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Introduction. The use of ultrasound during resuscitation is emphasized in the latest European resuscitation council guidelines of 2013 to identify treatable conditions such as pericardial tamponade. The recommended standard treatment of tamponade in various guidelines is pericardiocentesis. As ultrasound guidance lowers the complication rates and increases the patient’s safety, pericardiocentesis should be performed under ultrasound guidance. Acute care physicians actually need to train emergency pericardiocentesis. Methods. We describe in detail a pericardiocentesis ultrasound model, using materials at a cost of about 60 euros. During training courses of focused echocardiography n=67, participants tested the phantom and completed a 16-item questionnaire, assessing the model using a visual analogue scale (VAS). Results. Eleven of fourteen questions were answered with a mean VAS score higher than 60% and thus regarded as showing the strengths of the model. Unrealistically outer appearance and heart shape were rated as weakness of the model. A total mean VAS score of all questions of 63% showed that participants gained confidence for further interventions. Conclusions. Our low-cost pericardiocentesis model, which can be easily constructed, may serve as an effective training tool of ultrasound-guided pericardiocentesis for acute and critical care physicians.
Background: Lung ultrasound has become an emerging tool in acute and critical care medicine. Combined theoretical and hands-on training has been required to teach ultrasound diagnostics. Current computer technology allows for display, explanation, and animation of information in a remote-learning environment.
Objective: Development and assessment of an e-learning program for lung ultrasound.
Methods: An interactive online tutorial was created. A prospective learning success study was conducted with medical students using a multiple-choice test (Trial A). This e-learning program was used as preparation for a certified course followed by an evaluation of trained doctors (Trial B) by linear analogue scales. Pretests were compared with postcourse tests and sustainability tests as well as a posttest of a one-day custom classroom training.
Results: In Trial A, during the learning success study (n = 29), the increase of correct answers was 11.7 to 17/20 in the post-test and to 16.6/20 in the sustainability test (relative change 45.1%, P < 0.0001). E-learning almost equalled scores of classroom-based training regarding gain and retention of factual knowledge. In Trial B, nineteen participating doctors found a 79.5% increase of knowledge (median, 95% CI: 69%; 88%).
Conclusion: The basics of lung ultrasound can be taught in a highly effective manner using e-learning.
Background: Liver fibrosis in human immunodeficiency virus (HIV)-infected individuals is mostly attributable to co-infection with hepatitis B or C. The impact of other risk factors, including prolonged exposure to combined antiretroviral therapy (cART) is poorly understood. Our aim was to determine the prevalence of liver fibrosis and associated risk factors in HIV-infected individuals based on non-invasive fibrosis assessment using transient elastography (TE) and serum biomarkers (Fibrotest [FT]).
Methods: In 202 consecutive HIV-infected individuals (159 men; mean age 47 ± 9 years; 35 with hepatitis-C-virus [HCV] co-infection), TE and FT were performed. Repeat TE examinations were conducted 1 and 2 years after study inclusion.
Results: Significant liver fibrosis was present in 16% and 29% of patients, respectively, when assessed by TE (≥ 7.1 kPa) and FT (> 0.48). A combination of TE and FT predicted significant fibrosis in 8% of all patients (31% in HIV/HCV co-infected and 3% in HIV mono-infected individuals). Chronic ALT, AST and γ-GT elevation was present in 29%, 20% and 51% of all cART-exposed patients and in 19%, 8% and 45.5% of HIV mono-infected individuals. Overall, factors independently associated with significant fibrosis as assessed by TE (OR, 95% CI) were co-infection with HCV (7.29, 1.95-27.34), chronic AST (6.58, 1.30-33.25) and γ-GT (5.17, 1.56-17.08) elevation and time on dideoxynucleoside therapy (1.01, 1.00-1.02). In 68 HIV mono-infected individuals who had repeat TE examinations, TE values did not differ significantly during a median follow-up time of 24 months (median intra-patient changes at last TE examination relative to baseline: -0.2 kPa, p = 0.20).
Conclusions: Chronic elevation of liver enzymes was observed in up to 45.5% of HIV mono-infected patients on cART. However, only a small subset had significant fibrosis as predicted by TE and FT. There was no evidence for fibrosis progression during follow-up TE examinations.
Simple Summary: Penile cancer is a rare but aggressive malignancy characterized by rapid tumor growth as well as prompt metastasis in groin lymphatics. While localized diseases can be successfully cured by surgery in most cases, no truly effective treatment options have been established for metastatic diseases as of yet. In the current investigation, we assessed the value of selected members of the PI3K/mTOR/AKT pathway to serve as tumor markers or therapeutic targets for this disease. Higher expression of AKT was significantly more prevalent in high-grade tumors and independently predictive of the worse survival parameters, while increased expression of pmTOR was associated with an inferior prognosis as well. Treatment with the pan-AKT inhibitor capivasertib in PeCa cell lines induced significant reduction of cell viability and movement capacity. These findings might aid in the understanding of the molecular tumor background as well as development of novel treatment options for advanced penile cancer.
Abstract: The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.
Introduction: The estimation of age-at-death of unidentified cadavers is a central aspect of the identification process. With increasing age, the incidence of glomerulosclerosis and the thickness of the carotid wall have been observed to also increase. This correlation has been demonstrated in various international histological studies. The aim of our study was to assess whether these correlations also apply to a Western European population.
Methodology: In this retrospective observational study, kidney and common carotid artery samples from 216 cases autopsied at the Institute of Legal Medicine at the Justus-Liebig University in Giessen, Germany, were examined. Only cases with available tissue samples from both body sides were included. Exclusion criteria were poor sample quality and an age younger than 21 years. After histological processing, the tissue samples were assessed and digitally evaluated. Regression and classification analyses were used to investigate the correlation between age-at-death and intima-media thickness and age-at-death and the incidence of renal glomerular sclerosis.
Results: Of the 216 autopsy cases, 183 were included for evaluation. Analysis of the carotid artery segments showed a strong correlation (Pearson correlation coefficient r = 0.887) between the intima-media-complex thickness and chronological age. Classification of the glomerulosclerotic incidence showed a correlation of 37.7–43.1% with the predicted age group.
Discussion: Both the intima-media thickness and the proportion of sclerotic glomeruli can be used to estimate age in Western European cadavers. On the basis of these results, both methods are suited to supplement other already established methods for age-at-death estimation in the identification of an unknown cadaver.
This case series assessed a commercial airline flight from Tel Aviv, Israel, to Frankfurt, Germany, that occurred on March 9th, 2020. Among 102 passengers on a Boeing 737-900 aircraft were 24 members of a tourist group. Starting 7 days earlier, the group had contact with a hotel manager who later received a diagnosis of coronavirus disease 2019 (COVID-19). No member of the group had received a diagnosis of COVID-19 before the flight, and no measures to prevent transmission (eg, wearing of masks) had been applied. The flight duration was 4 hours 40 minutes.
Objectives: To evaluate peri-implant tissue dimensions following nonsurgical (NS) and surgical therapy (S) employing different decontamination protocols of advanced ligature-induced peri-implantitis in dogs.
Material & Methods: Peri-implantitis defects (n = 5 dogs, n = 30 implants) were randomly and equally allocated in a split-mouth design to NS or S treatment using either an Er:YAG laser (ERL), an ultrasonic device (VUS), or plastic curettes + local application of metronidazole gel (PCM), respectively. Horizontal bone thickness (hBT) and soft tissue thickness (hMT) were measured at different reference points: (v0) at the marginal portion of the peri-implant mucosa (PM); (v1) at 50% of the distance from PM to bone crest (BC); (v2) at the BC; (v3) at the most coronal extension of the bone-to-implant contact. Vertical peri-implant tissue height was calculated from PM to BC.
Results: All of the treatment groups showed a gradual hMT increase from v0 to the v2 reference point, followed by a reduction from v2 to the v3 region. The S-VUS subgroup tended to be associated with higher hMT values at the v0 region than the NS-VUS subgroup (0.44 mm versus 0.31 mm). PM-BC distance varied from 2.22 to 2.83 mm in the NS group, and from 2.07 to 2.38 in the S group.
Conclusion: Vertical and horizontal peri-implant tissue dimensions were similar in different treatment groups.
Assessment of the acute effects of 2C-B vs. psilocybin on subjective experience, mood, and cognition
(2023)
2,5-dimethoxy-4-bromophenethylamine (2C-B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it's acute effects and distinctions from classical progenitors have yet to be characterized in a controlled study. We assessed for the first time the immediate acute subjective, cognitive, and cardiovascular effects of 2C-B (20 mg) in comparison to psilocybin (15 mg) and placebo in a within-subjects, double-blind, placebo-controlled study of 22 healthy psychedelic-experienced participants. 2C-B elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution largest under psilocybin. Participants demonstrated equivalent psychomotor slowing and spatial memory impairments under either compound compared with placebo, as indexed by the Digit Symbol Substitution Test, Tower of London, and Spatial Memory Task. Neither compound produced empathogenic effects on the Multifaceted Empathy Test. 2C-B induced transient pressor effects to a similar degree as psilocybin. The duration of self-reported effects of 2C-B was shorter than that of psilocybin, largely resolving within 6 hours. Present findings support the categorization of 2C-B as a psychedelic of moderate experiential depth at doses given. Tailored dose-effect studies are needed to discern the pharmacokinetic dependency of 2C-B's experiential overlaps.
Background: Symptoms, severity, and acuteness of peripheral artery disease (PAD) are major determinants of severe limb symptoms, subsequent risk of cardiovascular events, and mortality. Lower-extremity revascularization (LER) is a key option to relieve symptoms and to prevent limb loss in symptomatic patients with PAD. This study aimed to quantify the burden of disease among patients with PAD-LER in England.
Methods: A retrospective population-based study of linked primary and secondary care electronic health records, included 13,869 adult patients (aged ⩾ 18 years) with PAD-LER from 2003 to 2018. The incidence of first ever PAD-LER was estimated both overall and by type of procedure (endovascular/surgical). Health resource utilization associated with PAD-related complications and treatment patterns were assessed.
Results: A high annual incidence of lower-limb revascularization (41.2 per 1000 person years) and a nearly double incidence of endovascular first revascularization compared with open surgery were observed. More than 70% of patients with PAD-LER had a history of hyperlipidemia and hypertension and roughly one-third were diabetic and had a history of coronary artery disease. Cardiovascular mortality accounted for one-third (34.1 per 1000 person years) of all-cause mortality. Over 93% of patients were hospitalized for any reason and the commonest reasons for hospitalization were cardiovascular diseases and PAD with about one-third hospitalized for revascularization reoccurrence.
Conclusion: There is a significant burden of PAD-LER to the individual and society with ongoing healthcare resource utilization, treatment, and increasing mortality.
Background: Number of positive prostate biopsy cores represents a key determinant between high versus very high-risk prostate cancer (PCa). We performed a critical appraisal of the association between the number of positive prostate biopsy cores and CSM in high versus very high-risk PCa. Methods: Within Surveillance, Epidemiology, and End Results database (2010–2016), 13,836 high versus 20,359 very high-risk PCa patients were identified. Discrimination according to 11 different positive prostate biopsy core cut-offs (≥2–≥12) were tested in Kaplan–Meier, cumulative incidence, and multivariable Cox and competing risks regression models. Results: Among 11 tested positive prostate biopsy core cut-offs, more than or equal to 8 (high-risk vs. very high-risk: n = 18,986 vs. n = 15,209, median prostate-specific antigen [PSA]: 10.6 vs. 16.8 ng/ml, <.001) yielded optimal discrimination and was closely followed by the established more than or equal to 5 cut-off (high-risk vs. very high-risk: n = 13,836 vs. n = 20,359, median PSA: 16.5 vs. 11.1 ng/ml, p < .001). Stratification according to more than or equal to 8 positive prostate biopsy cores resulted in CSM rates of 4.1 versus 14.2% (delta: 10.1%, multivariable hazard ratio: 2.2, p < .001) and stratification according to more than or equal to 5 positive prostate biopsy cores with CSM rates of 3.7 versus 11.9% (delta: 8.2%, multivariable hazard ratio: 2.0, p < .001) in respectively high versus very high-risk PCa. Conclusions: The more than or equal to 8 positive prostate biopsy cores cutoff yielded optimal results. It was very closely followed by more than or equal to 5 positive prostate biopsy cores. In consequence, virtually the same endorsement may be made for either cutoff. However, more than or equal to 5 positive prostate biopsy cores cutoff, based on its existing wide implementation, might represent the optimal choice.