A non‐inferiority comparative analysis of micro‐ultrasonography and MRI‐targeted biopsy in men at risk of prostate cancer

Objective: To compare the efficacy of multiparametric magnetic resonance imaging (mpMRI)-directed and micro-ultrasonography (micro-US)-directed biopsy for detecting clinically significant (Grade Group >1) prostate cancer (csPCa). Materials and methods: A total of 203 patients were prospectively enrolled at three institutions across Germany and Austria in the period from January 2019 to December 2019. During each biopsy, the urologist was blinded to the mpMRI report until after the micro-US targets had been assessed. After unblinding, targets were then sampled using software-assisted fusion, followed by systematic samples. The primary outcome measure was non-inferiority of micro-US to detect csPCa, with a detection ratio of at least 80% that of mpMRI. Results: A total of 79 csPCa cases were detected overall (39%). Micro-US-targeted biopsy detected 58/79 cases (73%), while mpMRI-targeted biopsy detected 60/79 (76%) and non-targeted (completion sampling) samples detected 45/79 cases (57%). mpMRI-targeted samples alone detected 7/79 (9%) csPCa cases which were missed by micro-US-targeted and non-targeted samples. Three of these seven were anterior lesions with 2/7 in the transition zone. Micro-US-targeted samples alone detected 5/79 (6%) and completion sampling alone detected 4/79 cases (5%). Micro-US was non-inferior to mpMRI and detected 97% of the csPCa cases detected by mpMRI-targeted biopsy (95% CI 80-116%; P = 0.023). Conclusions: This is the first multicentre prospective study comparing micro-US-targeted biopsy with mpMRI-targeted biopsy. The study provides further evidence that micro-US can reliably detect cancer lesions and suggests that micro-US biopsy might be as effective as mpMRI for detection of csPCA. This result has significant implications for increasing accessibility, reducing costs and expediting diagnosis

Melatonin and its metabolites ameliorate UVR-induced mitochondrial oxidative stress in human MNT-1 melanoma cells

Melatonin (Mel) is the major biologically active molecule secreted by the pineal gland. Mel and its metabolites, 6-hydroxymelatonin (6(OH)Mel) and 5-methoxytryptamine (5-MT), possess a variety of functions, including the scavenging of free radicals and the induction of protective or reparative mechanisms in the cell. Their amphiphilic character allows them to cross cellular membranes and reach subcellular organelles, including the mitochondria. Herein, the action of Mel, 6(OH)Mel, and 5-MT in human MNT-1 melanoma cells against ultraviolet B (UVB) radiation was investigated. The dose of 50 mJ/cm2 caused a significant reduction of cell viability up to 48%, while investigated compounds counteracted this deleterious effect. UVB exposure increased catalase activity and led to a simultaneous Ca++ influx (16%), while tested compounds prevented these disturbances. Additional analysis focused on mitochondrial respiration performed in isolated mitochondria from the liver of BALB/cJ mice where Mel, 6(OH)Mel, and 5-MT significantly enhanced the oxidative phosphorylation at the dose of 10−6 M with lower effects seen at 10−9 or 10−4 M. In conclusion, Mel, 6(OH)Mel and 5-MT protect MNT-1 cells, which express melatonin receptors (MT1 and MT2) against UVB-induced oxidative stress and mitochondrial dysfunction, including the uncoupling of oxidative phosphorylation

Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic

BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11034-w

Дослідження структури порушених відкритою розробкою земель й пошук шляхів вдосконалення рекультивації залишкових виробок кар'єрів

Стаття присвячена дослідженням структури порушених земель, на ділянках з видобутку корисних копалин відкритим способом. Наведено площі порушень земель при розробці основних видів корисних копалин. Проаналізовано ризики, що виникають із несвоєчасною рекультивацією земель гірничого відводу, а також від покинутих гірничих виробок старих кар'єрів. Паралельно розглянуті обсяги відходів гірничого виробництва та їх повторне використання в якості заповнювача для залишкових вироблених просторів кар'єрів.The article is devoted to the research of land violation indicators at the extraction of minerals by surface mining method. Data gives about the land violations area at the mining key minerals. Ana-lyzed the risks from the not-on-time reclamation of the mining clam and abandoned excavations of the old quarries. In parallel considered the volumes of mining wastes and their reuse as aggregate for filling residual spaces of surface mines.Статья посвящена исследованиям площадей нарушения земель, связанных с добычей полезных ископаемых открытым способом. Приведены площади нарушений земель при разработке основных видов полезных ископаемых. Проанализированы риски, представляемые несвоевременной рекультивацией земель горного отвода, а также заброшенными горными выработками старых карьеров. Параллельно рассмотрены объемы отходов горного производства и их повторное использование в качестве заполнителя для остаточных выработанных пространств карьеров

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis

Autoreactive CD4+ T lymphocytes play a vital role in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Since the discovery of T helper 17 cells, there is an ongoing debate whether T helper 1, T helper 17 or both subtypes of T lymphocytes are important for the initiation of autoimmune neuroinflammation. We examined peripheral blood CD4+ cells from patients with active and stable relapsing–remitting multiple sclerosis, and used mice with conditional deletion or over-expression of the transforming growth factor-β inhibitor Smad7, to delineate the role of Smad7 in T cell differentiation and autoimmune neuroinflammation. We found that Smad7 is up-regulated in peripheral CD4+ cells from patients with multiple sclerosis during relapse but not remission, and that expression of Smad7 strongly correlates with T-bet, a transcription factor defining T helper 1 responses. Concordantly, mice with transgenic over-expression of Smad7 in T cells developed an enhanced disease course during experimental autoimmune encephalomyelitis, accompanied by elevated infiltration of inflammatory cells and T helper 1 responses in the central nervous system. On the contrary, mice with a T cell-specific deletion of Smad7 had reduced disease and central nervous system inflammation. Lack of Smad7 in T cells blunted T cell proliferation and T helper 1 responses in the periphery but left T helper 17 responses unaltered. Furthermore, frequencies of regulatory T cells were increased in the central nervous system of mice with a T cell-specific deletion and reduced in mice with a T cell-specific over-expression of Smad7. Downstream effects of transforming growth factor-β on in vitro differentiation of naïve T cells to T helper 1, T helper 17 and regulatory T cell phenotypes were enhanced in T cells lacking Smad7. Finally, Smad7 was induced during T helper 1 differentiation and inhibited during T helper 17 differentiation. Taken together, the level of Smad7 in T cells determines T helper 1 polarization and regulates inflammatory cellular responses. Since a Smad7 deletion in T cells leads to immunosuppression, Smad7 may be a potential new therapeutic target in multiple sclerosis

Lebenszykluskosten von Brückenbauwerken in Vorarlberg

nicht vorhande

Predictors of Postoperative Cognitive Decline in Very Old Patients With Hip Fracture

Background: To investigate incidence and predictors of the various postoperative cognitive declines in old patients with hip fracture. Methods: This retrospective chart study evaluated 411 patients (age ≥80 years, follow-up 5 years). After exclusion of 82 patients (preexisting dementia or delirium), 70 patients showing either diagnosed postoperative delirium (POD; group 1; N = 18, 5.5%) or an unspecified cognitive dysfunction and behavior (group 2; N = 52, 15.8%) were analyzed and compared with those without any acute postoperative cerebral impairment (control group; N = 259, 78.7%). Medical history, anesthesiological, orthopedic, and rehabilitation data were assessed using the medical database of the hospital information system. Relative ratio was calculated with Fisher exact test: P value Bonferroni corrected ≤.003. Results: Acute cognitive complications were observed in 70 (21.3%) patients. Our data in group 1 showed that patients with a medical history of stroke (relative risk [RR] = 16.2, P = .0001) or nicotine abuse (RR = 14.4, P = .001) and perioperative surgical bleeding (RR = 6.54, P = .002) are more likely to develop POD. Unspecified cognitive dysfunction and behavior (group 2) was significantly associated with a medical history of stroke (RR = 12.5, P = .0001) and postoperatively with depression (RR = 3.32, P = .001). In the follow-up, significantly more patients in group 1 (55.6%, RR = 21.8, P = .0001) and group 2 (13.5%, RR = 3.88, P = .001) developed dementia as compared to controls (1.9%). Mortality did not differ significantly between the groups (group 1: RR = 1.75, P = .5 and group 2: RR = 0.66, P = 1.0). Conclusion: These data show that various predictors can identify a greater likelihood of developing postoperative cognitive decline in very old patients with hip fracture. Not identifying or labeling of POD limits the opportunity for evaluation, treatment, and planning. Thus, routine cognitive assessments need to be performed in the scope of multidisciplinary orthogeriatric comanagement

Peridural Anesthesia or Ultrasound-Guided Continuous 3-in-1 Block

Purpose: The aim of our study was to investigate the clinical relevance of preoperative acute pain management and cardiovascular stability by ultrasound-guided continuous 3-in-1 nerve block in very elderly patients with hip fracture when compared to epidural anesthesia (PDA). Methods: To study the analgesic effect, we enrolled 37 very elderly patients with hip fractures, of whom 3 patients with dementia had to be excluded. Thus, 34 patients were randomized to 1 of the 3 groups: group A (ultrasound-guided continuous 3-in-1 block, bupivacaine; n = 10, dropout rate: 0), group B (PDA, bupivacaine; n = 14, dropout rate: 8), and group C (systemic pain therapy, piritramide/paracetamol; n = 10, dropout rate: 0). Pain intensity was assessed preoperatively and up to 24 hours postoperatively using a visual analog scale, verbal rating scale, analgesic consumption, scale of well-being, and cardiocirculatory parameters (eg, serum troponin T). Results: Our data show that in the preoperative period both regional anesthesia (RA) procedures (analgesia responders after 1 hour: 86.7% and 100%; P = .001) were superior to systemic analgesia (analgesia responders: 46.7%), and the rescue medication requirement in the 2 RA groups was significantly lower ( P = .02). Serum troponin T level increased only in the systemic analgesia group ( P = .04). In the emergency department, the disadvantage of PDA in geriatric patients with hip fracture was the fact that procedures were more complex, resulting in a high dropout rate (57.1%). The use of PDA has to be critically discussed for ethical concerns. Conclusion: In the specific situation of acute hospital admission, the ultrasound-guided continuous 3-in-1 block appears to be indicated as a stress-free means of providing adequate preoperative pain relief in very elderly patients with hip fracture. However, these findings should be corroborated by studies involving larger numbers of patients