Prostate Cancers in the Prostate-specific Antigen Interval of 1.8-3 ng/ml: Results from the Göteborg-2 Prostate Cancer Screening Trial.

BACKGROUND: Magnetic resonance imaging (MRI) and targeted biopsies reduce overdiagnosis of prostate cancer (PC). It is uncertain how this strategy performs for low prostate-specific antigen (PSA) levels. OBJECTIVE: To investigate the Prostate Imaging Reporting and Data System (PI-RADS) distribution, frequency, and characteristics of screen-detected PC with PSA of 1.8-<3 ng/ml and 3-<10 ng/ml. DESIGN, SETTING, AND PARTICIPANTS: In the population-based Göteborg-2 screening study, 17974 men choose to participate by having a PSA test (2015-2020). One-third of the participants (n = 6006) were randomized to arm 3, men with a PSA value of ≥1.8 ng/ml were recommended for MRI. Men with positive MRI (PI-RADS 3-5) had four targeted biopsies from each MRI-visible lesion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinically significant PC was defined as Gleason score ≥3 + 4. RESULTS AND LIMITATIONS: A total of 6006 men were included. The median age was 55.9 yr (interquartile range [IQR] 52.6-59.6). Of them, 4929 (82%) had PSA of <1.8 ng/ml, 670 (11%) had PSA of 1.8-<3 ng/ml (low-PSA group, median PSA 2.1 ng/ml [IQR 1.9-2.5]), and 377 (6.3%) had PSA of 3-<10 ng/ml (high-PSA group, median PSA 3.9 ng/ml [IQR 3.3-5.0]). PI-RADS scores of 3, 4, and 5 were observed in 7.8%, 15%, and 1.0% of men in the low-PSA group, and in 6.9%, 17%, and 5.3% of men in the high-PSA group, respectively. PC was found in 64 men (41%, 95% confidence interval [CI] 0.33-0.49) with positive MRI findings in the low-PSA group, of whom 33 (21%) had Gleason 6 (insignificant PC) and 31 (20%) had Gleason ≥7 (significant PC). In the high-PSA group, PC was detected in 61 men (56%, 95% CI 0.46-0.66), of whom 26 (24%) had Gleason 6 (insignificant PC) and 35 (32%) had Gleason ≥7 (significant PC). Limitations include results from only a single screening round. CONCLUSIONS: A non-negligible number of men with PSA 1.8-3 ng/ml have clinically significant PC. Whether a delay in the diagnosis of these tumors until they reached PSA ≥3 ng/ml would impair their chance of cure remains to be evaluated. PATIENT SUMMARY: We studied screening using prostate-specific antigen (PSA) and magnetic resonance imaging in men with PSA 1.8-3 ng/ml. We found a non-negligible number of potentially harmful prostate cancers in these men.

Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders.

BACKGROUND: The growing number of identified genetic disease risk variants across dog breeds challenges the current state-of-the-art of population screening, veterinary molecular diagnostics, and genetic counseling. Multiplex screening of such variants is now technologically feasible, but its practical potential as a supportive tool for canine breeding, disease diagnostics, pet care, and genetics research is still unexplored. RESULTS: To demonstrate the utility of comprehensive genetic panel screening, we tested nearly 7000 dogs representing around 230 breeds for 93 disease-associated variants using a custom-designed genotyping microarray (the MyDogDNA® panel test). In addition to known breed disease-associated mutations, we discovered 15 risk variants in a total of 34 breeds in which their presence was previously undocumented. We followed up on seven of these genetic findings to demonstrate their clinical relevance. We report additional breeds harboring variants causing factor VII deficiency, hyperuricosuria, lens luxation, von Willebrand's disease, multifocal retinopathy, multidrug resistance, and rod-cone dysplasia. Moreover, we provide plausible molecular explanations for chondrodysplasia in the Chinook, cerebellar ataxia in the Norrbottenspitz, and familiar nephropathy in the Welsh Springer Spaniel. CONCLUSIONS: These practical examples illustrate how genetic panel screening represents a comprehensive, efficient and powerful diagnostic and research discovery tool with a range of applications in veterinary care, disease research, and breeding. We conclude that several known disease alleles are more widespread across different breeds than previously recognized. However, careful follow up studies of any unexpected discoveries are essential to establish genotype-phenotype correlations, as is readiness to provide genetic counseling on their implications for the dog and its breed.

Infections in status epilepticus: a retrospective 5-year cohort study.

PURPOSE: Status epilepticus (SE) has attracted renewed interest lately, and efforts are made to optimize every treatment stage. For refractory SE, optimal supporting care involves mechanical ventilation and intensive care unit (ICU) admission. Infections often complicate SE and recently a single-centre observational study demonstrated an association between infections and poor short-term outcome of SE in a cohort of severely ill patients. We have here attempted to replicate those findings in a different cohort. METHOD: We performed a retrospective observational study and included all patients with a diagnosis of SE during 2008-2012 at a Swedish tertiary referral centre. RESULTS: The cohort consisted of 103 patients (53% female, 47% male, median age 62 years, range 19-87 years). In house mortality was less than 2 and 70% of the patients' were discharged home. The most common aetiologies of SE were uncontrolled epilepsy (37%) and brain tumours (16%). A total of 39 patients suffered infections during their stay. Presence of infection was associated with mechanical ventilation (OR 3.344, 95% CI 1.44-7.79) as well as not being discharged home (OR2.705, 95% CI 1.14-6.44), and duration of SE was significantly longer in patients with infection (median 1 day vs. 2.5 days, p<0.001). CONCLUSION: We conclude that the previously described association between infections, a longer SE duration, and an unfavourable outcome of SE seems valid also in SE of less severe aetiology.

A new method of selective, rapid cooling of the brain: an experimental study.

PURPOSE: To determine whether retrograde perfusion of cooled blood into one internal jugular vein (IJV) in the pig can selectively reduce the brain temperature without affecting the core body temperature (CBT). METHODS: In 7 domestic pigs, the left IJV was catheterized on one side and a catheter placed with the tip immediately below the rete mirabile. Thermistors were placed in both brain hemispheres and the brain temperature continuously registered. Thermistors placed in the rectum registered the CBT. From a catheter in the right femoral vein blood was aspirated with the aid of a roller pump, passed through a cooling device, and infused into the catheter in the left IJV at an initial rate of 200 ml/min. RESULTS: Immediately after the start of the infusion of cooled blood (13.8 degrees C) into the IJV, the right brain temperature started to drop from its initial 37.9 degrees C and reached 32 degrees C within 5 min. By increasing the temperature of the perfusate a further drop in the brain temperature was avoided and the brain temperature could be kept around 32 degrees C during the experiment. In 4 of the animals a heating blanket was sufficient to compensate for the slight drop in CBT during the cooling period. CONCLUSIONS: We conclude that brain temperature can be reduced in the pig by retrograde perfusion of the internal jugular vein with cooled blood and that the core body temperature can be maintained with the aid of a heating blanket.