Notes

Intra-scanner repeatability of quantitative image capabilities in a 3 dimensional imprinted semi-anthropomorphic CT phantom.
54, 95% CI 1.71-3.77; p<0.001) were independently associated with clinically relevant bleeding events, while age >85years (adj.HR 2.22, 95% CI 1.14-4.30; p=0.018) was independently associated with major bleeding events (BARC types 3 or 5). Patients with a clinically relevant bleeding event had a higher rate of MACE at 1year (adj.HR 2.04, 95% CI 1.24-3.38; p=0.005), with a particularly strong effect on stroke (adj.HR 5.55, 95% CI 2.04-15.06; p<0.001).

Clinically relevant bleeding events were observed in one out of five elderly patients undergoing stenting for an ACS and were strongly associated with further stroke occurrence. Rather than the antiplatelet therapy, comorbidities and an age >85years predicted bleeding outcomes in this elderly population.

Clinicaltrials.gov identifier NCT01538446. https//www.clinicaltrials.gov .
Clinicaltrials.gov identifier NCT01538446. https//www.clinicaltrials.gov .
The SARS-CoV-2 genome has been detected in a variety of human samples including blood, urine, semen, and faeces. However, evidence of virus presence in tissues other than lung are limited.

We investigated whether SARS-CoV-2 could be detected in 50 autoptic specimens of endocrine organs from 29 patients who died of COVID-19.

The virus was detected in 25 specimens including ten abdominal subcutaneous adipose tissue samples (62%), six testes (67%), and nine thyroid (36%) samples. The analysis of multiple endocrine organ samples obtained from the same patients showed that, in virus-positive cases, the viral genome was consistently detected in all but two matched specimens.

Our findings show that the virus spread into endocrine organs is a common event in severe cases. Further studies should assess the rate of the phenomenon in clinically mild cases. The potential long-term effects of COVID-19 on endocrine functions should be taken into consideration.
Our findings show that the virus spread into endocrine organs is a common event in severe cases. Further studies should assess the rate of the phenomenon in clinically mild cases. The potential long-term effects of COVID-19 on endocrine functions should be taken into consideration.
Metformin, rosiglitazone and sulfonylureas enhance either insulin action or secretion and thus have been used extensively as early stage anti-diabetic medication, independently of the aetiology of the disease. When administered to newly diagnosed diabetes patients, these drugs produce variable results. Here, we examined the effects of the three early stage oral hypoglycaemic agents in mice with diabetes induced by multiple low doses of streptozotocin, focusing specifically on the developmental biology of pancreatic islets.

Streptozotocin-treated diabetic mice expressing a fluorescent reporter specifically in pancreatic islet α-cells were administered the biguanide metformin (100mg/kg), thiazolidinedione rosiglitazone (10mg/kg), or sulfonylurea tolbutamide (20mg/kg) for 10days. We assessed the impact of the treatment on metabolic status of the animals as well as on the morphology, proliferative potential and transdifferentiation of pancreatic islet cells, using immunofluorescence.

The effect of the therating insulin secretion.DFT calculations on the photochemical reaction of 1-n-N-butylpyridinium salt in water with hydroxide anion is in agreement with a singlet state process where the S2 state at λ = 253 nm can be converted into a Dewar isomer (2-butyl-2-azabicyclo[2.2.0]hexa-2,5-dien-2-yl cation). The Dewar isomer can react with hydroxide anion giving the product, 6-n-butyl-6-azabicyclo[3.1.0]hex-3-en-2-ol.Model-informed drug discovery and development (MID3) shows great advantages in facilitating drug development. A physiologically based pharmacokinetic model is one of the powerful computational approaches of MID3, and the emerging field of virtual bioequivalence is well recognized to be the future of the physiologically based pharmacokinetic model. Based on the translational link between in vitro, in silico, and in vivo, virtual bioequivalence study can evaluate the similarity and potential difference of pharmacokinetic and clinical performance between test and reference formulations. With the aid of virtual bioequivalence study, the pivotal information of clinical trials can be provided to streamline the development for both new and generic drugs. However, a regulatory framework of virtual bioequivalence study has not reached its full maturity. Therefore, this article aims to present an overview of the current status of bioequivalence study, identify the framework of virtual bioequivalence studies for oral drugs, and also discuss the future opportunities of virtual bioequivalence in supporting the waiver and optimization of in vivo clinical trials.Non-invasive methods to assess patients' fluid responsiveness during lung-protective ventilation are needed. We hypothesized changes in the corrected carotid flow time induced by the recruitment maneuver predict fluid responsiveness under general anesthesia. Thirty patients undergoing general anesthesia in the supine position were prospectively enrolled. The study protocol was conducted when the patient was hemodynamically stable during surgery. Flow time was measured on Doppler images of the common carotid artery. Carotid flow time, heart rate, stroke volume, stroke volume variation, and pulse pressure variation were recorded before and after a recruitment maneuver at a continuous airway pressure of 30 cmH2O for 30 s, and before and after volume expansion with 250 mL for 10 min. Patients were defined as fluid responders if the increase in stroke volume was > 10% after volume expansion. Twenty patients (67%) were fluid responders. All Doppler images for carotid flow time were obtained within 30 s. Changes in the corrected flow time accurately predicted fluid responsiveness (area under the curve 0.82, 95% confidence interval [CI] 0.64-0.94, p = 0.002). The optimal threshold for changes in the corrected flow time was - 11.7% with a sensitivity of 95.0% (95% CI 75.1-99.9%) and a specificity of 80.0% (95% CI 44.4-97.5%). The gray-zone of changes in the corrected flow time was from - 25.1 to - 12.2% and included 12 patients (40%). Changes in the corrected carotid flow time were a useful, technically easy-to-perform, and non-invasive method to predict fluid responsiveness without a need for hemodynamic monitoring or arterial cannulation.Continuous monitoring of the respiratory rate is crucial in an acute care setting. Contact respiratory monitoring modalities such as capnography and thoracic impedance pneumography are prone to artifacts, causing false alarms. Moreover, their cables can restrict patient behavior or interrupt patient care. A microwave Doppler sensor is a novel non-contact continuous respiratory rate monitor. We compared respiratory rate measurements performed with a microwave Doppler sensor mounted on the ceiling of an intensive care unit with those obtained by conventional methods in conscious and spontaneously breathing patients. Participants' respiratory rate was simultaneously measured by visual counting of chest wall movements for 60 s; a microwave Doppler sensor; capnography, using an oxygen mask; and thoracic impedance pneumography, using electrocardiogram electrodes. Bland-Altman analysis for repeated measures was performed to calculate bias and 95% limits of agreement between the respiratory rate measured by visual counting (reference) and that measured by each of the other methods. Among 52 participants, there were 336 (microwave Doppler sensor), 275 (capnography), and 336 (thoracic impedance pneumography) paired respiratory rate data points. Bias (95% limits of agreement) estimates were as follows microwave Doppler sensor, 0.3 (- 6.1 to 6.8) breaths per minute (bpm); capnography, - 1.3 (- 8.6 to 6.0) bpm; and thoracic impedance pneumography, 0.1 (- 4.4 to 4.7) bpm. Compared to visual counting, the microwave Doppler sensor showed small bias; however, the limits of agreement were similar to those observed in other conventional methods. Our monitor and the conventional ones are not interchangeable with visual counting.Trial registration number UMIN000032021, March/30/2018.Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 μg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI) risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P  less then  0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P  less then  0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. selleck compound Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.Skin signs in acute pancreatitis are well-known and frequently discussed manifestations accompanied by unfavorable prognoses although they may rarely appear in clinical and forensic medicine. In 2018, the district attorney's office ordered a forensic autopsy for a 74-year-old man with terminal stage pancreatic cancer. The autopsy was ordered based on accusations of the deceased's widow regarding alleged medical malpractice and poor hospital care. The widow filed a grievance about multiple unsuccessful attempts to draw blood from her husband in addition to a diaper dermatitis at the right groin. An autopsy and additional histological examinations were performed. After considering all findings, the diaper dermatitis was eventually assumed to be a Fox sign caused by acute pancreatitis, and the allegations of medical malpractice were refuted. This case led us to identify another case with suspected cutaneous manifestations in pancreatic disease. We performed immunohistochemical staining on those two cases and six control cases to examine whether there was detectable presence of pancreatic lipase and trypsin in the skin discolorations and whether it could be used as a feasible method to verify skin signs associated with pancreatitis. Based on our findings, a minor disseminated lipase and trypsin staining should be considered regular and is therefore not conclusive of a skin sign associated with pancreatitis. Moreover, trypsin does not seem to be as suitable as lipase for this suggested immunohistochemical method. Nevertheless, this method might be a useful addition for determining the origin of skin discoloration and verifying skin signs associated with pancreatitis.
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