Hibernating astronauts-science or fiction?

For long-duration manned space missions to Mars and beyond, reduction of astronaut metabolism by torpor, the metabolic state during hibernation of animals, would be a game changer: Water and food intake could be reduced by up to 75% and thus reducing payload of the spacecraft. Metabolic rate reduction in natural torpor is linked to profound changes in biochemical processes, i.e., shift from glycolysis to lipolysis and ketone utilization, intensive but reversible alterations in organs like the brain and kidney, and in heart rate control via Ca2+. This state would prevent degenerative processes due to organ disuse and increase resistance against radiation defects. Neuro-endocrine factors have been identified as main targets to induce torpor although the exact mechanisms are not known yet. The widespread occurrence of torpor in mammals and examples of human hypometabolic states support the idea of human torpor and its beneficial applications in medicine and space exploration.

Putting patients at the center of kidney care transitions: PREPARE NOW, a cluster randomized controlled trial.

Care for patients transitioning from chronic kidney disease to kidney failure often falls short of meeting patients' needs. The PREPARE NOW study is a cluster randomized controlled trial studying the effectiveness of a pragmatic health system intervention, 'Patient Centered Kidney Transition Care,' a multi-component health system intervention designed to improve patients' preparation for kidney failure treatment. Patient-Centered Kidney Transition Care provides a suite of new electronic health information tools (including a disease registry and risk prediction tools) to help providers recognize patients in need of Kidney Transitions Care and focus their attention on patients' values and treatment preferences. Patient-Centered Kidney Transition Care also adds a 'Kidney Transitions Specialist' to the nephrology health care team to facilitate patients' self-management empowerment, shared-decision making, psychosocial support, care navigation, and health care team communication. The PREPARE NOW study is conducted among eight [8] outpatient nephrology clinics at Geisinger, a large integrated health system in rural Pennsylvania. Four randomly selected nephrology clinics employ the Patient Centered Kidney Transitions Care intervention while four clinics employ usual nephrology care. To assess intervention effectiveness, patient reported, biomedical, and health system outcomes are collected annually over a period of 36 months via telephone questionnaires and electronic health records. The PREPARE NOW Study may provide needed evidence on the effectiveness of patient-centered health system interventions to improve nephrology patients' experiences, capabilities, and clinical outcomes, and it will guide the implementation of similar interventions elsewhere. TRIAL REGISTRATION: NCT02722382.

Registry report of the prevalence of ECG abnormalities and their relation to patient characteristics in an asymptomatic population.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in developed countries. Many patients do not experience symptoms before a first major cardiovascular event. Resting electrocardiogram (ECG) may help identify asymptomatic individuals with a high risk of cardiovascular disease. OBJECTIVE: We sought to determine the prevalence of ECG abnormalities in an apparently symptom-free adult population within a prospective registry. METHODS: The registry consisted of 4739 consecutive apparently healthy individuals [age 62.8 ± 6.2 (SD) years; 54% female], referred by their General Practitioners between 2009 and 2013. Patient demographics, and clinical data were obtained, alongside blood tests and a resting ECG. RESULTS: ECG abnormalities were present in 1509 (31.8%) subjects and were commoner with increasing age (F = 0.161, p = 0.01), systolic (F = 0.134, p = 0.01) and diastolic (F = 0.44, p = 0.01) blood pressure and waist circumference (F = 0.53, p = 0.01). Left ventricular hypertrophy (LVH) was the most common abnormality (n = 281) and was positively associated with systolic (F = 0.12, p = 0.01) and diastolic blood pressure (F = 0.99, p = 0.01) and male gender (X2 = 60.5, p < 0.01). All ECG abnormalities (except for LVH) were associated with an increasing age, while right bundle branch block (F = 0.041, p = 0.01) and atrial fibrillation (n = 29; F = 0.036, p = 0.05) were associated with the presence of diabetes mellitus (n = 211). Only left bundle branch block (n = 50) was associated with angina (F = 0.05, p = 0.01). CONCLUSIONS: Unrecognized cardiac abnormalities are common in middle-aged men and women with no overt symptoms. ECG offers the potential to identify these abnormalities and provide earlier intervention and treatment, and possibly improve cardiovascular outcome.

How confident are physicians in deprescribing for the elderly and what barriers prevent deprescribing?

WHAT IS KNOWN AND OBJECTIVE: Deprescribing is the process of discontinuing or reducing the dosage of medications that are no longer appropriate or aligned with goals of care, which is paramount in elderly patients with multiple comorbidities and polypharmacy. The objective of this study was to assess the perceptions of primary care physicians on deprescribing for elderly patients and potential barriers to deprescribing that physicians experience in the Local Health Authority (LHA) of Parma, Emilia-Romagna, Italy. METHODS: One hundred and sixty physicians (57% of the total number of primary care physicians in Parma) attended an educational session related to deprescribing and were asked to anonymously complete a paper survey. Participants were asked to assess their level of agreement on nine questions about their perception of deprescribing and potential factors affecting the deprescribing process using a seven-point Likert-type scale. A correlation coefficient was calculated to assess the association between physicians' confidence in deprescribing and attitudes or barriers associated with deprescribing. RESULTS AND DISCUSSION: Many physicians (72%) reported general confidence in their ability to deprescribe. Most respondents (78%) reported they were comfortable deprescribing preventive medications, yet only half (53%) were comfortable deprescribing guideline-recommended therapies. Lack of evidence on discontinuing preventive medicines and concern about withdrawal side effects were reported to impede deprescribing by more than one-third of physicians. When medications were initially prescribed by another physician, 40% of physicians reported hesitance in deprescribing them. About half of physicians (45%) did not feel comfortable deprescribing when patients/caregivers believed that continuation of the medication was needed. Lack of time and difficulty engaging patients/caregivers in the deprescribing process were cited as barriers by about one in four physicians. There was no strong correlation between physicians' confidence and attitudes or barriers associated with deprescribing. WHAT IS NEW AND CONCLUSION: The study results show that physicians believe they are generally comfortable with deprescribing, although there are still several factors that hamper their ability to engage in the process. An improved understanding of physicians' views on deprescribing may help guide further research, and policies to help patients remain healthy while streamlining their medication regimen.

[Acute Kidney Failure Due to Urachal Cyst?] / Akutes Nierenversagen bei Urachuszyste?

A 34-year-old para V woman was referred to our centre at 35+1 weeks of gestation for an assumed fetal malformation with prenatal renal impairment and anhydramnios. Prenatal ultrasound demonstrated unilateral renal agenesis; the bladder was not detectable. The baby was born by caesarian section at 36+2 weeks of gestation because of placental insufficiency. Postnatal adaptation was uneventful, but the newborn presented external stigmas of trisomy 21 and progressive renal impairment with anuria. Nevertheless, the postnatal ultrasound showed two enlarged kidneys in loco typico with impaired perfusion but without signs of malformations. In the lower abdomen, a rosette-shaped structure of unknown origin was noted. Its origin could not be cleared by imaging including voiding cystourethrography and colon contrast radiography. Explorative laparotomy identified the structure as a persistent urachal cyst with secondary obstruction of the upper urinary tract. After removal of the urachus with reconstruction of the bladder dome, renal function recovered completely while urine was drained continuously via suprapubic catheter. A voiding cystourethrogram 3 weeks later showed a posterior urethral valve as an additional unexpected diagnosis. The valve was slit at the age of 6 months without complications, the renal function remained stable in the further course. In retrospect, the main cause for the renal failure remains unclear. It appears to be the obstruction due to the space-consuming character of the urachal cyst, especially because the megacystis typically associated with urethral valve was not viewable. Alternatively, the additional proximal stenosis may have only masked the typical findings of PUV.

Local anesthetics induce autophagy in young permanent tooth pulp cells.

Pulp cells are essential for tooth development, and dentin repair and regeneration. In addition these cells have been identified as an important stem cell source. Local anesthetics are widely used in dental clinics, as well as the other clinical disciplines and have been suggested to interfere with human permanent tooth development and induce tooth agenesis through unknown mechanisms. Using pig model and human young permanent tooth pulp cells, our research has identified that the local anesthetics commonly used in clinics can affect cell proliferation. Molecular pathway profiling suggested that LC3II is one of the earliest molecules induced by the agents and p62 is the only common downstream target identified for all the drugs tested. The effect of the drugs could be partially recovered by V-ATPase inhibitor only if early intervention is performed. Our results provide novel evidence that local anesthetics could affect tooth cell growth that potentially can have impacts on tooth development.

Prospective validation study of transorbital Doppler ultrasound imaging for the detection of transient cerebral microemboli.

BACKGROUND: Transient cerebral microemboli are independent biomarkers of early risk of ischaemic stroke in acute carotid syndromes. Transcranial Doppler imaging (TCD) through the temporal bone is the standard method for detection of cerebral microemboli, but an acoustic temporal bone window for TCD is not available in around one in seven patients. Transorbital Doppler imaging (TOD) has been used when TCD is not possible. The aim of this study was to validate the use of TOD against TCD for detecting cerebral microemboli. METHODS: The study included patients undergoing elective carotid endarterectomy; all had confirmed temporal and orbital acoustic windows. Subjects gave written informed consent to postoperative TCD and TOD monitoring, which was performed simultaneously for 30 min by two vascular scientists. RESULTS: The study included 100 patients (mean(s.e.m.) age 72(1) years; 65 men). Microemboli were detected by one or both methods in 40·0 per cent of patients: by TOD and TCD in 24 patients, by TOD alone in ten and by TCD alone in six. For detecting microemboli, TOD had a sensitivity of 80·0 per cent, specificity of 86·1 per cent, positive predictive value of 71·6 per cent and negative predictive value of 91·2 per cent. Bland-Altman analysis revealed no significant bias (bias 0·11 (95 per cent c.i. -0·52 to 0·74) microemboli; P = 0·810) with upper and lower limits of agreement of +6 and -6 microemboli. CONCLUSION: TOD appears a valid alternative to TCD for detecting microembolic signals in patients with no suitable temporal acoustic window.