[Fatalities associated with failure to adjust drug dose in patients with renal insufficiency: A retrospective study at the Institute of Forensic Medicine in Munich (2019-2023)]. / Medikamenteninduzierte Todesfälle bei Niereninsuffizienz.

Comorbidities in the elderly not only make them more susceptible to kidney disease, but also increase the risk of drug interactions due to polypharmacy. Such patients require regular kidney function tests when treated with renally excreted drugs. We conducted a retrospective study of post-mortem cases over a five- year period. Of 3040 toxicologically investigated cases, 3.8% had a history of renal failure. Thirteen deaths were directly attributable to inadequate drug dosing, 46% of which were related to lactic acidosis due to metformin accumulation. Appropriate dose adjustment could prevent fatal drug toxicity in patients with renal insufficiency.

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage.

Recent studies of severe acute inflammatory lung disease including COVID-19 identify macrophages to drive pulmonary hyperinflammation and long-term damage such as fibrosis. Here, we report on the development of a first-in-class, carbohydrate-coupled inhibitor of microRNA-21 (RCS-21), as a therapeutic means against pulmonary hyperinflammation and fibrosis. MicroRNA-21 is among the strongest upregulated microRNAs in human COVID-19 and in mice with acute inflammatory lung damage, and it is the strongest expressed microRNA in pulmonary macrophages. Chemical linkage of a microRNA-21 inhibitor to trimannose achieves rapid and specific delivery to macrophages upon inhalation in mice. RCS-21 reverses pathological activation of macrophages and prevents pulmonary dysfunction and fibrosis after acute lung damage in mice. In human lung tissue infected with SARS-CoV-2 ex vivo, RCS-21 effectively prevents the exaggerated inflammatory response. Our data imply trimannose-coupling for effective and selective delivery of inhaled oligonucleotides to pulmonary macrophages and report on a first mannose-coupled candidate therapeutic for COVID-19.

Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease.

Disruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet the underlying mechanism has remained enigmatic. Immunostaining of sympathetic axons in optically cleared pineal glands from humans and mice with cardiac disease revealed their substantial denervation compared with controls. Spatial, single-cell, nuclear, and bulk RNA sequencing traced this defect back to the superior cervical ganglia (SCG), which responded to cardiac disease with accumulation of inflammatory macrophages, fibrosis, and the selective loss of pineal gland-innervating neurons. Depletion of macrophages in the SCG prevented disease-associated denervation of the pineal gland and restored physiological melatonin secretion. Our data identify the mechanism by which diurnal rhythmicity in cardiac disease is disturbed and suggest a target for therapeutic intervention.

Magnetic Tissue Engineering of the Vocal Fold Using Superparamagnetic Iron Oxide Nanoparticles.

Losing one's ability to speak, because of tissue deficiency at the vocal fold (VF), leads to serious impairment in the quality of life. Until now, there is no successful approach for regenerating the VF. The aim of this study was to show the advantage of magnetic nanoparticles in the generation of scaffold-free three-dimensional (3D) VF cell constructs by magnetic tissue engineering (MTE). Rabbit VF fibroblasts were used to establish MTE: after cellular uptake of superparamagnetic iron oxide nanoparticles (SPIONs), cells can be controlled with a magnetic field thereby forming solid 3D cell structures. To transfer this method into human cells, SPIONs were adapted accordingly and tested for their influence on human VF (hVF) cells and for their ability to perform MTE with hVF cells. Of interest, the cell number and the magnet's shape influence the form of the rabbit VF cell construct. After successful characterization of hVF cells, biocompatibility analyses revealed no significant influence of SPIONs on them, thus 3D hVF cell constructs could be successfully generated by MTE. These basic results are important to develop MTE as an innovative method to regenerate functional VFs. We expect that in vivo studies, including MTE as an elegant, far-field controlled and touchless technology, will translate MTE VF bioconstructs into reconstructive laryngeal medicine. Impact Statement This study aims at nanotechnology for regenerative medicine by magnetic tissue engineering (MTE). New approaches for vocal fold (VF) reconstruction are desperately needed. Superparamagnetic iron oxide nanoparticles offer innovative, scaffold-free potentials for tissue engineering: MTE. By using MTE we could generate functional multilayered human VF cell constructs, which can consequently be used to regenerate the voice in patients with VF injuries.

Analysis of Injury and Mortality Patterns in Deceased Patients with Road Traffic Injuries: An Autopsy Study.

BACKGROUND: Despite improvements in prevention and rescue, mortality rates after severe blunt trauma continue to be a problem. The present study analyses mortality patterns in a representative blunt trauma population, specifically the influence of demographic, injury pattern, location and timing of death. METHODS: Patients that died between 1 January 2004 and 31 December 2005 were subjected to a standardised autopsy. INCLUSION CRITERIA: death from blunt trauma due to road traffic injuries (Injury Severity Score ≥ 16), patients from a defined geographical area and death on scene or in hospital. EXCLUSION CRITERIA: suicide, homicide, penetrating trauma and monotrauma including isolated head injury. Statistical analyses included Student's t test (parametric), Mann-Whitney U test (nonparametric) or Chi-square test. RESULTS: A total of 277 consecutive injured patients were included in this study (mean age 46.1 ± 23 years; 67.5% males), 40.5% of which had an ISS of 75. A unimodal distribution of mortality was observed in blunt trauma patients. The most frequently injured body regions with the highest severity were the head (38.6%), chest (26.7%), or both head and chest (11.0%). The cumulative analysis of mortality showed that several factors, such as injury pattern and regional location of collisions, also affected the pattern of mortality. CONCLUSIONS: The majority of patients died on scene from severe head and thoracic injuries. A homogenous distribution of death was observed after an initial peak of death on scene. Moreover, several factors such as injury pattern and regional location of collisions may also affect the pattern of mortality.

Physical compared to mental diseases as reasons for committing suicide: a retrospective study.

BACKGROUND: Several studies investigated the relationship between mental disorders and suicidal ideation. However, little is known about physical illnesses being the major trigger for committed suicides. It is necessary to understand these risk factors to be able to meet the needs of patients in a palliative care setting. METHODS: Suicide, medical and police notes were retrospectively analysed from all autopsies conducted in 2009-11 at the University of Munich, Germany. Documented reasons for suicide were classified into a "physical disease" (PD) or "mental disease" (MD) group and compared with respect to their sociodemographic characteristics and autopsy outcomes. RESULTS: Of all 1069 cases, 18.9% gave a PD as reason for committing suicide (MD, 32.7%). Those indicating PD were older than MD (68.8 vs. 48.7 years; p < 0.001) with more men being in this group (72.8% vs. 59.1%; p=0.002). In PD, 30.7% suffered from cancer, 28.7% from chronic pain and 12.4% from lung disease. 38.8% of MD and 12.4% of PD had previous suicide attempts. CONCLUSIONS: In palliative care, it is necessary to screen patients on a regular basis for suicidal ideation, especially those with previous suicide attempts.

Invisible scar endoscopic thyroid surgery by the dorsal approach: importance of the spinal accessory nerve.

PURPOSE: With about 100,000 surgeries per year in Germany, thyroid operations count among the most common procedures performed in general and endocrine visceral surgery. Twentieth century technological development gives the opportunity to perform thyroid surgery without leaving visible scar like conventional approaches do. This study is part of the work on the videoendoscopic retro-auricular access to the thyroid gland using the EndoCATS method by Schardey and Schopf. To avoid possible complications with the spinal accessory nerve (SAN), like irritation or injury of the nerve as happened during a feasibility study, a systematic study of the surgical anatomy at the nerve's entry to the posterior cervical triangle is performed especially in relation to the EndoCATS operation method. METHODS: Sixty-one neck regions in fifty-three specimens were examined at the anatomical institute of Munich to investigate the course of the SAN relative to the anatomic landmarks tip of mastoid bone, sternal notch, and posterior border of the sternocleidomastoid muscle together with the SAN's course variants at its entry to the posterior cervical triangle. The results were then statistically analyzed. RESULTS: From this analysis, we derived a simple method to predict the course of the SAN preoperatively and offer a new approach to protect the SAN during EndoCATS surgery. Additionally, we found a significant difference of the SAN's course between male and female specimens. CONCLUSION: The EndoCATS method can be a safe alternative to conventional thyroid surgery, but the SAN is at risk during the surgery procedure. Here we give feasible solutions to eliminate the SAN-problem performing EndoCATS thyroid surgery.

[Macroscopical estimation of the post mortem interval (PMI) and exclusion of the forensically relevant resting period--a comparison of data presented in the literature with recent osteological findings]. / Makroskopische Abschätzung des postmortalen Intervalls (PMI) und Ausschluss einer forensisch relevanten Liegezeit--ein Vergleich von Literaturangaben mit rezenten osteologischen Funden.

The aim of the present study was to determine to what extent macroscopical parameters mentioned in the literature are suitable for the estimation of the post mortem interval (PMI) and particularly for the exclusion of the forensically relevant resting period for recent bone material. The macroscopical examination of recent bone material with a known PMI showed that only one published parameter (relics of adipocere in the cross section of the compacta) was consistent with our findings for this particular resting period (27-28 years). Other macroscopical parameters presented in the literature were contradictory to the results observed in this study. Among those are the rigidity of bones, the adhesion of soft tissue, the filling of the marrow cavity, and the permeation of the epiphyses with adipocere. Concerning the exclusion of the forensically relevant resting period, a similar result was observed. This study identified some diagnostic findings in bones with a resting period of less than 50 years which according to the literature should only be present after a resting period of more than 50 years. These features included the lack of macroscopical traces of adipocere, degradation of the compacta surface, detachment of the cortical substance, the ability of bone to be broken with bare hands, and superficial usures. Moreover, in one-third of our cases we identified some intra-individual differences not previously described in the literature. In addition to the other results, those intra-individual differences make an estimation of the PMI more difficult. However it should be noted that those published parameters were collected from bone material which was stored in a "relatively arid sand-grit-clay soil of the broken stone layer of Munich". The bones in the present study were stored in acidic and clayey-loamy soil, partly with lateral water flow. In conclusion, the present study demonstrates that one should use caution estimating the post mortem interval and excluding the forensically relevant resting period, even when all available results are considered.