ABSTRACT
OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed). RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36). CONCLUSIONS: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.
Subject(s)
BRCA1 Protein , Cystadenocarcinoma, Serous , Ovarian Neoplasms , Humans , Female , Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Middle Aged , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/pathology , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Aged, 80 and over , Age Factors , Adult , Homologous Recombination , Neoplasm Staging , Neoplasm Grading , Genetic Testing/methodsABSTRACT
The goal of this study was to examine the relationship between body mass index (BMI) and the success rate of sentinel lymph node (SLN) mapping using indocyanine green and near-infrared imaging. Sentinel lymph node mapping is recommended for patients with endometrial carcinoma to reduce the rate of full lymphadenectomy and its associated morbidity such as lymphedema. A retrospective review was conducted of robotic hysterectomy procedures for patients with a coded diagnosis of endometrial cancer and a cost code for indocyanine green discharged between March, 2016 and August, 2019. Preoperative characteristics included age, BMI, and number of prior abdominal surgeries (includes cervical, adnexal, uterine or rectal procedures, caesarian section, or appendectomy). Intra and postoperative characteristics included procedure time (incision to close), estimated blood loss, the American Society of Anesthesiologists (ASA) physical status classification, uterine weight, uterine diameter, FIGO Grade, myometrial depth, and depth of myometrial invasion. SLN and non-SLN number, location, and pathology were recorded. The primary outcome was the bilateral success rate for SLN mapping. Patients with class III obesity (BMI > 40) were found to have a significantly lower success rate for SLN mapping when compared with all other BMI categories (54.1% vs. 76.1%, respectively, p < 0.01).
Subject(s)
Endometrial Neoplasms , Obesity, Morbid , Robotic Surgical Procedures , Sentinel Lymph Node , Female , Humans , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathology , Sentinel Lymph Node Biopsy/methods , Indocyanine Green , Robotic Surgical Procedures/methods , Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathology , Lymph Node Excision/methods , Coloring AgentsABSTRACT
BACKGROUND: Homelessness is a risk factor for family involvement with child welfare services (CWS). Housing interventions are promising-but reasons for this are not well understood, and housing resources could be better targeted to families at risk of increased CWS involvement. OBJECTIVE: We sought to better understand the relationship between homelessness and CWS involvement and examine whether homeless shelter data could combine with CWS data to enhance intervention targeting. PARTICIPANTS AND SETTING: For 4 years, we followed 2063 families investigated by the San Francisco Human Services Agency in 2011. METHODS: Matching CWS data to homeless shelter data, we fit Cox models to examine the relationship between shelter use and subsequent CWS outcomes and produced ROC curves to judge model accuracy with and without shelter information. RESULTS: Absent CWS covariates (family demographics, CWS history, and family safety and risk), past shelter entry predicted repeat maltreatment referral (HR = 1.92, p < .001), in-home case opening (HR = 1.51, p < .05), and child removal (HR = 1.95, p < .01), but not child reunification. With CWS covariates, past shelter use no longer predicted case opening and child removal, but still predicted referral (HR = 1.58, p < .01). Shelter data did not contribute to models' predictive accuracy. CONCLUSIONS: We find mixed evidence that shelter use independently leads to CWS involvement. Housing interventions might help by addressing present housing problems and family experiences correlated with past shelter use. However, we find no evidence that data matches with shelter systems could enhance targeting.
Subject(s)
Child Protective Services/methods , Child Protective Services/trends , Family/psychology , Housing/trends , Ill-Housed Persons/psychology , Adult , California/epidemiology , Child , Female , Humans , Male , Risk Factors , Social Problems/psychology , Social Problems/trends , Social Welfare/psychology , Social Welfare/trends , Surveys and QuestionnairesABSTRACT
INTRODUCTION: Exposure to violence is a risk factor for firearm carriage. Youth exposed to violence also have difficulty envisioning positive future outcomes (e.g., educational outcomes), which can increase the likelihood of firearm carriage over time. Researchers, however, have not yet examined whether changes in exposure to violence over time can influence the developmental trajectories of firearm carriage. To address this gap, we (1) examined the longitudinal association between exposure to violence and firearm carriage (grades 9 to 12) and then (2) examined whether changes in future expectations mediated this longitudinal association. METHOD: The longitudinal association between exposure to violence and firearm carriage through future expectations was examined among 850 adolescents from the Flint Adolescent Study. Participants were recruited from four high schools in a midwestern city in the United States. Parallel latent growth models and latent growth mediation models were estimated. RESULTS: A positive association was observed between the rate of change in exposure to violence and firearm carriage. Exposure to violence also indirectly increased the risk for firearm carriage over time by decreasing future expectation in the 9th grade. CONCLUSIONS: Our results support the idea that helping youth develop positive attitude about educational success may help reduce firearm carriage. Increasing positive expectations about future may help prevent firearm carriage within the context of violence exposure.
Subject(s)
Exposure to Violence/psychology , Firearms/statistics & numerical data , Violence/prevention & control , Adolescent , Exposure to Violence/statistics & numerical data , Female , Humans , Longitudinal Studies , Male , Risk-Taking , Violence/trendsABSTRACT
While racial discrimination (RD) is associated with increased alcohol-related problems among African Americans (AAs), researchers have not examined how RD contributes to the physical consequences of alcohol consumption over time. In addition, the protective role of religious coping has been discussed but not formally tested in pathways connecting RD to the physical consequences of alcohol consumption. To address this gap, we estimated latent growth mediation models in a sample of 465 AA emerging adults. We found that RD increased physical consequences of alcohol consumption over time through psychological distress. After identifying two profiles of religious coping (i.e., low and high religious coping), RD indirectly influenced the physical consequences of alcohol consumption through psychological distress among AAs in the low religious coping group. Our results signal the importance of developing alcohol-misuse prevention programs that address the psychological consequences of RD. Integrating culturally tailored coping strategies (e.g., religious coping) may bolster the efficacy of these prevention programs.
Subject(s)
Adaptation, Psychological , Alcohol Drinking/ethnology , Black or African American/ethnology , Psychological Distress , Racism/ethnology , Religion and Psychology , Stress, Psychological/ethnology , Adolescent , Adult , Female , Humans , Male , Models, Statistical , Protective Factors , Young AdultABSTRACT
BACKGROUND: Evidence of the effectiveness of social prescribing is inconclusive causing commissioning challenges. This research focusses on a social prescribing scheme in Northern England which deploys 'Wellbeing Coordinators' who offer support to individuals, providing advice on local groups and services in their community. The research sought to understand the outcomes of the service and, in addition, the processes which supported delivery. METHODS: Quantitative data was gathered from service users at the point they entered the service and also at the point they exited. Qualitative interviews were also undertaken with service users to gather further understanding of the service and any positive or negative outcomes achieved. In addition, a focus group discussion was also conducted with members of social prescribing staff to ascertain their perspectives of the service both from an operational and strategic perspective. RESULTS: In total, 342 participants provided complete wellbeing data at baseline and post stage and 26 semi-structured qualitative interviews were carried out. Improvements in participants' well-being, and perceived levels of health and social connectedness as well as reductions in anxiety was demonstrated. In many cases, the social prescribing service had enabled individuals to have a more positive and optimistic view of their life often through offering opportunities to engage in a range of hobbies and activities in the local community. The data on reductions in future access to primary care was inconclusive. Some evidence was found to show that men may have greater benefit from social prescribing than women. Some of the processes which increased the likelihood of success on the social prescribing scheme included the sustained and flexible relationship between the service user and the Wellbeing Coordinator and a strong and vibrant voluntary and community sector. CONCLUSIONS: Social prescribing has the potential to address the health and social needs of individuals and communities. This research has shown a range of positive outcomes as a result of service users engaging with the service. Social prescribing should be conceptualised as one way to support primary care and tackle unmet needs.
Subject(s)
Social Work , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Delivery of Health Care , England , Female , Focus Groups , Humans , Male , Middle Aged , Primary Health Care/organization & administration , Qualitative Research , Social Work/organization & administration , Surveys and QuestionnairesABSTRACT
We used a GIS analysis of sodium and chloride concentrations in private water wells in a southeastern New York township to describe the pattern of distribution of road salt in aquifers tapped for drinking water. The primary source of road salt was sodium chloride, and sodium and chloride concentrations were significantly correlated ( = 0.80, < 0.01). Chloride concentrations in wells increased as the percentage of impervious surface cover (ISC) within a 250-m radius around wells increased ( = 0.87, < 0.01) and declined with increasing distance to the nearest road ( = 0.76, < 0.01). Wells that were located lower in elevation than the nearest road had higher concentrations of chloride than wells that were higher than the nearest road, but this occurred only when the nearest road was >30 m from the wells ( < 0.01). Chloride concentrations were not affected by well depth or adjacent road type (major or minor roads). Surface geology and hydrologic soil class had significant effects ( < 0.01) on chloride concentrations in wells, with porous surface geology types and well-drained soils having higher concentrations; these effects may be confounded by the fact that ISC was more likely to occur on these permeable surface geology and soil types. Hot and cold spot analysis revealed substantial unevenness in chloride concentrations. Results for sodium were similar to those for chloride. Overall, these results indicate that road salt contamination of groundwater is unevenly distributed and is affected by landscape factors that can be used to guide well testing and best management practices of deicing salt distribution.
Subject(s)
Drinking Water , Sodium Chloride/analysis , Water Pollutants, Chemical/analysis , Environmental Monitoring , New YorkABSTRACT
This study addresses whether providing housing vouchers through the Family Unification Program (FUP) to families involved in the child welfare system reduces child maltreatment and the need for child welfare services. The study uses child welfare administrative data on 326 children in Portland, Oregon, and 502 children in San Diego, California from the point at which their families were referred to the program through 18 months post-referral. Using a quasi-experimental waitlist comparison design, probit regressions show little impact of FUP on preventing child removal from home, but some positive impact on reunification among children already placed out of home. Hazard estimations show receipt of FUP speeds up child welfare case closure. Impacts on new reports of abuse and neglect are mixed, but point toward reduced reports. Low rates of removal among intact comparison families and high rates of reunification for children in out-of-home care suggest poor targeting of housing resources. Housing vouchers are being given to families not bearing the risks the program is intended to address. The presence of some positive findings suggests that housing vouchers might help reduce child welfare involvement if better targeting were practiced by child welfare agencies.
Subject(s)
Child Abuse , Child Protective Services , Child Welfare , Family , Housing , Ill-Housed Persons , Public Assistance , Adult , California , Case-Control Studies , Child, Preschool , Female , Humans , Infant , Male , Oregon , Proportional Hazards Models , Regression Analysis , Waiting ListsABSTRACT
The goal of this study was to compare outcomes for robotic, laparoscopic, and open hysterectomy procedures for endometrial cancer as well as to investigate whether specific patient demographic, comorbidity, and severity variables were associated with the type of hysterectomy performed. A retrospective review was conducted of hysterectomy procedures for patients discharged from October 1, 2008 and September 30, 2012. Preoperative characteristics included age, BMI, number of past abdominal surgeries, and comorbidities. Intraoperative and postoperative characteristics included uterine weight and diameter, American Society of Anesthesiologists physical status classification, lymph-vascular space involvement, FIGO stage and tumor grade. Outcomes included operative time, estimated blood loss, length of stay, conversion to open, other intraoperative and postoperative complications, readmissions within 30 days and lymph node yield. The robotic and laparoscopic cohorts show no significant differences in patient or tumor characteristics, while the open cases represent patients with increased complexity. In general, laparoscopic cases were shorter than robotic and open cases. Laparoscopic cases had fewer conversions to open than robotic cases. Robotic and open cases had significantly higher lymph node yield than laparoscopic cases. The reduction in surgical time and conversion rates in the laparoscopic cohort may be related to the reduction in node dissection performed.
Subject(s)
Endometrial Neoplasms/surgery , Hysterectomy/methods , Laparoscopy/methods , Robotic Surgical Procedures/methods , Blood Loss, Surgical , Conversion to Open Surgery/statistics & numerical data , Female , Humans , Length of Stay/statistics & numerical data , Lymph Node Excision/methods , Lymphatic Metastasis , Middle Aged , Operative Time , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: In 2015, the US Food and Drug Administration issued warning letters to three tobacco companies regarding use of the terms 'natural' and/or 'additive-free' to describe their products, as these terms inaccurately convey reduced harm. Yet, tobacco companies engage in a variety of alternate techniques to attempt to convey the same 'natural' (and thus reduced harm) message. It is critical to monitor these practices to inform regulatory action. OBJECTIVE: To describe the marketing techniques used in Natural American Spirit (American Spirit) ads that could convey a natural and less harmful product image. METHODS: Trained coders content analysed 142 American Spirit ads from 2012 to 2016. RESULTS: In addition to use of the terms 'natural' and 'additive-free', American Spirit ads engage in a variety of other linguistic and iconic techniques that could convey reduced harm, such as references to small, local or organic farming, eco-friendly practices, and plant, farming and other nature-related imagery. CONCLUSIONS: American Spirit ads use a wide range of marketing techniques to convey a natural product image, which could subsequently communicate reduced harm.
Subject(s)
Advertising/methods , Smoking , Tobacco Industry/methods , Tobacco Products , Advertising/standards , Humans , Marketing/methods , Marketing/standards , Smoking/adverse effects , Smoking/psychology , Tobacco Industry/standards , United States , United States Food and Drug AdministrationABSTRACT
PURPOSE: The study assessed the outcomes of patients at a single institution with locally advanced primary and recurrent pelvic malignancies treated with interstitial high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy (BT), using a modified Syed-Neblett template. MATERIAL AND METHODS: Between 1996 and 2010, 60 patients with primary or recurrent pelvic malignancies were treated with interstitial BT. Thirty three patients had primary malignancies with 6.1% being stage I, 33.3% stage II, 45.5% stage III, and 15.2% stage IV; the remaining 27 patients were recurrent malignancies. Fifty four patients received external beam radiotherapy (EBRT) as part of their treatment course. The median EBRT, BT, and EBRT + BT doses were 45 Gy, 20 Gy, and 65 Gy, respectively. Thirty eight patients received concurrent chemotherapy with EBRT. Complete response (CR) was defined by absence of clinical and radiographic disease on first follow-up. Toxicity was graded as per Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The median follow-up was 37 months (4-234 months) and initial CR was achieved in 91%. For primary cancers at diagnosis, 5-year local control (LC), 5-year progression-free survival (PFS), 5-year overall survival (OS) were 65%, 64%, and 42% respectively. For recurrent cancers at diagnosis, 5-year LC, 5-year PFS, and 5-year OS were 80%, 51%, and 37%, respectively. There was a significant difference in both OS and PFS among different tumor sites (p < 0.05), with vaginal cancers having the best 5-year OS (55%) and PFS (84%). There was a total of 1 acute toxicity ≥ grade 3, 6 late grade 3 toxicities, and late grade 4 toxicity. CONCLUSIONS: Our series suggests that interstitial BT using a modified Syed-Neblett template is a safe and effective treatment for primary or recurrent pelvic malignancies. This technique allowed effective LC and 97% of patients had preservation of both bladder and rectal function.
ABSTRACT
A retrospective cohort study was performed to evaluate the relationship of BMI to conversion rate in patients undergoing robotic surgery for endometrial cancer. Secondary outcomes were operative times, number of lymph nodes retrieved, and complications. Women with endometrial cancer scheduled for robotic surgery from September 2008 to September 2012 were included. Women were divided into three groups based on BMI, and conversion rates to laparotomy were compared. Descriptive and comparative analyses were performed among non-obese, obese, and morbidly obese women who completed robotic surgery. 298 women were scheduled for robotic surgery for endometrial carcinoma: 87 non-obese (BMI 19-29, µ 25.23), 110 obese (BMI 30-39, µ 34.21), and 101 morbidly obese (BMI 40-71, µ 47.38). Conversion to laparotomy occurred in 18 patients (6%), with no difference in conversion rate between BMI categories. Direct comparison between converted and completed robotic patients showed no significant differences in preoperative characteristics, except that patients who required conversion had a higher number of previous abdominal surgeries. Patients completing robotic surgery underwent node dissections at similar rates in all three BMI categories. Operating room time, but not surgical time, was increased in morbidly obese patients. There were no significant differences in complications, performance of lymphadenectomy, or lymph node yields between BMI categories. Increase in BMI was not associated with an increase in rate of conversion to laparotomy or complication rate in patients undergoing robotic surgery for endometrial carcinoma. Node dissections were pathologically equivalent between BMI categories.
Subject(s)
Endometrial Neoplasms , Obesity/complications , Postoperative Complications/epidemiology , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/statistics & numerical data , Adult , Aged , Aged, 80 and over , Body Mass Index , Endometrial Neoplasms/complications , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/surgery , Female , Humans , Middle Aged , Obesity/epidemiology , Retrospective StudiesABSTRACT
There is growing acknowledgement that housing can provide more than shelter, a basic need. Housing can also act as a foundation, helping families stay together.The provision of housing as a prevention or protective strategy against child maltreatment has not been widely used by child welfare agencies. A small subset of child welfare agencies across the country, however, is incorporating housing into their response to cases of child abuse and neglect. Using qualitative data from ongoing studies of HUD's Family Unification Program (FUP) and the Children's Bureau supportive housing demonstration for high-need child welfare involved families, we describe some of the promising practices agencies are implementing and testing. Though evaluations of these programs are not yet complete, there is a lot the field can learn from these approaches. This paper provides an overview of seven promising strategies: (1) partnering with public housing agencies and leveraging resources; (2) assessing the housing needs of child welfare involved families; (3) triaging and providing housing resources based on needs; (4) providing housing first, not. last; (5) developing housing stability plans and shared case plans; (6) screening families into housing, rather than screening out; and (7) providing housing search assistance.
Subject(s)
Child Welfare , Family Characteristics , Housing , Ill-Housed Persons , Social Work , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , United StatesABSTRACT
The Mirk/dyrk1B gene is commonly amplified or upregulated in ovarian cancers, and Mirk is an active kinase in these cancers. Mirk mediates cancer cell survival by decreasing toxic ROS levels through maintaining expression of a series of antioxidant genes, possibly through its transcriptional activator functions. Mirk has the unusual property of being most active in quiescent cancer cells because of marked transcriptional downregulation by Akt/mTOR signaling and by MEK/erk signaling in cycling cells. Metastatic ovarian cancer cells form ascites, non-adherent multicellular aggregates floating within the peritoneal fluid. Most ascites cancer cells are in a reversible quiescent, dormant state, suggesting that Mirk might be expressed in these quiescent cells and thus a therapeutic target. The current studies show that ovarian cancer cell line spheroids that mimic ascites cancer spheroids were largely quiescent in G0/G1, and enriched in Mirk and the quiescence proteins, p130/Rb2 and the CDKI p27. Mirk kinase inhibition in spheroids made from established cell lines and in patient-derived ascites cancer cell spheroids reduced spheroid volume, disrupted spheroid structure to single cells, increased apoptosis, and decreased cell numbers. Earlier studies had shown that the mTOR inhibitor RAD001 increased transcription of the Mirk/dyrk1B gene, so treatments combined RAD001 with the most active Mirk kinase inhibitor. The number of ascites cells from 9 patients was reduced a similar amount by cisplatin, Mirk kinase inhibition or RAD001, but reduced substantially more, about 90%, by concurrent treatment with both the Mirk kinase inhibitor EHT5372 and RAD001. Addition of RAD001 increased the amount of toxic ROS induced by Mirk kinase inhibition. Two ascites samples taken one month apart gave similar drug responses, showing reproducibility of the techniques. Thus Mirk/dyrk1B kinase may be a therapeutic target in ovarian cancer ascites.
ABSTRACT
Sensitivity to habitat fragmentation often has been examined in terms of thresholds in landscape composition at which a species is likely to occur. Observed thresholds often have been low or absent, however, leaving much unexplained about habitat selection beyond initial thresholds of occurrence, even for species with strong habitat preferences. We examined responses to varying amounts of tree cover, a widely influential measure of habitat loss, for 40 woodland bird species in a mixed woodland/grassland landscape in eastern North Dakota, USA. We used LOESS smoothing to describe incidence for each species at three scales: within 200, 400, and 1200 m around sample locations. For the 200-m scale, we also calculated the most-preferred range of tree cover (within which at least half of observations were predicted to occur) for each species. Only 10 of 40 species had occurrence thresholds greater than about 10% tree cover. After initial occurrence, species showed three general patterns: some increased monotonically with tree cover; some increased up to an asymptote; some peaked at intermediate amounts of tree cover and then declined. These patterns approximate selection for interior woodlands and for edge-rich environments, but incidence plots provide greater detail in landscape-scale selection than do those categories. For most species, patterns persisted at larger scales, but for some, larger scales had distinctly different patterns than local scales. Preferred ranges of tree cover varied from <20% tree cover (common grackle, Quiscalus quiscula) to >60% (veery, Catharus fuscescens). We conclude that incidence patterns provide more information on habitat selection than do threshold measures for most species: in particular, they differentiate species preferring concentrated woodlands from those preferring mixed landscapes, and they show contrasting degrees of selectiveness. [Correction added on 16 October 2012, after first online publication: the Abstract section has been reworded].
ABSTRACT
OBJECTIVE: We sought to examine the effects of bronchodilator treatment on the incidence of postoperative atrial fibrillation (POAF) after cardiac surgery. METHODS: A cross-sectional design using a retrospective chart review was performed in patients who underwent cardiac surgery. Those who had previous atrial fibrillation or preoperative bronchodilator treatment were excluded from the final sample (n = 506). The Statistical Package for the Social Sciences (SPSS, Inc., Chicago, IL) was used for statistical analyses. RESULTS: The incidence of POAF in this study was 27.9%, and was associated with age (P < .01) and type of cardiac surgery (P < .05), indicating that increasing age, and combined cardiac surgery were more likely to precipitate POAF. Bronchodilator treatment did not increase POAF. However, combined therapy significantly (P < .01) precipitated more POAF (48.7%) than did albuterol (21.4%) or levalbuterol (18.5%). CONCLUSIONS: Postoperative atrial fibrillation continues to be a common complication after cardiac surgery. Bronchodilator treatment with either albuterol or levalbuterol did not precipitate POAF, unless both agents were given to the same patients postoperatively.
Subject(s)
Atrial Fibrillation/epidemiology , Bronchodilator Agents/pharmacology , Cardiac Surgical Procedures/adverse effects , Postoperative Care/methods , Atrial Fibrillation/drug therapy , Atrial Fibrillation/etiology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Missouri/epidemiology , Retrospective Studies , Treatment OutcomeABSTRACT
MicroRNAs (miRNAs) are non-coding regulatory RNA molecules that bind target messenger RNAs (mRNA) and suppress their translation into proteins. When an organism is exposed to a toxic compound, cells respond by altering the pattern of gene expression, including miRNAs. Altered miRNA expression affects protein translation, which in turn alters cellular physiology causing adverse biological effects. Moreover, different types of cellular stress have been shown to affect miRNA expression as a mechanism of adaptation or tolerance to stress factors in order to survive. Besides an updated theoretical background concerning miRNAs biology, biogenesis, function, and roles in disease; this mini review provides an overview of miRNAs response to exogenous agents such as environmental stressors and toxic compounds. The implications of miRNAs in toxicogenomics as well as the new avenues of research of miRNAs in toxicology are discussed.
Subject(s)
Gene Expression Regulation , MicroRNAs/physiology , Toxicogenetics/methods , Animals , Gene Expression Regulation/physiology , Humans , MicroRNAs/biosynthesis , MicroRNAs/genetics , RNA Processing, Post-Transcriptional , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
STUDY DESIGN: Retrospective study of patients enrolled in a prospective randomized Food and Drug Administration trial with single level cervical disc replacement (CDR) with the ProDisc-C (Synthes, Paoli, PA). OBJECTIVE: Evaluate the segmental range of motion (ROM) in the cervical spine pre- and postoperative after CDR. SUMMARY OF BACKGROUND INFORMATION: Each cervical level is believed to have its own biomechanical characteristics, ultimately leading to different sagittal and lateral ROM. Our understanding of the factors that influence motion after CDR continues to change and expand. METHODS: One hundred sixty-four patients with single level ProDisc-C arthroplasty were evaluated radiographically using Medical Metrics (QMATM, Medical Metrics, Inc., Houston, TX). Pre- and postoperative disc height and ROM were measured from standing lateral and flexion-extension radiographs. Of these 164 patients, 44 had a CDR at C6/C7, 96 at C5/C6, 18 at C4/C5, and 6 at C3/C4. The mean follow-up was of 24 months. Statistical analysis evaluated the difference in mean ROM between the groups. RESULTS: Before surgery, C4/C5 had more sagittal ROM compared with C3/C4, C5/C6, and C6/C7 (P < 0.001.) Before surgery, C4/C5 also had more lateral ROM compared with C3/C4, C5/C6, and C6/C7 (P = 0.015). After surgery, there were no significant differences in sagittal and lateral ROM between C3/C4, C4/C5, C5/C6, and C6/C7. The delta (difference between pre- and postoperative) proved that the C4/C5 CDR actually lost sagittal ROM (-2.5 degrees ) compared with the other levels, which gained sagittal ROM, C3/C4 (0.9 degrees ), C5/C6 (1.8 degrees ), and C6/C7 (1.6 degrees ); P = 0.037. There was no significant difference in the delta lateral ROM between the segments: C3/C4, C4/C5, C5/C6, and C6/C7. CONCLUSION: CDR approximates the different segmental sagittal and lateral ROM. Although C4/C5 had negative delta ROM in the sagittal and lateral planes, it provided a satisfactory final ROM. Long-term clinical outcome studies are needed to properly evaluate if these differences could ultimately affect the patients everyday life.
Subject(s)
Cervical Vertebrae/physiology , Cervical Vertebrae/surgery , Diskectomy/instrumentation , Intervertebral Disc Displacement/surgery , Prosthesis Implantation/instrumentation , Spondylosis/surgery , Adult , Aged , Cervical Vertebrae/pathology , Cohort Studies , Diskectomy/methods , Female , Humans , Intervertebral Disc/anatomy & histology , Intervertebral Disc/physiology , Intervertebral Disc/surgery , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/pathology , Male , Middle Aged , Outcome Assessment, Health Care/methods , Prospective Studies , Prostheses and Implants/standards , Prostheses and Implants/statistics & numerical data , Prosthesis Implantation/methods , Radiography , Range of Motion, Articular/physiology , Recovery of Function/physiology , Retrospective Studies , Spondylosis/diagnostic imaging , Spondylosis/pathology , Treatment Outcome , Zygapophyseal Joint/anatomy & histology , Zygapophyseal Joint/physiology , Zygapophyseal Joint/surgeryABSTRACT
STUDY DESIGN: Systematic review of cohort studies comparing surgical treatment options for cervical spondylotic myelopathy. OBJECTIVE: Compare results of major surgical treatments. SUMMARY OF BACKGROUND DATA: Controversy exists between various surgical options for the treatment of multilevel cervical spondylotic myelopathy, including multilevel corpectomy (CORP) and fusion, anterior cervical discectomy and fusion, laminoplasty (LAMP), and laminectomy and fusion (LAMI). A systematic review was done in order to compare results and complications among these procedures. METHODS: Systematic review of retrospective cohort studies comparing anterior cervical discectomy and fusion (ACDF), CORP, LAMP, and LAMI from 1980 to January 2008. Separately, a review was performed of case series with greater than 10-year follow-up. RESULTS: About 1735 articles found initially, 591 abstracts screened, 36 articles retrieved in full, 11 studies included in review. All comparison studies are retrospective cohort studies. Four studies compared multilevel CORP versus LAMP, 1 study compared LAMI with LAMP, and 2 studies compared ACDF with LAMP. There were 3 case studies with greater than 10-year follow-up. CONCLUSION: All approaches yield similar neuro recovery rates. Laminoplasty has a significant incidence of neck pain compared with multilevel CORP. ACDFs increase the rate of adjacent secondary spondylosis compared with LAMP. Multilevel CORP and laminectomy with fusion have a significantly higher rate of graft, instrumentation, and approach related complications. Multilevel CORP and laminectomy with fusion have a significant decrease in range of motion of neck compared with LAMP.
Subject(s)
Cervical Vertebrae/surgery , Spondylosis/surgery , Cohort Studies , Humans , Laminectomy/methods , Spinal Fusion/methods , Treatment OutcomeABSTRACT
STUDY DESIGN: Prospective inter-rater and intrarater reliability analysis. OBJECTIVE: To compare the inter-rater and intrarater reliability of magnetic resonance imaging (MRI) and computed tomography (CT) for grading of facet arthropathy as well as determining whether there is a contraindication to total disc replacement (TDR). SUMMARY OF BACKGROUND DATA: Several classifications attempted to evaluate lumbar facet joints and their degree of arthropathy. The Fujiwara-MRI and Pathrea-CT classifications remain the most commonly used. METHODS: A total of 10 fellowship-trained orthopedic spine surgeons and 3 orthopedic spine fellows evaluated 50 levels from L3-L4 through L5-S1 on parallel axial MRI (T1 and T2) and CT images. The degree of osteoarthritis was graded on a 4-point scale (Fujiwara-MRI and Pathrea-CT). Surgeons evaluated whether the degree of facet disease represented a contraindication to TDR. Grading was performed during 2 sessions. Weighted kappa statistics were used to describe inter- and intraobserver agreement. RESULTS: The inter-rater reliability for MRI was 0.21 and 0.07 (fair to slight) among attendings and fellows, respectively. inter-rater reliability for CT was 0.33 and 0.27 (fair), respectively. The mean intrarater reliability for MRI was fair, 0.36 (attendings) and 0.26 (fellows). The mean intrarater reliability for CT was moderate, 0.52 (attendings) and 0.51 (fellows). For possible TDR contraindication, the inter-rater reliability for MRI was 0.22 and 0.01 (fair to slight) among attendings and fellows, respectively. Inter-rater reliability for CT was 0.33 and 0.45 (fair), respectively. The mean intrarater reliability for MRI was fair, 0.36 (attendings) and 0.26 (fellows). The mean intrarater reliability for CT was moderate, 0.52 (attendings) and 0.51 (fellows). CONCLUSION: The current grading system for facet arthropathy has only fair agreement. CT is slightly more reliable for grading. Intrarater reliability was only fair for MRI and moderate for CT. Only limited agreement existed between surgeons as to the extent of facet disease that would pose as a contraindication for TDR.