Metabolomics investigation of post-mortem human pericardial fluid.

INTRODUCTION: Due to its peculiar anatomy and physiology, the pericardial fluid is a biological matrix of particular interest in the forensic field. Despite this, the available literature has mainly focused on post-mortem biochemistry and forensic toxicology, while to the best of authors' knowledge post-mortem metabolomics has never been applied. Similarly, estimation of the time since death or post-mortem interval based on pericardial fluids has still rarely been attempted. OBJECTIVES: We applied a metabolomic approach based on 1H nuclear magnetic resonance spectroscopy to ascertain the feasibility of monitoring post-mortem metabolite changes on human pericardial fluids with the aim of building a multivariate regression model for post-mortem interval estimation. METHODS: Pericardial fluid samples were collected in 24 consecutive judicial autopsies, in a time frame ranging from 16 to 170 h after death. The only exclusion criterion was the quantitative and/or qualitative alteration of the sample. Two different extraction protocols were applied for low molecular weight metabolites selection, namely ultrafiltration and liquid-liquid extraction. Our metabolomic approach was based on the use of 1H nuclear magnetic resonance and multivariate statistical data analysis. RESULTS: The pericardial fluid samples treated with the two experimental protocols did not show significant differences in the distribution of the metabolites detected. A post-mortem interval estimation model based on 18 pericardial fluid samples was validated with an independent set of 6 samples, giving a prediction error of 33-34 h depending on the experimental protocol used. By narrowing the window to post-mortem intervals below 100 h, the prediction power of the model was significantly improved with an error of 13-15 h depending on the extraction protocol. Choline, glycine, ethanolamine, and hypoxanthine were the most relevant metabolites in the prediction model. CONCLUSION: The present study, although preliminary, shows that PF samples collected from a real forensic scenario represent a biofluid of interest for post-mortem metabolomics, with particular regard to the estimation of the time since death.

Comparative Impact Analysis of Low-Deductible Insurance Versus In-house Hospital Assumption of Risk and Management on Medical Malpractice Claims.

OBJECTIVES: Claims management is critical to ensure the safe and high-quality medical care for which liability insurers and/or hospitals are responsible. The aim of this research is to determine whether increasing hospital malpractice risk exposure, with increasing deductibles, has an impact on malpractice claims and payouts. METHODS: The study was conducted at a single tertiary hospital, the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. Payouts on closed reported and registered claims were analyzed during 4-study periods, which ranged from 1.5 million euro annual aggregate deductibles entirely managed by the insurance company to 5 million euro annual aggregate deductibles entirely managed by the hospital. We retrospectively analyzed 2034 medical malpractice claims submitted between January 1, 2007, and August 31, 2021. Four periods were examined depending on the claims management model adopted, ranging from total outsourcing to the insurer (period A) to an almost total hospital assumption of risk method (period D). RESULTS: We found that progressive hospital assumption of risk is associated with a decrease in the incidence of medical malpractice claims (average variation per year: -3.7%; P = 0.0029 if the 2 initial periods and the 2 last periods-characterized by the highest risk retention-are respectively aggregated and compared), an initial decrease in the mean claims cost followed by an increase that is still lower than the national increase (-5.4% on average), and an increase in the total claims cost (when compared with the period where the insurer solely managed claims). We also found that the rate of increase in payouts was less than the national average. CONCLUSIONS: The assumption of more malpractice risk by the hospital was associated with the adoption of numerous patient safety and risk management initiatives. The decrease in claims incidence could be due to the implementation of patient safety policies, while the cost increase could be attributed to inflation and rising costs of healthcare services and claims. Notably, only the hospital assumption of risk model with a high-deductible insurance coverage is sustainable for the studied hospital, while also being profitable for the insurer. In conclusion, as hospitals progressively assumed more risk and management responsibility of malpractice claims, there was a progressive decrease in the total number of claims, and a less rapid rise in claim payouts as compared with the national average. Even a small assumption of risk appeared to elicit meaningful changes in claim filings and payouts.

A Fatal Case of Metastatic Pulmonary Calcification during the Puerperium.

We present an unusual case of a fatal respiratory failure in a young woman developed two weeks after she gave birth at home. Circumstantial and clinical features of the case were strongly suggestive for a 'classical' septic origin of the respiratory symptoms. Autopsy, together with histopathological and immunohistochemical analyses allowed demonstrating a massive calcium redistribution consisting of an important osteolysis, especially from cranial bones and abnormal accumulation in lungs and other organs. Such physiopathology was driven by a primary hyperparathyroidism secondary to a parathyroid carcinoma as demonstrated by immunohistochemistry. This very rare case is furthermore characterised by a regular pregnancy course, ended with the birth of a healthy new-born. A complex interaction between pregnancy physiology and hyperparathyroidism might be hypothesised, determining the discrepancy between the relative long period of wellness and the tumultuous cascade occurred in the puerperium.

Dying "from" or "with" COVID-19 during the Pandemic: Medico-Legal Issues According to a Population Perspective.

There is still a lack of knowledge concerning the pathophysiology of death among COVID-19-deceased patients, and the question of whether a patient has died with or due to COVID-19 is still very much debated. In Italy, all deaths of patients who tested positive for SARS-CoV-2 are defined as COVID-19-related, without considering pre-existing diseases that may either contribute to or even cause death. Our study included nine subjects from two different nursing homes (Cases 1-4, Group A; Cases 5-9, Group B). The latter included patients who presumably died from CO poisoning due to a heating system malfunction. All subjects tested positive for COVID-19 both ante- and post-mortem and were examined using post-mortem computed tomography prior to autopsy. COVID-19 was determined to be a contributing cause in the deaths of four out of nine subjects (death due to COVID-19; i.e., pneumonia and sudden cardiac death). In the other five cases, for which CO poisoning was identified as the cause of death, the infection presumably had no role in exitus (death with COVID-19). In our attempt to classify our patients as dying with or due to COVID-19, we found the use of complete assessments (both histological analyses and computed tomography examination) fundamental.

Repeated Application of Transcranial Diagnostic Ultrasound Towards the Visual Cortex Induced Illusory Visual Percepts in Healthy Participants.

Transcranial magnetic stimulation (TMS) of the visual cortex can induce phosphenes as participants look at a visual target. So can non-diagnostic ultrasound (nDU), delivered in a transcranial fashion, while participants have closed their eyes during stimulation. Here, we sought to determine if DU, aimed at the visual cortex, could alter the perception of a visual target. We applied a randomized series of actual or sham DU, transcranially and towards the visual cortex of healthy participants while they stared at a visual target (a white crosshair on a light-blue background), with the ultrasound device placed where TMS elicited phosphenes. These participants observed percepts seven out of ten times, which consisted of extra or extensions of lines relative to the original crosshair, and additional colors, an average of 53.7 ± 2.6% of the time over the course of the experiment. Seven out of ten different participants exposed to sham-only DU observed comparable percepts, but only an average of 36.3 ± 1.9% of the time, a statistically significant difference (p < 0.00001). Moreover, on average, participants exposed to a combination of sham and actual ultrasound reported a net increase of 47.9 percentage points in the likelihood that they would report a percept by the end of the experiment. Our results are consistent with the hypothesis that a random combination of sham-only and actual DU, applied directly over the visual cortex of participants, increased the likelihood that they would observe visual effects, but not the type of effects, with that likelihood increasing over the course of the experiment. From this, we conclude that repeated exposures by DU may make the visual cortex more responsive to stimulation of their visual cortex by the visual target itself. Future studies should identify the biophysical mechanism(s) and neural pathways by which DU, in our hands and others, can generate its observed effects on brain function. These observations, consistent with other's observation of effects of DU stimulation of the human motor cortex and amygdala, as well as the FDA approved nature of DU, may lead to increased use of DU as a means of altering brain function.