To estimate prevalence of childhood-onset Duchenne and Becker muscular dystrophies (DBMD) in 6 sites in the United States by race/ethnicity and phenotype (Duchenne muscular dystrophy DMD or Becker ...muscular dystrophy BMD).
In 2002, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to conduct longitudinal, population-based surveillance and research of DBMD in the United States. Six sites conducted active, multiple-source case finding and record abstraction to identify MD STARnet cases born January 1982 to December 2011. We used cross-sectional analyses to estimate prevalence of DBMD per 10 000 boys, ages 5 to 9 years, for 4 quinquennia (1991-1995, 1996-2000, 2001-2005, and 2006-2010) and prevalence per 10 000 male individuals, ages 5 to 24 years, in 2010. Prevalence was also estimated by race/ethnicity and phenotype.
Overall, 649 cases resided in an MD STARnet site during ≥1 quinquennia. Prevalence estimates per 10 000 boys, ages 5 to 9 years, were 1.93, 2.05, 2.04, and 1.51, respectively, for 1991-1995, 1996-2000, 2001-2005, and 2006-2010. Prevalence tended to be higher for Hispanic individuals than non-Hispanic white or black individuals, and higher for DMD than BMD. In 2010, prevalence of DBMD was 1.38 per 10 000 male individuals, ages 5 to 24 years.
We present population-based prevalence estimates for DBMD in 6 US sites. Prevalence differed by race/ethnicity, suggesting potential cultural and socioeconomic influences in the diagnosis of DBMD. Prevalence also was higher for DMD than BMD. Continued longitudinal surveillance will permit us to examine racial/ethnic and socioeconomic differences in treatment and outcomes for MD STARnet cases.
Background
As more women survive breast cancer, long-term complications that affect quality of life, such as lymphedema of the arm, gain greater importance. Numerous studies have attempted to ...identify treatment and prognostic factors for arm lymphedema, yet the magnitude of these associations remains inconsistent.
Methods
A PubMed search was conducted through January 2008 to locate articles on lymphedema and treatment factors after breast cancer diagnosis. Random-effect models were used to estimate the pooled risk ratio.
Results
The authors identified 98 independent studies that reported at least one risk factor of interest. The risk ratio (RR) of arm lymphedema was increased after mastectomy when compared with lumpectomy RR = 1.42; 95% confidence interval (CI) 1.15–1.76, axillary dissection compared with no axillary dissection (RR = 3.47; 95% CI 2.34–5.15), axillary dissection compared with sentinel node biopsy (RR = 3.07; 95% CI 2.20–4.29), radiation therapy (RR = 1.92; 95% CI 1.61–2.28), and positive axillary nodes (RR = 1.54; 95% CI 1.32–1.80). These associations held when studies using self-reported lymphedema were excluded.
Conclusions
Mastectomy, extent of axillary dissection, radiation therapy, and presence of positive nodes increased risk of developing arm lymphedema after breast cancer. These factors likely reflected lymph node removal, which most surgeons consider to be the largest risk factor for lymphedema. Future studies should consider examining sentinel node biopsy versus no dissection with a long follow-up time post surgery to see if there is a benefit of decreased lymphedema compared with no dissection.
Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive ...disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans.
Pancreatic neuroendocrine neoplasms (pNENs) are slow growing cancers of increasing incidence that lack effective treatments once they become metastatic. Unfortunately, nearly half of pNEN patients ...present with metastatic liver tumors at diagnosis and current therapies fail to improve overall survival. Pre-clinical models of pNEN metastasis are needed to advance our understanding of the mechanisms driving the metastatic process and for the development of novel, targeted therapeutic interventions. To model metastatic dissemination of tumor cells, human pNEN cell lines (BON1 and Qgp1) stably expressing firefly luciferase (luc) were generated and introduced into NSG immunodeficient mice by intracardiac (IC) or intravenous (IV) injection. The efficiency, kinetics and distribution of tumor growth was evaluated weekly by non-invasive bioluminescent imaging (BLI). Tumors formed in all animals in both the IC and IV models. Bioluminescent Qgp1.luc cells preferentially metastasized to the liver regardless of delivery route, mimicking the predominant site of pNEN metastasis in patients. By comparison, BON1.luc cells most commonly formed lung tumors following either IV or IC administration and colonized a wider variety of tissues than Qgp1.luc cells. These models provide a unique platform for testing candidate metastasis genes and anti-metastatic therapies for pNENs.
It has been shown that threshold estimates below approximately 20 dB have little effect on the ability to detect visual field progression in glaucoma. We aimed to compare stimulus size V to stimulus ...size III, in areas of visual damage, to confirm these findings by using (1) a different dataset, (2) different techniques of progression analysis, and (3) an analysis to evaluate the effect of censoring on mean deviation (MD).
In the Iowa Variability in Perimetry Study, 120 glaucoma subjects were tested every 6 months for 4 years with size III SITA Standard and size V Full Threshold. Progression was determined with three complementary techniques: pointwise linear regression (PLR), permutation of PLR, and linear regression of the MD index. All analyses were repeated on "censored'' datasets in which threshold estimates below a given criterion value were set to equal the criterion value.
Our analyses confirmed previous observations that threshold estimates below 20 dB contribute much less to visual field progression than estimates above this range. These findings were broadly similar with stimulus sizes III and V.
Censoring of threshold values < 20 dB has relatively little impact on the rates of visual field progression in patients with mild to moderate glaucoma. Size V, which has lower retest variability, performs at least as well as size III for longitudinal glaucoma progression analysis and appears to have a larger useful dynamic range owing to the upper sensitivity limit being higher.
Objective/Background
Discussion of treatment goals between oncologists and patients is challenging. Patients frequently misunderstand goals of therapy. There are several methods to document goals of ...chemotherapy, however, and are frequently not incorporated into patient charts.
Methods/Design
Cancer patients receiving their first cycle of chemotherapy were interviewed. Patients’ recall of discussions with their oncologist regarding therapy intent was assessed and compared to documentation. An adjusted McNemar's test was utilised. A one‐sample proportion test was used to evaluate whether the overall observed rate of discordance was significantly different from the proposed 33% rate; a rate posited as a threshold too high in the clinical sense.
Results
Two hundred and seven eligible patients were interviewed. Oncologist identified treatment goals were not documented in 24.6% of cases and had to be excluded. There was not a significant difference in the directionality of discordance present. Inter‐rater agreement between patient and oncologist was found to be adequate (κ = 0.64). The overall rate of discordance (17.29%) was found to be significantly less than the proposed acceptable level of 33% (p < 0.01). Upon univariable analysis, age, gender, marital and employment status were not found to be associated with discordance.
Conclusions
Discordance between treatment goals documentation and their understanding exists, indicating continued miscommunication between the patient and oncologist.
Background Patients with small cell lung cancer (SCLC) often respond to first-line chemoimmunotherapy. However, relapse is inevitable and is associated with a poor prognosis. Treatments for relapsed ...SCLC, such as lurbinectedin and topotecan, are limited by modest efficacy and significant hematologic adverse events, leaving a need for newer therapeutic agents or regimens. The combination of gemcitabine and nab-paclitaxel is active and safe in other types of malignancies, such as pancreatic cancer. Patients and methods We conducted a phase II trial evaluating the efficacy and safety of gemcitabine and nab-paclitaxel in patients with relapsed/refractory SCLC. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with confirmed complete or partial response. Secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety. Results Between October 2016 and May 2021, 32 patients were enrolled. Patients were followed for a median of 9.3 months (range 1.8–65.2). Median age was 65 years (range 48–81). Fifty percent of patients were female. Fifty-three percent of patients had platinum-resistant/refractory relapsed SCLC. The ORR was 28.1% (95% confidence interval CI 15.5–100%). Median PFS was 2.9 months (95% CI 2.4–3.6), and median OS was 9.3 months (95% CI 5.2–12.4). Seven patients (21.9%) developed grade 3 or 4 neutropenia. Conclusion Our study showed that the combination of gemcitabine and nab-paclitaxel led to encouraging outcomes in relapsed/refractory SCLC. Further studies are needed to compare this combination with other treatments used for relapsed SCLC, including lurbinectedin, temozolomide, and topotecan. Clinical trial registration https://clinicaltrials.gov/study/NCT02769832?cond=NCT02769832&rank=1 , identifier NCT02769832.
This is the first case-control study investigating an association between gallbladder hyperkinesia and symptomatic acalculous chronic cholecystitis.
This retrospective study in a single academic ...center compared resolution of biliary pain in adults with gallbladder hyperkinesia, defined as a hepatobiliary iminodiacetic acid scan ejection fraction ≥80%, undergoing cholecystectomy (study group) with those treated medically without cholecystectomy (control group). Of 1,477 hepatobiliary iminodiacetic acid scans done between 2013 and 2018, a total of 296 adults without gallstones had an ejection fraction ≥80%, of whom 46 patients met predetermined eligibility criteria. Demographic data, hepatobiliary iminodiacetic acid scan ejection fraction, chronicity of pain, and resolution of pain were compared between groups.
Demographics (mean ± standard deviation) in the control group (n = 25) and in the study group (n = 21) were, respectively, age 40 y ± 16 y and 39 y ± 14 y, body mass index 28.9 ± 5.2 and 29.1 ± 7.1 kg/m2, with 15 (60%) and 18 (86%) females in each. Resolution of pain after cholecystectomy occurred in 18 of 21 patients (86%); however, pain persisted in 20 of 25 patients (80%) treated medically after mean follow-up of 36 ± 28 months (range 10–120 months) (P < .01). Pain resolution with cholecystectomy was independent of demographic variables, hepatobiliary iminodiacetic acid scan ejection fraction, and chronicity of pain. The odds of pain resolution was 19.7 times greater with cholecystectomy than without (odds ratio, 19.7; 95% confidence interval, 4.34, 89.43; P < .01), and remained robust even with the odds adjusted for each covariate. Gallbladder histopathology confirmed chronic cholecystitis in all 21 cholecystectomy specimens.
Symptomatic gallbladder hyperkinesia could be a new indication for cholecystectomy in adults.
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