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Purpose To evaluate the long-term effect of subthreshold nanosecond laser (SNL) treatment on progression to late age-related macular degeneration (AMD). Design Observational extension study of a randomized, sham-controlled trial. Participants Two hundred twelve participants with bilateral large drusen. Methods The Laser Intervention in the Early Stages of AMD (LEAD) study was a 36-month trial where participants were randomized to receive SNL or sham treatment in 1 eye at 6-monthly intervals up to 30 months. After the completion of the LEAD study, the 2 largest recruiting sites offered remaining participants an opportunity to enroll in a 24-month observational extension study. This study thus examined all participants from these 2 sites who were enrolled in the LEAD study at baseline, including the additional observational data. Main Outcome Measures Time to develop late AMD, defined on multimodal imaging, between those randomized the SNL or sham treatment. Results Overall, no significant difference was found in the rate of progression over a 60-month period in those randomized to the SNL compared with the sham group (adjusted hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.36–1.09; P = 0.098), similar to the findings at 36 months in the LEAD Study. However, evidence of treatment effect modification continued to emerge based on the coexistence of reticular pseudodrusen (RPD; P = 0.007, adjusted interaction). Namely, progression was slowed significantly with SNL treatment for those without coexistent RPD (adjusted HR, 0.34; 95% CI, 0.16–0.71; P = 0.004), but it was not significantly different for those with RPD (adjusted HR, 1.81; 95% CI, 0.67–4.88; P = 0.239). Conclusions A 24-month observational extension study to the LEAD Study confirmed that SNL treatment did not significantly reduce the overall rate of progression to late AMD in a cohort with intermediate AMD. However, the persistence of a potential beneficial treatment effect in those without coexistent RPD over a longer follow-up duration of an additional 24 months without additional treatment is encouraging. These findings provide further justification for future trials to examine the potential value of SNL treatment for slowing progression in intermediate AMD.

Increased physical activity has shown positive effects on various hippocampal memory functions through accumulating evidence that physical exercise and higher cardiorespiratory fitness can enhance human performance on nonspatial mnemonic discrimination tasks that rely on hippocampal pattern separation. However, there is less direct evidence of exercise effects on spatial pattern separation in humans, despite evidence for this association in rodent models. We examined the influence of strenuous exercise habits on spatial mnemonic discrimination among 176 young adults. We used a delayed match-/non-match-to-sample (same/different) task to assess pattern separation for spatial locations across varying degrees of similarity. Participants who reported regularly engaging in strenuous exercise three or more times per week performed significantly better than those who reported engaging in strenuous exercise fewer than three times per week, even when pattern separation tasks involved higher spatial similarity. These apparent exercise effects were observed for female, but not male, participants. These findings support likely benefits of strenuous exercise habits for human spatial pattern separation skills, and they suggest a need to explore potential interaction effects of exercise and gender.

Introduction: This study reviews malpractice, also called medical professional liability (MPL), claims involving adult patients cared for in emergency departments (ED) and urgent care settings. Methods: We conducted a retrospective review of closed MPL claims of adults over 18 years, from the Medical Professional Liability Association’s Data Sharing Project database from 2001–2015, identifying 6,779 closed claims. Data included the total amount, origin, top medical specialties named, chief medical factors, top medical conditions, severity of injury, resolution, average indemnity, and defense costs of closed claims. Results: Of 6,779 closed claims, 65.9% were dropped, withdrawn, or dismissed. Another 22.8% of claims settled for an average indemnity of $297,709. Of the 515 (7.6%) cases that went to trial, juries returned verdicts for the defendant in 92.6% of cases (477/515). The remaining 7.4% of cases (38/515) were jury verdicts for the plaintiff, with an average indemnity of $816,909. The most common resulting medical condition cited in paid claims was cardiac or cardiorespiratory arrest (10.4%). Error in diagnosis was the most common chief medical error cited in closed claims. Death was the most common level of severity listed in closed (38.5%) and paid (42.8%) claims. Claims reporting major permanent injury had the highest paid-to-closed ratio, and those reporting grave injury had the highest average indemnity of $686,239. Conclusion: This retrospective review updates the body of knowledge surrounding medical professional liability and represents the most recent analysis of claims in emergency medicine. As the majority of emergency providers will be named in a MPL claim during their career, it is essential to have a better understanding of the most common factors resulting in MPL claims.

BACKGROUND: High diet quality is associated with a lower risk of chronic diseases. Metabolomics can be used to identify objective biomarkers of diet quality. OBJECTIVES: We used metabolomics to identify serum metabolites associated with 4 diet indices and the components within these indices in 2 samples from African Americans and European Americans. METHODS: We studied cross-sectional associations between known metabolites and Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension Trial (DASH) diet, alternate Mediterranean diet (aMED), and their components using untargeted metabolomics in 2 samples (n(1) = 1,806, n(2) = 2,056) of the Atherosclerosis Risk in Communities study (aged 45–64 y at baseline). Dietary intakes were assessed using an FFQ. We used multivariable linear regression models to examine associations between diet indices and serum metabolites in each sample, adjusting for participant characteristics. Metabolites significantly associated with diet indices were meta-analyzed across 2 samples. C-statistics were calculated to examine if these candidate biomarkers improved prediction of individuals in the highest compared with lowest quintile of diet scores beyond participant characteristics. RESULTS: Seventeen unique metabolites (HEI: n = 6; AHEI: n = 5; DASH: n = 14; aMED: n = 2) were significantly associated with higher diet scores after Bonferroni correction in sample 1 and sample 2. Six of 17 significant metabolites [glycerate, N-methylproline, stachydrine, threonate, pyridoxate, 3-(4-hydroxyphenyl)lactate)] were associated with ≥1 dietary pattern. Candidate biomarkers of HEI, AHEI, and DASH distinguished individuals with highest compared with lowest quintile of diet scores beyond participant characteristics in samples 1 and 2 (P value for difference in C-statistics

The Latarjet procedure to treat instability was first described by the eponymous surgeon in 1954. Long-term results from this procedure have been favorable. In 2007, Lafosse et al. first described an all-arthroscopic technique for the Latarjet procedure. In the United States, the Latarjet procedure is most predictably indicated by surgeons in cases of significant glenoid bone loss, revision instability, and patients engaging in high-risk sport. In some European centers, the Latarjet has broader indications and is often also used as a first-line surgical intervention when conservative treatment has failed, including for those without bone loss or with multidirectional instability. • Achieve exposure of the inferior pole of coracoid and anterior glenoid rim; • coracoid is prepared; axillary nerve and brachial plexus are exposed; • coracoid portal is created; • coracoid is drilled and osteotomy is made; • coracoid transferred to anterior glenoid rim through split in subscapularis; • the bone graft is fixed in place with screws. Arthroscopic Latarjet can have a difficult learning curve compared with the open procedure. Both arthroscopic and open Latarjet have similar complication rates. The most common complications include graft fracture, non-union, and infection and are less than 2%. Arthroscopic Latarjet is reported to be less painful initially, but this equalizes by 1 month. Studies have shown that arthroscopic Latarjet results in excellent graft position. Recurrent instability for arthroscopic Latarjet ranges from 0.3% to 4.8% and is comparable with open Latarjet procedures. In summary, the arthroscopic Latarjet procedure results in less pain early, excellent coracoid graft position, and has a similar complication rate to open Latarjet.

Cognitive performance and cerebral hemispheric function are known to vary with fluctuating levels of estradiol and progesterone across the menstrual cycle in naturally cycling females. However, the literature is mixed with regard to how each hemisphere may be affected by elevated ovarian hormones. To better understand this, the current study employed a dual-task paradigm to examine potential shifts in hemispheric involvement for a verbal problem-solving task across the menstrual cycle in 30 right-handed, normally cycling young adult females (18–21 years old). To our knowledge, no study to date has utilized dual-task procedures to directly investigate the potential shifts in hemispheric function across the menstrual cycle. Specifically, participants were tested during both menses and their estimated midluteal phase where they engaged in repetitive unilateral finger-tapping while concurrently solving anagrams silently or aloud. Analysis of finger-tapping interference during the dual-task conditions revealed that solving anagrams silently was lateralized to the left hemisphere while solving anagrams aloud yielded a pattern of more bilateral hemispheric involvement, both of which were consistent across both menses and midluteal phases. Analysis of cognitive performance, however, revealed that silent anagrams performance while tapping with the right, but not left, hand significantly increased during the midluteal phase. Consistent with a number of other studies using different methodological approaches, the current dual-task findings suggest that when ovarian hormone levels are putatively elevated, there is enhanced recruitment of left hemisphere resources while performing a lateralized verbal task.

Bariatric surgery (BS) produces superior weight loss compared to non-surgical interventions. However, studies suggest bariatric patients who have undergone gastric-bypass surgery have an increased risk of developing new onset substance use disorder (SUD) or suffer negative outcomes after surgery. As such, many bariatric programs consider alcohol/ illicit drug misuse a contraindication to BS. The purpose of this systematic review was to investigate weight loss outcomes, post-surgery substance use patterns and other morbidity/mortality in BS patients with a history of substance use/SUD. Studies were identified by searching Ovid Medline(R), Embase, and PsychInfo. We included all study types investigating humans of any age/sex who had undergone any BS procedure with data regarding substance use before and/or after surgery. Outcome measures included metabolic outcomes and psychiatric outcomes after bariatric surgery in patients reporting substance use prior to bariatric surgery and substance use patterns after bariatric surgery. Fifty-eight studies were included in the review. Studies reporting weight loss after BS did not demonstrate an association between substance use and negative weight loss outcomes. Several studies reported a significant portion of participants having new onset or increased substance use after BS. Factors associated with new onset or increased substance use/SUD after BS included the type of surgery, a history of SUD, a family history of SUD, coping skills/life stressors, age, male sex and alcohol sensitization after surgery. Substance use history does not appear to influence weight loss after BS, however it may contribute to increased substance use after BS. Clinicians should ensure valid screening tools when assessing BS candidates for substance use history and ensure long term follow-up care post-operatively.

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

To report contemporary trends in hip arthroscopy case volume in the United States using a large cross-sectional cohort with accurate laterality tracking for assessment of revision surgery and rates of conversion to total hip arthroplasty (THA).Using Current Procedural Terminology codes, we queried the Mariner PearlDiver dataset for patients who underwent hip arthroscopy from 2010 to 2017. Patient demographics were recorded and subsequent hip arthroscopy procedures and THA conversion within 2 years after surgery were tracked using International Classification of Diseases, Tenth Revision codes to accurately identify laterality. Emergency department and hospital admission within 30 days after surgery were queried.Of the 53,103 patients undergoing hip arthroscopy procedures, hip arthroscopy case volume increased 2-fold from 2010 to 2014 but remained relatively unchanged from 2014 to 2017. The most common age group undergoing surgery was 40 to 49 years, and female patients represented 70% of cases. Two-year subsequent surgery rate was 19%, with 15.1% undergoing a revision arthroscopy and 3.9% converting to THA. The most common revision arthroscopy procedures were femoroplasty (9.5%), labral repair (8.5%), and acetabuloplasty (4.3%). Younger patients were more likely to undergo revision arthroscopy (18% age 10-19 years; 15% age 20-29 years). Older patients had a significant risk for conversion to THA within 2 years (36% age 60-69 years; 28% age 50-59 years). Female patients also demonstrated a slightly greater rate of conversion to THA (4.1% female, 3.5% male, P.0001). Patients 20 to 29 years had the greatest risk of emergency department admission (5.4%) and hospital admission (0.8%) within 30 days of surgery.The rise in hip arthroscopy procedures may be starting to plateau in the United States. Cross-sectional data also indicate that there is a greater than previously reported rate of revision hip arthroscopy in patients younger than 30 years of age and conversion to THA in patients older than 50 years of age.III, cross-sectional study.

PURPOSE To describe the key clinical, imaging, and arthroscopic characteristics of anchor arthropathy after arthroscopic shoulder stabilization procedures and, secondarily, to define risk factors for the development of anchor-induced arthropathy. METHODS A total of 23 patients who underwent revision arthroscopic shoulder surgery and were diagnosed with glenohumeral arthropathy were retrospectively identified from prospectively collected data registries between January 2000 and May 2018. Data included initial diagnosis and index procedure performed, presenting arthropathy symptoms including duration, and examination findings before revision surgery. Pre-revision imaging was used to assess presence of glenohumeral osteoarthritis and chondromalacia, anchors/sutures, loose bodies, and labral pathology. The same parameters were recorded intraoperatively during revision surgery. Descriptive statistics were performed for demographic data and means with standard deviations were calculated for continuous data. A McNemar-Bowker test was used to analyze marginal homogeneity between preoperative imaging and intraoperative findings. RESULTS Mean age at presentation was 33.4 ± 11.7 years (range 16-59, 17 male patients; 6 female patients). More than one half (13/23) developed symptoms within 10 months after index arthroscopic procedure (mean 32.2 ± 59.9 months, range

Background The onset of the COVID-19 pandemic led to the postponement of low-acuity surgical procedures in an effort to conserve resources and ensure patient safety. This study aimed to characterize patient-reported concerns about undergoing surgical procedures during the pandemic. Methods We administered a cross-sectional survey to patients who had their general and plastic surgical procedures postponed at the onset of the pandemic, asking about barriers to accessing surgical care. Questions addressed dependent care, transportation, employment and insurance status, as well as perceptions of and concerns about COVID-19. Mixed methods and inductive thematic analyses were conducted. Results One hundred thirty-five patients were interviewed. We identified the following patient concerns: contracting COVID-19 in the hospital (46%), being alone during hospitalization (40%), facing financial stressors (29%), organizing transportation (28%), experiencing changes to health insurance coverage (25%), and arranging care for dependents (18%). Nonwhite participants were 5 and 2.5 times more likely to have concerns about childcare and transportation, respectively. Perceptions of decreased hospital safety and the consequences of possible COVID-19 infection led to delay in rescheduling. Education about safety measures and communication about scheduling partially mitigated concerns about COVID-19. However, uncertainty about timeline for rescheduling and resolution of the pandemic contributed to ongoing concerns. Conclusions Providing effective surgical care during this unprecedented time requires both awareness of societal shifts impacting surgical patients and system-level change to address new barriers to care. Eliciting patients’ perspectives, adapting processes to address potential barriers, and effectively educating patients about institutional measures to minimize in-hospital transmission of COVID-19 should be integrated into surgical care.

Background Mental health conditions are associated with poor outcomes in patients with chronic disease as well as various orthopedic conditions. The purpose of this study was to describe the relationship between mental health, preoperative disability, and postoperative outcomes in patients undergoing shoulder arthroplasty. Methods Data, including mental health diagnoses, were prospectively collected from patients undergoing total shoulder arthroplasty or reverse total shoulder arthroplasty from 2009 to 2015 at a single academic institution. Shoulder range of motion, visual analog scale, 12-Item Short Form Health Survey, and American Shoulder and Elbow Surgeons scores were collected preoperatively and at 1 and 2 years postoperatively. Data were analyzed using multivariate mixed-effect regression analysis. Results The study included 280 patients, 105 (37.5%) of whom had a mental health diagnosis of depression, anxiety, schizophrenia, or bipolar disorder. Both groups of patients had similar shoulder range of motion, pain, and function before shoulder arthroplasty. Hospital length of stay, discharge destination, and readmissions were similar for both groups. There were similar improvements in pain, function, and range of motion after shoulder arthroplasty in patients with and without diagnosed mental health conditions. Conclusions Overall, the presence of a psychiatric diagnosis was not predictive of outcomes. Although psychiatric conditions are often considered surgical comorbidities, mental health diagnoses should not be a barrier to performing clinically indicated shoulder arthroplasty, because both groups of patients appear to benefit from pain relief and improved shoulder function.

Complementary and alternative medicine (CAM) is popular among Chinese-speaking cancer patients (CSCPs), but little research examines CAM use by Canadian CSCPs. The use of CAM is controversial because of potential interactions with conventional cancer treatments. The purpose of this study was to explore CSCPs’ use of CAM, sources of CAM information, and decision support needs, as well as their experience of making CAM decisions. A sequential, multi-method research design was used: a secondary data analysis of a CAM use survey conducted in a Western Canadian regional cancer agency followed by a qualitative interpretive description approach to inquiry using semi-structured interviews with CSPCs and support persons. More than 65% of CSCPs reported using CAM. CSCPs favored biologically-based therapies, including traditional Chinese medicine herbs and other natural health products. Many CSCPs were using CAM without adequate culturally appropriate information and decision support. Those who made decisions spontaneously relied on peers for advice whereas deliberate decision makers sought information from multiple sources, including peers and the Internet, selecting therapies congruent with their cultural health perspectives and previous experiences with CAM. CSCPs rarely spoke with oncology healthcare providers (HCPs) about CAM use. CSCPs reported using CAM at rates significantly higher than for non-CSCPs. Given the predominance of biological-based therapies and the lack of consultation with oncology HCPs, it is imperative that CAM use be assessed and documented to ensure CSCPs’ safety during cancer treatment. Culturally appropriate information and decision support is required to ensure that CSCPs are making safe and informed CAM decisions.

Specialization of the auditory cortices for pure tone listening may develop with age. In adults, the right hemisphere dominates when listening to pure tones and music; we thus hypothesized that (a) asymmetric function between auditory cortices increases with age and (b) this development is specific to tonal rather than broadband/non‐tonal stimuli. Cortical responses to tone‐bursts and broadband click‐trains were recorded by multichannel electroencephalography in young children (5.1 ± 0.8 years old) and adolescents (15.2 ± 1.7 years old) with normal hearing. Peak dipole moments indicating activity strength in right and left auditory cortices were calculated using the Time Restricted, Artefact and Coherence source Suppression (TRACS) beamformer. Monaural click‐trains and tone‐bursts in young children evoked a dominant response in the contralateral right cortex by left ear stimulation and, similarly, a contralateral left cortex response to click‐trains in the right ear. Responses to tone‐bursts in the right ear were more bilateral. In adolescents, peak activity dominated in the right cortex in most conditions (tone‐bursts from either ear and to clicks from the left ear). Bilateral activity was evoked by right ear click stimulation. Thus, right hemispheric specialization for monaural tonal stimuli begins in children as young as 5 years of age and becomes more prominent by adolescence. These changes were marked by consistent dipole moments in the right auditory cortex with age in contrast to decreases in dipole activity in all other stimulus conditions. Together, the findings reveal increasingly asymmetric function for the two auditory cortices, potentially to support greater cortical specialization with development into adolescence.

The objective was to assess sustainability of a statewide program of HIV rapid testing (RT) for pregnant women presenting for delivery with unknown HIV status. This is a population-based retrospective cohort study of women delivered in Illinois hospitals (2012–15). Deidentified data on RT metrics from state-mandated surveillance reports were compared using descriptive statistics and non-parametric tests of trend. Over 95% of the 608,408 women delivered had documented HIV status at presentation. The rate of undocumented HIV status rose from 4.19 to 4.75% (p < 0.001). However, overall 99.60% of women with undocumented status appropriately received RT and the proportion who did not receive RT declined (p = 0.003). The number of neonates discharged with unknown HIV status declined (p = 0.011). RT identified 23 new HIV diagnoses, representing 4.62% of maternal HIV diagnoses. In conclusion, statewide perinatal HIV RT resulted in nearly 100% of Illinois mother-infant dyads with known HIV status. Sustained RT completion represents an important prevention safety net.

Cesarean delivery is the most common surgical procedure performed in the USA. We evaluated the postoperative analgesic properties of neuraxial hydromorphone compared to neuraxial morphine for post-cesarean delivery analgesia.A retrospective chart review was performed of women who underwent cesarean delivery and received neuraxial anesthesia from March to November 2011 and from March to November 2012. A total of 450 patients received intrathecal morphine 200μg and 387 patients received intrathecal hydromorphone 60μg. Eighty-one patients received epidural morphine 3mg and 102 patients received epidural hydromorphone 0.6mg.Median time to first opioid after intrathecal morphine was 17.0h versus 14.6h after intrathecal hydromorphone (P0.0001). Patients who received intrathecal hydromorphone consumed more opioids in the first 24h; 37.0mg versus 26.4mg oral morphine equivalents (P0.001). The side effect profile between the intrathecal groups was similar. Median time to first opioid with epidural morphine was 20.1h versus 13.0h with epidural hydromorphone (P=0.0007). Total opioid consumption was not significantly different between the epidural groups. The side effect profiles were similar.Hydromorphone is a reasonable alternative to morphine for post-cesarean delivery analgesia. With the dosing used in our study, analgesia from morphine lasted longer than hydromorphone via intrathecal and epidural routes; however, neuraxial hydromorphone remains a reasonable option for long-acting analgesia post cesarean delivery.

Tonsil-related complaints are very common among the adult population. Tonsillectomy under general anesthesia is currently the most performed surgical treatment in adults for such complaints. Unfortunately, tonsillectomy is an invasive treatment associated with a high complication rate and a long recovery time. Complications and a long recovery time are mostly related to removing the vascular and densely innervated capsule of the tonsils. Recently, CO2-lasertonsillotomy under local anesthesia has been demonstrated to be a viable alternative treatment for tonsil-related disease with a significantly shorter and less painful recovery period. The milder side-effect profile of CO2-lasertonsillotomy is likely related to leaving the tonsil capsule intact. The aim of the current report is to present a concise protocol detailing the execution of CO2-lasertonsillotomy under local anesthesia. This intervention has been performed successfully in our hospital in more than 1,000 patients and has been found to be safe and to be associated with a steep learning curve.

BACKGROUND: Data on how baseline characteristics, acuity, morbidity, and nutrition work in combination to affect the growth of very-low-birth-weight (VLBW

Humans comprehend speech despite the various challenges such as mispronunciation and noisy environments. Our auditory system is robust to these thanks to the integration of the sensory input with prior knowledge and expectations built on language-specific regularities. One such regularity regards the permissible phoneme sequences, which determine the likelihood that a word belongs to a given language (phonotactic probability; "blick" is more likely to be an English word than "bnick"). Previous research demonstrated that violations of these rules modulate brain-evoked responses. However, several fundamental questions remain unresolved, especially regarding the neural encoding and integration strategy of phonotactics in naturalistic conditions, when there are no (or few) violations. Here, we used linear modelling to assess the influence of phonotactic probabilities on the brain responses to narrative speech measured with non-invasive EEG. We found that the relationship between continuous speech and EEG responses is best described when the stimulus descriptor includes phonotactic probabilities. This indicates that low-frequency cortical signals (9 Hz) reflect the integration of phonotactic information during natural speech perception, providing us with a measure of phonotactic processing at the individual subject-level. Furthermore, phonotactics-related signals showed the strongest speech-EEG interactions at latencies of 100-500 ms, supporting a pre-lexical role of phonotactic information.

Background:Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.Objective:To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.Methods:Clinical isolates ofStaphylococcus aureus,Enterococcus faecium,Pseudomonas aeruginosa, andKlebsiella pneumoniaewere obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.Results:Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.Conclusions:Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.

Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves suitable for their own specific anatomical pathology. The in vivo bioreactor strategy facilitates the generation of large autologous vascularized bony tissue of customized geometry without the addition of exogenous growth factors or cells. To translate this technology, we investigated its success in reconstructing a mandibular defect of physiologically relevant size in sheep. We fabricated and implanted 3D-printed in vivo bioreactors against rib periosteum and utilized biomaterial-based space maintenance to preserve the native anatomical mandibular structure in the defect site before reconstruction. Nine weeks after bioreactor implantation, the ovine mandibles were repaired with the autologous bony tissue generated from the in vivo bioreactors. We evaluated tissues generated in bioreactors by radiographic, histological, mechanical, and biomolecular assays and repaired mandibles by radiographic and histological assays. Biomaterial-aided mandibular reconstruction was successful in a large superior marginal defect in five of six (83%) sheep. Given that these studies utilized clinically available biomaterials, such as bone cement and ceramic particles, this strategy is designed for rapid human translation to improve outcomes in patients with large mandibular defects.

BACKGROUND: Optimal management of neutropenic appendicitis (NA) in children undergoing cancer therapy remains undefined. Management strategies include upfront appendectomy or initial nonoperative management. We aimed to characterize the effect of management strategy on complications and length of stay (LOS) and describe implications for chemotherapy delay or alteration. METHODS: Sites from the Pediatric Surgery Oncology Research Collaborative performed a retrospective review of children with NA over a 6-year period. RESULTS: Sixty-six children, with a median age of 11 years (range 1–17), were identified with NA while undergoing cancer treatment. The most common cancer diagnoses were leukemia (62%) and brain tumor (12%). Upfront appendectomy was performed in 41% of patients; the remainder had initial nonoperative management. Rates of abscess or perforation at diagnosis were equivalent in the groups (30% vs 24%; P = .23). Of patients who had initial nonoperative management, 46% (17 of 37) underwent delayed appendectomy during the same hospitalization. Delayed appendectomy was due to failure of initial nonoperative management in 65% (n = 11) and count recovery in 35% (n = 6). Cancer therapy was delayed in 35% (n = 23). Initial nonoperative management was associated with a delay in cancer treatment (46% vs. 22%, P = .05) and longer LOS (29 vs 12 days; P = .01). Patients who had initial nonoperative management and delayed appendectomy had a higher rate of postoperative complications (P CONCLUSIONS: In pediatric patients with NA from oncologic treatment, upfront appendectomy resulted in lower complication rates, reduced LOS, and fewer alterations in chemotherapy regimens compared to initial nonoperative management.

OBJECTIVE To describe antithrombin concentrate use and to compare thrombotic and hemorrhagic outcomes throughout the hospital stay in pediatric subjects who received extracorporeal membrane oxygenation in a Pediatric Health Information System-participating children's hospital. DESIGN Retrospective, multi-center, cohort study. SETTING Forty-three free-standing children's hospitals participating in Pediatric Health Information System. SUBJECTS Children older than or equal to 18 years of age who underwent extracorporeal membrane oxygenation between 2003 and 2012. INTERVENTIONS Subjects were classified as receiving antithrombin if they received at least one dose of antithrombin while on extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS International Classification of Diseases, Ninth Revision, Clinical Modification codes codes were used to identify hemorrhagic and thrombotic complications during their hospitalization. Pediatric Health Information System data were analyzed to determine hospital-length of stay and in-hospital mortality. A total of 1,931 of 8,601 eligible subjects (21.5%) received at least one dose of antithrombin during their extracorporeal membrane oxygenation course. Antithrombin use during extracorporeal membrane oxygenation increased from 2.4% to 51.9% (p < 0.001) over the 10-year study period. Subjects who received antithrombin while on extracorporeal membrane oxygenation were younger (p = 0.02), had more chronic conditions (p < 0.001), and longer hospital stays (p < 0.001). On multivariate analysis, antithrombin use was associated with thrombotic events (odds ratio, 1.55; 95% CI, 1.36-1.77; p < 0.001), hemorrhagic events (odds ratio, 1.27; 95% CI, 1.14-1.42; p < 0.001), and longer hospital length of stays (slope coefficient, 1.05 d; 95% CI, 1.04-1.06; p < 0.001). No difference was observed in mortality (odds ratio, 0.99; 95% CI, 0.89-1.11; p = 0.90). CONCLUSIONS In this multicenter retrospective cohort study, subjects who received antithrombin during extracorporeal membrane oxygenation had a higher number of thrombotic and hemorrhagic events throughout the hospitalization and longer length of stays without an associated difference in mortality. While limitations exist with this analysis and results should be interpreted with caution, the fact remains that over half of pediatric patients on extracorporeal membrane oxygenation are currently receiving antithrombin without clear benefit, with extra cost, and potential harms, there needs to be strong consideration for a clinical trial.

Background Abdominal aortic aneurysm (AAA) continues to be a significant health burden yet few countries have implemented a comprehensive screening programme. Screening typically places emphasis on men aged over 65 years; however, there is concern that other at-risk groups may be underidentified. The present study examined three potential screening strategies based on cardiovascular risk. Methods The prevalence of AAA was determined by abdominal ultrasound imaging in over 50-year-olds of either sex undergoing coronary angiography, vascular laboratory assessment of peripheral arterial disease, or community-based cardiovascular disease (CVD) event risk assessment. A fourth group, consisting of volunteers aged over 60 years who had no symptoms or signs of cardiovascular disease, was used as a comparator group. Results A total AAA prevalence of 4·4 per cent was detected across all three strategies (137 of 3142 individuals), compared with 1·0 per cent in the CVD-free group. Male sex, age and smoking were all associated with greater AAA prevalence. Although AAA prevalence was lowest using the community-based strategy, those with an AAA detected were on average 7 years younger than those with AAAs detected with the other two strategies (P < 0·001). Conclusion Different strategies, based on CVD risk, resulted in AAA prevalence rates that were significantly greater than that in CVD-free individuals. This may provide opportunities for a targeted approach to community AAA screening in parts of the world where more sophisticated national screening programmes do not exist.

Total shoulder arthroplasty and reverse total shoulder arthroplasty are increasingly used to improve pain and function in patients with glenohumeral arthritis or cuff tear arthropathy. Our objective was to determine if preoperative patient-reported outcome measures predict which patients will achieve clinically meaningful improvements after shoulder arthroplasty.Preoperative and 1-year postoperative 12-Item Short Form Health Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores and American Shoulder and Elbow Surgeons (ASES) pain and function scores were prospectively collected from 107 patients who underwent total or reverse shoulder arthroplasty. The minimum clinically important difference (MCID) defined meaningful clinical improvement. Receiver operating characteristic analysis was used to calculate threshold values and C statistic. Multivariate logistic regression analysis was performed to determine preoperative measures that were indicative of achieving the MCID postoperatively.Threshold values below which patients were more likely to achieve MCID were 12 for ASES function, 25 for ASES pain, 46 for SF-12 PCS, and 42 for SF-12 MCS. Multivariate analysis revealed that preoperative ASES function (area under the curve, 0.79; P = .006) and ASES pain (area under the curve, 0.90; P .001) measures were predictive of achieving the MCID postoperatively. Patients with higher preoperative SF-12 MCS scores had a higher likelihood of achieving MCID for each measure.We determined threshold values that predict clinically meaningful improvement after shoulder arthroplasty. Patients with higher preoperative mental health scores and lower physical function and pain scores were more likely to gain significant benefits from surgery. These results can be used to facilitate shared decision-making and to forecast expected benefits after shoulder arthroplasty.

BACKGROUND Sleep-wake disturbances are experienced by as many as 75% of patients with cancer and are associated with poor symptom management, lower functionality, and decreased quality of life. Although promising sleep interventions exist, they require extensive resources and time. OBJECTIVES The objectives of this study were to develop a brief, self-administered sleep intervention and to evaluate the feasibility and potential efficacy of its implementation with adult patients with cancer who were about to receive, were receiving, or had received radiation therapy in an ambulatory cancer care setting. METHODS Pre- and postintervention surveys and qualitative interviews were conducted with patients with cancer experiencing insomnia (N = 28) and receiving radiation treatment within the past six months. Patients received instruction on breathing, visualization, and intonation. Adherence and sleep quality were primary study outcomes. Analyses included descriptive statistics and repeated measure regression analysis. Thematic analysis was conducted on qualitative data. FINDINGS Adherence to the sleep intervention was high (75%), and significant improvement was found in global sleep quality (p < 0.0001) regardless of level of adherence. Sleep onset latency (p = 0.0005), sleep duration (p = 0.0016), and sleep quality (p < 0.0001) were significantly improved. Age was significantly correlated with sleep quality (p = 0.0094), with older participants reporting greater benefit from the intervention. Participants reported that the intervention was easy to learn and implement and that it "calmed the mind."

A polymer prodrug, composed of doxorubicin (Dox) conjugated covalently to poly(methacryloyloxyethyl phosphorylcholine) (polyMPC), was evaluated for the treatment of human ovarian tumors in animals. PolyMPC-Dox prodrugs were prepared using facile conjugation chemistry to yield conjugates soluble in water and injectable saline, with a Dox loading of ∼19 weight percent. Toxicity evaluation showed that polyMPC was well-tolerated in mice at doses up to 800 mg/kg, confirming the biocompatibility of the polymer carrier at a high concentration. Additionally, the polyMPC-Dox prodrug was well-tolerated in animals at a Dox equivalent dose of 10 mg/kg, greater than twice the maximum tolerated dose of free Dox (∼4 mg/kg) in the same mouse strain. In a human ovarian tumor model (SKOV-3), polyMPC-Dox accumulated in tumors at twice the level of free Dox, with no additional off-target organ uptake, a result of improved pharmacokinetics afforded by the prodrug and passive targeting attributed to an enhanced permeability and retention effect. When administered to human ovarian tumor-bearing mice using a recurring dosing regimen comparable to that used clinically, polyMPC-Dox significantly retarded tumor growth relative to treatment with free Dox. Moreover, animals treated with multiple doses of polyMPC-Dox (eight total doses) exhibited enhanced survival, with a notably reduced incidence of toxicity or adverse events relative to mice treated with free Dox. These in vivo results demonstrate advantages of treating human ovarian tumors with polyMPC-Dox, including reduced systemic toxicity, improved drug accumulation in tumors, and enhanced therapeutic efficacy.

Theophylline is a commonly used bronchodilator. However, due to its narrow therapeutic range, moderate elevation of serum concentration can result in adverse drug reactions (ADRs). ADRs occur because of interhuman pharmacokinetic variability and interactions with coprescribed medicines. We developed a physiologically based pharmacokinetic (PBPK) model of theophylline, caffeine, and ciprofloxacin metabolisms to: examine theophylline pharmacokinetic variability, and predict population-level outcomes of drug-drug interactions (DDIs). A simulation-based equation for personalized dosing of theophylline was derived. Simulations of DDI show that calculated personalized doses are safe even after cotreatment with large doses of strong inhibitors. Simulations of adult populations indicate that the elderly are most susceptible to ADRs stemming from theophylline-ciprofloxacin and theophylline-caffeine interactions. Females, especially Asians, due to their smaller average size, are more susceptible to DDI-induced ADRs following typical dosing practices. Our simulations also show that the higher adipose and lower muscle fractions in females significantly alter the pharmacokinetics of theophylline or ciprofloxacin.

Scope Serum metabolomic markers of the Dietary Approaches to Stop Hypertension (DASH) diet were previously reported. We investigated if urine metabolomic markers were similar in an independent clinical trial. Methods and results In the DASH-Sodium trial, participants were randomly assigned to the DASH diet or control diet, and received three sodium interventions (high, intermediate, low) within each randomized diet group in random order for 30 days each. Urine samples were collected at the end of the intervention period and analyzed for 938 metabolites. We conducted two comparisons of metabolomic profiles: 1) DASH-high sodium (n = 199) versus control-high sodium (n = 193), and 2) DASH-low sodium (n = 196) versus control-high sodium. We compared significant metabolites identified using multivariable linear regression and the top 10 influential metabolites identified using partial least-squares discriminant analysis to the results from a previous analysis of the DASH trial. Nine out of 10 predictive metabolites of the DASH-high sodium and DASH-low sodium diets were identical. Most candidate biomarkers from the DASH trial replicated. N-methylproline, chiro-inositol, stachydrine, and theobromine replicated as influential metabolites of DASH diets. Conclusions Candidate biomarkers of the DASH diet identified in serum replicated in urine. Replicated influential metabolites are likely to be objective biomarkers of the DASH diet. This article is protected by copyright. All rights reserved.

Objective: To determine the prevalence, sonographic spectrum, and clinical significance of echogenic material in the fetal gallbladder in our population.Methods: Sonographic visualization of the fe...

Dermatomyositis is an idiopathic inflammatory myopathy known to occur as a paraneoplastic syndrome. The course of dermatomyositis is commonly reported to mirror the course of the malignancy. Here, we report a case of dermatomyositis that developed in a patient after lump- ectomy and completed chemotherapeutic treatment.

ObjectiveTypical executive functioning (EF) measurements do not reflect the complexity of daily life. We derived an executive behavior screener from the BASC-2-PRS-A using a previously derived four-component model of EF and provided support for the use of the screener in adolescent populations.MethodsA total of 2,722 census-matched American adolescents were sampled. We assigned 25 items a priori to four executive factors (problem solving, attentional control, behavioral control, and emotional control) and evaluated via confirmatory factor analysis, invariance testing and differential item functioning (DIF) models.ResultsWe found acceptable-to-good reliability and that the four-factor model had the best fit. We showed DIF for age and socioeconomic status (SES). While groups were invariant based on sex, latent mean comparisons showed significant differences.ConclusionsConstruct validity of the adolescent four-factor model as measured through the screener was supported. Females demonstrated fewer executive behavior problems. Standardized norms are available and split by age and sex. SES may influence the interpretation of T-scores. Continued exploration and development of the screener is suggested.

Microparticles (MPs) bearing tissue factor (TF) are potent activators of the coagulation system. To investigate whether MPs originating from platelets or trophoblast cells contribute to coagulation changes in pregnancy, we aimed to characterize whether pregnancy, labor, and delivery are associated with changes in the origin and composition of circulating maternal MPs. We performed a prospective cohort study. Blood samples were collected in 20 non-pregnant women, 20 term pregnant women not in labor, and 20 term pregnant women in labor. Two samples were collected in the pregnant groups, the first prior to delivery and the second 1 h after delivery. MPs from platelets and trophoblasts and MPs expressing TF were identified using flow cytometry. Comparisons were made among the non-pregnant and pregnant groups, non-laboring and laboring groups, and predelivery and postdelivery values within the pregnant groups. Pregnancy was not associated with changes in MP origin or number of TF-expressing MPs. Neither labor nor delivery was associated with changes in the percentage of trophoblast-derived MPs in the pregnant groups. The percentage of platelet-derived MPs among laboring women increased after delivery (8.5 vs. 20.5 %, p = 0.02), although there was no difference with delivery in the non-laboring group. TF expression was not associated with delivery in either laboring or non-laboring women. In conclusion, pregnancy was not associated with changes in cell origin of circulating maternal MPs or in the number of TF-expressing MPs. However, labor and delivery appear to be associated with an increase in the number of platelet-derived MPs.

The severe forms of thalassemia are the most common inherited anemias managed with regular blood transfusion therapy. Transfusion policies and complications are critical to quality of life and survival, but there is a lack of standardized care.A survey of 58 items was completed in 2016 by 11 centers in California, Washington, Oregon, Nevada, and Arizona providing long-term care for thalassemia. The questionnaire addressed demographic information, transfusion practices and complications, and educational needs.The centers followed 717 patients with β-thalassemia (314, 43.8%) or α-thalassemia (394, 55%). One-third (34.7%) of patients were transfusion-dependent. Indications and goals of transfusion therapy differed between centers. Prestorage leukoreduction was universal, while routine irradiation of units was limited to one site. Red blood cell antigen phenotype was determined before the first transfusion and patients received Rh/Kell-matched units. However, more than half of the transfused patients had received blood at multiple hospitals within or outside the United States. Alloantibodies were seen in 16.9% of transfused group, but management of such patients was variable. Unusual or emerging transfusion-transmitted pathogens were not observed. Multiple educational needs were recognized, with iron overload as the biggest challenge; the approach to iron chelation varied within the group.This study identified many patients not included in earlier surveys limited to major national centers, suggesting that the thalassemia population in the United States is vastly underestimated. Lack of evidence-based guidelines is a barrier to optimal care, which should be addressed through regional consortia of thalassemia centers.

Background Gender differences may exist for patients undergoing shoulder arthroplasty. Limited data suggest that women may have worse preoperative disability and outcomes. Our objective was to determine whether gender influences preoperative disability and patient-reported outcomes after reverse total shoulder arthroplasty. Methods Data were prospectively collected for patients who underwent reverse total shoulder arthroplasty for rotator cuff arthropathy or osteoarthritis with a rotator cuff tear at a single institution between 2009 and 2015. Range of motion, visual analog scale, 12-Item Short Form Health Survey (SF-12), and American Shoulder and Elbow Surgeons (ASES) scores were collected at the preoperative, 1-year, and 2-year postoperative time points. Data were analyzed using multivariate mixed-effect regression analysis. Results There were 117 patients included. Men and women had similar demographics, preoperative range of motion, pain, and function. Length of stay was similar (men, 2.32 days; women, 2.58 days; P = .18). Controlling for patient variables, men achieved higher ASES function (P = .009) and SF-12 Physical Component Summary (P = .008) scores compared with women. There was no difference between men and women in ASES pain and SF-12 Mental Component Summary scores, visual analog scale score, or range of motion. Conclusion Improvements in pain and range of motion were similar in men and women; however, men achieved higher ASES function and SF-12 Physical Component Summary scores. Women may be more functionally impaired on the basis of differences in activities of daily living. These results may be used to guide discussion about expected benefits after reverse shoulder arthroplasty.

Medscape Continuing Medical Education online This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint providership of Medscape, LLC and the American Society of Hematology

Purpose The purpose of this study is to measure the effectiveness of compressive orthotic brace therapy for the treatment of pectus carinatum using an adjusted Haller Index (HI) measurement calculated from 3D body scan (BS) images. Methods Pediatric patients with pectus carinatum were treated with either compressive orthotic bracing or observation. An adjusted BS Haller index (HI) was calculated from serial 3D BS images obtained on all patients. Medical records were evaluated to determine treatment with bracing and brace compliance more than 12hours daily. Compliant patient measurements were compared to non-compliant and non-brace groups. Results Forty patients underwent compressive orthotic bracing, while ten were observed. Twenty-three patients were compliant with bracing, and seventeen patients were non-compliant. Compliant patients exhibited an 8.2% increase, non-compliant patients had a 1.5% increase, and non-brace patients exhibited a 2.5% increase in BS HI. The change in BS HI of compliant patients was significantly different compared to non-brace patients (p=0.004) and non-compliant patients (p Conclusions Three dimensional BS is an effective, radiation free, and objective means to evaluate patients treated with compressive orthotic bracing.

Background. The proportion of patients with clinical findings referable to peroneal pathology and magnetic resonance imaging (MRI)–diagnosed peroneal tendon pathology is unknown. Previous studies have correlated surgical findings with clinical data and preoperative MRI, but there are no published studies that reference clinical examination findings to imaging findings. Purpose. To determine the relationship between peroneal tendon pathology as diagnosed by MRI and clinical findings of peroneal tendon pathology. Methods. Fifty-six patients who had both MRI evidence of peroneal tendon pathology and an associated clinical examination of the ankle were evaluated over a 3-year period at a tertiary care institution. Clinical examination criteria included lateral ankle tenderness, dislocation/snapping, and lateral ankle pain. A board-certified, fellowship-trained musculoskeletal radiologist confirmed the presence of MRI findings consistent with peroneal tendon pathology. Results. Of the 56 patients with positive findings on MRI, 27 patients had an associated positive clinical exam and 29 patients had a negative clinical exam. The positive predictive value of MRI for peroneal tendon tears with positive clinical findings was 48% (95% confidence interval = 35% to 61%). Conclusion. Patients with MRI findings of peroneal tendon pathology should undergo careful clinical examination, as the positive predictive value of MRI for peroneal tendon pathology with actual clinical findings is low. This study demonstrates that peroneal tendon tears are often incidental findings on MRI. Levels of Evidence: Diagnostic, Level III

Unilateral hearing in childhood restricts input along the bilateral auditory pathways, possibly causing permanent reorganization. In this study we asked: (i) do the auditory pathways develop abnormally in children who are bilaterally deaf and hear with a unilateral cochlear implant? and (ii) can such differences be reversed by restoring input to the deprived ear? We measured multichannel electroencephalography in 34 children using cochlear implants and seven normal hearing peers. Dipole moments of activity became abnormally high in the auditory cortex contralateral to the first implant as unilateral cochlear implant use exceeded 1.5 years. This resulted in increased lateralization of activity to the auditory cortex contralateral to the stimulated ear and a decline in normal contralateral activity in response to stimulation from the newly implanted ear, corresponding to poorer speech perception. These results reflect an abnormal strengthening of pathways from the stimulated ear in consequence to the loss of contralateral activity including inhibitory processes normally involved in bilateral hearing. Although this reorganization occurred within a fairly short period (∼1.5 years of unilateral hearing), it was not reversed by long-term (3-4 years) bilateral cochlear implant stimulation. In bilateral listeners, effects of side of stimulation were assessed; children with long periods of unilateral cochlear implant use prior to bilateral implantation showed a reduction in normal dominance of contralateral input in the auditory cortex ipsilateral to the stimulated ear, further confirming an abnormal strengthening of pathways from the stimulated ear. By contrast, cortical activity in children using bilateral cochlear implants after limited or no unilateral cochlear implant exposure normally lateralized to the hemisphere contralateral to side of stimulation and retained normal contralateral dominance of auditory input in both hemispheres. Results demonstrate that the immature human auditory cortex reorganizes, potentially permanently, with unilateral stimulation and that bilateral auditory input provided with limited delay can protect the brain from such changes. These results indicate for the first time that there is a sensitive period for bilateral auditory input in human development with implications for functional hearing.

Objective To assess non-visualization of the choroid plexus of the fourth ventricle (CP-4V) as a simple, qualitative and reproducible first-trimester ultrasound feature of the posterior fossa for the prediction of central nervous system (CNS) anomalies and chromosomal defects. Methods First-trimester three-dimensional ultrasound datasets of the fetal brain were obtained prospectively from 65 consecutive normal singletons and retrospectively from 27 fetuses identified as having an abnormal posterior fossa on first-trimester ultrasound examination, and randomly combined to form the final study group. The stored ultrasound volumes were analyzed offline by two accredited sonologists, who were not aware of the final diagnoses. The CP-4V was assessed by multiplanar navigation and classified as visible or non-visible in its normal position depending on whether or not the echogenic structure that separates the fourth ventricle from the cisterna magna was identified in both midsagittal and axial planes. Correlation with subsequent second-trimester ultrasound, fetal magnetic resonance imaging, or postmortem or postnatal findings was performed to determine the predictive value of the first-trimester findings. Results Among the 92 ultrasound datasets analyzed, 73 (79%) were acquired transabdominally and 19 (21%) transvaginally. The CP-4V was classified as visible in 64 cases and non-visible in 28 cases, with agreement between the two observers in both sagittal and axial planes in all but one case. Twelve of the 28 (43%) fetuses with non-visible CP-4V were subsequently diagnosed as having a CNS malformation (open spina bifida (n = 6), Dandy–Walker malformation (n = 2), Blake's pouch cyst (n = 2), cephalocele (n = 1) and megacisterna magna (n = 1)). In addition, 20 of these 28 (71%) fetuses had aneuploidy (trisomy 18 (n = 10), triploidy (n = 5), trisomy 13 (n = 3), Turner syndrome (n = 1) or trisomy 21 (n = 1)). There was only one false-positive case, in which the CP-4V was classified as absent in a normal fetus. Conclusions Non-visualization of the CP-4V in the first trimester appears to be a strong marker of posterior fossa anomalies and chromosomal defects. Qualitative evaluation of this anatomic structure is simple, feasible and reproducible, and its routine assessment during the first-trimester scan may facilitate the early detection of CNS anomalies and associated fetal aneuploidy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Purpose Reconstruction of hard tissue continuity defects caused by ablative tumor surgery has been traditionally reconstructed with autogenous bone grafts or microvascular free flaps. Although results have been predictable from these 2 methods of reconstruction, the morbidity associated with bone harvest is quite serious for the patient. Predictable results have been obtained with using a combination of 100% cadaver bone, bone marrow aspirate concentrate (BMAC), and recombinant human bone morphogenic protein in immediate reconstruction for benign tumor extirpations through the extraoral approach. In light of these successful outcomes, the same combination was evaluated with an intraoral approach. This study evaluated the success of immediate mandibular reconstruction through the intraoral approach without any autogenous bone harvesting. Patients and Methods The aim of this retrospective study was to share the authors' experience with the use of 100% allogeneic bone in combination with bone morphogenic protein and BMAC through the transoral approach for immediate reconstruction of continuity defects that resulted from benign tumor surgery. A retrospective chart review was performed of all patients undergoing bone graft reconstruction at the University of Texas Health Sciences Center at Houston (UTHealth) Department of Oral and Maxillofacial Surgery from December 2014 through January 2016. Inclusion criteria were biopsy-proven benign tumors, American Society of Anesthesiologists I or II health status, and adequate intraoral soft tissue for primary closure determined during initial consultation. Results Five patients who underwent this procedure at the UTHealth Department of Oral and Maxillofacial Surgery from December 2014 through January 2016 are presented. The success rate was 100%. All patients showed excellent bone quality clinically and radiographically for endosseous dental implant placement. With the transoral approach and no autogenous bone harvesting, the average operating time was 3.4 hours and the hospital stay was 2.4 days. Conclusions Composite allogeneic tissue engineering is an effective and predictable technique for immediate reconstruction of continuity defects from ablative benign tumor surgery. Overall, there was no donor site morbidity, the intraoperative time was shorter, there were fewer admission days, and total costs overall were lower compared with traditional methods.

Contains fulltext : 165760.pdf (Publisher’s version ) (Closed access) Reconstruction of large mandibular defects is clinically challenging due to the need for donor tissue of appropriate shape and volume to facilitate high fidelity repair. In order to generate large vascularized tissues of custom geometry, bioreactors were implanted against the rib periosteum of 3-4year-old sheep for nine weeks. Bioreactors were filled with either morcellized autologous bone, synthetic ceramic particles, or a combination thereof. Tissues generated within synthetic graft-filled bioreactors were transferred into a large right-sided mandibular angle defect as either avascular grafts (n=3) or vascularized free flaps (n=3). After twelve additional weeks, reconstructed mandibular angles were harvested and compared to contralateral control angles. Per histologic and radiologic evaluation, a greater amount of mineralized tissue was generated in bioreactors filled with autologous graft although the quality of viable bone was not significantly different between groups. Genetic analyses of soft tissue surrounding bioreactor-generated tissues demonstrated similar early and late stage osteogenic biomarker expression (Runx2 and Osteocalcin) between the bioreactors and rib periosteum. Although no significant differences between the height of reconstructed and control mandibular angles were observed, the reconstructed mandibles had decreased bone volume. There were no differences between mandibles reconstructed with bioreactor-generated tissues transferred as flaps or grafts. Tissues used for mandibular reconstruction demonstrated integration with native bone as well as evidence of remodeling. In this study, we have demonstrated that synthetic scaffolds are sufficient to generate large volumes of mineralized tissue in an in vivo bioreactor for mandibular reconstruction. STATEMENT OF SIGNIFICANCE: A significant clinical challenge in craniofacial surgery is the reconstruction of large mandibular defects. In this work, we demonstrated that vascularized tissues of large volume and custom geometry can be generated from in vivo bioreactors implanted against the rib periosteum in an ovine model. The effects of different bioreactor scaffold material on tissue ingrowth were measured. To minimize donor site morbidity, tissues generated from bioreactors filled with synthetic graft were transferred as either vascularized free flaps or avascular grafts to a large mandibular defect. It was demonstrated that synthetic graft in an in vivo bioreactor is sufficient to produce free tissue bone flaps capable of integrating with native tissues when transferred to a large mandibular defect in an ovine model.

Objective: In this study a type of partial tonsil surgery, CO2-laser tonsillotomy, was compared to regular tonsillectomy. The effectiveness and post-operative recovery rate of both interventions in adult patients was assessed by using a questionnaire.Study design: Prospective follow-up non-randomized cohort study.Method: One hundred and seven adults were included; 46 tonsillectomies and 61 tonsillotomies were performed. Patients in the tonsillectomy group underwent general anaesthesia, while tonsillotomy was performed in an ambulatory setting with local anaesthesia. Post-operative questionnaires were administered by mail after 2 weeks, 6 months, and 1 year to assess recovery rate and symptom recurrence.Results: In total, 72.5% of patients were cured from their initial symptoms after tonsillotomy. Three patients (7.5%) required re-surgery for their initial complaints. After tonsillectomy, 97.2% of patients were cured. Both groups showed equally high satisfaction scores after treatment. Post-operative evaluation after 2 weeks showed a mean pain-intensity score of 5.4 (Visual Analogue Scale 0-10) after tonsillotomy and a mean pain-intensity score of 7.7 after tonsillectomy. The post-operative use of analgesics was twice as long in the tonsillectomy group compared to the tonsillotomy group and the tonsillectomy group required twice as many days for full recovery. After tonsillectomy a higher rate of major post-operative haemorrhage was seen.Conclusion: CO2-laser tonsillotomy is associated with a shorter and less painful recovery period. Both surgical methods are equal in terms of long-term satisfaction, although tonsillotomy comes with a higher recurrence rate of mild symptoms. A strict pre-operative patient selection for CO2-laser tonsillotomy is necessary

Molecular testing of lung adenocarcinomas (ADCs) is crucial for therapy stratification of patients. Because of the often limited diagnostic material, the authors aimed to explore the suitability of cytology smears for next-generation sequencing (NGS) and compared the results with concurrent histological specimens or cell blocks.A total of 16 formalin-fixed paraffin-embedded (FFPE) ADCs with known genetic alterations were used as the first cohort for targeted DNA and RNA sequencing. In the second cohort of 8 cases, 8 cytological smears were compared with matching histological specimens or cell blocks for the study. For NGS library amplification, commercially available panels for DNA and RNA sequencing were applied. The Ion Torrent Personal Genome Machine and the Ion Reporter workflow (version 5.0) were used for sequencing.All DNA libraries derived from FFPE and non-formalin-fixed cytological smear samples produced acceptable quality metrics, thereby enabling successful targeted DNA sequencing (100% performance). Targeted RNA sequencing failed in 1 FFPE case and 1 cytology probe by not reaching enough mapped fusion reads (92% performance rate). All previously detected mutations and gene rearrangements could be confirmed (sensitivity of 100%), whereas specificity of the DNA-based NGS assay reached 96%.The results of the current study demonstrated the suitability of non-formalin cytology specimens for the simultaneous NGS testing of lung ADCs using amplicon resequencing panels. These assays allowed for the input of cytological smears equal to concurrent histology or cell blocks and proved to be accurate in the detection of therapeutically actionable somatic mutations and gene rearrangements. Cancer Cytopathol 2017;125:30-40. © 2016 American Cancer Society.

Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination., Author Summary Annually, more than two million people worldwide are infected with HIV, the virus that causes AIDS. Rhesus macaques can be infected with SIV, a close relative and ancestor of HIV, resulting in simian AIDS, recapitulating key aspects of human HIV infection. SIVΔnef, a live attenuated form of SIV, protects rhesus macaques from subsequent challenge with pathogenic SIV and is widely viewed as the most effective SIV vaccine. Here we demonstrate that SIVΔnef persistence during the vaccination period drives both cell-mediated and humoral immune response maturation. During the vaccination period, cell-mediated immune responses elicited by SIVΔnef target more conserved regions of the virus rendering immune escape more difficult. Furthermore, the localization of the cell-mediated immune responses is shifted over time from peripheral blood to sites of viral production that are rich in uninfected SIV target cells, thereby positioning cell-mediated immune responses where they are most needed after wild-type SIV challenge. Similarly, SIVΔnef persistence during the vaccination period also leads to the accumulation and maturation of the humoral immune response. Our findings highlight the unique capacity of persistent vaccines to elicit durable and effective immune responses against wild-type SIV challenge.

Unilateral single-duct nipple discharge is associated with an increased risk for underlying breast malignancy. There is no consensus whether color of nipple discharge independently indicates the risk of malignancy. We sought to assess the relationship between the color of discharge and the risk of malignancy. Patients with unilateral single-duct nipple discharge without abnormalities on clinical and radiologic examination were included. Prior to diagnostic microdochectomy nipple discharge characteristics were registered. Multiple logistic regressions were performed to assess the relationship between color of nipple discharge and malignancy, corrected for age. During a mean follow-up period of 7.1 years we determined complication rate and false-negative rate of microdochectomy. A total of 184 patients were included (median age 53 years, range 19-84). Histologic examination revealed (in situ or invasive) breast carcinoma in 10.9% (20) of patients and high-risk lesions in 11.4% (21). Malignancy or high-risk lesions were found in 25% (OR: 1.37; 95% CI: 0.62-3.00) of patients with bloody discharge. Risk of underlying malignancy increased in patients >60 years (OR: 2.35; 95% CI: 1.14-4.83). Complication rate of microdochectomy was 2.7%. Single-duct, unilateral nipple discharge is a sign of underlying malignancy in a substantial proportion of cases. The majority of patients with unilateral single-duct nipple discharge, diagnosed with breast cancer, present with bloody discharge. However, the association between bloody nipple discharge and malignancy is not strong enough to distinguish high-risk patients. Therefore, invasive diagnostic procedures like microdochectomy should be offered to all patients with unilateral uniductal nipple discharge to search for underlying malignancy.

Objective To describe a new ultrasound technique that may be useful for the diagnosis of micrognathia in the first trimester of pregnancy. Methods The retronasal triangle (RNT) view is a technique that captures the coronal plane of the face in which the primary palate and the frontal processes of the maxilla are visualized simultaneously. Normal first-trimester fetuses display a characteristic gap between the right and left body of the mandible in this view (the ‘mandibular gap’). The presence or absence of this gap was evaluated and measured prospectively during real-time scanning (n = 154) and retrospectively by analyzing three-dimensional (3D) datasets (n = 50) in normal first-trimester fetuses undergoing screening for aneuploidy at 11–13 weeks' gestation. 3D datasets from 12 fetuses with suspected micrognathia were also collected and examined retrospectively for the same features. Results The mandibular gap was identified in all 204 normal fetuses and increased linearly with increasing crown–rump length (y = 0.033x + 0.435; R2 = 0.316), with no statistically significant differences between measurements obtained by two-dimensional ultrasound and 3D offline analysis. Among fetuses with suspected micrognathia, three 3D datasets were excluded from analysis because of poor image quality in one and the diagnosis of a normal chin in two. In the remaining nine fetuses, the mandibular gap was absent and was replaced by a bony structure representing the receding chin in seven (77.8%) cases and was not visualized due to severe retrognathia in the remaining two (22.2%) cases. All fetuses with micrognathia had associated anomalies, including seven with aneuploidy and two with skeletal dysplasia. Conclusions The RNT view may be a helpful technique for detecting micrognathia in the first trimester. The absence of the mandibular gap or failure to identify the mandible in this view is highly suggestive of micrognathia and should prompt a targeted ultrasound scan to assess for other anomalies. Further research is needed to determine the false-positive and false-negative rates of this technique. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Objectives To determine the feasibility of obtaining adequate 3-dimensional (3D) data sets to examine the fetal secondary palate during the second-trimester anatomy scan. Methods During a 3-month period, 3D data sets of the fetal secondary palate were obtained from consecutive women undergoing routine second-trimester scans. Only structurally normal singleton fetuses with a normal upper lip on 2-dimensional (2D) sonography were included. Three-dimensional data sets were obtained using a mechanical transducer with a 45° sweep and the same settings as for the standard 2D scan, ideally when the fetus was facing the transducer, with mild extension of the head, and the ultrasound beams projecting caudally to cranially to avoid shadowing from the primary palate or mandible. No additional scanning time was allocated for examination of the palate. Acquired 3D data sets were analyzed offline using dedicated software, and the secondary palate was assessed using the "flipped face" technique. Results Ninety-seven women met entry criteria and underwent second-trimester scans at a median gestational age of 22 completed weeks (range, 18-23 weeks). In 13 (13.4%) cases, it was not possible to obtain a midsagittal view of the face for capturing 3D volume data sets due to fetal position. Additional factors limiting visualization were shadowing from the primary palate in fetuses with flexion of the head in 30 (30.9%) cases, interposition of, or shadowing from, fetal arms or legs in 11 (11.3%), inability to reproduce a true midsagittal plane in 8 (8.2%), and poor image quality in 1 (1%). Therefore, it was only possible to assess the secondary palate in 34 (35.1%) cases. Conclusions It is not feasible to obtain adequate 3D data sets for offline analysis of the fetal secondary palate in almost two-thirds of second-trimester fetuses during the routine scan. However, suboptimal visualization is primarily due to factors related to fetal position rather than equipment or image quality. This finding suggests that a dedicated scan, during which adequate time can be devoted to obtaining a satisfactory position in which the fetal face can be evaluated, may be warranted in high-risk cases.

Objective To examine patient and provider attitudes toward first trimester nuchal translucency (NT) screening for Down syndrome and to assess how patients consent to screening in a country where abortion is illegal. Methods Patients presenting for first trimester ultrasound including NT screening in two obstetric units in Chile completed a questionnaire about their attitudes toward NT screening and perspectives on the consent process. A follow-up questionnaire assessed satisfaction with the test. Prenatal care providers also completed a questionnaire ascertaining their perspectives on NT screening. Results A total of 107 patients completed the initial questionnaire and 78 completed the follow-up questionnaire. Although 98 (94%) patients desired NT screening only 38 (38%) indicated that they would undergo diagnostic testing if they received screen positive results. Only 3 patients screened positive; however, 15 (20%) participants experienced increased anxiety after the test. Almost all of the 36 providers surveyed indicated that they counsel their patients thoroughly, but 38 (39%) patients reported that they received adequate information. Conclusion NT screening is often performed without patients’ full understanding of the implications of potential results and may cause anxiety. Providers should elicit patients’ preferences regarding prenatal testing and engage them in shared decision making about whether to undergo screening, particularly when abortion is not an option.