that it cannot be performed without considering the other genetic aberrations which may be present in patients. The study also provides promising opportunities for elucidating the physiopathology and clinical evolution of breast cancer, by using iPS cells.


BRCA1 Protein/genetics , Breast Neoplasms/pathology , DNA Damage , DNA Repair , Genetic Predisposition to Disease , Induced Pluripotent Stem Cells/pathology , Mutation , Breast Neoplasms/classification , Breast Neoplasms/genetics , Female , Genetic Testing , Humans , Induced Pluripotent Stem Cells/metabolism
8.
Female Pelvic Med Reconstr Surg ; 27(1): e223-e226, 2021 01 01.
Article En | MEDLINE | ID: mdl-32541298

OBJECTIVE: With the introduction of robotic sacrocolpopexy (RSC) at our institution in 2008, we noted a reduction in residents' vaginal hysterectomy (VH) experience. In 2012, we made a transition to perform VH on all robotic sacrocolpopexies. Our objective was to report our short-term outcomes and adverse events. METHODS: In this case series, we evaluated women who underwent VH with concomitant RSC for stages II to IV pelvic organ prolapse between 2012 and 2017. In these cases, the vesicovaginal and rectovaginal spaces were developed transvaginally. Descriptive analysis including demographics, short-term outcomes, and adverse events are reported. RESULTS: In this group of 209 women, median (interquartile interval) duration of follow-up was 49 (26-60) weeks. The majority of the women were white (84.7%) and postmenopausal (80.9%), with a mean (SD) age of 59 (9) years. At a median follow-up time of 49 weeks, pelvic organ prolapse quantification revealed 20 patients (12.4%) with Ba or Bp greater or equal to 0 and 1.4% of patients required repeat prolapse surgery. Among 9 women (4.3%) with postoperative fever, 4 (1.9%) were treated for pelvic collection/abscess. Of 5 women (2.4%) who had venous thromboembolism, 3 (1.4%) were diagnosed with pulmonary embolism. There were 18 patients (8.6%) treated for urinary tract infection within 6 postoperative weeks. Mesh exposure was noted in 16 (7.7%) of the patients, and 11 (6.2%) required reoperation. CONCLUSIONS: Vaginal hysterectomy at the time of RSC may increase the risk of infection and mesh exposure compared with procedures without concomitant hysterectomy.


Hysterectomy, Vaginal , Pelvic Organ Prolapse/surgery , Robotic Surgical Procedures , Aged , Female , Gynecologic Surgical Procedures/adverse effects , Gynecologic Surgical Procedures/methods , Humans , Hysterectomy, Vaginal/adverse effects , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Sacrum/surgery , Time Factors , Treatment Outcome , Vagina/surgery
9.
Female Pelvic Med Reconstr Surg ; 26(8): e33-e36, 2020 08.
Article En | MEDLINE | ID: mdl-32487884

OBJECTIVES: Traditionally, sacrospinous ligament fixation is performed unilaterally with a posterior dissection for correction of apical vaginal prolapse. There is limited information on alternative techniques including bilateral application and use of anterior vaginal dissection for this procedure. The objective of this study is to evaluate the anatomic and perioperative outcomes in women who have undergone bilateral sacrospinous ligament fixation through an anterior approach. METHODS: This cohort represents women in our prospective repository who underwent anterior approach bilateral sacrospinous ligament fixation between September 2011 and June 2014. Concomitant procedures were performed as indicated. Pelvic organ prolapse quantification points were measured preoperatively and at 6 weeks and 6 months postoperatively and were compared. Perioperative outcome measures and adverse events were also analyzed. RESULTS: In this cohort, 144 women underwent anterior approach to bilateral sacrospinous ligament fixation. The patients' mean age was 57.8 ± 10.9 years, and the average body mass index was 29.6 ± 5.8 kg/m. In patients who underwent anterior approach bilateral sacrospinous ligament fixation, points Aa, Ba, C, Gh, Ap, and Bp remained at stage I or less when compared with pelvic organ prolapse quantification measurements at the baseline. Perioperative and postoperative complications were minimal, with 1 (0.7%) patient requiring a blood transfusion and 3 (2%) patients suffered from intraoperative lower urinary tract injuries, none of which were attributable to the sacrospinous fixation part of the procedure. CONCLUSIONS: Anterior approach bilateral sacrospinous ligament fixation is a safe and effective procedure for reestablishing apical support in a patient with apical vaginal prolapse.


Hysterectomy, Vaginal/methods , Ligaments/surgery , Pelvic Organ Prolapse/surgery , Aged , Female , Humans , Hysterectomy, Vaginal/adverse effects , Middle Aged , Prospective Studies
10.
Obstet Gynecol Clin North Am ; 46(3): 527-540, 2019 Sep.
Article En | MEDLINE | ID: mdl-31378293

Pelvic floor disorders commonly affect women and may cause distress and difficulty with daily functions and self-image. Urinary incontinence may present as stress incontinence, urgency incontinence, or in some combination (mixed incontinence). Symptomatic pelvic organ prolapse (POP) occurs when the patient is bothered by the sensation of a herniation of the pelvic organs through the vagina. Although POP is often distressing and embarrassing, it is not considered life-threatening unless the patient cannot urinate or defecate. There are numerous ways to treat these conditions, including conservative (including observation), medical, and surgical management.


Pelvic Floor Disorders/therapy , Adult , Aged , Female , Humans , Middle Aged , Pelvic Floor Disorders/diagnosis , Pelvic Organ Prolapse/diagnosis , Pelvic Organ Prolapse/epidemiology , Pelvic Organ Prolapse/therapy , Pessaries , Quality of Life , Sexual Dysfunction, Physiological , Urinary Incontinence/diagnosis , Urinary Incontinence/epidemiology , Urinary Incontinence/therapy
11.
Female Pelvic Med Reconstr Surg ; 25(1): e4-e6, 2019.
Article En | MEDLINE | ID: mdl-30180049

OBJECTIVES: The aim of this article is to report the outcomes of sling plications performed on women who presented with persistent stress urinary incontinence after midurethral sling. METHODS: All women who underwent sling plication for persistent stress urinary incontinence after placement of either retropubic or transobturator midurethral sling were included in this case series. For plication, first, the suburethral incision was opened. After mobilization of the mesh in the midline, the sling was plicated with absorbable sutures. Descriptive data were extracted from the electronic medical record. Postoperative stress urinary incontinence was diagnosed based on patients' response to the relevant question on the urinary distress inventory and compared this outcome with respect to the original sling placement approach. RESULTS: We identified 36 women who underwent sling plication between March 2013 and November 2016: 26 (72.2%) following a retropubic and 10 (27.7%) following a transobturator sling. Median time between midurethral sling and plication procedure was 6.8 weeks (range, 2-148 weeks). Median follow-up after sling plication was 17 weeks (range, 2-104 weeks). Overall, 24 women (66.6%) reported subjective resolution of stress incontinence. Success rate for plication of retropubic slings was 20 (76.9%) of 26 and significantly higher compared with 4 (40%) of 10 for transobturator slings (P = 0.034). There were no mesh erosions or persistent urinary retention after sling plication. CONCLUSIONS: Sling shortening by plication is an effective low-risk option for the management of persistent stress urinary incontinence following a midurethral sling. This approach was found to be more successful after retropubic slings.


Reoperation/methods , Suburethral Slings/adverse effects , Surgical Mesh/adverse effects , Urinary Incontinence, Stress/surgery , Adult , Aged , Female , Humans , Middle Aged , Retrospective Studies , Surveys and Questionnaires
12.
Am J Transplant ; 18(6): 1370-1379, 2018 06.
Article En | MEDLINE | ID: mdl-29392897

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.


Genome-Wide Association Study , Kidney Transplantation , Tissue Donors , Transplant Recipients , Adult , DNA Replication , Female , Genotype , Graft Survival/immunology , Histocompatibility Testing , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Transplantation, Homologous
13.
Blood ; 131(6): 636-648, 2018 02 08.
Article En | MEDLINE | ID: mdl-29191918

A hallmark of acute promyelocytic leukemia (APL) is altered nuclear architecture, with disruption of promyelocytic leukemia (PML) nuclear bodies (NBs) mediated by the PML-retinoic acid receptor α (RARα) oncoprotein. To address whether this phenomenon plays a role in disease pathogenesis, we generated a knock-in mouse model with NB disruption mediated by 2 point mutations (C62A/C65A) in the Pml RING domain. Although no leukemias developed in PmlC62A/C65A mice, these transgenic mice also expressing RARα linked to a dimerization domain (p50-RARα model) exhibited a doubling in the rate of leukemia, with a reduced latency period. Additionally, we found that response to targeted therapy with all-trans retinoic acid in vivo was dependent on NB integrity. PML-RARα is recognized to be insufficient for development of APL, requiring acquisition of cooperating mutations. We therefore investigated whether NB disruption might be mutagenic. Compared with wild-type cells, primary PmlC62A/C65A cells exhibited increased sister-chromatid exchange and chromosome abnormalities. Moreover, functional assays showed impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ) repair pathways, with defective localization of Brca1 and Rad51 to sites of DNA damage. These data directly demonstrate that Pml NBs are critical for DNA damage responses, and suggest that Pml NB disruption is a central contributor to APL pathogenesis.


DNA Repair/genetics , Intranuclear Inclusion Bodies/metabolism , Leukemia, Promyelocytic, Acute/genetics , Leukemia, Promyelocytic, Acute/pathology , Promyelocytic Leukemia Protein/physiology , Animals , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , DNA Damage/genetics , DNA End-Joining Repair/genetics , Intranuclear Inclusion Bodies/genetics , Leukemia, Promyelocytic, Acute/metabolism , Mice , Mice, Transgenic , Mutagenesis/genetics , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Promyelocytic Leukemia Protein/genetics , Signal Transduction/genetics
14.
Endocr Pathol ; 28(1): 41-48, 2017 Mar.
Article En | MEDLINE | ID: mdl-27704398

The REarranged during Transfection (RET) proto-oncogene is a receptor tyrosine kinase involved in growth and differentiation during embryogenesis and maintenance of the urogenital and nervous systems in mammals. Distinct mutations across hotspot RET exons can cause Multiple Endocrine Neoplasia Type 2A (MEN2A) characterised by development of medullary thyroid cancer (MTC), phaeochromocytoma (PCC) and primary hyperparathyroidism (PHPT), with a strong correlation between genotype and phenotype. Here, we report a 42-year-old man presented in the clinic with a unilateral PCC, with subsequent investigations revealing a nodular and cystic thyroid gland. He proceeded to thyroidectomy, which showed bilateral C-cell hyperplasia (CCH) without evidence of MTC. His brother had neonatal Hirschsprung disease (HSCR). Genetic testing revealed the presence of a heterozygous variant of unknown significance (VUS) in the cysteine-rich region of exon 10 in the RET gene (c.1846G>C, p.E616Q), in both affected siblings and their unaffected mother. Exon 10 RET mutations are known to be associated with HSCR and MEN2. Variants in the cysteine-rich region of the RET gene, outside of the key cysteine residues, may contribute to the development of MEN2 in a less aggressive manner, with a lower penetrance of MTC. Currently, a VUS in RET cannot be used to inform clinical management and direct future care. Analysis of RETE616Q reveals a gain of function mutant phenotype for this variant, which has not previously been reported, indicating that this VUS should be considered at risk for future clinical management.


Multiple Endocrine Neoplasia Type 2a/genetics , Proto-Oncogene Proteins c-ret/genetics , Adult , Blotting, Western , Female , Humans , Male , Mutagenesis, Site-Directed , Mutation , Pedigree , Proto-Oncogene Mas
15.
N Engl J Med ; 374(5): 422-33, 2016 Feb 04.
Article En | MEDLINE | ID: mdl-26789727

BACKGROUND: Despite the molecular heterogeneity of standard-risk acute myeloid leukemia (AML), treatment decisions are based on a limited number of molecular genetic markers and morphology-based assessment of remission. Sensitive detection of a leukemia-specific marker (e.g., a mutation in the gene encoding nucleophosmin [NPM1]) could improve prognostication by identifying submicroscopic disease during remission. METHODS: We used a reverse-transcriptase quantitative polymerase-chain-reaction assay to detect minimal residual disease in 2569 samples obtained from 346 patients with NPM1-mutated AML who had undergone intensive treatment in the National Cancer Research Institute AML17 trial. We used a custom 51-gene panel to perform targeted sequencing of 223 samples obtained at the time of diagnosis and 49 samples obtained at the time of relapse. Mutations associated with preleukemic clones were tracked by means of digital polymerase chain reaction. RESULTS: Molecular profiling highlighted the complexity of NPM1-mutated AML, with segregation of patients into more than 150 subgroups, thus precluding reliable outcome prediction. The determination of minimal-residual-disease status was more informative. Persistence of NPM1-mutated transcripts in blood was present in 15% of the patients after the second chemotherapy cycle and was associated with a greater risk of relapse after 3 years of follow-up than was an absence of such transcripts (82% vs. 30%; hazard ratio, 4.80; 95% confidence interval [CI], 2.95 to 7.80; P<0.001) and a lower rate of survival (24% vs. 75%; hazard ratio for death, 4.38; 95% CI, 2.57 to 7.47; P<0.001). The presence of minimal residual disease was the only independent prognostic factor for death in multivariate analysis (hazard ratio, 4.84; 95% CI, 2.57 to 9.15; P<0.001). These results were validated in an independent cohort. On sequential monitoring of minimal residual disease, relapse was reliably predicted by a rising level of NPM1-mutated transcripts. Although mutations associated with preleukemic clones remained detectable during ongoing remission after chemotherapy, NPM1 mutations were detected in 69 of 70 patients at the time of relapse and provided a better marker of disease status. CONCLUSIONS: The presence of minimal residual disease, as determined by quantitation of NPM1-mutated transcripts, provided powerful prognostic information independent of other risk factors. (Funded by Bloodwise and the National Institute for Health Research; Current Controlled Trials number, ISRCTN55675535.).


Leukemia, Myeloid, Acute/genetics , Mutation , Nuclear Proteins/genetics , Base Sequence , DNA, Neoplasm/analysis , Exome , Gene Expression Profiling , Humans , Molecular Sequence Data , Neoplasm, Residual/genetics , Nuclear Proteins/metabolism , Nucleophosmin , Prognosis , Recurrence , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , Transcriptome
16.
Neurourol Urodyn ; 35(8): 975-979, 2016 11.
Article En | MEDLINE | ID: mdl-26227401

AIMS: To determine if music (at 60 beats/min) or watching a pre-procedure educational video decreases pain and anxiety in women undergoing multichannel urodynamic testing compared to usual care. METHODS: Women undergoing multichannel urodynamic testing at a tertiary care center were randomized to one of three groups: usual care (UC), music (M), in which music was played throughout the urodynamic test, or video (V), in which subjects watched an informational video on the procedure prior to undergoing the test. Visual analog scales (VAS) were used to measure patient's pain and anxiety before and after the test. Demographic information was obtained and five-item Likert questionnaires were given to assess information seeking behavior, preparedness, embarrassment, and privacy. RESULTS: 98 subjects were included in this analysis. In the overall group, mean perceived pain on the pre-test VAS was significantly higher than the post-test VAS with pre-test mean (SD) 47(±30) and post-test mean (SD) 26(±23), P = 0.0001. Overall the anxiety pre-test VAS was significantly greater than post-test VAS with pre-test mean (SD) 46.9(±29) and post-test mean 17.9(±18), P = 0.0001. There were no differences in pain and anxiety scores between the two intervention groups and usual care. Patients who were randomized to usual care or the video arm felt more prepared for the test compared to patients who were randomized to the music arm, with (mean ± SD): usual care (42 ± 8), video (43 ± 9), music (37 ± 11), P = 0.002. CONCLUSIONS: Music and an educational video do not decrease pain or anxiety in subjects undergoing multichannel urodynamics compared to usual care. Neurourol. Urodynam. 35:975-979, 2016. © 2015 Wiley Periodicals, Inc.


Anxiety/etiology , Anxiety/psychology , Pain Management/methods , Pain/etiology , Pain/prevention & control , Urodynamics , Adult , Aged , Female , Humans , Middle Aged , Music , Pain Measurement , Photic Stimulation , Treatment Outcome , Urinary Bladder Diseases/complications , Urinary Bladder Diseases/diagnosis , Urinary Bladder Diseases/psychology , Young Adult
17.
Blood ; 125(19): 2985-94, 2015 May 07.
Article En | MEDLINE | ID: mdl-25805812

The gene CXXC5 on 5q31 is frequently deleted in acute myeloid leukemia (AML) with del(5q), suggesting that inactivation of CXXC5 might play a role in leukemogenesis. Here, we investigated the functional and prognostic implications of CXXC5 expression in AML. CXXC5 mRNA was downregulated in AML with MLL rearrangements, t(8;21) and GATA2 mutations. As a mechanism of CXXC5 inactivation, we found evidence for epigenetic silencing by promoter methylation. Patients with CXXC5 expression below the median level had a lower relapse rate (45% vs 59%; P = .007) and a better overall survival (OS, 46% vs 28%; P < .001) and event-free survival (EFS, 36% vs 21%; P < .001) at 5 years, independent of cytogenetic risk groups and known molecular risk factors. In gene-expression profiling, lower CXXC5 expression was associated with upregulation of cell-cycling genes and co-downregulation of genes implicated in leukemogenesis (WT1, GATA2, MLL, DNMT3B, RUNX1). Functional analyses demonstrated CXXC5 to inhibit leukemic cell proliferation and Wnt signaling and to affect the p53-dependent DNA damage response. In conclusion, our data suggest a tumor suppressor function of CXXC5 in AML. Inactivation of CXXC5 is associated with different leukemic pathways and defines an AML subgroup with better outcome.


Carrier Proteins/genetics , Gene Expression Regulation, Leukemic , Leukemia, Myeloid, Acute/genetics , Mutation/genetics , Wnt Proteins/antagonists & inhibitors , Adolescent , Adult , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/metabolism , Cell Cycle , Cohort Studies , DNA Methylation , DNA-Binding Proteins , Down-Regulation , Female , Follow-Up Studies , Gene Expression Profiling , Humans , Immunoenzyme Techniques , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Prognosis , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Survival Rate , Transcription Factors , Tumor Cells, Cultured , Young Adult
18.
Obstet Gynecol ; 125(1): 58-61, 2015 Jan.
Article En | MEDLINE | ID: mdl-25560104

BACKGROUND: The retropubic tension-free vaginal tape (TVT) procedure is a common procedure with complications attributed to voiding dysfunction, bladder perforation, and bleeding. We present a case of successful removal of a retropubic midurethral sling from the urethra using a head lamp and a combination of ear, nose, and throat instruments. CASE: A 63-year-old woman presented to our clinic with the symptom of gross hematuria after having undergone a TVT procedure. On office cystoscopy, the sling was noted to be placed within the urethral mucosa. Removal of the mesh was performed using a nasal speculum, left and right ethmoid scissors, left and right Blakesley graspers, and a head lamp to dissect the mesh directly out of the urethra. CONCLUSION: The utilization of ear, nose, and throat tools allowed us to resect the intraurethral mesh without necessitating incision of the urethral sphincter.


Device Removal/instrumentation , Suburethral Slings , Surgical Mesh , Urologic Surgical Procedures/instrumentation , Female , Humans , Middle Aged , Otolaryngology/instrumentation , Suburethral Slings/adverse effects , Surgical Mesh/adverse effects , Urethra/surgery , Urinary Bladder/surgery
19.
Int Urogynecol J ; 26(1): 145-6, 2015 Jan.
Article En | MEDLINE | ID: mdl-25224146

It is difficult to determine what types of procedures should be attempted in patients who have recurrent prolapse. We present a case of recurrent lateral enterocele and rectocele after the patient had undergone multiple surgeries for pelvic organ prolapse (POP), including a vaginal hysterectomy, bladder-neck suspension, anterior colporrhaphy, site-specific rectocele repair, apical mesh implant, iliococcygeus vault suspension, and transobturator suburethral sling procedure. With recurrence, the patient underwent robot-assisted laparoscopic sacral colpopexy, tension-free vaginal tape transobturator sling insertion, rectocele repair, and perineorrhaphy with cystoscopy. She then presented with defecatory outlet obstruction and constipation and subsequently was treated with a stapled transanal rectal resection. The patient returned with continued defecatory dysfunction and a recurrent lateral enterocele and rectocele. The recurrence was treated laparoscopically using a lightweight polypropylene mesh. The postoperative period was uneventful. Two years later, the patient reported decreased defecatory symptoms and no further symptomatic prolapse.


Gynecologic Surgical Procedures/methods , Herniorrhaphy/methods , Rectocele/surgery , Female , Humans , Laparoscopy , Middle Aged , Recurrence , Reoperation
20.
Int Urogynecol J ; 26(4): 591-5, 2015 Apr.
Article En | MEDLINE | ID: mdl-25377295

INTRODUCTION AND HYPOTHESIS: The objective of this study was to compare the histological characteristics of pathological specimens of excised midurethral sling mesh and surrounding vaginal tissue in patients who presented preoperatively with pain and/or exposure of mesh to patients who underwent mesh excision for voiding dysfunction without pain and/or erosion. METHODS: This is a retrospective case-control study of women who underwent excision of midurethral sling mesh between 2008 and 2013. Three groups were identified: (1) voiding dysfunction without pain or exposure (control group), (2) pain and/or mesh exposure, and (3) voiding dysfunction with pain and/or mesh exposure. All original pathological specimens were rereviewed by one pathologist blinded to indication for excision and the previous pathology report. Degree of inflammation and fibrosis were recorded based on a 4-point scale along with the presence of giant cell reaction. RESULTS: A total of 130 subjects met inclusion criteria: 60 (46.2 %) with voiding dysfunction only, 21 (16.2 %) with pain/erosion, and 49 (37.7 %) with both pain/exposure and voiding dysfunction. The voiding dysfunction only group was found to have significantly higher levels of inflammation, median grade 2 (1-3), compared to the other two groups with a p value of 0.007. There were no statistical differences in fibrosis and giant cell reaction between the three groups. CONCLUSIONS: Midurethral sling mesh excised for voiding dysfunction demonstrates elevated levels of inflammation compared to mesh that is excised for pain and/or exposure. The vaginal tissue fibrosis and giant cell reaction are similar in patients who undergo mesh excision for voiding dysfunction and pain, and/or mesh exposure.


Pain/pathology , Suburethral Slings/adverse effects , Surgical Mesh/adverse effects , Urination Disorders/pathology , Vagina/pathology , Adult , Case-Control Studies , Device Removal , Female , Fibrosis/pathology , Giant Cells, Foreign-Body/pathology , Humans , Inflammation/pathology , Middle Aged , Pain/etiology , Retrospective Studies , Urination Disorders/etiology
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