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Trauma associated sleep disorder is a proposed parasomnia that develops after trauma with clinical features of trauma related nightmares, disruptive nocturnal behaviors, and autonomic disturbances. The purpose of this case series is to better characterize the clinical and video-polysomnographic features of patients meeting clinical criteria for this proposed parasomnia.Semistructured clinical interview and detailed video-polysomnography review of 40 patients. Movements and vocalizations in rapid eye movement sleep were quantified according to the rapid eye movement sleep behavior disorder severity scale.Patients (n = 40, 32 males) were service members and veterans with a median age of 38.9 years (range 24-57 years) who reported trauma related nightmares and disruptive nocturnal behaviors at home. On video-polysomnography, 28 (71.8%) patients had disruptive nocturnal behaviors in rapid eye movement sleep consisting of limb, head, and axial movements; vocalizations were present in 8 (20%). On the rapid eye movement sleep behavior disorder severity scale, most (n = 28, 71.8%) had a low rating but those with greater severity (n = 11, 28.2%) had a higher prevalence of posttraumatic stress disorder (Disruptive nocturnal behaviors can be captured on video-polysomnography during rapid eye movement sleep, although they may be less pronounced than what patients report in their habitual sleeping environment. Clinical and video-polysomnographic correlations are invaluable in assessing patients with trauma associated sleep disorder to document objective abnormalities. This case series provides a further basis for establishing trauma associated sleep disorder as a unique parasomnia.Brock MS, Matsangas P, Creamer JL, et al. Clinical and polysomnographic features of trauma associated sleep disorder.

BACKGROUND Complications following vascular procedures involving the groin can lead to significant morbidity. Achieving stable soft tissue coverage over sites of revascularization can help mitigate complications. Prior evidence supports the use of muscle flaps in reoperative groins and in high risk patient populations to reduce postoperative complications. Data regarding the use of prophylactic muscle flap coverage of the groin is lacking. Therefore, the purpose of this study is to evaluate the effect of immediate prophylactic muscle flap coverage of vascular wounds involving the groin. METHODS A retrospective cohort study was performed on all patients undergoing primary open vascular procedures involving the groin for occlusive, aneurysmal, or oncologic disease between 2014 and 2020 at a single institution where plastic surgery was involved in closure. Patient demographics, comorbidities, surgical details, and postoperative complications were compared between patients who had sartorius muscle flap coverage of the vascular repair versus layered closure alone. RESULTS A total of 133 consecutive groins were included in our analysis. A sartorius flap was used in 115 groins (86.5%) and a layered closure was used in 18 (13.5%). Wound breakdown was similar between groups (25.2% sartorius vs. 38.9% layered closure, P = 0.26). However, the rate of reoperation was significantly higher in the layered closure group (50.0% vs. 12.2%, P < 0.01). Among patients who experienced wound breakdown (N = 36), a larger proportion of layered closure patients required operative intervention (71.4% vs. 20.7%, P = 0.02). Other rates of complications were not statistically different between groups. CONCLUSIONS In patients undergoing primary open vascular procedures involving the groin, patients who underwent prophylactic sartorius muscle flap closure had lower rates of reoperation. Although incisional breakdown was similar between the groups overall, the presence of a vascularized muscle flap overlying the vascular repair was associated with reduced need for reoperation and allowed more wounds to be managed with local wound care alone. Consideration should be given to this low morbidity local muscle flap in patients undergoing vascular procedures involving the groin.

Sulfonylureas (SUs) provide an efficacious first-line treatment in patients with hepatocyte nuclear factor 1α (HNF1A) diabetes, but SUs have limitations due to risk of hypoglycemia. Treatment based on the incretin hormones glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1) is characterized by their glucose-dependent insulinotropic actions without risk of hypoglycemia. The effect of SUs together with GIP or GLP-1, respectively, on insulin and glucagon secretion in patients with HNF1A diabetes is currently unknown. To investigate this, 10 HNF1A mutation carriers and 10 control subjects without diabetes were recruited for a double-blinded, placebo-controlled, crossover study including 6 experimental days in a randomized order involving 2-h euglycemic-hyperglycemic clamps with coadministration of: 1) SU (glimepiride 1 mg) or placebo, combined with 2) infusions of GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min), or saline (NaCl). In HNF1A mutation carriers, we observed: 1) hypoinsulinemia, 2) insulinotropic effects of both GIP and GLP-1, 3) additive to supra-additive effects on insulin secretion when combining SU+GIP and SU+GLP-1, respectively, and 4) increased fasting and arginine-induced glucagon levels compared with control subjects without diabetes. Our study suggests that a combination of SU and incretin-based treatment may be efficacious in patients with HNF1A diabetes via potentiation of glucose-stimulated insulin secretion.

Background Oshikhandass is a rural village in northern Pakistan where a 1989–1991 verbal autopsy study showed that diarrhea and pneumonia were the top causes of under-5 mortality. Intensive surveillance, active community health education and child health interventions were delivered in 1989–1996; here we assess improvements in under-5 mortality, diarrhea, and pneumonia over this period and 15 years later. Methods Two prospective open-cohort studies in Oshikhandass from 1989 to 1996 (Study 1) and 2011–2014 (Study 2) enrolled all children under age 60 months. Study staff trained using WHO guidelines, conducted weekly household surveillance and promoted knowledge on causes and management of diarrhea and pneumonia. Information about household characteristics and socioeconomic status was collected. Hurdle models were constructed to examine putative risk factors for diarrhea and pneumonia. Results Against a backdrop of considerable change in the socioeconomic status of the community, under-5 mortality, which declined over the course of Study 1 (from 114.3 to 79.5 deaths/1000 live births (LB) between 1989 and 1996), exceeded Sustainable Development Goal 3 by Study 2 (19.8 deaths/ 1000 LB). Reductions in diarrhea prevalence (20.3 to 2.2 days/ Child Year [CY]), incidence (2.1 to 0.5 episodes/ CY), and number of bloody diarrhea episodes (18.6 to 5.2%) seen during Study 1, were sustained in Study 2. Pneumonia incidence was 0.5 episodes /CY in Study 1 and 0.2/CY in Study 2; only 5% of episodes were categorized as severe or very severe in both studies. While no individual factors predicted a statistically significant difference in diarrhea or pneumonia episodes, the combined effect of water, toilet and housing materials was associated with a significant decrease in diarrhea; higher household income was the most protective factor for pneumonia in Study 1. Conclusions We report a 4-fold decrease in overall childhood mortality, and a 2-fold decrease in childhood morbidity from diarrhea and pneumonia in a remote rural village in Pakistan between 1989 and 2014. We conclude that significant, sustainable improvements in child health may be achieved through improved socioeconomic status and promoting interactions between locally engaged health workers and the community, but that continued efforts are needed to improve health worker training, supervision, and the rational use of medications. Trial registration Not Applicable.

Interleukin 17A (IL-17A) is a candidate mediator of inflammation-driven hypertension, but its direct effect on blood pressure is obscure. The present study was designed to test the hypothesis that systemic IL-17A concentration-dependently increases blood pressure and amplifies ANGII-induced hypertension in mice. Blood pressure was measured by indwelling chronic femoral catheters before and during IL-17A infusion w/wo angiotensin II (ANGII, 60ng/kg/min) in male FVB/n mice. Baseline blood pressure was recorded, and three experimental series were conducted: (1) IL-17A infusion with increasing concentrations over 6 days (two series with IL-17A from two vendors, n = 11); (2) ANGII infusion with IL-17A or vehicle for 9 days (n = 11); and (3) acute bolus infusions with four different concentrations (n = 5). Plasma IL-17A and IL-6 concentrations were determined by ELISA. Mean arterial and systolic blood pressures (MAP, SBP) decreased significantly after IL-17A infusion while heart rate was unchanged. In these mice, plasma IL-17A and IL-6 concentrations increased up to 3500- and 2.4-fold, respectively, above baseline. ANGII infusion increased MAP (~ 25 mmHg) and co-infusion of IL-17A attenuated ANGII-induced hypertension by 4.0 mmHg. Here, plasma IL-17A increased 350-fold above baseline. Acute IL-17A bolus infusion did not change blood pressure or heart rate. IL-17A receptor and IL-6 mRNAs were detected in aorta, heart, and kidneys of mice after IL-17A infusion. Nonphysiologically high concentrations of IL-17A reduce baseline blood pressure and increase IL-6 formation in male FVB/n mice. It is concluded that IL-17A is less likely to drive hypertension as the sole cytokine mediator during inflammation in vivo.

Background: International guidelines recommend work-up of relatives to autopsy negative sudden cardiac death victims, denoted as sudden unexplained death (SUD) and nonautopsied possible sudden cardiac death (pSCD) victims. This study assesses and compare baseline characteristics and clinical outcome at initial evaluation and during follow-up of relatives to SUD and pSCD victims. Methods: We retrospectively included data from systematic screening and routine follow-up of first-degree relatives to SUD and pSCD victims referred to our Unit for Inherited Cardiac Diseases, Copenhagen, 2005–2018. Victims with an antemortem known inherited cardiac disease were excluded. Results: We included 371 first-degree relatives from 187 families (120 SUD, 67 pSCD): 276 SUD relatives (age 33 ± 18 years, 54% men) and 95 pSCD relatives (age 40 ± 15 years, 51% men). The diagnostic yields of inherited cardiac diseases in SUD and pSCD families were 16% and 13%, respectively (p =.8). The diagnoses in SUD families were mainly channelopathies (68%), whereas pSCD families were equally diagnosed with cardiomyopathies, channelopathies, and premature ischemic heart disease. Ninety-three percent of diagnosed families were diagnosed at initial evaluation and 7% during follow-up (5.4 ± 3.3 years). During follow-up 34% of relatives with a diagnosed inherited cardiac disease had an arrhythmic event, compared to 5% of relatives without established diagnosis (p

The pathophysiological link between adiposity and blood pressure is not completely understood, and evidence suggests an influence of sex and genetic determinants. We aimed to identify the relationship between adiposity and blood pressure, independent of a robust set of lifestyle and metabolic factors, and to examine the modulating role of sex and Angiotensin-Converting Enzyme (ACE) insertion/deletion (I/D) polymorphisms. In the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) study cohort, 1211 normotensive individuals, aged 30 to 60 years and followed-up after 3.3 years, were characterized for lifestyle and metabolic factors, body composition, and ACE genotype. Body mass index (BMI) and waist circumference (WC) were independently associated with mean arterial pressure, with a stronger relationship in women than men (BMI: r =0.40 versus 0.30; WC: r =0.40 versus 0.30, both P ID and II ACE genotypes in both sexes ( P ACE genotype only in women ( P =0.03). A 5 cm larger WC at baseline increased the risk of developing hypertension at follow-up only in women (odds ratio, 1.56 [95% CI, 1.15–2.10], P =0.004) and in II genotype carriers (odds ratio, 1.87 [95% CI, 1.09–3.20], P =0.023). The hypertensive effect of adiposity is more pronounced in women and in people carrying the II variant of the ACE genotype, a marker of salt sensitivity.

Summary Treatment of boutonniere Dupuytren disease is rare and is resistant to treatment because of altered tendon dynamics. The authors used a small dose of collagenase clostridium histolyticum for an enzymatic tenotomy of the distal interphalangeal joint and showed that hyperextension at the distal interphalangeal joint improved significantly. Fifteen patients with boutonniere Dupuytren disease with severe proximal interphalangeal joint contractures averaging -69 degrees of extension were included in the study. Ten patients had at least one previous intervention, including surgical fasciectomy, Digit Widget treatment, and needle aponeurotomy. Collagenase clostridium histolyticum enzymatic tenotomy was performed in-office as a wide-awake procedure. All patients received varying doses of collagenase clostridium histolyticum for volar Dupuytren disease enzymatic fasciotomy and 0.1 mg of collagenase clostridium histolyticum into the distal extensor tendon for tenotomy to treat boutonniere deformity at the same time. Collagenase clostridium histolyticum enzymatic tenotomy significantly improved total active motion of the finger by 41.0 degrees (p = 0.001). Loss of extension at both the metacarpophalangeal joint and the proximal interphalangeal joint also improved with gains of 11.7 (p = 0.04) and 20.7 degrees (p = 0.0005) of extension, respectively. The average distal interphalangeal joint hyperextension was improved from 29.7 degrees to 14.0 degrees (p = 0.002). The authors show that collagenase injection led to significant average improvement in joint contracture at all finger joints and significantly increased the arc of motion at the proximal interphalangeal joint and metacarpophalangeal joint. Although collagenase has been previously used for flexion contractures in Dupuytren disease, we believe it has a role in treating the distal interphalangeal joint hyperextension deformity associated with boutonniere deformity in Dupuytren disease as well. Clinical question/level of evidence Therapeutic, IV.

The purpose of this work was to describe the leg-muscle-generated push force characteristics in sprint kayak paddlers for females and males on water. Additionally, the relationship between leg pushing force characteristics and velocity was investigated. Twenty-eight paddlers participated in the study. The participants had five minutes of self-chosen warm-up and were asked to paddle at three different velocities, including maximal effort. Left- and right-side leg extension force were collected together with velocity. Linear regression analyses were performed with leg extension force characteristics as independent variables and velocity as the dependent variable. A second linear regression analysis investigated the effect of paddling velocity on different leg extension force characteristics with an explanatory model. The results showed that the leg pushing force elicits a sinus-like pattern, increasing and decreasing throughout the stroke cycle. Impulse over 10 s showed the highest correlation to maximum velocity (r = 0.827, p &lt, 0.01), while a strong co-correlation was observed between the impulse per stroke cycle and mean force (r = 0.910, p &lt, 0.01). The explanatory model results revealed that an increase in paddling velocity is, among other factors, driven by increased leg force. Maximal velocity could predict 68% of the paddlers’ velocity within 1 km/h with peak leg force, impulse over 10 s, and stroke rate (p-value &lt, 0.001, adjusted R-squared = 0.8). Sprint kayak paddlers elicit a strong positive relationship between leg pushing forces and velocity. The results confirm that sprint kayakers’ cyclic leg movement is a key part of the kayaking technique.

Background Adolescence is a critical point in the realization of human capital, as health and educational decisions with long-term impacts are made. We examined the role of early childhood experiences on health, cognitive abilities, and educational outcomes of adolescents followed up from a longitudinal cohort study in Pakistan, hypothesizing that early childhood experiences reflecting poverty would manifest in reduced health and development in adolescence. Methods and findings Adolescents/young adults previously followed as children aged under 5 years were interviewed. Childhood data were available on diarrhea, pneumonia, and parental/household characteristics. New data were collected on health, anthropometry, education, employment, and languages spoken; nonverbal reasoning was assessed. A multivariable Bayesian network was constructed to explore structural relationships between variables. Of 1,868 children originally enrolled, 1,463 (78.3%) were interviewed as adolescents (range 16.0–29.3 years, mean age 22.6 years); 945 (65%) lived in Oshikhandass. While 1,031 (70.5%) of their mothers and 440 (30.1%) of their fathers had received no formal education, adolescents reported a mean of 11.1 years of education. Childhood diarrhea (calculated as episodes/child-year) had no association with nonverbal reasoning score (an arc was supported in just 4.6% of bootstrap samples), health measures (with BMI, 1% of bootstrap samples; systolic and diastolic blood pressure, 0.1% and 1.6% of bootstrap samples, respectively), education (0.7% of bootstrap samples), or employment (0% of bootstrap samples). Relationships were found between nonverbal reasoning and adolescent height (arc supported in 63% of bootstrap samples), age (84%), educational attainment (100%), and speaking English (100%); speaking English was linked to the childhood home environment, mediated through maternal education and primary language. Speaking English (n = 390, 26.7% of adolescents) was associated with education (100% of bootstrap samples), self-reported child health (82%), current location (85%) and variables describing childhood socioeconomic status. The main limitations of this study were the lack of parental data to characterize the home setting (including parental mental and physical health, and female empowerment) and reliance on self-reporting of health status. Conclusions In this population, investments in education, especially for females, are associated with an increase in human capital. Against the backdrop of substantial societal change, with the exception of a small and indirect association between childhood malnutrition and cognitive scores, educational opportunities and cultural language groups have stronger associations with aspects of human capital than childhood morbidity., In a cohort study, Zeba A Rasmussen and colleagues examine the relationship between early childhood experiences on health, cognitive abilities and education, and health outcomes in adolescents and young adults in Pakistan., Author summary Why was this study done? Childhood diarrhea and pneumonia remain leading causes of morbidity and mortality, and their effects are hypothesized to have long-lasting impacts that could potentially negatively affect adolescent/young adult nutrition, reasoning skills, and educational status. Studies across different geographical settings have focused on outcomes during early childhood and on nutritional status or interventions, though very few have extended into adolescence/young adulthood. Other studies have noted negative associations between poverty, morbidity, and malnutrition and childhood attainment and physical and cognitive development. What did the researchers do and find? We conducted a prospective longitudinal study on a cohort of children (n = 1,868, 1989–1996) from a poor, remote rural Pakistani village who were followed up 20 years later (n = 1,463, 2011–2014), when they were adolescents and young adults (mean age 22.6 years old). Most of their mothers (70.5%) and fathers (30.1%) had received no formal education, but the adolescents had, on average, 11.1 years of education. Childhood illness was not related to nonverbal reasoning score, health measures, education, or employment. Education (including speaking English) was strongly related to nonverbal reasoning score. Speaking English was related to improved childhood socioeconomic status, better child health, more years of education by adolescence, and greater likelihood of having left the village. What do these findings mean? Investment in education, especially for females, is important in the development of human capital. Childhood undernutrition was related to adolescent height, and thereby weakly to cognitive score, whereas educational opportunities and cultural language group were more strongly associated with human capital than childhood illness was. This population underwent substantial secular changes, including economic growth and expanded educational opportunities, that may have overcome deficits from childhood undernutrition.

Vitamin D appears essential for normal neurodevelopment and cognitive and behavioral function. We examined neonatal vitamin D in relation to the child's later diagnosis of autism spectrum disorder (ASD) or developmental delay (DD). Children aged 24-60 months enrolled in the population-based CHARGE case-control study were evaluated clinically for ASD (n = 357), DD (n = 134), or typical development (TD, n = 234) at the MIND Institute (Sacramento, CA) using standardized assessments. Total 25-hydroxyvitamin D (25[OH]D) was measured using sensitive isotope dilution liquid chromatography-tandem mass spectrometry in archived dried blood spots collected for the California Department of Public Health's Newborn Screening Program. Multinomial logistic regression was used to calculate ORs as measures of the associations between 25 nmol/L change in 25(OH)D and ASD and DD. Associations between 25(OH)D and scores on Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales were assessed using robust linear regression. Effect modification was examined using stratified models and interaction product terms. Unadjusted mean (SD) 25(OH)D was lower for DD (73.2 [37.6]) than for TD (82.7 [39.3]) and ASD (80.1 [37.4]). After adjustment for maternal prepregnancy body mass index and education, a 25 nmol/L increase in total 25(OH)D was not associated with ASD (OR = 0.97; CI: 0.87-1.08) or DD (OR = 0.91; 95% CI: 0.78-1.06). Neonatal 25(OH)D was associated with significantly reduced ASD only in females (adjusted OR = 0.74; 95% CI: 0.55-0.99, Pinteraction = 0.03), and significantly reduced DD only in non-Hispanic white children (adjusted OR = 0.79; 95% CI: 0.63-0.98, Pinteraction = 0.11 for Hispanic, Pinteraction = 0.31 for other), driven by DD children with trisomy 21. This study provides evidence that neonatal vitamin D could be associated with ASD in females and with DD in non-Hispanic white children. Autism Res 2019, 12: 976-988. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Vitamin D appears essential for brain development and function. We examined neonatal total 25-hydroxyvitamin D (25[OH]D) measured in dried blood spots in relation to later diagnoses of autism spectrum disorder (ASD) or developmental delay (DD) and related assessment scores. Higher neonatal 25(OH)D was associated with a 26% reduction in the odds for ASD only in females. After taking into account factors that could contribute to vitamin D status, a significant association with 21% reduced odds for DD was found only in non-Hispanic white children. Though results were nonsignificant overall, certain subgroups might benefit from higher neonatal vitamin D.

Objective.Observational axial spondyloarthritis (axSpA) research in large datasets has been limited by a lack of adequate methods for identifying patients with axSpA, because there are no billing codes in the United States for most subtypes of axSpA. The objective of this study was to develop methods to accurately identify patients with axSpA in a large dataset.Methods.The study population included 600 chart-reviewed veterans, with and without axSpA, in the Veterans Health Administration between January 1, 2005, and June 30, 2015. AxSpA identification algorithms were developed with variables anticipated by clinical experts to be predictive of an axSpA diagnosis [demographics, billing codes, healthcare use, medications, laboratory results, and natural language processing (NLP) for key SpA features]. Random Forest and 5-fold cross validation were used for algorithm development and testing in the training subset (n = 451). The algorithms were additionally tested in an independent testing subset (n = 149).Results.Three algorithms were developed: Full algorithm, High Feasibility algorithm, and Spond NLP algorithm. In the testing subset, the areas under the curve with the receiver-operating characteristic analysis were 0.96, 0.94, and 0.86, for the Full algorithm, High Feasibility algorithm, and Spond NLP algorithm, respectively. Algorithm sensitivities ranged from 85.0% to 95.0%, specificities from 78.0% to 93.6%, and accuracies from 82.6% to 91.3%.Conclusion.Novel axSpA identification algorithms performed well in classifying patients with axSpA. These algorithms offer a range of performance and feasibility attributes that may be appropriate for a broad array of axSpA studies. Additional research is required to validate the algorithms in other cohorts.

Case A 37-year-old man presented with an absent right elbow joint secondary to trauma, subsequent ankylosis, total elbow arthroplasty (TEA), and TEA explantation after infection. The patient also had a contralateral complete brachial plexus injury, but an intact elbow joint. Given that the patient had a functional right hand/wrist, composite vascularized autograft elbow transplant was performed from left to right upper extremity. Four years postoperatively, the patient could independently complete activities of daily living. Conclusion This case is the first to report composite vascularized autograft elbow transplant. Although indications are limited, this case illuminates novel uses of standard techniques for a difficult problem.

The incidence of vaccine preventable disease in Pakistan remains high despite a long-standing Expanded Program on Immunization (EPI). We describe vaccine completeness, timeliness and determinants of coverage from a remote rural cohort (2012–2014). Vaccination histories were taken from EPI records. Vaccination was complete if all doses were received according to the EPI schedule and timely if doses were not ≥3 days early or ≥ 28 days late. Three models are presented: a multivariable logistic regression of household demographic and socioeconomic factors associated with complete vaccination, a multivariable mixed effects logistic regression assessing whether or not the vaccine was administered late (versus on-time), and a mixed effects multivariable Poisson regression model analysing the interval (in days) between vaccine doses. Of 959 enrolled children with full vaccination histories, 88.2 and 65.1% were fully vaccinated following either the pentavalent or DPT/HBV schedules if measles was excluded; coverage dropped to 50.0 and 27.1% when both doses of measles were included. Sixty-four (6.7%) were unvaccinated. Coverage and timeliness declined with subsequent doses. Migrating into the village after 1995 (95%CI 1.88 to 5.17) was associated with late vaccination. Being male, having an older father, and having parents with at least some formal education reduced the likelihood of a late dose. The interval between doses was consistent at 5 weeks (compared with the 4 weeks recommended by EPI). None of the socio-demographic variables were related to the likelihood of receiving full coverage. Vaccine coverage in Oshikhandass was higher than national averages. Measles vaccine coverage and timeliness were low; special consideration should be paid to this vaccine. The local vaccination schedule differed from the EPI, but the consistency suggests good local administration.

COVID-19, although a respiratory illness, has been clinically associated with non-respiratory symptoms. We conducted a negative case–control study to identify the symptoms associated with SARS-CoV-2-positive results in Portugal. Twelve symptoms and signs included in the clinical notification of COVID-19 were selected as predictors, and the dependent variable was the RT-PCR test result. The χ2 tests were used to compare notified cases on sex, age group, health region and presence of comorbidities. The best-fit prediction model was selected using a backward stepwise method with an unconditional logistic regression. General and gastrointestinal symptoms were strongly associated with a positive test (P < 0.001). In this sense, the inclusion of general symptoms such as myalgia, headache and fatigue, as well as diarrhoea, together with actual clinical criteria for suspected cases, already updated and included in COVID-19 case definition, can lead to increased identification of cases and represent an effective strength for transmission control.

To assess the efficacy of bis-glycinate bound Zn, 36 crossbred wethers (34 ± 2 kg) were sorted by body weight into three groups and stagger started on a Zn-deficient diet (18 mg Zn/kg dry matter [DM]; 22.5% neutral detergent fiber [NDF]) for 45 d prior to a 15-d metabolism period (10 d adaptation and 5 d collection). On day 46, lambs were randomly assigned to dietary treatments (four lambs treatment−1group−1): no supplemental Zn (CON) or 15 mg supplemental Zn/kg DM (ZINC) as Zn sulfate (ZS) or bis-glycinate (GLY; Plexomin Zn, Phytobiotics). Blood was collected from all lambs on days 1, 44, 56, and 61. Liver, jejunum, and longissimus dorsi samples were collected after euthanasia on day 61. Gene expression was determined via quantitative real-time polymerase chain reaction. Data were analyzed using ProcMixed of SAS (experimental unit = lamb; fixed effects = treatment, group, and breed) and contrast statements assessed the effects of supplemental Zn concentration (ZINC vs. CON) and source (GLY vs. ZS). After 15 d of Zn supplementation, plasma Zn concentrations were greater for ZINC vs. CON and GLY vs. ZS (P ≤ 0.01); tissue Zn concentrations were unaffected (P ≥ 0.27). Liver Cu concentrations were lesser for ZINC vs. CON (P = 0.03). Longissimus dorsi Mn concentrations were greater for ZINC vs. CON (P = 0.05) and tended to be lesser for GLY vs. ZS (P = 0.09). Digestibility of DM, organic matter (OM), and NDF was lesser for ZINC vs. CON (P ≤ 0.05); acid detergent fiber digestibility tended to be greater for GLY vs. ZS (P = 0.06). Nitrogen retention (g/d) tended to be greater for GLY vs. ZS (P = 0.10), and N apparent absorption was lesser for ZINC vs. CON (P = 0.02). Zinc intake, fecal output, retention, and apparent absorption were greater for ZINC vs. CON (P ≤ 0.01). Apparent absorption of Zn was −5.1%, 12.8%, and 15.0% for CON, ZS, and GLY, respectively. Nitrogen and Zn retention and apparent absorption were not correlated for CON (P ≥ 0.14) but were positively correlated for ZINC (retention: P = 0.02, r = 0.52; apparent absorption: P < 0.01, r = 0.73). Intestinal expression of Zn transporter ZIP4 was lesser for ZINC vs. CON (P = 0.02). Liver expression of metallothionein-1 (MT1) tended to be greater for GLY vs. ZS (P = 0.07). Although Zn apparent absorption did not differ between sources (P = 0.71), differences in post-absorptive metabolism may be responsible for greater plasma Zn concentrations and liver MT1 expression for GLY-supplemented lambs, suggesting improved bioavailability of GLY relative to ZS.

Objective The aim of this study was to evaluate which mesh type yields lower recurrence and complication rates after ventral hernia repair. Summary background data More than 400,000 ventral hernia repairs are performed annually in the United States. Although the most effective method for repairing ventral hernias involves using mesh, whether to use biologic mesh versus synthetic mesh is controversial. Methods Single-blind, randomized, controlled, pragmatic clinical trial conducted from March 2014 through October 2018; 165 patients enrolled with an average follow up of 26 months. Patients were randomized 1:1 to have their ventral hernias repaired using either a biologic (porcine) or synthetic (polypropylene) mesh. The primary study outcome measure was hernia recurrence at 2 years. Results A total of 165 patients (68 men), mean age 55 years, were included in the study with a mean follow-up of 26 months. An intention-to-treat analysis noted that hernias recurred in 25 patients (39.7%) assigned to biologic mesh and in 14 patients (21.9%) assigned to synthetic mesh (P = 0.035) at 2 years. Subgroup analysis identified an increased rate of hernia recurrence in the biologic versus the synthetic mesh group under contaminated wound conditions (50.0% vs 5.9%; P for interaction = 0.041). Postoperative complication rates were similar for the 2 mesh types. Conclusions The risk of hernia recurrence was significantly higher for patients undergoing ventral hernia repair with biologic mesh compared to synthetic mesh, with similar rates of postoperative complications. These data indicate that the use of synthetic mesh over biologic mesh to repair ventral hernias is effective and can be endorsed, including under contaminated wound conditions. Trial registration ClinicalTrials.gov Identifier: NCT02041494.

This study aimed to gain deeper knowledge about the relationship between vitamin D and physical activity in a sample of forensic inpatients. Sixty-seven male forensic inpatients participated. Participants were randomly assigned into an Intervention group (vitamin D) or a Control group (placebo). The Physical Activity–Rating (PA-R) questionnaire was used to measure physical activity from January to May. Vitamin D status was measured as 25-hydroxy vitamin D (25-OHD) pre- and post-intervention. The results revealed that vitamin D status at post-test was positively correlated with physical activity, but there was no effect of vitamin D supplementation looking at the two randomized groups. However, controlling for body mass index (BMI), the results showed an effect of BMI and a main effect of groups with a higher level of physical activity in the Intervention group. No interaction effects were found. Participants were also assigned into High and Low vitamin D groups based on the vitamin D status at post-test, i.e., the upper (75.1 nmol/L) and lower quartile (46.7 nmol/L). T-tests revealed that participants with a vitamin D status above 75 nmol/L showed significantly higher levels of physical activity than participants with a vitamin D status below 46.7 nmol/L. Thus, a vitamin D status above 75 nmol/L seems to be an optimal level.

Vitamin D status may be important for stress resilience. This study investigated the effects of vitamin D supplements during winter on biological markers of stress resilience such as psychophysiological activity, serotonin, and cortisol in a placebo-controlled, randomized clinical trial. Eighty-six participants were randomly assigned to the Intervention (vitamin D) or Control (placebo) groups. Before and after the intervention participants were exposed to an experimental stress procedure. Psychophysiological activity was measured during three main conditions: baseline, stress, and recovery. Fasting blood samples were taken in the morning and saliva samples were collected at seven different time points across 24 h. Prior to intervention both groups had normal/sufficient vitamin D levels. Both groups showed a normal pattern of psychophysiological responses to the experimental stress procedure (i.e., increased psychophysiological responses from resting baseline to stress-condition, and decreased psychophysiological responses from stress-condition to recovery, all p &lt, 0.009). Post-intervention, the Intervention group showed increased vitamin D levels (p &lt, 0.001) and normal psychophysiological responses to the experimental stress procedure (p &lt, 0.001). Importantly, the Control group demonstrated a classic nadir in vitamin D status post-intervention (spring) (p &lt, 0.001) and did not show normal psychophysiological responses. Thus, physiologically the Control group showed a sustained stress response. No significant effects of vitamin D were found on serotonin and cortisol.

Aims The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9–39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes. Methods In a double-blinded, placebo-controlled, randomized, crossover study, 15 participants with metformin-treated type 2 diabetes (age: 57–85 years, HbA1c: 40–74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a 6-week wash-out period. At the end of each period, two randomized 4-h liquid mixed meal tests with concomitant infusion of exendin(9–39)NH2 and saline, respectively, were performed. Results Compared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9–39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± s.d.) during exendin(9–39)NH2 infusion in the acarbose period vs a 39 ± 27% increase during the placebo period (P = 0.0163). Conclusions We confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9–39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9–39)NH2 was most pronounced during acarbose treatment.

Objective Information on nutritional rehabilitation for underweight patients with avoidant/restrictive food intake disorder (ARFID) is scarce. This study characterized hospitalized youth with ARFID treated in an inpatient (IP)-partial hospitalization behavioral eating disorders (EDs) program employing an exclusively meal-based rapid refeeding protocol and compared weight restoration outcomes to those of patients with anorexia nervosa (AN). Method Data from retrospective chart review of consecutive underweight admissions (N = 275; age 11-26 years) with ARFID (n = 27) were compared to those with AN (n = 248) on clinical features, reason for discharge, and weight restoration variables. For patients with ARFID, presenting phenomenology was further characterized by detailed chart review. Results At admission, 53% of patients with ARFID were vomiting regularly. The predominant ARFID subtype was ARFID-aversive, with close to a third being mixed subtype. Gastrointestinal (GI) symptomatology (81.5%) was the most commonly endorsed reason for restriction. A third had undergone unsuccessful parenteral or enteral tube feeding. Patients with ARFID were more likely male, had higher admission BMI, and slower IP weight gain (1.36 kg /week vs 1.92) compared to patients with AN. Fewer patients with ARFID transitioned to the partial hospitalization program, although the proportion discharged for clinical improvement did not differ and both groups had a mean program discharge BMI >18.5. Discussion GI symptoms appear a common contributor to restrictive eating amongst hospitalized youth with ARFID. Despite a slightly lower rate of IP weight gain, clinical improvement and weight restoration at discharge were similar for patients with ARFID compared to AN.

To assess relative bioavailability (RBV) of hydroxy and organic Cu sources compared with CuSO(4) in steers fed a high Cu antagonist diet, 84 steers were stratified by BW to pens randomly assigned to dietary treatments for 90 d. Steers received a common corn silage-based diet supplemented with Cu antagonists (diet analyzed 0.25% S; 6.8 mg Mo/kg DM). Supplemental (SUPP) Cu treatments included: control (CON; no SUPP Cu), low or high inorganic (ING5 or ING10; 5 or 10 mg Cu/kg DM from CuSO(4); Old Bridge Chemical Inc., Old Bridge, NJ, USA), low or high organic (ORG5 or ORG10; 5 or 10 mg Cu/kg DM from Cu lysine; CuPlex 100, ZinPro Corp., Eden Prairie, MN), and low or high hydroxy (HYD5 or HYD10; 5 or 10 mg Cu/kg DM; IntelliBond C(II), Micronutrients USA LLC, Indianapolis, IN). Body weights were recorded on days −7, −6, 28, 56, 84, and 85, and plasma samples collected on days −7, 28, 56, and 85. Liver samples were collected to start and end the trial. Data were analyzed using the mixed procedure of SAS and the model included treatment with initial liver Cu values used as a covariate in analysis of final liver Cu. Contrast statements were used to separate treatment means: 0 vs. 5 mg SUPP Cu/kg DM, 0 vs. 10 mg SUPP Cu/kg DM, 5 vs. 10 mg SUPP Cu/kg DM, HYD vs. ORG, HYD vs. ING, and ORG vs. ING. Initial liver Cu concentrations were similar across all treatment comparisons (P ≥ 0.22). Final liver Cu concentrations were lesser in CON compared with either 5 or 10 mg Cu/kg DM (P ≤ 0.001). Final liver concentrations were lesser in ORG compared with HYD and ING (P ≤ 0.009), but HYD was similar to ING (P = 0.14). There was a treatment × time interaction (P ≤ 0.001) for plasma Cu concentrations where CON exhibited a rapid decline in plasma Cu, steers receiving 5 mg SUPP Cu/kg DM were decreased to a greater extent in ORG, and steers supplemented with 10 mg Cu/kg DM did not differ at the end of the trial. Assessment of RBV was conducted for liver and plasma Cu concentrations using a slope-ratio assay in the GLM procedure. The RBV of Cu tended (P = 0.07) to be increased in HYD (112%) compared with ING (100%) for liver Cu values, but RBV was similar for all other source comparisons based on liver and plasma Cu values (P ≥ 0.22). These data suggest in steers fed high antagonist diets hydroxy Cu may be more available. Based on plasma and liver Cu concentrations, supplementation of 10 mg Cu/kg DM is needed to maintain Cu status in cattle fed diets high in S and Mo.

The affiliation details for Geltrude Mingrone are corrected below.

The purpose of the present study was to assess changes in body perception when visual feedback was removed from the hand and arm with the purpose of resembling the visual deprivation arising from amputation. The illusion was created by removing the visual feedback from the participants’ own left forearm using a mixed reality (MR) and green screen environment. Thirty healthy persons (15 female) participated in the study. Each subject experienced two MR conditions, one with and one without visual feedback from the left hand, and a baseline condition with normal vision of the limb (no MR). Body perception was assessed using proprioceptive drift, questionnaires on body perception, and thermal sensitivity measures (cold, warm, heat pain and cold pain detection thresholds). The proprioceptive drift showed a significant shift of the tip of the index finger ( p 0.001 ) towards the elbow in the illusion condition (mean drift: −3.71 cm). Self-report showed a significant decrease in ownership ( p 0.001 ), shift in perceptual distortions, (e.g. “ It feels as if my lower arm has become shorter ”) ( p = 0.025 ), and changes in sensations of the hand (tingling, tickling) ( p = 0.025 ). A significant decrease was also observed in cold detection threshold ( p 0.001 ), i.e. the detection threshold was cooler than for the control conditions. The proprioceptive drift together with the self-reported questionnaire showed that the participants felt a proximal retraction of their limb, resembling the telescoping experienced by phantom limb patients. The study highlights the influence of missing visual feedback and its possible contribution to phantom limb phenomena.

Objective The aims of this study are two-fold: 1) To explore how cardiac patients experience their use of a telerehabilitation tool for recuperation from surgery, and 2) To study how the patients’ use of the interactive ‘Active Heart’ web portal affected their eHealth literacy skills. Methods The ‘Active Heart’ telerehabilitation web portal offers patients and their relatives information and exercises for recovery from cardiac surgery. 109 cardiac patients were using the Active Heart web portal for a duration of three months. Results 49 patients completed questionnaires that were administered both before and after their use of the portal, resulting in a 45% response rate. Respondents had a mean age of 60.64 ± 10.75 years, and 82% of the respondents were males. The respondents had a positive impression of Active Heart, reporting that it was easy to access, user-friendly, and written in an understandable language. The patients’ eHealth literacy skills increased during the trial period. Conclusion Use of a cardiac telerehabilitation web portal can be beneficial for patient education and can increase cardiac patients’ eHealth literacy skills. Practice implications Online telerehabilitation portals may be used as a tool in patient education and cardiac rehabilitation.

ObjectiveBehavioral therapies are first-line for preschoolers with attention-deficit hyperactivity disorder (ADHD). Studies support yoga for school-aged children with ADHD; this study evaluated yoga in preschoolers on parent- and teacher-rated attention/challenging behaviors, attentional control (Kinder Test of Attentional Performance [KiTAP]), and heart rate variability (HRV).MethodsThis randomized waitlist-controlled trial tested a 6-week yoga intervention in preschoolers with ≥4 ADHD symptoms on the ADHD Rating Scale-IV Preschool Version. Group 1 (n = 12) practiced yoga first; Group 2 (n = 11) practiced yoga second. We collected data at 4 time points: baseline, T1 (6 weeks), T2 (12 weeks), and follow-up (3 months after T2).ResultsAt baseline, there were no significant differences between groups. At T1, Group 1 had faster reaction times on the KiTAP go/no-go task (p = 0.01, 95% confidence interval [CI], -371.1 to -59.1, d = -1.7), fewer distractibility errors of omission (p = 0.009, 95% CI, -14.2 to -2.3, d = -1.5), and more commission errors (p = 0.02, 95% CI, 1.4-14.8, d = 1.3) than Group 2. Children in Group 1 with more severe symptoms at baseline showed improvement at T1 versus control on parent-rated Strengths and Difficulties Questionnaire hyperactivity inattention (β = -2.1, p = 0.04, 95% CI, -4.0 to -0.1) and inattention on the ADHD Rating Scale (β = -4.4, p = 0.02, 95% CI, -7.9 to -0.9). HRV measures did not differ between groups.ConclusionYoga was associated with modest improvements on an objective measure of attention (KiTAP) and selective improvements on parent ratings.

In this study, a single microphone speech enhancement algorithm is proposed to improve speech intelligibility for cochlear implant recipients. The proposed algorithm combines harmonic structure estimation with a subsequent statistical based speech enhancement stage. Traditional minimum mean square error (MMSE) based speech enhancement methods typically focus on statistical characteristics of the noise and track the noise variance along time dimension. The MMSE method is usually effective for stationary noise, but not as useful for non-stationary noise. To address both stationary and non-stationary noise, the current proposed method not only tracks noise over time, but also estimates the noise structure along the frequency dimension by exploiting the harmonic structure of the target speech. Next, the estimated noise is employed in the traditional MMSE framework for speech enhancement. To evaluate the proposed speech enhancement solution, a formal listener evaluation was performed with 6 cochlear implant recipients. The results suggest that a substantial improvement in speech intelligibility performance can be gained for cochlear implant recipients in noisy environments.

Angus-cross steers (n = 288; 427 ± 0.4 kg) were utilized in a finishing study to evaluate the influence of increasing dietary Zn concentration on growth performance and carcass characteristics of steers fed ractopamine hydrochloride (RAC). In a randomized complete block design, steers were blocked by weight (6 steers/pen) and fed a dry-rolled corn-based diet for 79 d containing no supplemental Zn (CON; n = 8), 60 mg Zn/kg from ZnSO(4) and no supplemental Zn-amino acid complex (ZnAA; ZnAA0; n = 8) or ZnAA0 diet supplemented with 60 (ZnAA60; n = 8), 90 (ZnAA90; n = 7), 120 (ZnAA120; n = 8), or 150 (ZnAA150; n = 8) mg Zn/kg DM from ZnAA. Thirty-one days prior to harvest (day 48 of study) all steers began receiving RAC at 300 mg⋅steer(–1)⋅d(–1). This study was organized as 2 groups (GRP) of steers and groups were stagger started so that GRP1 started and ended 2 wk before GRP2. Pen was the experimental unit, and the statistical model included the fixed effects of treatment and block nested within GRP. Three a priori single degree of freedom contrasts were developed: linear and quadratic effects of ZnAA supplementation (ZnAA0, ZnAA60, ZnAA90, ZnAA120, and ZnAA150), and CON vs. Zn (CON vs. ZnAA0, ZnAA60, ZnAA90, ZnAA120, and ZnAA150). Dietary Zn concentration did not affect growth performance prior to RAC supplementation (P ≥ 0.17). During the RAC-period ADG and DMI were not affected by dietary Zn (P ≥ 0.16), while there was a linear effect of dietary Zn supplementation to decrease G:F (P = 0.04). Marbling scores were greatest in CON steers (P = 0.03). Liver Cu (day 45 and 80) and meat Cu (harvest) concentrations were greater in CON steers relative to Zn-supplemented steers (P ≤ 0.05), and plasma Zn linearly increased as dietary Zn increased (P = 0.007). Warner-Bratzler shear force was not different among treatments (P ≥ 0.25), and meat total collagen was quadratically affected by dietary Zn supplementation (P ≤ 0.002) where ZnAA0 was greatest. Overall, there was no effect of dietary Zn concentration on growth performance of RAC-supplemented steers in this study.

Respiratory syncytial virus (RSV) mortality estimates have not been updated since 2009, and no study has assessed changes in influenza mortality after the 2009 pandemic. Updated burden estimates are needed to characterize long-term changes in the epidemiology of these viruses.To evaluate excess mortality from RSV and influenza in the US from 1999 to 2018.This cross-sectional study used data from 50.3 million US death certificates from 1999 to 2018 to create age-specific linear regression models and assess weekly mortality fluctuations above a seasonal baseline associated with RSV and influenza. Statistical analysis was performed for 1043 weeks from January 3, 1999, to December 29, 2018.Excess mortality associated with RSV and influenza estimated from the difference between observed and expected underlying respiratory mortality each season.There were 50.3 million death certificates (50.1% women and 49.9% men; mean [SD] age at death, 72.7 [18.6] years) included in this analysis, 1.0% for children younger than 1 year and 73.4% for adults aged 65 years or older. A mean of 6549 (95% CI, 6140-6958) underlying respiratory deaths were associated with RSV annually, including 96 (95% CI, 92-99) deaths among children younger than 1 year. For influenza, there were 10 171 (95% CI, 9652-10 691) underlying respiratory deaths per year, with 23 deaths (95% CI, 19-27) among children younger than 1 year. The highest mean mortality rate per 100 000 population for both viruses was among adults aged 65 years or older at 14.7 (95% CI, 13.8-15.5) for RSV and 20.5 (95% CI, 19.4-21.5) for influenza. A lower proportion of influenza deaths occurred among those aged 65 years or older compared with earlier estimates (75.1% [95% CI, 67.4%-82.8%]). Influenza mortality was highest among those aged 65 years or older in seasons when A/H3N2 predominated (18 739 [95% CI, 16 616-21 336] deaths in 2017-2018) and among those aged 5 to 49 years when A/H1N1pdm2009 predominated (1683 [95% CI, 1583-1787] deaths in 2013-2014). Results were sensitive to the choice of mortality outcome and method, with the broadest outcome associated with annual means of 23 352 (95% CI, 21 814-24 891) excess deaths for RSV and 27 171 (95% CI, 25 142-29 199) for influenza.This study suggests that RSV poses a greater risk than influenza to infants, while both are associated with substantial mortality among elderly individuals. Influenza has large interannual variability, affecting different age groups depending on the circulating virus. The emergence of the influenza A/H1N1pdm2009 pandemic virus in 2009 shifted mortality toward middle-aged adults, a trend still observed to date. This study's estimates provide a benchmark to evaluate the mortality benefits associated with interventions against respiratory viruses, including new or improved immunization strategies.

To investigate the effect of a long-term fatty fish intervention on a pure cognitive mechanism important for self-regulation and mental health, i.e. working memory (WM), controlling for age and IQ. A randomized controlled trial. A forensic facility. Eighty-four young to middle aged male forensic inpatients with psychiatric disorders. Consumption of farmed salmon or control meal (meat) three times a week during 23 weeks. Performance on WM tasks, both accuracy and mean reaction time, were recorded pre and post intervention. Performance on a cognitive functioning tasks taxing WM seemed to be explained by age and IQ. Fatty fish consumption did not improve WM performance in a group of young to middle aged adults with mental health problems, as less impressionable factors such as aging and intelligence seemed to be the key components. The present study improves the knowledge concerning the interaction among nutrition, health and the aging process.

Background The deep breathing test (DB) and Valsalva maneuver (VM) are used to detect autonomic dysfunction. The VM induces sympathetically mediated changes in blood pressure (phase II late, phase IV, and recovery time) and both tests induce vagally mediated heart rate changes. There is limited information on effects of key variables, compliance with testing and the effects of non-compliance This study has twin goals of evaluating compliance with standard instructions and the effects of changes in key variables. We also evaluated the effect of position on the VM. Material and methods Forty healthy males performed DB at air exchange volumes of 50, 80, and 100% of vital lung capacity (VLC). The VM was performed at 40 and 30 mm Hg expiratory pressure for 15 and 10 s in sitting and supine position, respectively. Results Participants performed DB at lower volumes than intended and were not able to maintain 100% VLC for the duration of the test. The DB heart rate response decreased 6.3 beats/min per liter below VLC. During the VM, subjects blew at lower pressures than instructed. The VM responses were significantly larger with longer expiration durations, higher expiratory pressures and when performed sitting. Performing the VM at 40 mm Hg for 10 s in supine position increased the odds ratio of experiencing flat-top responses. Conclusion The ability of subjects to strictly comply with methodological guidelines significantly improves results. Recording of both test parameters and ensuing results is suggested.

Purpose To evaluate sub-differentiation of PI-RADS-3 prostate lesions using pre-defined T2- and diffusion-weighted (DWI) MRI criteria, to aid the biopsy decision process. Methods 143 patients with PIRADS-3 index lesions on MRI underwent targeted transperineal-MR/US fusion biopsy. Radiologists with 2 and 7-years experience performed blinded retrospective second-reads using set criteria and assigned biopsy recommendations. Inter-reader agreement, Gleason score (GS), positive (PPV) predictive values (±95% confidence intervals) were calculated and compared by Fisher’s exact test with Bonferroni-Hom correction. Results 43% (61/143) patients had GS 6–10 and 21% (30/143) GS ≥ 3 + 4 cancer. For peripheral zone lesions, significant differences in any cancer detection were found for shape (0.26 ± 0.13 geographical vs. 0.69 ± 0.23 rounded; p = 0.0055) and ADC (mild 0.21 ± 0.12 vs marked 0.81 ± 0.19; p = 0.0001). For transition zone, significantly increased cancer detection was shown for location (anterior 0.63 ± 0.15 vs. mid/posterior 0.31 ± 0.14; p = 0.0048), border (pseudo-capsule 0.32 ± 0.14 vs. ill-defined 0.61 ± 0.15; p = 0.0092), and ADC (mild 0.35 ± 0.12 vs marked restriction 0.68 ± 0.17; p = 0.0057). Biopsy recommendations had 62% inter-reader agreement (89/143). Experienced reader PPVs were significantly higher for any cancer with “biopsy-recommended” 0.61 ± 0.11 vs. “no biopsy” 0.21 ± 0.10 (p = 0.0001), and for GS 7–10 cancers: 0.32 ± 0.10 vs. 0.08 ± 0.07, respectively (p = 0.0003). Conclusion Identification of certain objective imaging criteria as well as a subjective biopsy recommendation from an experienced radiologist can help to increase the predictive value of equivocal prostate lesions and inform the decision making process of whether or not to biopsy.

Bronchiectasis is an incurable pulmonary disorder that is characterized pathologically by permanent bronchial dilatation and severe bronchial inflammation and clinically by chronic productive cough and recurrent infectious exacerbations; bronchiectasis often occurs in the presence of chronic obstructive pulmonary disease. It is widely believed that increasing use of high-resolution computed tomography has led to a marked rise in the number of persons with diagnosed bronchiectasis in current US clinical practice; up-to-date evidence, however, is lacking. Using a retrospective cohort design and health-care claims data (2009–2013), we estimated the prevalence of bronchiectasis (noncystic fibrosis)—based on narrow case-finding criteria—to be 139 cases per 100,000 persons, to be higher among women versus men (180 vs. 95 per 100 K), and to increase substantially with age (from 7 per 100 K to 812 per 100 K aged 18–34 years and ≥75 years, respectively); annual incidence was estimated to be 29 cases per 100,000 persons. Disease prevalence based on broad case-finding criteria was estimated to be 213 cases per 100,000 persons. The findings of this study suggest that between 340,000 and 522,000 adults were receiving treatment for bronchiectasis and that 70,000 adults were newly diagnosed with bronchiectasis, in 2013 US clinical practice. The findings of this study also suggest that bronchiectasis is much more common than previously reported (annual growth rate since 2001, 8%), presumably due—at least in part—to recent advances in, and increased use of, radiologic techniques. Additional research is needed to validate the findings of this study, to identify the reasons for increased prevalence, and to promote education about bronchiectasis nationally.

Purpose To evaluate the effect of rectal distension on the quality of anatomical and functional prostate multiparametric (mp) MRI. Materials and methods Multiparametric (mp) 3T-MRI images of 173 patients were independently evaluated by two radiologists in this retrospective study. Planimetry rectal volumes were derived and a subjective assessment of rectal distension was made using a 5-point Likert scale (1 = no stool/gas, 5 = large amount of stool/gas). Image quality of diffusion-weighted imaging (DWI) was evaluated using a 5-point Likert scale. DWI was further scored for distortion and artefact. T2W images were evaluated for image sharpness and the presence of motion artefact. The stability of the dynamic contrast-enhancement acquisition was assessed by recording the number of corrupt data points during the wash-out phase. Results There was a strong correlation between subjective scoring of rectal loading and objectively measured rectal volume (r = 0.82), p < 0.001. A significant correlation was shown between increased rectal distension and both reduced DW image quality (r = −0.628, p < 0.001), and increased DW image distortion (r = 0.814, p < 0.001). There was also a significant trend for rectal distension to increase artefact at DWI (r = 0.154, p = 0.042). Increased rectal distension led to increased motion artefact on T2 (p = 0.0096), but did not have a significant effect on T2-sharpness (p = 0.0638). There was no relationship between rectal distension and DCE image quality (p = 0.693). 63 patients underwent lesion-targeted biopsy post MRI, there was a trend to higher positive predictive values in patients with minor rectal distension (34/38, 89.5%) compared to those with moderate/marked distension (18/25, 72%), p = 0.09. Conclusion Rectal distension has a significant negative effect on the quality of both T2W and DW images. Consideration should therefore be given to bowel preparation prior to prostate mpMRI to optimise image quality., The authors acknowledge research support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre.

The aim of the present randomized double-blind placebo control trial was to investigate if vitamin D supplementation had an effect on vitamin D status, executive functioning and self-perceived mental health in a group of Norwegian adolescents during winter time. Fifty adolescents were randomly assigned into an intervention group (vitamin D pearls) or a control group (placebo pearls). Before (pre-test in December/January) and after (post-test in April/May) the intervention period the participants were exposed to a test procedure, consisting of blood draw, completion of cognitive tests (Tower of Hanoi and Tower of London), and the Youth Self-report version of the Child Behavior Checklist. Multivariate data analysis showed that participants with low vitamin D status scored worse on the Tower of London tests and the more difficult sub-tasks on the Tower of Hanoi tests. They also had a tendency to report higher frequency of externalizing behavior problems and attention deficit. At pre-test, the overall mean vitamin D status measured as 25-hydroxy vitamin D was 42 nmol/L, defining deficiency (Intervention group = 44 nmol/L, Control group = 39 nmol/L). However, vitamin D supplementation caused a significant increase in vitamin D status resulting in a sufficient level in the Intervention group at post-test (mean 62 nmol/L). The results also revealed that the intervention group improved their performance on the most demanding sub-tasks on the ToH. Overall, the study indicates that vitamin D status in adolescents may be important for both executive functioning and mental health.

Background Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD. Methods We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains. Results Interleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = −3.63, SE=1.33, p = .04). Conclusions This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD.

Objective: Patiromer is a sodium-free, non-absorbed, potassium (K+) binder approved for the treatment of hyperkalemia (HK). Among US Veterans with HK, this retrospective, observational cohort study evaluated patiromer utilization, RAASi continuation, and K+ concentration change following patiromer initiation. Methods: Using data from the Veterans Affairs Corporate Data Warehouse, Veterans with HK (K+ ≥5.1 mmol/L) were included upon patiromer initiation (index date) during the study period (1/2016–8/2018). All patients had heart failure (HF), diabetes, or chronic kidney disease (CKD). Patients with end-stage renal disease were excluded. The following outcomes were assessed within 6-months post-patiromer initiation: patiromer utilization (using proportion of days covered); K+ concentration change (pre- vs post-initiation); and RAASi continuation. Results: 288 Veterans with HK were included. Baseline characteristics were: median age 70 years, African-American race 24%, diabetes 83%, HF 32%, CKD 95%, and median K+ concentration 5.7 mmol/L. At 1, 3, and 6 months post-index, the median patiromer PDC was 100%, 66%, and 44%, respectively. K+ concentration reductions post-patiromer initiation were, on average, – 1.0 mmol/L (P < 0.001). At 3–6 months, 71% of patiromer initiators had K+ + 80%–90% of patiromer-treated patients. Conclusions: The real-world utilization results suggest patiromer is used for the chronic management of HK. Clinically relevant K+ concentration reductions were observed at all study time points. The successful management of HK may have contributed to the observed high rate of RAASi therapy continuation. Further research is warranted to corroborate and extend these findings.

Recent studies deciphering the transcriptional profile of choroidal neovascularization (CNV) in body donor eyes with neovascular age-related macular degeneration are limited by the time span from death to preservation and the associated 5′-RNA degradation. This study therefore used CNV and control specimens that were formalin-fixed and paraffin-embedded immediately after surgical extraction and analyzed them by a 3′-RNA sequencing approach. Transcriptome profiles were analyzed to estimate content of immune and stromal cells and to define disease-associated gene signatures by using statistical and bioinformatics methods. This study identified 158 differentially expressed genes (DEGs) that were significantly increased in CNV compared with control tissue. Cell type enrichment analysis revealed a diverse cellular landscape with an enrichment of endothelial cells, macrophages, T cells, and natural killer T cells in the CNV. Gene ontology enrichment analysis found that DEGs contributed to blood vessel development, extracellular structure organization, response to wounding, and several immune-related terms. The S100 calcium-binding proteins A8 (S100A8) and A9 (S100A9) emerged among the top DEGs, as confirmed by immunohistochemistry on CNV tissue and protein analysis of vitreous samples. This study provides a high-resolution RNA-sequencing–based transcriptional signature of human CNV, characterizes its compositional pattern of immune and stromal cells, and reveals S100A8/A9 to be a novel biomarker and promising target for therapeutics and diagnostics directed at age-related macular degeneration.

Summary Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3.0 mg for 16 weeks in 14 obese individuals with pathogenic MC4R mutations (BMI 37.5 ± 6.8) and 28 matched control participants without MC4R mutation (BMI 36.8 ± 4.8). Liraglutide decreased body weight by 6.8 kg ± 1.8 kg in individuals with pathogenic MC4R mutations and by 6.1 kg ± 1.2 kg in control participants. Total body fat, waist circumference, and fasting and postprandial glucose concentrations similarly decreased in both groups. Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide is preserved in MC4R causal obesity and that liraglutide acts independently of the MC4R pathway. Thus, liraglutide could be an effective treatment of the most common form of monogenic obesity.

STUDY OBJECTIVES: Pulmonary hypertension (PH) has been reported as a serious complication of obstructive sleep apnea (OSA) in children; however, estimated prevalence rates vary widely (zero to 85%). The purpose of this study is to determine the prevalence of PH in children with OSA and identify factors that may predict an increased PH risk in children with OSA. METHODS: A retrospective review of all pediatric beneficiaries (88,058) in the San Antonio Military Health System with a diagnosis of OSA and a clinical evaluation by a pediatric cardiologist. OSA severity and nadir oxygen saturation were recorded from overnight polysomnography. Reason for referral, comorbid disorders, echocardiogram results, and cardiac diagnoses were obtained from cardiology records. RESULTS: OSA was identified in 2,020 pediatric patients (2.3%). A pediatric cardiology consultation was reported for 296 patients with OSA. After excluding 95 patients for incorrect OSA diagnoses, incomplete data, or OSA treatment before cardiology evaluation, 163 patients were included in the final analysis. A diagnosis of PH was found in 3 patients with OSA (1.8%). Two of these patients had obesity, and all three had comorbid cardiac disorders. CONCLUSIONS: Prevalence of PH in pediatric patients with OSA is low and none of the patients with PH had severe OSA. Current guidelines recommend PH screening in patients with severe OSA, yet OSA severity may not accurately predict risk. Factors evaluated in this study did not demonstrate an increased PH risk; additional research is necessary to improve screening in pediatric patients with OSA. CITATION: Burns AT, Hansen SL, Turner ZS, Aden JK, Black AB, Hsu DP. Prevalence of pulmonary hypertension in pediatric patients with obstructive sleep apnea and a cardiology evaluation: a retrospective analysis. J Clin Sleep Med. 2019;15(8):1081–1087.

Interventional radiology (IR) is a growing field but is underrepresented in most medical school curricula. We tested whether endovascular simulator training improves medical students’ attitudes towards IR. We conducted this prospective study at two university medical centers; overall, 305 fourth-year medical students completed a 90-min IR course. The class consisted of theoretical and practical parts involving endovascular simulators. Students completed questionnaires before the course, after the theoretical and after the practical part. On a 7-point Likert scale, they rated their interest in IR, knowledge of IR, attractiveness of IR, and the likelihood to choose IR as subspecialty. We used a crossover design to prevent position-effect bias. The seminar/simulator parts led to the improvement for all items compared with baseline: interest in IR (pre-course 5.2 vs. post-seminar/post-simulator 5.5/5.7), knowledge of IR (pre-course 2.7 vs. post-seminar/post-simulator 5.1/5.4), attractiveness of IR (pre-course 4.6 vs. post-seminar/post-simulator 4.8/5.0), and the likelihood of choosing IR as a subspecialty (pre-course 3.3 vs. post-seminar/post-simulator 3.8/4.1). Effect was significantly stronger for simulator training compared with that for seminar for all items (p

Objectives To assess cancer detection rates of different target-dependent transperineal magnetic resonance (MR)/ultrasonography (US) fusion-guided biopsy templates with reduced number of systematic cores. Patients and methods Single-centre outcome of transperineal MR/US fusion-guided biopsies of 487 men with a single target MR imaging (MRI) lesion, prospectively collected between 2012 and 2016. All men underwent transperineal targeted biopsy (TB) with two cores, followed by 18-24 systematic sector biopsies (SB) using the Ginsburg protocol. Gleason score ≥7 prostate cancer detection rates for two-core TB, four-core extended TB (eTB), 10- to 20-core saturation TB (sTB) including cores from sectors adjacent to the target, and 14 core ipsilateral TB (iTB) were compared to combined TB+SB. Results Cancer was detected in 345 men and Gleason score 7-10 cancer in 211 men. TB alone detected 67%, eTB 76%, sTB 91% and iTB 91% of these Gleason score 7-10 cancers. In the subgroup of 33 men (7% of cohort) with an anterior >0.5 mL highly suspicious MRI lesion and a prostate volume ≤45 mL, four-core eTB detected 31 of 32 cancers (97%) and all 26 Gleason score 7-10 cancers. Conclusion sTB detected Gleason score 7-10 cancer in 25% more of the men than a two-core TB approach, and in almost as many men (91%) as the 20-26-core combined TB+SB, while needing only 10-20 cores. A four-core extended TB may suffice for large, highly suspicious anterior lesions in small or slightly enlarged prostates.

Objectives: The present study investigated the effects of 3-dimensional deep search (3DDS) signal processing on the enhancement of consonant perception in bimodal and normal hearing listeners. Methods: Using an articulation-index gram and 3DDS signal processing, consonant segments that greatly affected performance were identified and intensified with a 6-dB gain. Then consonant recognition was measured unilaterally and bilaterally before and after 3DDS processing both in quiet and noise. Results: The 3DDS signal processing provided a benefit to both groups, with greater benefit occurring in noise than quiet. The benefit rendered by 3DDS was the greatest in binaural listening condition. Ability to integrate acoustic features across ears was also enhanced with 3DDS processing. In listeners with normal hearing, manner and place of articulation were improved in binaural listening condition. In bimodal listeners, voicing and manner and place of articulation were also improved in bimodal and hearing aid ear–alone conditions. Conclusions: Consonant recognition was improved with 3DDS in both groups. This observed benefit suggests 3DDS can be used as an auditory training tool for improved integration and for bimodal users who receive little or no benefit from their current bimodal hearing.

Background The identification of an early biomarker for autism spectrum disorder (ASD) would improve the determination of risk, leading to earlier diagnosis and, potentially, earlier intervention and improved outcomes. Methods Data were generated from the Early Markers for Autism study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (n = 370), children with developmental delay (n = 140), and general population (GP) controls (n = 378) were analyzed for 42 different immune markers using a Luminex multiplex platform. Comparisons of immune marker concentrations between groups were examined using logistic regression and partial least squares discriminant analysis. Results Children with ASD had significantly increased neonatal levels of interleukin-6 (IL-6) and IL-8 compared with GP controls. An increase in IL-8 was especially significant in the ASD group with early onset compared with the GP group, with an adjusted odds ratio of 1.97 (95% confidence interval, 1.39–2.83; p = .00014). In addition, children with ASD had significantly elevated levels of eotaxin-1, interferon-γ, and IL-12p70 relative to children with developmental delay. We observed no significant differences in levels of immune markers between the developmental delay and GP groups. Conclusions Elevated levels of some inflammatory markers in newborn bloodspots indicated a higher degree of immune activation at birth in children who were subsequently diagnosed with ASD. The data from this exploratory study suggest that with further expansion, the development of neonatal bloodspot testing for cytokine/chemokine levels might lead to the identification of biomarkers that provide an accurate assessment of ASD risk at birth.

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AIMS: To investigate the region-specific effects of painful trigeminal capsaicin stimulation in healthy participants.METHODS: Twenty healthy participants (10 men and 10 women) participated in four sessions in which they received application of 0.05 mL Vaseline (placebo) or capsaicin cream (0.1%) to a different area innervated by the three branches of the trigeminal nerve: the supraorbital area (V1), the nasal mucosa (V1/V2), and the maxillary (V2) and mandibular (V3) oral mucosa. The participants rated their perceived sensations on a 0-50-100 numeric rating scale (NRS). Thermal (5°C, 23°C, and 50°C) and mechanical (32 mN and 256 mN) sensitivities were assessed. The Schirmer tearing test was used to monitor the lacrimation level as a local measure of autonomic activity, and the Task Force Monitor was used to record systemic autonomic activity. Data were analyzed using repeated measures analysis of variance.RESULTS: Capsaicin application evoked significantly higher overall NRS scores (P < .001) and induced significantly higher ratings to the heat stimuli (P < .009) in all sessions compared to control. For lacrimation level, capsaicin stimulation resulted in a significant increase compared to control (P < .0002) only in the nasal mucosa session.CONCLUSION: Topical application of capsaicin cream to the different branches of the trigeminal nerve caused higher NRS scores along with an altered somatosensory sensitivity. Furthermore, in the nasal mucosa session, a robust local and generalized parasympathetic activation appeared following capsaicin application.

Recent research suggests that bronchiectasis (BE) may be more common than previously believed and that comorbid chronic obstructive pulmonary disease (COPD) is widespread in this patient population. Little is known about the economic burden among patients with BE, and less is known about the burden among those with comorbid BE + COPD. A retrospective matched-cohort design and data from a US health-care claims repository were employed. From the source population comprising adults who had comprehensive medical/drug benefits for ≥1 day in 2013 (i.e. the referent year) and evidence of BE and/or COPD at any time from 2009 to 2013, patients with BE + COPD were age/sex-matched (1:1:1) to patients with BE only and patients with COPD only. For each matched subgroup, annualized levels of respiratory-related and all-cause health-care utilization and expenditures in 2013 were summarized. Source population included 679,679 patients; among those with BE ( n = 31,027), 50% had comorbid COPD. Mean (95% CI) annual levels of respiratory-related utilization and expenditures among matched patients with BE + COPD ( n = 11,685) were higher by 2.4–3.5 times versus patients with BE only and 2.0–2.5 times versus patients with COPD only: hospitalizations, 0.39 (0.37–0.41) versus 0.11 (0.09–0.12) and 0.16 (0.14–0.17); ambulatory encounters, 16.5 (16.1–16.9) versus 6.8 (6.6–7.0) and 8.2 (7.9–8.4); and total expenditures, US$15,685 (14,693–16,678) versus US$5605 (5059–6150) and US$6262 (5655–6868). Respiratory-related utilization and expenditures are high among patients with BE or COPD receiving medical care in US clinical practice and are especially high among those with comorbid BE + COPD receiving medical care, emphasizing the importance of identifying and treating this unique patient population. Funding for this research was provided by RespirTech to Policy Analysis Inc. (PAI).

A mycotic aneurysm of the distal radial artery following access for cardiac catheterisation is a rare complication that has not been described in the literature. We present the case of an 84-year-old man who developed bacteraemia and cellulitis over his left first dorsal webspace 2 days after undergoing cardiac catheterisation through the distal radial artery at the anatomic snuffbox. Ultrasound scanning and CT imaging were concerning for a possible pseudoaneurysm at that location. Once we confirmed that the patient had adequate flow through his hand with angiography and an Allen’s test, we explored his left hand and found a mycotic aneurysm of the distal radial artery with surrounding frank purulence. We resected the aneurysm and ligated the artery. Pathology confirmed that this was a mycotic aneurysm. The patient quickly recovered from his infection after this definitive treatment.

OBJECTIVE: To report our experience with a combination of prostate magnetic resonance imaging (MRI) and transperineal ultrasound biopsy for evaluating the prostate in patients with elevated prostate-specific antigen (PSA) who have previously undergone abdominoperineal resection (APR). PATIENTS AND METHODS: We reviewed the records of 11 patients with a history of APR and clinical suspicion of prostate cancer due to elevated PSA levels over a 5-year period. All patients underwent multiparametric MRI at our institution prior to biopsy. MR diagnoses were validated either by transperineal ultrasound biopsy (Likert 3-5) guided by visual registration or clinical follow-up >6 months (Likert 1-2). RESULTS: All 7 cases with highly suspicious lesions (Likert 4-5) on MRI demonstrated cancer-1 case of Gleason 3 + 3 and 6 cases of Gleason ≥3 + 4 disease. Two cases with Likert 3 MR lesions revealed benign tissue upon biopsy. Two patients with no suspicious lesions on MRI were followed-up clinically, with PSA levels remaining stable over a mean period of 17.5 months (range 7-28 months). CONCLUSION: The use of prebiopsy multiparametric prostate MRI and subsequent cognitively targeted transperineal biopsy guided by visual registration can aid in the diagnostic pathway of patients with APR and a suspicion of prostate cancer.

Background Prostate biopsy supported by transperineal image fusion has recently been developed as a new method to the improve accuracy of prostate cancer detection. Objective To describe the Ginsburg protocol for transperineal prostate biopsy supported by multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) image fusion, provide learning points for its application, and report biopsy results. The article is supplemented by a Surgery in Motion video. Design, setting, and participants This single-centre retrospective outcome study included 534 patients from March 2012 to October 2015. A total of 107 had no previous prostate biopsy, 295 had benign TRUS-guided biopsies, and 159 were on active surveillance for low-risk cancer. Surgical procedure A Likert scale reported mpMRI for suspicion of cancer from 1 (no suspicion) to 5 (cancer highly likely). Transperineal biopsies were obtained under general anaesthesia using BiopSee fusion software (Medcom, Darmstadt, Germany). All patients had systematic biopsies, two cores from each of 12 anatomic sectors. Likert 3–5 lesions were targeted with a further two cores per lesion. Outcome measurements and statistical analysis Any cancer and Gleason score 7–10 cancer on biopsy were noted. Descriptive statistics and positive predictive values (PPVs) and negative predictive values (NPVs) were calculated. Results and limitations The detection rate of Gleason score 7–10 cancer was similar across clinical groups. Likert scale 3–5 MRI lesions were reported in 378 (71%) of the patients. Cancer was detected in 249 (66%) and Gleason score 7–10 cancer was noted in 157 (42%) of these patients. PPV for detecting 7–10 cancer was 0.15 for Likert score 3, 0.43 for score 4, and 0.63 for score 5. NPV of Likert 1–2 findings was 0.87 for Gleason score 7–10 and 0.97 for Gleason score ≥4+3=7 cancer. Limitations include lack of data on complications. Conclusions Transperineal prostate biopsy supported by MRI/TRUS image fusion using the Ginsburg protocol yielded high detection rates of Gleason score 7–10 cancer. Because the NPV for excluding Gleason score 7–10 cancer was very high, prostate biopsies may not be needed for all men with elevated prostate-specific antigen values and nonsuspicious mpMRI. Patient summary We present our technique to sample (biopsy) the prostate by the transperineal route (the area between the scrotum and the anus) to detect prostate cancer using a fusion of magnetic resonance and ultrasound images to guide the sampling.