Abstract
Study Objectives:
To determine whether arousals that terminate obstructive events in obstructive sleep apnea (OSA) (1) induce hypocapnia and (2) subsequently reduce genioglossus muscle ...activity following the return to sleep.
Methods:
Thirty-one untreated patients with OSA slept instrumented with sleep staging electrodes, nasal mask and pneumotachograph, end-tidal CO2 monitoring, and intramuscular genioglossus electrodes. End-tidal CO2 was monitored, and respiratory arousals were assigned an end-arousal CO2 change value (PETCO2 on the last arousal breath minus each individual’s wakefulness PETCO2). This change value, in conjunction with the normal sleep related increase in PETCO2, was used to determine whether arousals induced hypocapnia and whether the end-arousal CO2 change was associated with genioglossus muscle activity on the breaths following the return to sleep.
Results:
Twenty-four participants provided 1137 usable arousals. Mean ± SD end-arousal CO2 change was −0.2 ± 2.4 mm Hg (below wakefulness) indicating hypocapnia typically developed during arousal. Following the return to sleep, genioglossus muscle activity did not fall below prearousal levels and was elevated for the first two breaths. End-arousal CO2 change and genioglossus muscle activity were negatively associated such that a 1 mm Hg decrease in end-arousal CO2 was associated with an ~2% increase in peak and tonic genioglossus muscle activity on the breaths following the return to sleep.
Conclusions:
Arousal-induced hypocapnia did not result in reduced dilator muscle activity following return to sleep, and thus hypocapnia may not contribute to further obstructions via this mechanism. Elevated dilator muscle activity postarousal is likely driven by non-CO2–related stimuli.
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an increasingly utilized strategy for patients with peritoneal surface malignancies (PSM).
The US HIPEC ...Collaborative was retrospectively reviewed to compare the indications and perioperative outcomes of patients who underwent CRS ± HIPEC between 2000 and 2012 (P1) versus 2013–2017 (P2).
Among 2,364 patients, 39% were from P1 and 61% from P2. The most common primary site was appendiceal (64%) while the median PCI was 13 and most patients had CCR 0 (60%) or 1 (25%). Over time, median estimated blood loss, need for transfusion, and length of hospital stay decreased. While the incidence of any (55% vs. 57%; p = 0.426) and Clavien III/IV complications did not change over time, there was a decrease in 90-day mortality (5% vs. 3%; p = 0.045).
CRS-HIPEC is increasingly performed for PSM at high-volume centers. Despite improvements in some perioperative outcomes and a reduction in postoperative mortality, morbidity rates remain high.
•Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an increasingly utilized strategy.•The current study examines indications and perioperative outcomes of patients undergoing CRS ± HIPEC over time.•Over time median estimated blood loss, need for transfusion, and length of hospital stay decreased.•While the incidence of any complication did not change over time, there was a decrease in 90-day mortality.•Despite improvements in some perioperative outcomes and a reduction in postoperative mortality, morbidity rates remain high.
Incompatible living donor kidney transplant recipients (ILDKTr) have pre‐existing donor‐specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, ...including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25‐center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.031.682.72). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.452.093.02; PFNC = 1.672.403.46; PCC = 1.482.243.37). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.341.621.95) than CLDKT (aHR = 1.962.292.67) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.
The impact of acute rejection on the risk of graft loss is less consequential for incompatible compared to compatible living donor kidney transplant recipients, while the impact of delayed graft function on mortality and graft loss is comparable.
Introduction
Metastatic castration‐resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration‐resistant diagnosis. Optimal ...first‐line therapy for those with different prognoses is unknown.
Methods
We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first‐line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow‐up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan–Meier methods to examine prostate specific antigen (PSA) progression‐free and overall survival (OS) according to prognostic group and first‐line therapy, and multivariable cox regression to determine variables associated with survival outcomes.
Results
Among 4135 patients, median PSA progression‐free survival (PFS) was 6.9 months (95% confidence interval CI 6.6–7.3), and median OS 18.8 months (95% CI 18.0–19.6), ranging from 5.7 months (95% CI 4.8–7.0) in the poor prognosis group to 31.3 months (95% CI 29.7–32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2–3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34–2.31; intermediate HR 1.78, 95% CI 1.41–2.25; poor HR 8.01, 95% CI 2.93–21.9).
Conclusion
Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First‐line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start.
Hemoglobin, albumin, and alkaline phosphatase, used to categorize patients with metastatic castration resistant prostate cancer at start of new treatment into prognostic groups, was strongly predictive of survival, but survival did not vary substantially based on which treatment patients received within prognostic groups.
Protease-activated quantum dot probes Chang, Emmanuel; Miller, Jordan S.; Sun, Jiantang ...
Biochemical and biophysical research communications,
09/2005, Letnik:
334, Številka:
4
Journal Article
Recenzirano
We have developed a novel nanoparticulate luminescent probe with inherent signal amplification upon interaction with a targeted proteolytic enzyme. This construct may be useful for imaging in cancer ...detection and diagnosis. In this system, quantum dots (QDs) are bound to gold nanoparticles (AuNPs) via a proteolytically degradable peptide sequence to non-radiatively suppress luminescence. A 71% reduction in luminescence was achieved with conjugation of AuNPs to QDs. Release of AuNPs by peptide cleavage restores radiative QD photoluminescence. Initial studies observed a 52% rise in luminescence over 47
h of exposure to 0.2
mg/mL collagenase. These probes can be customized for targeted degradation simply by changing the sequence of the peptide linker.
Objective:The authors sought to characterize the 3-year prevalence of mental disorders and nonnicotine substance use disorders among male and female primary care patients with documented opioid use ...disorder across large U.S. health systems.Methods:This retrospective study used 2014–2016 data from patients ages ≥16 years in six health systems. Diagnoses were obtained from electronic health records or claims data; opioid use disorder treatment with buprenorphine or injectable extended-release naltrexone was determined through prescription and procedure data. Adjusted prevalence of comorbid conditions among patients with opioid use disorder (with or without treatment), stratified by sex, was estimated by fitting logistic regression models for each condition and applying marginal standardization.Results:Females (53.2%, N=7,431) and males (46.8%, N=6,548) had a similar prevalence of opioid use disorder. Comorbid mental disorders among those with opioid use disorder were more prevalent among females (86.4% vs. 74.3%, respectively), whereas comorbid other substance use disorders (excluding nicotine) were more common among males (51.9% vs. 60.9%, respectively). These differences held for those receiving medication treatment for opioid use disorder, with mental disorders being more common among treated females (83% vs. 71%) and other substance use disorders more common among treated males (68% vs. 63%). Among patients with a single mental health condition comorbid with opioid use disorder, females were less likely than males to receive medication treatment for opioid use disorder (15% vs. 20%, respectively).Conclusions:The high rate of comorbid conditions among patients with opioid use disorder indicates a strong need to supply primary care providers with adequate resources for integrated opioid use disorder treatment.
Background
The measurement of physical fitness has a history that dates back nearly 200 years. Recently, there has been an increase in international research and surveillance on physical fitness ...creating a need for setting international priorities that could help guide future efforts.
Objective
This study aimed to produce a list of the top 10 international priorities for research and surveillance on physical fitness among children and adolescents.
Methods
Using a twin-panel Delphi method, two independent panels consisting of 46 international experts were identified (panel 1 = 28, panel 2 = 18). The panel participants were asked to list up to five priorities for research or surveillance (round 1), and then rated the items from their own panel on a 5-point Likert scale of importance (round 2). In round 3, experts were asked to rate the priorities identified by the other panel.
Results
There was strong between-panel agreement (panel 1:
r
s
= 0.76,
p
< 0.01; panel 2:
r
s
= 0.77,
p
< 0.01) in the priorities identified. The list of the final top 10 priorities included (i) “conduct longitudinal studies to assess changes in fitness and associations with health”. This was followed by (ii) “use fitness surveillance to inform decision making”, and (iii) “implement regular and consistent international/national fitness surveys using common measures”.
Conclusions
The priorities identified in this study provide guidance for future international collaborations and research efforts on the physical fitness of children and adolescents over the next decade and beyond.
Introduction
Weight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio‐metabolic disease. We assessed relationships ...between ART drug class and weight change among treatment‐naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD).
Methods
Adult, treatment‐naïve PWH in NA‐ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non‐nucleoside reverse‐transcriptase inhibitor (NNRTI)‐based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV‐1 RNA level and CD4+ cell count. Due to shorter follow‐up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.
Results
Among 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI‐, 31% started PI‐ and 20% started INSTI‐based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI‐based regimens had mean estimated five‐year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two‐year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI‐based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).
Conclusions
PWH initiating INSTI‐based regimens gained, on average, more weight compared to NNRTI‐based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.
To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 × 10−9) in ...ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 × 10−8, rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.
Objective:The study was designed to validate use of electronic health records (EHRs) for diagnosing bipolar disorder and classifying control subjects.Method:EHR data were obtained from a health care ...system of more than 4.6 million patients spanning more than 20 years. Experienced clinicians reviewed charts to identify text features and coded data consistent or inconsistent with a diagnosis of bipolar disorder. Natural language processing was used to train a diagnostic algorithm with 95% specificity for classifying bipolar disorder. Filtered coded data were used to derive three additional classification rules for case subjects and one for control subjects. The positive predictive value (PPV) of EHR-based bipolar disorder and subphenotype diagnoses was calculated against diagnoses from direct semistructured interviews of 190 patients by trained clinicians blind to EHR diagnosis.Results:The PPV of bipolar disorder defined by natural language processing was 0.85. Coded classification based on strict filtering achieved a value of 0.79, but classifications based on less stringent criteria performed less well. No EHR-classified control subject received a diagnosis of bipolar disorder on the basis of direct interview (PPV=1.0). For most subphenotypes, values exceeded 0.80. The EHR-based classifications were used to accrue 4,500 bipolar disorder cases and 5,000 controls for genetic analyses.Conclusions:Semiautomated mining of EHRs can be used to ascertain bipolar disorder patients and control subjects with high specificity and predictive value compared with diagnostic interviews. EHRs provide a powerful resource for high-throughput phenotyping for genetic and clinical research.
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