Clock-Generated Temporal Codes Determine Synaptic Plasticity to Control Sleep.

Neurons use two main schemes to encode information: rate coding (frequency of firing) and temporal coding (timing or pattern of firing). While the importance of rate coding is well established, it remains controversial whether temporal codes alone are sufficient for controlling behavior. Moreover, the molecular mechanisms underlying the generation of specific temporal codes are enigmatic. Here, we show in Drosophila clock neurons that distinct temporal spike patterns, dissociated from changes in firing rate, encode time-dependent arousal and regulate sleep. From a large-scale genetic screen, we identify the molecular pathways mediating the circadian-dependent changes in ionic flux and spike morphology that rhythmically modulate spike timing. Remarkably, the daytime spiking pattern alone is sufficient to drive plasticity in downstream arousal neurons, leading to increased firing of these cells. These findings demonstrate a causal role for temporal coding in behavior and define a form of synaptic plasticity triggered solely by temporal spike patterns.

Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit.

Prolonged wakefulness leads to an increased pressure for sleep, but how this homeostatic drive is generated and subsequently persists is unclear. Here, from a neural circuit screen in Drosophila, we identify a subset of ellipsoid body (EB) neurons whose activation generates sleep drive. Patch-clamp analysis indicates these EB neurons are highly sensitive to sleep loss, switching from spiking to burst-firing modes. Functional imaging and translational profiling experiments reveal that elevated sleep need triggers reversible increases in cytosolic Ca(2+) levels, NMDA receptor expression, and structural markers of synaptic strength, suggesting these EB neurons undergo "sleep-need"-dependent plasticity. Strikingly, the synaptic plasticity of these EB neurons is both necessary and sufficient for generating sleep drive, indicating that sleep pressure is encoded by plastic changes within this circuit. These studies define an integrator circuit for sleep homeostasis and provide a mechanism explaining the generation and persistence of sleep drive.

Tob Regulates the Timing of Sleep Onset at Night in Drosophila.

Sleep is regulated by homeostatic sleep drive and the circadian clock. While tremendous progress has been made in elucidating the molecular components of the core circadian oscillator, the output mechanisms by which this robust oscillator generates rhythmic sleep behavior remain poorly understood. At the cellular level, growing evidence suggests that subcircuits in the master circadian pacemaker suprachiasmatic nucleus (SCN) in mammals and in the clock network in Drosophila regulate distinct aspects of sleep. Thus, to identify novel molecules regulating the circadian timing of sleep, we conducted a large-scale screen of mouse SCN-enriched genes in Drosophila Here, we show that Tob (Transducer of ERB-B2) regulates the timing of sleep onset at night in female fruit flies. Knockdown of Tob pan-neuronally, either constitutively or conditionally, advances sleep onset at night. We show that Tob is specifically required in "evening neurons" (the LNds and the fifth s-LNv) of the clock network for proper timing of sleep onset. Tob levels cycle in a clock-dependent manner in these neurons. Silencing of these "evening" clock neurons results in an advanced sleep onset at night, similar to that seen with Tob knockdown. Finally, sharp intracellular recordings demonstrate that the amplitude and kinetics of LNd postsynaptic potentials (PSPs) cycle between day and night, and this cycling is attenuated with Tob knockdown in these cells. Our data suggest that Tob acts as a clock output molecule in a subset of clock neurons to potentiate their activity in the evening and enable the proper timing of sleep onset at night.

Sleep Duration Polygenic Risk and Phenotype: Associations with Biomarkers of Accelerated Aging in the Baltimore Longitudinal Study of Aging.

We sought to explore whether genetic risk for, and self-reported, short sleep are associated with biological aging and whether age and sex moderate these associations. Participants were a subset of individuals from the Baltimore Longitudinal Study of Aging who had complete data on self-reported sleep (n = 567) or genotype (n = 367). Outcomes included: Intrinsic Horvath age, Hannum age, PhenoAge, GrimAge, and DNAm-based estimates of plasminogen activator inhibitor-1 (PAI-1) and granulocyte count. Results demonstrated that polygenic risk for short sleep was positively associated with granulocyte count; compared to those reporting <6 hr sleep, those reporting >7 hr demonstrated faster PhenoAge and GrimAge acceleration and higher estimated PAI-1. Polygenic risk for short sleep and self-reported sleep duration interacted with age and sex in their associations with some of the outcomes. Findings highlight that polygenic risk for short sleep and self-reported long sleep is associated with variation in the epigenetic landscape and subsequently aging.

Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Versus the Standard of Care Imaging in the Diagnosis of Peritoneal Carcinomatosis.

OBJECTIVE: To compare positron emission tomography (PET)/magnetic resonance imaging (MRI) to the standard of care imaging (SCI) for the diagnosis of peritoneal carcinomatosis (PC) in primary abdominopelvic malignancies. SUMMARY BACKGROUND DATA: Identifying PC impacts prognosis and management of multiple cancer types. METHODS: Adult subjects were prospectively and consecutively enrolled from April 2019 to January 2021. Inclusion criteria were: 1) acquisition of whole-body contrast-enhanced (CE) 18F-fluorodeoxyglucose PET/MRI, 2) pathologically confirmed primary abdominopelvic malignancies. Exclusion criteria were: 1) greater than 4 weeks interval between SCI and PET/MRI, 2) unavailable follow-up. SCI consisted of whole-body CE PET/computed tomography (CT) with diagnostic quality CT, and/or CE-CT of the abdomen and pelvis, and/or CE-MRI of the abdomen±pelvis. If available, pathology or surgical findings served as the reference standard, otherwise, imaging followup was used. When SCI and PET/MRI results disagreed, medical records were checked for management changes. Follow-up data were collected until August 2021. RESULTS: One hundred sixty-four subjects were included, 85 (52%) were female, and the median age was 60 years (interquartile range 50-69). At a subject level, PET/MRI had higher sensitivity (0.97, 95% CI 0.86-1.00) than SCI (0.54, 95% CI 0.37-0.71), P < 0.001, without a difference in specificity, of 0.95 (95% CI 0.90-0.98) for PET/MRI and 0.98 (95% CI 0.93-1.00) for SCI, P » 0.250. PET/MRI and SCI results disagreed in 19 cases. In 5/19 (26%) of the discordant cases, PET/MRI findings consistent with PC missed on SCI led to management changes. CONCLUSION: PET/MRI improves detection of PC compared with SCI which frequently changes management.

Does Order of Operation Matter in Patients Who Have Concomitant Hip and Spine Pathology?

BACKGROUND: In patients, who have coexisting lumbar spine and degenerative hip disease, there remains uncertainty regarding whether hip or spine surgery should be performed first. We hypothesized that undergoing total hip arthroplasty (THA) would protect against subsequent lumbar spine surgery (LSS) in patients who have 'hip-spine syndrome.' METHODS: A retrospective cohort study was performed from 2013 to 2021 on patients who had radiographically-confirmed hip osteoarthritis and degenerative lumbar spine pathology, evaluated separately in spine and arthroplasty clinics prior to surgical intervention. Included patients ultimately underwent THA and/or LSS. The primary outcome was survivorship free of LSS or THA after the other was initially performed. RESULTS: Of 256 patients, 206 (80.5%) underwent THA first. Only 14 of 206 (6.8%) who underwent THA required subsequent LSS, while 31 of 50 (62%) who underwent LSS required subsequent THA, (P < .001). At 5 years, there was 93.9% survivorship-free of LSS in the THA first group, compared to 44.7% survivorship-free of subsequent THA in the LSS group. Multivariate analyses showed that patients who had THA first had lower odds of undergoing subsequent surgery (odds ratio [OR]: 0.61, CI: 0.52-0.70, P < .001) compared to those who underwent LSS first. Additionally, those who have higher initial Kellgren-Lawrence grade hip osteoarthritis had lower odds (OR: 0.94, CI: 0.89-0.99, P = .04), and those who have progressive neurologic deficits (OR: 2.64, CI: 1.89-3.7, P < .001) and neurogenic claudication (OR: 1.15, CI: 1.06-1.24, P = .001) had increased odds of undergoing subsequent LSS. CONCLUSION: Patients with 'hip-spine syndrome' may receive more initial benefit from undergoing THA, potentially reducing the subsequent need for LSS. The exceptions were those patients who had lower-severity hip osteoarthritis and symptoms of major spinal stenosis.

Does a fibula-sparing approach improve outcomes in tibiotalocalcaneal arthrodesis?

BACKGROUND: Tibiotalocalcaneal (TTC) arthrodesis is considered a salvage procedure for either complex deformity or arthritis about the hindfoot, and can be performed via fibula-resection (FR) or fibula-sparing (FS) approaches. The primary aim of this study was to investigate differences in outcomes in FR versus FS TTC arthrodeses. METHODS: This was a retrospective cohort study reviewing outcomes of TTC arthrodesis at a single institution. Patients who underwent a TTC arthrodesis from 2005 to 2017 and had minimum two-year follow-up were included. Preoperative diagnosis, pre- and post-operative radiographic coronal alignment, fixation methods, and complications were compared between groups. RESULTS: 107 patients (110 ankles) underwent TTC arthrodesis, with a mean age of 57.0 years (sd, 14.0 years). The mean clinical follow-up was 50.7 months (range, 24-146) and mean radiographic follow-up was 45.8 months (range, 6-146 months). Pre-operative diagnoses included arthritis (N = 40), prior non-union (N = 21), Charcot neuro-arthropathy (N = 15), failed total ankle arthroplasty (N = 15) and avascular necrosis of the talus (N = 19). Sixty-nine ankles comprised the FS group and 41 comprised the FR group. There was no significant difference in the non-union rate between groups (29% FR vs 38% FS, p = 0.37), complication rate (59% FR vs 64% FS, p = 0.59), or post-operative coronal standing radiographic alignment (89.6 degrees FR, 90.5 degrees FS, p = 0.26). Logistic regression analyses demonstrated a pre-operative diagnosis of failed TAA was associated with post-operative nonunion (OR:3.41,CI:1.13-11.04,p = 0.03). Pre-operative indication for TTC arthrodesis of arthritis alone was associated with a decreased risk of non-union (OR:0.27,CI:0.11-0.62,p = 0.002). CONCLUSION: TTC arthrodesis is a successful surgical option for complex hindfoot deformity, arthritis, and limb salvage regardless of surgical approach. We did not detect a difference in the union rate, incidence of complications, or coronal plane radiographic alignment in fibula-sparing versus fibula-resection constructs. Patients with a pre-operative indication for surgery of arthritis may be at decreased risk of developing non-union. LEVEL OF EVIDENCE: III - Retrospective cohort study.

Risk Factors for Delayed Discharge and Adverse Outcomes Following Outpatient Billed Total Knee Arthroplasty.

BACKGROUND: The volume of outpatient total knee arthroplasty (TKA) has increased with advances in perioperative protocols, patient selection, and recent policy changes regarding insurance authorization. This study analyzed 30-day outcomes from a national database to better understand risk factors for delayed discharge (length of stay [LOS] ≥1), readmission, and reoperation after outpatient TKA. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was utilized to collect TKA (CPT 27447) billed as outpatient surgery performed from 2013 to 2018. Patient demographics, comorbidities, and short-term outcomes were collected and compared in LOS 0 versus LOS ≥1 cohorts. Subgroup analysis was completed for TKA performed in 2018, after the Center for Medicare Services removal of TKA from the inpatient-only list. RESULTS: A total of 13,669 patients had outpatient TKA performed from 2013 to 2018. Most patients had LOS ≥1 day (77.1%). The LOS 0 cohort demonstrated a lower 30-day readmission rate (1.8%) compared to LOS ≥1 (2.8%), P > .01. Both groups demonstrated a low 30-day reoperation rate, LOS 0 (0.7%) and LOS ≥1 (1.1%), P = .05. Regression analysis demonstrated risk factors for LOS ≥1 day included COPD, ASA ≥3, age >75, and BMI >35 kg/m2. Regression analysis demonstrated male gender, age >75, ASA ≥3, and albumin <3.5 g/dL were risk factors for readmission. Hypertension was a risk factor for 30-day reoperation. CONCLUSION: Risk factors for LOS ≥1 day include age >75, ASA ≥3, BMI >35 kg/m2. In addition, BMI >35 kg/m2 was a risk factor for readmission and reoperation. These findings reinforce appropriate patient selection when considering outpatient TKA.

Cutibacterium Positive Cultures in Total Hip Arthroplasty: Contaminant or Pathogen?

BACKGROUND: Cutibacterium spp. is an emerging pathogen in total hip arthroplasty (THA) that is not well evaluated in the literature. This study reported on the presentation and management of THA complicated by positive intraoperative Cutibacterium cultures. METHODS: This is a retrospective review of 27 revision THAs with positive monomicrobial intraoperative Cutibacterium cultures from 2014 to 2020 at one academic center. These patients were divided into two cohorts based on meeting Musculoskeletal Infection Society (MSIS) criteria for prosthetic joint infections (PJI). Patient demographics, preoperative labs, and hip aspirate results were collected. Procedure performed, postoperative antibiotic regimens, and repeat infections were recorded. Data were compared with univariate analysis. RESULTS: Nine of the 27 patients preoperatively met MSIS criteria for PJI. Patients with positive MSIS criteria had significantly higher median synovial cell count (P = .048) and neutrophil percentage in a preoperative aspirate (P = .050). Eight patients with positive MSIS criteria received six weeks of postoperative antibiotics compared to two patients with negative criteria. Two patients with positive MSIS criteria had a postoperative infection that required further surgical intervention. Four patients with negative criteria who required further surgical intervention did not receive postoperative antibiotics after initial revision. CONCLUSION: While often categorized as a contaminant, Cutibacterium is an increasingly recognized pathogen in THA. Cutibacterium can often present with normal serology, which may result in misdiagnosis as aseptic THA failure. Without the administration of postoperative antibiotics after positive cultures, there is a risk for persistent infection requiring further surgical intervention.

Patterns and Predictors of Weight Change Before and After Total Hip Arthroplasty in Class 2 and 3 Obese Patients.

BACKGROUND: This study aimed to better understand body mass index (BMI) change patterns and factors associated with BMI change before and after total hip arthroplasty (THA) in Class 2 and 3 obese patients, and assess if preoperative or postoperative BMI change affects postoperative clinical outcomes. METHODS: We retrospectively reviewed World Health Organization Class 2 and 3 obese patients (BMI > 35.0 at surgery) who underwent THA at a tertiary medical center from 2010 to 2020. BMI was recorded at 1 year preoperatively (mean 11.6 months), and at most recent postoperative visit (mean 29.0 months). Baseline demographics and postoperative clinical outcomes were recorded. RESULTS: We reviewed 436 THAs with a mean age of 59.9 (11.5) years. Leading up to surgery 55.5% had unchanged BMI, and postoperatively 48.2% had unchanged BMI. Multivariate logistic regression revealed that those who lost BMI preoperatively were more likely to gain BMI postoperatively (odds ratio [OR] 3.28, confidence interval [CI] 1.83-5.97, P = .005), but those who gained >5% BMI preoperatively had no association with BMI change postoperatively. Those in a higher BMI class preoperatively were less likely to gain BMI preoperatively (Class 3 obese patients: OR 0.001, CI 0.0002-0.004, P < .001). African American patients were more likely to gain BMI preoperatively (OR 2.32, CI 1.16-4.66, P = .017). We did not detect an association between BMI change and postoperative clinical outcomes. CONCLUSION: In World Health Organization Class 2 or 3 obese patients, most maintained BMI between their first preoperative and final postoperative visit. Preoperatively, Class 3 obese patients were less likely to gain weight than Class 2 obese patients. The primary predictor of postoperative weight gain was preoperative weight loss. Weight change preoperatively and postoperatively were not associated with worse clinical outcomes.

Preoperative Weight Loss and Postoperative Weight Gain Independently Increase Risk for Revision After Primary Total Knee Arthroplasty.

BACKGROUND: The current American Association of Hip and Knee Surgeons (AAHKS) guidelines recommend preoperative weight loss before total knee arthroplasty (TKA) in patients with body mass index (BMI) ≥40 kg/m2. However, there is a paucity of evidence on TKA outcomes after preoperative weight loss. This study therefore evaluated predictors of preoperative and postoperative BMI changes and their impact on outcomes after TKA. METHODS: This is a retrospective review of 3058 primary TKAs at an academic institution from 2015 to 2019. BMI was collected on the day of surgery. Preoperative and postoperative BMI at 6 months and 1 year were also obtained. BMI change of ≥5% was considered clinically significant. Mean follow-up was 3.2 years. Patient demographics, acute postoperative outcomes, and all-cause revisions were compared between patients who gained, lost, or maintained weight using univariate and multivariable analyses. RESULTS: Preoperative weight loss was predictive of postoperative weight gain (P < .001), and preoperative weight gain was predictive of postoperative weight loss (P < .001). Cox regression analysis revealed that ≥5% BMI loss preoperatively increased risk for all-cause revisions (P = .030), while ≥5% BMI gain postoperatively increased risk for prosthetic joint infections (P = .016). Patients who lost significant weight both before and after surgery had the highest risk for all-cause revisions (P = .022). CONCLUSION: Weight gain postoperatively was associated with inferior outcomes. Significant weight loss before surgery led to a "rebound" in weight gain, and independently increased risk for all-cause revision. Therefore, current recommendations for weight loss before TKA in morbidly obese patients should be re-evaluated.

Racial and Ethnic Disparities in the Imaging Workup and Treatment of Knee and Hip Osteoarthritis.

BACKGROUND: There is limited evidence on sociodemographic differences in osteoarthritis management, particularly in non-African American (AA) minorities. We sought to identify differences in imaging modalities, administration of intra-articular injections, and total joint arthroplasty (TJA) between racial/ethnic groups. METHODS: We retrospectively reviewed patients presenting to outpatient clinics with a diagnosis of hip or knee osteoarthritis from January 2013 to March 2020 at a tertiary center. Univariate analyses compared differences between groups. Multivariate logistic regression analyses determined sociodemographic predictors of imaging workup and treatment. RESULTS: In total, 105,873 patients were included. There were 74,769 (70.6%) Caucasian, 27,117 (25.6%) AA, 1,878 (1.8%) Hispanic, 1,479 (1.4%) Asian, and 630 (0.6%) Native American patients. Multivariate analyses demonstrated that AAs had decreased odds of undergoing a knee magnetic resonance imaging (odds ratio [OR] 0.77, P < .001) or injection (OR 0.94, P = .006). Asian patients had lower odds of receiving any hip X-ray (OR 0.72, P = .047) or knee injection (OR 0.83, P = .017). AA (total knee arthroplasty [TKA]: OR 0.51, P < .001; total hip arthroplasty [THA]: OR 0.57, P < .001), Hispanic (TKA: OR 0.69, P = .003; THA: OR 0.60, P = .006), and Asian (TKA: OR 0.73, P = .010; THA: OR 0.56, P = .010) patients had lower odds of undergoing TJA compared to Caucasians. We found that higher income quartiles had greater odds of receiving a magnetic resonance imaging and TJA, males had lower odds of receiving injections and greater odds of undergoing TJA, and Medicaid and self-pay patients had lower odds of undergoing TJA (P < .05). CONCLUSION: After adjusting for sociodemographic factors, we found disparities in the imaging, administration of injections, and/or arthroplasty for AA, Asian, and Hispanic patients. Insurance status, income, and gender were also associated with imaging and treatments performed in managing hip and knee osteoarthritis.

Time for Bed: Genetic Mechanisms Mediating the Circadian Regulation of Sleep.

Sleep is an evolutionarily conserved behavior that is increasingly recognized as important for human health. While its precise function remains controversial, sleep has been suggested to play a key role in a variety of biological phenomena ranging from synaptic plasticity to metabolic clearance. Although it is clear that sleep is regulated by the circadian clock, how this occurs remains enigmatic. Here we examine the genetic mechanisms by which the circadian clock regulates sleep, drawing on recent work in fruit flies, zebrafish, mice, and humans. These studies reveal that central and local clocks utilize diverse mechanisms to regulate different aspects of sleep, and a better understanding of this multilayered regulation may lead to a better understanding of the functions of sleep.

Effect of phase of enhancement on texture analysis in renal masses evaluated with non-contrast-enhanced, corticomedullary, and nephrographic phase-enhanced CT images.

OBJECTIVE: To compare texture analysis (TA) features of solid renal masses on renal protocol (non-contrast enhanced [NECT], corticomedullary [CM], nephrographic [NG]) CT. MATERIALS AND METHODS: A total of 177 consecutive solid renal masses (116 renal cell carcinoma [RCC]; 51 clear cell [cc], 40 papillary, 25 chromophobe, and 61 benign masses; 49 oncocytomas, 12 fat-poor angiomyolipomas) with three-phase CT between 2012 and 2017 were studied. Two blinded radiologists independently assessed tumor heterogeneity (5-point Likert scale) and segmented tumors. TA features (N = 25) were compared between groups and between phases. Accuracy (area under the curve [AUC]) for RCC versus benign and cc-RCC versus other masses was compared. RESULTS: Subjectively, tumor heterogeneity differed between phases (p < 0.01) and between tumors within the same phase (p = 0.03 [NECT] and p < 0.01 [CM, NG]). Inter-observer agreement was moderate to substantial (intraclass correlation coefficient = 0.55-0.73). TA differed in 92.0% (23/25) features between phases (p < 0.05) except for GLNU and f6. More TA features differed significantly on CM (80.0% [20/25]) compared with NG (40.0% [10/25]) and NECT (16.0% [4/25]) (p < 0.01). For RCC versus benign, AUCs of texture features did not differ comparing CM and NG (p > 0.05), but were higher for 20% (5/25) and 28% (7/25) of features comparing CM and NG with NECT (p < 0.05). For cc-RCC versus other, 36% (9/25) and 40% (10/25) features on CM had higher AUCs compared with NECT and NG images (p < 0.05). CONCLUSION: Texture analysis of renal masses differs, when evaluated subjectively and quantitatively, by phase of CT enhancement. The corticomedullary phase had the highest discriminatory value when comparing masses and for differentiating cc-RCC from other masses. KEY POINTS: • Subjectively evaluated renal tumor heterogeneity on CT differs by phase of enhancement. • Quantitative CT texture analysis features in renal tumors differ by phases of enhancement with the corticomedullary phase showing the highest number and most significant differences compared with non-contrast-enhanced and nephrographic phase images. • For diagnosis of clear cell RCC, corticomedullary phase texture analysis features had improved accuracy of classification in approximately 40% of features studied compared with non-contrast-enhanced and nephrographic phase images.

Shape Analysis of Peripheral Zone Observations on Prostate DWI: Correlation to Histopathology Outcomes After Radical Prostatectomy.

OBJECTIVE. The objective of our study was to subjectively and quantitatively assess shape features of peripheral zone (PZ) tumors at DWI compared with pathologic outcomes. MATERIALS AND METHODS. During the study period, 241 consecutive men with PZ dominant prostate tumors underwent 3-T MRI including DWI before undergoing radical prostatectomy. DW images of these patients were retrospectively assessed by two blinded radiologists. The reviewers assigned Prostate Imaging Reporting and Data System (PI-RADS) shape categories (round or oval, crescentic [i.e., conforming to PZ], linear or wedge-shaped) and segmented tumors for quantitative shape analysis. Discrepancies were resolved by consensus. Comparisons were performed with Gleason score (GS) and pathologic stage. RESULTS. Consensus review results were as follows: 63.9% (154/241) of tumors were round or oval; 22.8% (55/241), crescentic; and 13.3% (32/241), linear or wedge-shaped. Agreement for shape assessment was moderate (κ = 0.41). Round or oval tumors were higher grade (GS 6 = 1.3%, GS 7 = 78.0%, GS ≥ 8 = 20.7%) than crescentic tumors (GS 6 = 9.1%, GS 7 = 74.6%, GS ≥ 8 = 16.3%) and linear or wedge-shaped tumors (GS 6 = 6.3%, GS 7 = 78.1%, GS ≥ 8 = 15.6%) (p = 0.011). In addition, round or oval tumors had higher rates of extraprostatic extension (EPE) and seminal vesicle invasion (SVI) (EPE and SVI: 70.1% and 26.0%) than crescentic tumors (67.3% and 9.1%; p = 0.003) and linear or wedge-shaped tumors (40.6% and 9.4%; p = 0.008). Quantitatively, the shape features termed "circularity" and "roundness" were associated with EPE (p < 0.001 and p = 0.003), SVI (p < 0.001 and p = 0.029), and increasing GS (p = 0.009 and p = 0.021), but there was overlap between groups. CONCLUSION. In this study, approximately 10% of resected PZ tumors were linear or wedge-shaped on DWI. PZ tumors that were judged subjectively and evaluated quantitatively to be round or oval were associated with increased prostate cancer aggressiveness.

Early Results of Surgical Treatment of Triangular Fibrocartilage Complex Tears in Children and Adolescents.

PURPOSE: To investigate the clinical results and patient-reported outcomes following surgical treatment for triangular fibrocartilage complex (TFCC) tears in the pediatric and adolescent population. METHODS: We reviewed 149 patients with 153 arthroscopy-confirmed TFCC tears. Mean age at surgery was 15.5 years (range, 7-19 years). There were 86 females. Plain radiographs and magnetic resonance imaging were used to characterize bony and soft tissue pathology. Mayo Modified Wrist Score (MMWS) and Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity Short Form assessed functional outcomes. Median patient follow-up was 21.8 months (IQR:5.9-55.4). RESULTS: Pre-operatively, all patients had wrist pain or instability with activities. The median pre-operative MMWS was 80 (interquartile range [IQR], 65-90). Fifty-six (35%) presented with positive ulnar variance. Concomitant pathology included distal radioulnar joint (DRUJ) instability (14%), ulnocarpal impaction (20%), ulnar styloid nonunion (33%), and distal radius growth arrest (30%). On arthroscopy, there were 15 (10%) isolated 1A, 79 (52%) 1B, 1 (1%) 1C, 30 (20%) 1D tears, and 25 (16%) cases of multiple tears. Twenty-six percent of wrists underwent TFCC debridement, 68% arthroscopy-assisted repair, 6% both for combined tears. Fifty-one percent of wrists underwent bony procedures-most commonly ulnar-shortening osteotomy to achieve neutral ulnar variance (40%) and symptomatic ulnar styloid nonunion excision with concomitant TFCC repair (39%). At final follow-up, pain, wrist range of motion, DRUJ stability, ulnar variance, and MMWS (median, 95 [IQR, 86.5-100]) improved significantly. The median PROMIS T-score at final follow-up was 57 (IQR, 45-57). The MMWS was better in those with concomitant bony procedures at index surgery than those with only repair or debridement of TFCC tears. CONCLUSIONS: Most pediatric TFCC tears are posttraumatic and peripheral. Surgical treatment of TFCC tears and concomitant pathology in the pediatric and adolescent population results in decreased pain, improved motion and stability, and excellent functional outcomes in the majority of patients. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Transition zone prostate cancer: Logistic regression and machine-learning models of quantitative ADC, shape and texture features are highly accurate for diagnosis.

BACKGROUND: The limitation of diagnosis of transition zone (TZ) prostate cancer (PCa) using subjective assessment of multiparametric (mp) MRI with PI-RADS v2 is related to overlapping features between cancers and stromal benign prostatic hyperplasia (BPH) nodules, particularly in small lesions. PURPOSE: To evaluate modeling of quantitative apparent diffusion coefficient (ADC), texture, and shape features using logistic regression (LR) and support vector machine (SVM) models for the diagnosis of transition zone PCa. STUDY TYPE: Retrospective. POPULATION: Ninety patients; 44 consecutive TZ PCa were compared with 61 consecutive BPH nodules (26 glandular/35 stromal). FIELD STRENGTH/SEQUENCE: 3 T/T2 -weighted (T2 W) fast spin-echo, diffusion weighted imaging. ASSESSMENT: A radiologist manually segmented lesions on axial images for quantitative ADC (mean, 10th , 25th -centile-ADC), T2 W-shape (circularity, convexity) and T2 W-texture (kurtosis, skewness, entropy, run-length nonuniformity [RLNU], gray-level nonuniformity [GLNU]) analysis. A second radiologist segmented one-fifth of randomly selected lesions to determine the reproducibility of measurements. The reference standard was histopathology for all lesions. STATISTICAL TESTS: Quantitative features were selected a priori and were compared using univariate and multivariate analysis. LR and SVM models of statistically significant features were constructed and evaluated using receiver operator characteristic (ROC) analysis. Subgroup analysis of TZ PCa vs. only stromal BPH and in lesions measuring <15 mm was performed. Agreement in measurements was assessed using the Dice similarity coefficient (DSC). RESULTS: Mean, 25th and 10th -centile ADC, circularity, and texture (entropy, RLNU, GLNU) features differed between groups (P < 0.0001-0.0058); however, at multivariate analysis only circularity and ADC metrics (P < 0.001) remained significant. LR and SVM models were highly accurate for the diagnosis of TZ PCa (sensitivity/specificity/AUC): 93.2%/98.4%/0.989 and 93.2%/96.7%/0.949, respectively, with no significance difference between the LR and SVM models (P = 0.2271). Reproducibility of segmentation was excellent (DSC 0.84 tumors and 0.87 BPH). Subgroup analyses of TZ PCa vs. stromal BPH (AUC = 0.976) and in <15 mm lesions (AUC = 0.990) remained highly accurate. DATA CONCLUSION: LR and SVM models incorporating previously described quantitative ADC, shape and texture analysis features are highly accurate for the diagnosis of TZ PCa and remained accurate when comparing TZ PCa with stromal BPH and in smaller lesions. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:940-950.

Sleep Duration and Cognition in a Nationally Representative Sample of U.S. Older Adults.

OBJECTIVE: Excessive and insufficient sleep have been associated with cognitive dysfunction in older adults in U.S. and non-U.S. STUDIES: However, the U.S. studies were not in nationally representative samples. The authors investigated the association between sleep duration and cognitive performance in a nationally representative sample of U.S. older adults. PARTICIPANTS: The authors studied 1,496 survey participants aged 60 years or older from the National Health and Nutrition Examination Survey 2013-2014 dataset. MEASUREMENTS: Our primary predictor was weekday (or workday) nighttime sleep duration, categorized as 2-4, 5, 6, 7 (reference), 8, 9, and 10 hours or more. The authors studied five cognitive outcomes: Consortium to Establish a Registry for Alzheimer's Disease Word Learning (CERAD-WL) immediate recall, CERAD-WL delayed recall, Animal Fluency Test (AFT), Digital Symbol Substitution Test (DSST), and subjective cognitive problems (SCP). RESULTS: After adjusting for age, sex, race, education, depressive symptoms, and sedative-hypnotic use, sleep duration of 10 hours or more was significantly associated with lower scores on CERAD-WL immediate recall, CERAD-WL delayed recall, AFT, and DSST, and greater odds of SCP; sleep duration of 8 hours or more was associated with lower CERAD-WL delayed recall scores: 8, 9, and 10 hours or more. After adjustment, there were no significant associations of shorter sleep duration with cognition. CONCLUSION: In U.S. adults aged 60 years or older, long nighttime weekday or workday sleep duration is associated with poorer verbal memory, semantic fluency, working memory, and processing speed in addition to greater odds of self-reported cognitive problems. Long sleep duration may be a marker of fragmented sleep or neurodegeneration in U.S. older adults.

Citation bias in imaging research: are studies with higher diagnostic accuracy estimates cited more often?

OBJECTIVES: To assess the risk of citation bias in imaging diagnostic accuracy research by evaluating whether studies with higher accuracy estimates are cited more frequently than those with lower accuracy estimates. METHODS: We searched Medline for diagnostic accuracy meta-analyses published in imaging journals from January 2005 to April 2016. Primary studies from the meta-analyses were screened; those assessing the diagnostic accuracy of an imaging test and reporting sensitivity and specificity were eligible for inclusion. Studies not indexed in Web of Science, duplicates, and inaccessible articles were excluded. Topic (modality/subspecialty), study design, sample size, journal impact factor, publication date, times cited, sensitivity, and specificity were extracted for each study. Negative binomial regression was performed to evaluate the association of citation rate (times cited per month since publication) with Youden's index (sensitivity + specificity -1), highest sensitivity, and highest specificity, controlling for the potential confounding effects of modality, subspecialty, impact factor, study design, sample size, and source meta-analysis. RESULTS: There were 1016 primary studies included. A positive association between Youden's index and citation rate was present, with a regression coefficient of 0.33 (p = 0.016). The regression coefficient for sensitivity was 0.41 (p = 0.034), and for specificity, 0.32 (p = 0.15). CONCLUSION: A positive association exists between diagnostic accuracy estimates and citation rates, indicating that there is evidence of citation bias in imaging diagnostic accuracy literature. Overestimation of imaging test accuracy may contribute to patient harm from incorrect interpretation of test results. KEY POINTS: • Studies with higher accuracy estimates may be cited more frequently than those with lower accuracy estimates. • This citation bias could lead clinicians, reviews, and clinical practice guidelines to overestimate the accuracy of imaging tests, contributing to patient harm from incorrect interpretation of test results.

Improved and expanded Q-system reagents for genetic manipulations.

The Q system is a repressible binary expression system for transgenic manipulations in living organisms. Through protein engineering and in vivo functional tests, we report here variants of the Q-system transcriptional activator, including QF2, for driving strong and ubiquitous expression in all Drosophila tissues. Our QF2, Gal4QF and LexAQF chimeric transcriptional activators substantially enrich the toolkit available for transgenic regulation in Drosophila melanogaster.