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1.
Article in English | MEDLINE | ID: mdl-38816189

ABSTRACT

BACKGROUND: Understanding the sequential progression of cognitive impairments in Parkinson's disease (PD) is crucial for elucidating neuropathological underpinnings, refining the assessment of PD-related cognitive decline stages and enhancing early identification for targeted interventions. The first aim of this study was to use an innovative event-based modeling (EBM) analytic approach to estimate the sequence of cognitive declines in PD. The second aim was to validate the EBM by examining associations with EBM-derived individual-specific estimates of cognitive decline severity and performance on independent cognitive screening measures. METHODS: This cross-sectional observational study included 99 people with PD who completed a neuropsychological battery. Individuals were classified as meeting the criteria for mild cognitive impairment (PD-MCI) or subtle cognitive decline by consensus. An EBM was constructed to compare cognitively healthy individuals with those with PD-MCI or subtle cognitive disturbances. Multivariable linear regression estimated associations between the EBM-derived stage of cognitive decline and performance on two independent cognitive screening tests. RESULTS: The EBM estimated that tests assessing executive function and visuospatial ability become abnormal early in the sequence of PD-related cognitive decline. Each higher estimated stage of cognitive decline was associated with approximately 0.24 worse performance on the Dementia Rating Scale (p<0.001) and 0.26 worse performance on the Montreal Cognitive Assessment (p<0.001) adjusting for demographic and clinical variables. CONCLUSION: Findings from this study will have important clinical implications for practitioners, on specific cognitive tests to prioritise, when conducting neuropsychological evaluations with people with PD. Results also highlight the importance of frontal-subcortical system disruption impacting executive and visuospatial abilities.

2.
Laryngoscope ; 134(5): 2262-2268, 2024 May.
Article in English | MEDLINE | ID: mdl-37983884

ABSTRACT

OBJECTIVE: Patients undergoing laryngectomy are particularly vulnerable to postoperative complications secondary to social and nutritional barriers, substance abuse, and prior cancer treatment. Enhanced Recovery After Surgery (ERAS) programs may mitigate this vulnerability and improve postoperative complications and oncologic outcomes. The objective of this study is to evaluate the postoperative complication rate and oncologic outcomes of patients undergoing laryngectomy before and after ERAS program implementation. METHODS: A historic cohort of 50 patients who underwent laryngectomy at the Levine Cancer Institute, Charlotte, North Carolina from 2014 to 2019 (pre-ERAS) was compared to 33 patients who underwent laryngectomy after ERAS implementation from 2019 to 2020. The primary outcomes included length of stay (LOS), Clavien-Dindo postoperative complications through 30 days following discharge, overall survival (OS), and recurrence-free survival between pre-ERAS and ERAS groups. RESULTS: Demographic characteristics between the two groups were similar. ERAS pathway implementation led to core care element consistency and improvement in the clinical perioperative course, including preoperative nutritional intervention (p = 0.009), postoperative ventilator independence (p = 0.0004), and refractory nausea/emesis (p = 0.18). Severe (≥ grade 3) complications (p = 0.49) and LOS (p = 0.68) were similar between groups. No significant difference in Cox proportional modeling of OS (p = 0.60) or recurrence-free survival (p = 0.17) was noted. CONCLUSIONS: ERAS did not improve LOS, major postoperative complications, or oncologic outcomes in this cohort of patients who underwent laryngectomy. However, ERAS positively influenced secondary endpoints within the laryngectomy perioperative course, conferring qualitative health care benefits. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2262-2268, 2024.


Subject(s)
Enhanced Recovery After Surgery , Humans , Laryngectomy , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Period , Preoperative Care , Length of Stay , Retrospective Studies , Perioperative Care
3.
Brain Imaging Behav ; 18(1): 57-65, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37855955

ABSTRACT

Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in Parkinson's disease (PD). Studies have focused on the role of basal ganglia PVS with cognition in PD, but the role of white matter PVS is unknown. This study examined the relationship of white matter and basal ganglia PVS with domain-specific and global cognition in individuals with PD. Fifty individuals with PD underwent 3T T1w magnetic resonance imaging (MRI) to determine PVS volume fraction, defined as PVS volume normalized to total regional volume, within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of global cognitive function (Montreal Cognitive Assessment, and global cognitive composite score), and cognitive-specific domains (executive function, memory, visuospatial function, attention, and language). Higher white matter rostral middle frontal PVS was associated with lower scores in both global cognitive and visuospatial function. In the basal ganglia higher PVS was associated with lower scores for memory with a trend towards lower global cognitive composite score. While previous reports have shown that greater amount of PVS in the basal ganglia is associated with decline in global cognition in PD, our findings suggest that increased white matter PVS volume may also underlie changes in cognition.


Subject(s)
Glymphatic System , Parkinson Disease , White Matter , Humans , Parkinson Disease/complications , White Matter/pathology , Glymphatic System/diagnostic imaging , Glymphatic System/pathology , Magnetic Resonance Imaging/methods , Cognition , Basal Ganglia/diagnostic imaging
4.
Ann Plast Surg ; 91(6): 679-685, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37856209

ABSTRACT

BACKGROUND: Tissue expanders in breast reconstruction are traditionally placed retropectoral. Increasingly, patients are undergoing prepectoral placement. The impact of this placement on the initiation of adjuvant treatment is unknown. METHODS: A retrospective review was conducted to identify women diagnosed with breast cancer who underwent mastectomy followed by radiation and/or chemotherapy. Women were divided into 3 groups: prepectoral tissue expander placement, retropectoral tissue expander placement, and no immediate reconstruction. A treatment delay was defined as greater than 8 weeks between tissue expander placement and adjuvant therapy. RESULTS: Of 634 women, 205 (32%) underwent tissue expander placement, and 429 (68%) did not have immediate reconstruction. Of those with tissue expanders placed, 84 (41%) had prepectoral placement, and 121 (59%) had retropectoral placement. The median time to adjuvant therapy was 49 days for the entire cohort: no reconstruction, 47 days; prepectoral, 57 days; and retropectoral, 55 days. Treatment delays were observed in 34% of women: no reconstruction, 28%; prepectoral, 51%; and retropectoral, 46% ( P < 0.001). Tissue expander placement was associated with a delay to adjuvant therapy when compared with no reconstruction ( P < 0.001). The location of the tissue expander did not impact the odds of having a delay. On multivariable analysis, having reconstruction, having postoperative infection, not undergoing chemotherapy treatment, and being a current smoker were associated with a delay to adjuvant therapy. A delay to treatment was not associated with worse survival. CONCLUSIONS: Placement of a tissue expander delayed adjuvant therapy. The location of tissue expander placement, retropectoral versus prepectoral, did not impact the time to adjuvant treatment.


Subject(s)
Breast Implants , Breast Neoplasms , Mammaplasty , Humans , Female , Breast Neoplasms/surgery , Mastectomy , Tissue Expansion Devices , Combined Modality Therapy , Retrospective Studies , Postoperative Complications/surgery
5.
Brain Struct Funct ; 228(8): 1865-1884, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37306809

ABSTRACT

The basal ganglia are important modulators of the cognitive and motor benefits of exercise. However, the neural networks underlying these benefits remain poorly understood. Our study systematically analyzed exercise-associated changes in metabolic connectivity in the cortico-basal ganglia-thalamic network during the performance of a new motor task, with regions-of-interest defined based on mesoscopic domains recently defined in the mouse brain structural connectome. Mice were trained on a motorized treadmill for six weeks or remained sedentary (control), thereafter undergoing [14C]-2-deoxyglucose metabolic brain mapping during wheel walking. Regional cerebral glucose uptake (rCGU) was analyzed in 3-dimensional brains reconstructed from autoradiographic brain sections using statistical parametric mapping. Metabolic connectivity was assessed by calculating inter-regional correlation of rCGU cross-sectionally across subjects within a group. Compared to controls, exercised animals showed broad decreases in rCGU in motor areas, but increases in limbic areas, as well as the visual and association cortices. In addition, exercised animals showed (i) increased positive metabolic connectivity within and between the motor cortex and caudoputamen (CP), (ii) newly emerged negative connectivity of the substantia nigra pars reticulata with the globus pallidus externus, and CP, and (iii) reduced connectivity of the prefrontal cortex (PFC). Increased metabolic connectivity in the motor circuit in the absence of increases in rCGU strongly suggests greater network efficiency, which is also supported by the reduced involvement of PFC-mediated cognitive control during the performance of a new motor task. Our study delineates exercise-associated changes in functional circuitry at the subregional level and provides a framework for understanding the effects of exercise on functions of the cortico-basal ganglia-thalamic network.


Subject(s)
Connectome , Humans , Mice , Animals , Basal Ganglia/metabolism , Brain , Globus Pallidus , Prefrontal Cortex , Neural Pathways , Magnetic Resonance Imaging
6.
Vaccine X ; 14: 100289, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37020982

ABSTRACT

Purpose: Cancer patients are at high risk of developing severe illness from SARS-CoV-2 infection, but risk is lowered with receipt of COVID-19 vaccine. COVID-19 vaccination uptake among previously infected cancer patients may be influenced by an assumption of natural immunity, predicted weak immune response, or concerns about vaccine safety. The objective of this study was to evaluate COVID-19 vaccine uptake trends in cancer patients previously infected with SARS-CoV-2. Materials and Methods: Medical records of 579 sequential cancer patients undergoing active treatment at Levine Cancer Institute who tested positive for COVID-19 between January 2020 and January 2021 were evaluated. Patients who died prior to vaccine eligibility were excluded from the analysis. Demographic, clinical, and COVID-19 related characteristics were analyzed to identify prognostic factors for COVID-19 vaccine uptake as this information could be important for health policy design for future pandemics. Results: Eighty-one patients died prior to the availability of COVID-19 vaccines. The acceptance rate of COVID-19 vaccination among 498 previously infected cancer patients was 54.6%. Of the patients with known vaccination dates, 76.8% received their first vaccine by April 17th, 2021. As of November 30, 2021, 23.7.% of eligible patients were boosted. In univariate models, older age, female sex, higher income, solid tumor cancer type, and hormone therapy were significantly associated with higher vaccine uptake, while Hispanic/Latino ethnicity was significantly associated with lower vaccine uptake. In a multivariable model, age (OR 1.18, 95% CI 1.10-1.28; p < 0.001), female sex (OR 1.80, 95% CI 1.22-2.66; p = 0.003), and higher income (OR 1.11, 95% CI 1.01-1.22; p = 0.032), were predictive of COVID-19 vaccine uptake. Conclusions: Overall, vaccine uptake was low among our cohort of previously infected cancer patients. Older age, female sex, and higher income were the only variables associated with COVID-19 vaccine uptake within this vulnerable patient population.

7.
Transl Androl Urol ; 12(2): 228-240, 2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36915891

ABSTRACT

Background: Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are carbohydrate binding proteins with a wide range of biological activity, including regulation of cellular adhesion, proliferation, and apoptosis in solid tumors. Prior small studies have reported that Gal-3 expression is associated with progression of disease in urothelial carcinoma (UC), from non-muscle invasive UC progression to muscle invasive UC. We assessed Gal-1 and Gal-3 protein expression H-score utilizing a tissue microarray (TMA) created from 301 cystectomy specimens. Methods: Immunohistochemistry for Gal-1 and Gal-3 was performed on TMA generated from tumor blocks from chemotherapy naïve cystectomy specimens. The variable of interest, H-score, was defined as the product of the percentage of cells staining positive (0-100) and intensity score (0-3) scored by a single pathologist. Survival end points were analyzed using Kaplan-Meier and Cox Proportional Hazards methods. Clinical data including Charlson Comorbidity Index (CCI), pathologic tumor (T) stage, tumor size, node stage, and surgical margins, were included in multivariable analysis. Results: We found that Gal-1 and Gal-3 expression correlated with intratumoral T stage (median Gal-1 H-score was 0 across non-invasive tissue types and 200 in invasive, P<0.01 and median Gal-3 score was 270 across non-invasive tissue types and 70 in invasive, P<0.01). However, the highest intratumoral H-score per cystectomy core did not independently predict for recurrence-free survival (RFS) (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.65) or OS (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.72) in this cohort. Significant intratumoral heterogeneity was present for both Gal-1 and Gal-3, with an average difference between the highest and lowest H score was 95 for Gal-1 and 109 for Gal-3 for cystectomy specimens with more than one biopsy. Conclusions: Gal-1 and Gal-3 H-score per bladder did not independently predict for RFS or OS. Intra-tumoral Gal-1/Gal-3 heterogeneity complicates the use of Gal-1 and Gal-3 expression as a prognostic biomarker. Future studies should consider the evaluation of serum and urinary galectins as an approach to mitigate tumor heterogeneity.

8.
Curr Oncol ; 30(2): 2482-2492, 2023 02 18.
Article in English | MEDLINE | ID: mdl-36826150

ABSTRACT

The National Surgical Quality Improvement Project (NSQIP) dataset was used to identify perioperative variables associated with the length of stay (LOS) and early discharge among cancer patients undergoing colectomy. Patients who underwent non-emergent right colectomy for colon cancer from 2012 to 2019 were identified from the NSQIP and colectomy-targeted databases. Postoperative LOS was analyzed based on postoperative day (POD) of discharge, with patients grouped into Early Discharge (POD 0-2), Standard Discharge (POD 3-5), or Late Discharge (POD ≥ 6) cohorts. Multivariable ordinal logistic regression was performed to identify risk factors associated with early discharge. The NSQIP query yielded 26,072 patients: 3684 (14%) in the Early Discharge, 13,414 (52%) in the Standard Discharge, and 8974 (34%) in the Late Discharge cohorts. The median LOS was 4.0 days (IQR: 3.0-7.0). Thirty-day readmission rates were 7% for Early Discharge, 8% for Standard Discharge, and 12% for Late Discharge. On multivariable regression analysis, risk factors significantly associated with a shorter LOS included independent functional status, minimally invasive approach, and absence of ostomy or additional bowel resection (all p < 0.001). Perioperative variables can be used to develop a model to identify patients eligible for early discharge after right colectomy for colon cancer. Efforts to decrease the overall median length of stay should focus on optimization of modifiable risk factors.


Subject(s)
Colonic Neoplasms , Quality Improvement , Humans , Patient Discharge , Retrospective Studies , Colectomy/adverse effects , Postoperative Complications/etiology
9.
Curr Res Neurobiol ; 3: 100039, 2022.
Article in English | MEDLINE | ID: mdl-36518341

ABSTRACT

Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated. In this study in a rodent model of PD, we sought to examine whether exercise improves cognitive processing and flexibility, important features of EF. Rats received 6-hydroxydopamine lesions of the bilateral striatum (caudate-putamen, CPu), specifically the dorsomedial CPu, a brain region central to EF. Rats were exercised on motorized running wheels or horizontal treadmills for 6-12 weeks. EF-related behaviors including attention and processing, as well as flexibility (inhibition) were evaluated using either an operant 3-choice serial reaction time task (3-CSRT) with rule reversal (3-CSRT-R), or a T-maze task with reversal. Changes in striatal transcript expression of dopamine receptors (Drd1-4) and synaptic proteins (Synaptophysin, PSD-95) were separately examined following 4 weeks of exercise in a subset of rats. Exercise/Lesion rats showed a modest, yet significant improvement in processing-related response accuracy in the 3-CSRT-R and T-maze, as well as a significant improvement in cognitive flexibility as assessed by inhibitory aptitude in the 3-CSRT-R. By four weeks, exercise also elicited increased expression of Drd1, Drd3, Drd4, synaptophysin, and PSD-95 in the dorsomedial and dorsolateral CPu. Our results underscore the observation that exercise, in addition to improving motor function may benefit cognitive performance, specifically EF, and that early changes (by 4 weeks) in CPu dopamine modulation and synaptic connectivity may underlie these benefits.

10.
Parkinsonism Relat Disord ; 104: 7-14, 2022 11.
Article in English | MEDLINE | ID: mdl-36191358

ABSTRACT

BACKGROUND: Cognitive impairment is common in Parkinson's disease (PD) and often leads to dementia, with no effective treatment. Aging studies suggest that physical activity (PA) intensity has a positive impact on cognition and enhanced functional connectivity may underlie these benefits. However, less is known in PD. This cross-sectional study examined the relationship between PA intensity, cognitive performance, and resting state functional connectivity in PD and whether PA intensity influences the relationship between functional connectivity and cognitive performance. METHODS: 96 individuals with mild-moderate PD completed a comprehensive neuropsychological battery. Intensity of PA was objectively captured over a seven-day period using a wearable device (ActiGraph). Time spent in light and moderate intensity PA was determined based on standardized actigraphy cut points. Resting-state fMRI was assessed in a subset of 50 individuals to examine brain-wide functional connectivity. RESULTS: Moderate intensity PA (MIPA), but not light PA, was associated with better global cognition, visuospatial function, memory, and executive function. Individuals who met the WHO recommendation of ≥150 min/week of MIPA demonstrated better global cognition, executive function, and visuospatial function. Resting-state functional connectivity associated with MIPA included a combination of brainstem, hippocampus, and regions in the frontal, cingulate, and parietal cortices, which showed higher connectivity across the brain in those achieving the WHO MIPA recommendation. Meeting this recommendation positively moderated the associations between identified functional connectivity and global cognition, visuospatial function, and language. CONCLUSION: Encouraging MIPA, particularly the WHO recommendation of ≥150 min of MIPA/week, may represent an important prescription for PD cognition.


Subject(s)
Cognitive Dysfunction , Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Brain Mapping , Neural Pathways , Neuropsychological Tests , Cross-Sectional Studies , Cognition , Magnetic Resonance Imaging , Exercise
13.
Ann Surg Oncol ; 29(13): 8060-8069, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35980548

ABSTRACT

BACKGROUND: The residual cancer burden class informs survival outcomes after neoadjuvant chemotherapy. We evaluated the prognostic ability of the RCB for survival outcomes in women with different phenotypic subtypes of breast cancer treated with neoadjuvant chemotherapy. Additional variables were assessed for inclusion with the RCB to further improve the model's discriminative ability. PATIENTS AND METHODS: We conducted a retrospective review of patients completing at least 75% of the recommended cycles of neoadjuvant chemotherapy between 1 January 2010 and 31 December 2016. Phenotypic subtypes were defined by hormone receptor and human epidermal growth factor receptor 2 (HER2) status at diagnosis, classified as HR+/HER2-, HER2+, or triple-negative breast cancer (TNBC). The RCB class was calculated and survival endpoints of overall survival, recurrence-free survival, and distant recurrence-free survival were analyzed using Kaplan-Meier and Cox proportional hazards methods. The discriminative ability of the models was quantified by Harrell's C-index. RESULTS: Overall, 532 women met the inclusion criteria. Median follow-up was 65 months. In univariate models, RCB was significantly associated with OS, RFS, and DRFS. The RCB class had good discriminative ability for OS, RFS, and DRFS survival, with Harrell's C-indices of 0.68, 0.67, and 0.68, respectively. The RCB class discriminated well for each survival endpoint within HER2+ and TNBC, but did not discriminate well for HR+/HER2- (OS Harrell's C-indices of 0.77, 0.75, and 0.52, respectively). CONCLUSIONS: The RCB class was prognostic for OS, RFS, and DRFS after neoadjuvant chemotherapy, but prognostic discrimination between patients with subtype HR+/HER2- was not observed during the follow-up period for which the overall event rate was low.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Neoadjuvant Therapy , Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/drug therapy , Neoplasm, Residual/drug therapy , Receptor, ErbB-2/metabolism , Prognosis , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant
14.
J Minim Invasive Gynecol ; 29(11): 1248-1252, 2022 11.
Article in English | MEDLINE | ID: mdl-35940525

ABSTRACT

STUDY OBJECTIVE: To determine the effect of the coronavirus disease 2019 (COVID-19) pandemic on the rate of same-day discharge (SDD) after minimally invasive surgery for endometrial cancer. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: A total of 166 patients underwent a minimally invasive surgery procedure for the indication of endometrial cancer at a large academic institution from September 1, 2019, to October 1, 2020-80 patients before the implementation of the COVID-19 restrictions and 86 patients after. INTERVENTIONS: COVID-19 pandemic with visitor restrictions and hospital policy changes placed on March 17, 2020. MEASUREMENTS AND MAIN RESULTS: SDD rate was increased by 18% after the start of the COVID-19 pandemic (40% vs 58%, p = .02). There were no differences between the 2 groups with regard to operative time (p = .07), estimated blood loss (p = .21), uterine weight (p = .12), age (p = .06), body mass index (p = .42), or surgery start time (p = .15). In a multivariable logistic regression model, subjects in the COVID-19 group had 3.08 times (95% confidence interval, 1.40-6.74; p = .01) higher odds of SDD than those in the pre-COVID-19 group. There was no difference in 30-day readmission rates (7.5% vs 5.8%, p = .66). CONCLUSION: There was a significant increase in the SDD of patients with endometrial cancer since the start of the COVID-19 pandemic. The pandemic has strained hospital resources and motivated patients and physicians to avoid hospitalization. This shows that with proper motivation, an increase in SDD rates is possible without an increase in complications or rehospitalization.


Subject(s)
COVID-19 , Endometrial Neoplasms , Laparoscopy , Female , Humans , Patient Discharge , COVID-19/epidemiology , Retrospective Studies , Pandemics , Laparoscopy/methods , Endometrial Neoplasms/surgery , Postoperative Complications/epidemiology
15.
Ann Surg Oncol ; 29(12): 7716-7724, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35810226

ABSTRACT

BACKGROUND: The extent of residual disease after neoadjuvant chemotherapy (NAC) can be quantified by the Residual Cancer Burden (RCB), a prognostic tool used to estimate survival outcomes in breast cancer. This study investigated the association between RCB and locoregional recurrence (LRR). METHODS: The study reviewed 532 women with breast cancer who underwent NAC between 2010 and 2016. Relapse in the ipsilateral breast, skin/subcutis at the surgical site, chest wall, pectoralis, or regional lymph nodes defined an LRR. The LRR cumulative incidence (LRCI) was estimated using the Fine and Gray competing-risks model, with death and distant recurrence defined as competing events. The association of LRCI with prognostic variables was evaluated. RESULTS: Overall, 5.5% of the patients experienced an LRR after a median follow-up period of 65 months. The 5-year LRCI rates by RCB were as follows: RCB-0 (0.9%), RCB-1 (3.2%), RCB-2 (6.0%), and RCB-3 (12.9%). In the univariable analysis, LRCI varied significantly by RCB (p = 0.010). The multivariable analysis showed a significant association of LRCI with increasing RCB, and the patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) phenotype were at lower risk for LRR than those with HER2+ and triple-negative cancers (p < 0.032). The patients with RCB-3 were at a higher risk for local relapse than those with RCB-0 (hazard ratio, 13.78; confidence interval, 2.25-84.45; p = 0.04). Type of operation (p = 0.04) and use of adjuvant radiation (p = 0.046) were statistically significant in the multivariable model. CONCLUSIONS: The study results demonstrate a significant association between LRCI and increasing RCB, although distant recurrence is a substantial driver of disease outcomes. Future prospective studies should examine the role of RCB in clinical decisions regarding indications for adjuvant therapy.


Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Female , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm, Residual/pathology , Prospective Studies , Receptor, ErbB-2/metabolism
16.
Neuroreport ; 33(7): 291-296, 2022 05 04.
Article in English | MEDLINE | ID: mdl-35594442

ABSTRACT

OBJECTIVE: Higher volume fraction of perivascular space (PVS) has recently been reported in Parkinson's disease (PD) and related disorders. Both elevated PVS and altered levels of neurometabolites, assayed by proton magnetic resonance spectroscopy (MRS), are suspected indicators of neuroinflammation, but no published reports have concurrently examined PVS and MRS neurometabolites. METHODS: In an exploratory pilot study, we acquired multivoxel 3-T MRS using a semi-Localization by Adiabatic SElective Refocusing (sLASER) pulse-sequence (repetition time/echo time = 2810/60 ms, voxels 10 × 10 × 10 mm3) from a 2D slab sampling bilateral frontal white matter (FWM) and anterior middle cingulate cortex (aMCC). PVS maps obtained from high-resolution (0.8 × 0.8 × 0.8 mm3) T1-weighted MRI were co-registered with MRS. In each MRS voxel, PVS volume and neurometabolite levels were measured. RESULTS: Linear regression accounting for age, sex, and BMI found greater PVS volume for higher levels of choline-containing compounds (Cho; P = 0.047) in FWM and lower PVS volume for higher levels of N-acetyl compounds (NAA; P = 0.012) in aMCC. Since (putatively) higher Cho is associated with inflammation while NAA has anti-inflammatory properties, these observations add to evidence that higher PVS load is a sign of inflammation. Additionally, lower Montreal Cognitive Assessment scores were associated with lower NAA in aMCC (P = 0.002), suggesting that local neuronal dysfunction and inflammation contribute to cognitive impairment in PD. CONCLUSION: These exploratory findings indicate that co-analysis of PVS and MRS is feasible and may help elucidate the cellular and metabolic substrates of glymphatic and inflammatory processes in PD.


Subject(s)
Parkinson Disease , Aspartic Acid/metabolism , Brain/diagnostic imaging , Brain/metabolism , Creatine/metabolism , Feasibility Studies , Humans , Inflammation/metabolism , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy/methods , Parkinson Disease/metabolism , Pilot Projects
17.
BMC Pregnancy Childbirth ; 22(1): 344, 2022 Apr 21.
Article in English | MEDLINE | ID: mdl-35448967

ABSTRACT

BACKGROUND: Most existing evidence about the prevalence of prenatal cannabis use relies on self-reported measures, which is limited by social desirability bias and recall bias. To date, several studies have examined the validity of self-reported measures of prenatal cannabis use, but this evidence has yet to be synthesized. To address this gap, we performed a scoping review to systematically identify and synthesize existing evidence on the validity of self-reported measures of cannabis use among pregnant women. METHODS: We searched PubMed, PyschINFO, CINAHL, Cochrane/CENTRAL, and Google Scholar for peer-reviewed studies published in English between January 2010 and June 2021. We included studies that compared self-reported measures of cannabis use to a biochemical measure of cannabis (e.g., urine, hair, meconium) in pregnant women. We excluded studies reporting solely on prenatal cannabis use prevalence as well as those that examined self-reported drug use in which cannabis use was not a distinct category. RESULTS: We found 12 unique studies (11 primary studies and one systematic review) that examined the validity of self-reported prenatal cannabis use, compared to a biochemical sample. Most studies were conducted in the US and conducted in either a hospital or clinical setting. We found that self-report was more valid in populations with a current or prior history of drug use. Self-report was also more valid when assessed via interviews by research team members than health care provider screenings or self-administered surveys. The most commonly used biochemical measure used was urine drug testing, which was found to have the highest level of concordance with self-report. CONCLUSIONS: This scoping review systematically mapped existing evidence on the validity of self-reported prenatal cannabis use. Although much remains unknown in this area, an important next step is a systematic review that would provide robust evidence on clinical utilization of self-reported use in conjunction with biochemical samples. Further research is needed to examine validity by type of measure and mode of administration. Additionally, future studies could assess factors associated with disclosure of use across different critical maternal health periods beyond pregnancy.


Subject(s)
Cannabis , Substance-Related Disorders , Female , Humans , Infant, Newborn , Male , Maternal Health , Meconium , Pregnancy , Pregnant Women , Self Report
18.
BMC Womens Health ; 22(1): 95, 2022 03 27.
Article in English | MEDLINE | ID: mdl-35346156

ABSTRACT

BACKGROUND: Cannabis use among women of reproductive age has increased substantially in recent decades. Understanding reasons for cannabis use in this population is critical for cannabis use prevention efforts. Thus, this scoping review aimed to identify and synthesize current measures on reasons for cannabis use in women of reproductive age. METHODS: We searched PubMed, PyschINFO, CINAHL, and Google Scholar for relevant studies published in English between January 2010 and April 2021. Peer-reviewed, quantitative studies reporting on measures of cannabis-related knowledge, attitudes, perceptions, motivations, and influences among women of reproductive age were eligible for inclusion. We excluded studies not focused on women of reproductive age and studies reporting cannabis use prevalence data only. RESULTS: We included 11 studies (10 primary studies and 1 review) with varying subpopulation samples of women, including non-pregnant women (n = 2), women experiencing infertility (n = 1), pregnant women (n = 4), postpartum women (n = 3), and women in the perinatal period (n = 1). Measurement topic areas included information received from health care professionals, attitudes, perceptions and experiences about cannabis use, knowledge of potential harms, and motivations for cannabis use. Most studies including measures of risk perceptions were conducted among pregnant or postpartum women (n = 4). A single study measured influences of cannabis use; no studies measured social or peer influences of use. Most studies (n = 7) created their own measures, with 2 studies using secondary data via measures from population-based surveillance systems in the United States, and one using a previously validated instrument. Recommendations for future research were centered around addressing knowledge gaps of health effects of cannabis use across different time periods, and etiology of cannabis use. CONCLUSIONS: We found vast measurement gaps in current measures of antecedents of cannabis use among women of reproductive age, providing clear direction for future research in this area. Findings necessitate psychometric evaluation of existing measures to ascertain validity and reliability, as well as development of additional measures of women's cannabis-related attitudes, perceptions, motivations, and influences. This work is critical to guide not only epidemiologic studies, but cannabis-related prevention work as well.


Subject(s)
Cannabis , Female , Health Knowledge, Attitudes, Practice , Humans , Motivation , Peer Group , Pregnancy , Reproducibility of Results , United States
19.
Ann Surg Oncol ; 29(5): 3291-3301, 2022 May.
Article in English | MEDLINE | ID: mdl-35015183

ABSTRACT

BACKGROUND: Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients. METHODS: Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.S. institutions. Predicted 5- and 10-year overall survival (OS) and distant metastases cumulative incidence (DMCI), and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated with Sarculator and MSKCC nomograms, respectively. Predicted survival probabilities stratified in quintiles were compared in calibration plots to observed survival assessed by Kaplan-Meier estimates. Cumulative incidence was estimated for DMCI. Harrell's concordance index (C-index) assessed discriminative ability of nomograms. RESULTS: A total of 1326 patients underwent resection of primary extremity STS. Common histologies included: undifferentiated pleomorphic sarcoma (35%), fibrosarcoma (13%), and leiomyosarcoma (9%). Median tumor size was 8.0 cm (IQR 4.5-13.0). Tumor grade distribution was: Grade 1 (13%), Grade 2 (9%), Grade 3 (78%). Median OS was 172 months, with estimated 5- and 10-year OS of 70% and 58%. C-indices for 5- and 10-year OS (Sarculator) were 0.72 (95% CI 0.70-0.75) and 0.73 (95% CI 0.70-0.75), and 0.72 (95% CI 0.69-0.75) for 5- and 10-year DMCI. C-indices for 4-, 8-, and 12-year DSS (MSKCC) were 0.71 (95% CI 0.68-0.75). Calibration plots showed good prognostication across all outcomes. CONCLUSIONS: Sarculator and MSKCC nomograms demonstrated good prognostic ability for survival and recurrence outcomes in a modern, multi-institutional validation cohort of resected primary extremity STS patients. External validation of these nomograms supports their ongoing incorporation into clinical practice.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Extremities/pathology , Extremities/surgery , Humans , Nomograms , Prognosis , Sarcoma/pathology , Soft Tissue Neoplasms/surgery
20.
Ann Surg Oncol ; 29(2): 1327-1333, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34625880

ABSTRACT

BACKGROUND: For locally advanced esophageal squamous cell carcinoma (ESCC), chemoradiation (ChemoRT) followed by surgery offers the best chance of cure, with a 35-50% pathologic complete response (pCR) rate. Given the morbidity of esophagectomy and the possibility of pCR with ChemoRT, a 'watch and wait' strategy has been proposed, particularly for squamous cell carcinoma. The ability to accurately predict which patients will have pCR from ChemoRT is critical in treatment decision making. This study assessed positron emission tomography (PET) in predicting pCR after neoadjuvant ChemoRT for ESCC. METHODS: ESCC patients treated with ChemoRT followed by surgery were identified. Maximum standard uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and first-order textual features of standard deviation, kurtosis and skewness were measured from PET. Univariable and multivariable generalized linear method analyses were performed. A metabolic complete response (mCR) was defined as a post-therapy PET scan with maximum SUV < 4.0. RESULTS: Twenty-seven patients underwent ChemoRT followed by surgery, with overall pCR seen in 11 (41%) patients and radiographic mCR seen in 12 (44%) patients. Final pathology for these 12 patients revealed pCR (ypT0N0M0) in 5 (42%) patients and persistent disease in 7 (58%) patients. Univariate analysis did not reveal PET parameters predictive of pCR. CONCLUSION: Treatment of ESCC with ChemoRT often results in a robust clinical response. Among patients with an mCR after ChemoRT, disease persistence was found in 58%. The inability of PET to predict pCR is important in the context of a 'watch and wait' strategy for ESCC treated with ChemoRT.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Chemoradiotherapy , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/therapy , Esophagectomy , Fluorodeoxyglucose F18 , Humans , Neoadjuvant Therapy , Positron-Emission Tomography , Radiopharmaceuticals/therapeutic use , Retrospective Studies
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