Arthroscopic Shaver-based Harvest of Minced Cartilage Results in Reduced Chondrocyte Viability and Reduced Quality of Cartilaginous Repair Tissue Compared With Open Harvest and Conventional Fragmentation.

PURPOSE: To characterize and compare the quality of regenerative cartilage tissue (ReCT) after conventional minced cartilage (CMC) and arthroscopic minced cartilage (AMC), in terms of cell viability, gene expression, and matrix synthesis and to investigate the influence of different shaver types. METHODS: Chondral tissue was harvested from the knees of 8 porcine donors. Porcine specimens were euthanized one day before harvest. AMC was created with 2 shaver blades in 2 operating modes (oscillating vs forward) and compared with a scalpel-fragmented CMC control. Before histologic analysis, 50% of the tissue was digested to prevent dedifferentiation of chondrocytes to fibroblasts. Cells were cultured and analyzed for cell viability, gene expression of cartilage-specific markers (aggrecan [ACAN], collagen type II, alpha1 [COL2A1], collagen type I, alpha1 [COL1A1], fibronectin-1 [FN1]), and matrix synthesis (Alcian-blue). RESULTS: AMC tissue contained fewer viable chondrocytes (41%-54% vs 91%; P = .001-.048) compared with CMC. After culture, CMC showed greater expressions of ACAN (27 virtual copy numbers [VCN]/housekeeping gene) and COL2A1 (30 VCN) compared with AMC (ACAN 2-9 VCN, COL2A1 2-7 VCN, P = .001-.039). AMC presented greater expressions of COL1A1 (9-21 VCN) and FN1 (12-17 VCN) than CMC (1 and 6 VCN, P = .001-.050). The signal intensity of the cartilage matrix formed by CMC (86/mm2) was greater than by AMC (7-10 mm2, P = .001-.032). CONCLUSIONS: CMC contained high numbers of viable chondrocytes, resulting in high-quality, hyaline-like ReCT. In contrast, AMC showed impaired chondrocyte quantity and viability, showing greater expressions of fibroblast markers and a decreased formation of mature cartilage matrix in porcine samples. The high chondrogenic potential of CMC to form hyaline-like ReCT was not confirmed for AMC. CLINICAL RELEVANCE: On the basis of our findings, arthroscopic harvest of minced cartilage leads to reduced chondrocyte viability and ReCT quality. Accordingly, CMC and AMC cannot be regarded as synonymous techniques, as arthroscopic techniques seem to be less efficacious.

Relation of native acetabular anteversion to the orientation of transverse acetabular ligament.

BACKGROUND: Precise positioning of the acetabular component during total hip replacement is the key to achieving optimal implant function and ensuring long-term patient comfort. However, different anatomical variations, degenerative changes, dysplasia, and other diseases make it difficult. In this study, we discuss a method based on the three-dimensional direction of the transverse ligament, predicting native acetabular anteversion with higher accuracy. METHODS: Angular positions of the acetabulum and direction of the transverse ligament were automatically calculated from routine computed tomography data of 270 patients using a registration algorithm. The relationship between acetabular angles and ligament direction and their relationship with sex, age, and pelvic tilt were sought. These relationships were then modelled using multilinear regression. RESULTS: Including the direction of the transverse ligament in the sagittal and transverse planes as a regressor in the multilinear model explained the variation in acetabular anteversion (R2 = 0.76 for men, R2 = 0.63 for women; standard deviation in prediction: men, 3.92° and women, 4.00°). CONCLUSIONS: The results indicate that the ligament was suitable as a guidance structure almost insensitive to the ligament in the sagittal and transverse planes must be considered. Estimation based on the direction in only 1 plane was not sufficiently accurate. The operative acetabular inclination was not correlated with the direction of the ligament. The correlations were higher in men than in women.

Cement Leakage after Augmentation of Osteoporotic Vertebral Bodies. / Zementaustritt nach Augmentation osteoporotischer Wirbelkörper.

Cement leakage is the most common complication of vertebral cement augmentation. The present study investigated cement leakage rates in spinal cement augmentation procedures and identified potential risk factors for cement leakage.140 cases (258 vertebrae) in 131 consecutive patients and nine postmortem cases were evaluated. A total of 258 cement-augmented vertebrae were studied. The data for this were obtained from the hospital records of 131 patients who underwent such operations in 2 orthopaedic trauma surgery clinics in the FRG and from the examinations of 9 postmortem cases at the Institute of Forensic Medicine of the University Medical Centre Hamburg-Eppendorf.Cement leaks were identified in 64 of the 140 cases (45.7%). Local cement leaks were the most common type of leak, accounting for 73.4% of leaks (n = 47). Venous leaks were evaluated in 15 cases (23.4%) and pulmonary embolisations in 2 cases (3.1%). Within the group of retrospectively studied cases (n = 131), only one patient (0.8%) suffered a symptomatic cement leak. Cement augmentation of fractures to lumbar vertebrae and application of large doses of cement were identified as risk factors for cement leakage.Both the data in the literature relevant to the topic and the results of this work demonstrate a high incidence of cement leakage after vertebral body augmentation procedures. Risk factors for cement leakage are described. Despite the low percentage of symptomatic cases, the possible factors influencing cement leakage should be considered and included in the surgical planning when planning and performing cement augmentations on vertebral bodies.

Small design modifications can improve the primary stability of a fully coated tapered wedge hip stem.

Increasing the stem size during surgery is associated with a higher incidence of intraoperative periprosthetic fractures in cementless total hip arthroplasty with fully coated tapered wedge stems, especially in femurs of Dorr type A. If in contrast a stem is implanted and sufficient primary stability is not achieved, such preventing successful osseointegration due to increased micromotions, it may also fail, especially if the stem is undersized. Stem loosening or periprosthetic fractures due to stem subsidence can be the consequence. The adaptation of an established stem design to femurs of Dorr type A by design modifications, which increase the stem width proximally combined with a smaller stem tip and an overall shorter stem, might reduce the risk of distal locking of a proximally inadequately fixed stem and provide increased stability. The aim of this study was to investigate whether such a modified stem design provides improved primary stability without increasing the periprosthetic fracture risk compared to the established stem design. The established (Corail, DePuy Synthes, Warsaw, IN, US) and modified stem designs (Emphasys, DePuy Synthes, Warsaw, IN, US) were implanted in cadaveric femur pairs (n = 6 pairs) using the respective instruments. Broaching and implantation forces were recorded and the contact areas between the prepared cavity and the stem determined. Implanted stems were subjected to two different cyclic loading conditions according to ISO 7206-4 using a material testing machine (1 Hz, 600 cycles @ 80 to 800 N, 600 cycles @ 80 to 1600 N). Translational and rotational relative motions between stem and femur were recorded using digital image correlation. Broaching and implantation forces for the modified stem were up to 40% higher (p = 0.024), achieving a 23% larger contact area between stem and bone (R2 = 0.694, p = 0.039) resulting in a four times lower subsidence during loading (p = 0.028). The slight design modifications showed the desired effect in this in-vitro study resulting in a higher primary stability suggesting a reduced risk of loosening. The higher forces required during the preparation of the cavity with the new broaches and during implantation of the stem could bare an increased risk for intraoperative periprosthetic fractures, which did not occur in this study.

Pronounced cortical porosity and sex-specific patterns of increased bone and osteocyte lacunar mineralization characterize the human distal fibula with aging.

The high occurrence of distal fibula fractures among older women suggests a potential link to impaired bone health. Here we used a multiscale imaging approach to investigate the microarchitecture, mineralization, and biomechanics of the human distal fibula in relation to age and sex. Micro-computed tomography was performed to analyze the local volumetric bone mineral density and various microarchitectural parameters of the trabecular and the cortical compartment. Bone mineral density distribution and osteocyte lacunar parameters were quantified using quantitative backscattered electron imaging in periosteal, endocortical, and trabecular regions. Additionally, cortical hardness and Young's modulus were assessed by nanoindentation. While cortical porosity strongly increased with age independent of sex, trabecular microarchitecture remained stable. Notably, nearly half of the specimens showed non-bony hypermineralized tissue located at the periosteum, similar to that previously detected in the femoral neck, with no consistent association with advanced age. Independent of this finding, cortical and trabecular mineralization, i.e., mean calcium content, as well as endocortical tissue hardness increased with age in males but not females. Importantly, we also observed mineralized osteocyte lacunae that increased with age specifically in females. In conclusion, our results indicate that skeletal aging of the distal fibula is signified not only by pronounced cortical porosity but also by an increase in mineralized osteocyte lacunae in females. These findings may provide an explanation for the increased occurrence of ankle fractures in older women.

Morphine concentrations in fatalities after palliative treatment of acute burn injury.

The evaluation of a morphine concentration in postmortem blood is routine for a forensic toxicologist. We here report three fatal cases where we found high morphine concentrations with 7.96, 4.30, and 5.82 mg/l in femoral blood that have to be estimated as unusually high. All these individuals died due to severe burn injuries and obtained morphine in the context of their palliative care in the last hours of their lives. According to the autopsy results, the cause of death in case 1 was burn disease with burns of about 90% of the body surface area (BSA), case 2 burn trauma, and case 3 burn shock. Besides morphine, propofol, fentanyl, sufentanil, midazolam, diazepam, lorazepam, cefazolin, and rocuronium were detected in femoral blood. The findings fitted well with the detailed clinical documentation. Further evidence of therapeutic concentrations of quetiapine, duloxetine, and melperone could be matched to preexisting medication of the individuals. Physiologically based pharmacokinetic modelling (PBPK) was applied, developed for the intravenous administration of morphine, to find an explanation for the high morphine concentrations in femoral blood. Quantification of morphine in body fluids and tissue was performed to calculate morphine tissue concentration ratios to the morphine concentration in femoral blood. The presented cases show that pharmacokinetic simulations can reflect decreased renal clearance and decreased hepatic metabolism in general. However, this prediction is not sufficient to explain the high morphine concentrations in femoral blood measured here. It can be assumed that burn shock in particular leads to altered pharmacokinetics, namely decreased distribution of morphine.

Stem size and stem alignment affects periprosthetic fracture risk and primary stability in cementless total hip arthroplasty.

The ideal stem size and stem position is important for the success of total hip arthroplasty, since it can affect early implant loosening and periprosthetic fractures (PPF). This study aimed to investigate how small deviations from the ideal stem size and position influences the PPF risk and primary stability. Six experienced surgeons performed preoperative templating based on which the benchmark size for each femur was determined. Consecutive implantations were performed in six cadaveric femur pairs-one side was implanted with an undersized stem followed by the benchmark size and the contralateral side with a benchmark size followed by an oversized stem (Corail, Depuy Synthes). Moreover, three different alignments (six varus, six neutral, six valgus-undersized) were compared using 18 femurs. Cortical strains during broaching and implantation were measured, and laser scans were used to determine final stem position. All specimens underwent dynamic loading. Primary stability was estimated from stem subsidence and pull-out forces. Templated stem size varied between surgeons (±1 size; p = 0.005). Undersizing increased stem subsidence by 320% (p < 0.001). Oversized stems exhibited 52% higher pull-out forces (p = 0.001) and 240% higher cortical strains (p = 0.056). Cortex strains increased with varus alignment (R2 = 0.356, p = 0.011) while primary stability decreased with valgus stem alignment (p = 0.043). Surgeons should be aware that small deviations from the ideal stem size and malalignments of the stem can significantly alter the mechanical situation and affect the success of their surgery.

Microstructural analysis on the innervation of the anterior, medial, and lateral human hip capsule: Preliminary evidence on its neuromechanical contribution.

OBJECTIVE: Capsular repair aims to minimize damage to the hip joint capsular complex (HJCC) and subsequent dislocation risk following total hip arthroplasty (THA). Numerous explanations for its success have been advocated, including neuromuscular feedback loops originating from within the intact HJCC. This research investigates the hypothesis that the HJCC contributes to hip joint stability by analyzing HJCC innervation. METHOD: Twenty-nine samples from the anterior, medial, and lateral aspects of the midportion HJCC of 29 individuals were investigated stereologically and immunohistochemically to identify encapsulated mechanoreceptors according to a modified Freeman and Wyke classification, totaling 11,745 sections. Consecutive slices were observed to determine the nerve course within the HJCC. RESULTS: Few encapsulated mechanoreceptors were found in the HJCC subregions and overlying tissues across the cohort studied. Of regions studied, no significant regional differences in the density of mechanoreceptors were found. No significant difference in mechanoreceptor density was found between sides (left, 10.2×10-4/mm3, 4.0×10-4 - 19.0×10-4/mm3; right 12.9×10-4/mm3, 5.0×10-4 - 22.0×10-4/mm3; mean, 95% confidence intervals) sexes (female 10.4×10-4/mm3, 4.0×10-4 - 18.0×10-4/mm3; male 11.6×10-4/mm3, 5.0×10-4 - 20.0×10-4/mm3; mean, 95% confidence intervals), nor in correlation with age demographics. Myelinated nerves coursed consistently within the HJCC in various orientations. CONCLUSION: Sparse mechanoreceptor density suggests that the HJCC contributes to a limited extent to hip joint stabilization. HJCC nerve terminals may potentially contribute to neuromuscular feedback loops with associated muscles to mediate joint stability in tandem with the active and passive components of the joint.

Minimally Invasive Tissue Sampling via Post Mortem Ultrasound: A Feasible Tool (Not Only) in Infectious Diseases-A Case Report.

In the past years the number of hospital autopsies have declined steadily, becoming almost excluded from medical training. Medicolegal (forensic) autopsies account for almost all autopsies, whereas hospital autopsies are becoming increasingly rare. Minimally invasive tissue sampling (MITS) using post mortem ultrasound offers the opportunity to increase the number of post mortem examinations in a clinical and even forensic context. MITS is a needle-based post mortem procedure that uses (radiological) imaging techniques to examine major organs of the body, acquire tissue samples and aspirate fluid from the body cavities or hollow organs. In this study, MITS was used to determine the presence of other co-existing diseases in a deceased infected 97-year-old woman with severe acute respiratory syndrome coronavirus 2. The examination of her body was carried out using ultrasound as an imaging tool and to gather ultrasound-guided biopsies as conventional autopsy was rejected by the next of kin. Ultrasound and histology identified an intravesical mass leading to an obstruction of the urinary outlet resulting in bilateral hydronephrosis and purulent pyelonephritis, which was unknown during her lifetime. Histopathological examination revealed the tumor mass to be a squamous cell carcinoma. This study has shown that MITS can be used to determine the cause of death and the presence of concomitant diseases in the infectious deceased.

TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.

[One and a half years of e-scooters in Hamburg]. / Eineinhalb Jahre E-Scooter ­ Zwischenbilanz in Hamburg: Teil 2: Unfallcharakteristika.

Background: Since the spread of the so-called electric scooters (e-scooters) through rental services in Hamburg as of June 2019, accidents due to the use of this means of transportation have been regularly registered. The most frequent injury patterns among e­scooter riders involved accidents concerning the upper extremities and the head. There was a relevant accumulation of drunk drivers among the injured persons. Objective: The aim of the study is to compare injury patterns in drunk versus non-drunk e­scooter riders who had an accident. Material and methods: Data from the Department of Trauma Surgery at the University Medical Center Hamburg-Eppendorf were retrospectively analyzed for accidents involving e­scooters and the resulting injury patterns. For this purpose, the gender, age, injury pattern of the persons, the course of the accident, and information on previous alcohol consumption were recorded descriptively for the period from June 2019 to December 2021. Results: Drivers were on average 32 (interval: 15-88 years) years old and those under the influence of alcohol were predominantly male (69.9%). Accidents occurred mainly in summer and at night. Common injury patterns were injuries to the face, head, and extremities. Conclusion: It should be noted that injuries to the face and head occurred more frequently under the influence of alcohol than in the cohort without alcohol. Education about the health and legal consequences of riding an e­scooter under the influence of alcohol should be provided to all users. In addition, wearing a helmet or banning driving at night are possible measures to reduce accidents associated with drunk riding.

Influence of bone morphology and femur preparation method on the primary stability of hip revision stems.

Aseptic loosening is one of the major reasons for re-revisions of cementless revision stems. Insufficient primary stability is associated with bone characteristics and the surgical process. This study aimed to investigate how femur morphology and preparation methods influence the primary stability of revision stems. The Femur morphology was described by the upper femoral curvature (UFC) and an individualized Dorr type classification based on the ratio between the canal-to-calcar ratio (CCR*) and the cortical index (CI*) introduced as the cortical-canal shape (CCS). Manual and powered reaming in combination with helical and straight reamers were used to prepare the bone cavity of 10 cadaveric human femur pairs. Forces during stem impaction were recorded (Reclaim, Depuy Synthes). Micromotion at the bone-implant interface during cyclic axial loading and torsional load to failure was determined. The CCS and impaction forces (R2 = 0.817, p < 0.001) or torsional strength (R2 = 0.577, p < 0.001) are inversely related. CCS did not correlate with micromotion during axial loading (R2 = 0.001, p > 0.999), but proximal femoral curvature did (R2 = 0.462, p = 0.015). Powered reaming and straight reamers led to an improved torsional strength (both: p = 0.043). The Individualized Dorr classification CCS and UFC allows a good estimation of the primary stability of revision stems. For severely curved Dorr type-C femurs, an alternative anchorage method should be considered clinically.

Full endoscopic anterior intrapelvic plate osteosynthesis: a cadaveric feasibility study.

In this investigation, it was assumed that it must be possible to visualize the intrapelvic aspect as accustomed by pelvic surgeons using the anterior intrapelvic (modified Stoppa) approach. Moreover, it was hypothesized, that plate mountings will not only be possible for the symphysis but also at the supra- and infrapectineal aspect as well as to the posterior column. Ten anonymized cadaveric specimens were included in this study. A standard laparoscopic totally extraperitoneal (TEP) approach was used. A total of 10 landmarks were defined that are usually within reach in the open anterior intrapelvic (AIP) approach. Moreover, five different plate mountings were tested. The locations were chosen in accordance with the indication spectrum suitable for open surgery through the traditional AIP approach. It was possible to gain intrapelvic visibility in seven of ten cases. In all of those seven cases, it was technically possible to place plates to the symphysis, superior pubic ramus, as well as longer anterior column plates up to the aspect posterior of the acetabulum. In the last four of the seven cases, it was possible to mount plates to the infrapectineal aspect as well as the posterior column, too. The team, previously trained in arthroscopic surgical techniques as well as pelvic trauma surgery, observed a steep learning curve. This investigation demonstrated, that endoscopic anterior intrapelvic plate osteosynthesis was feasible in the majority of the cases in a series of ten cadaveric models. New instruments will be needed such as extra-long rasp elevators, ball-spikes as well as devices to hold and position plates and extra-long self-holding screwdrivers. With these, endoscopic pelvic surgery will likely be a realistic option for selected pelvic trauma cases in the future.

Is There a Nerve-free Zone in Which a Subscapularis Split Can Safely be Performed? An Anatomical Study Using Embalmed Specimens.

BACKGROUND: The subscapularis muscle, which is part of the rotator cuff, is located anterior to the shoulder. In anterior approaches to the shoulder, its supplying nerves are at risk of iatrogenic injury, which may cause postoperative complications. It is unclear whether there is any nerve-free zone in which a subscapularis split can be performed without risking nerve damage. QUESTIONS/PURPOSES: In an anatomical study, we asked: (1) With the arm abducted 60° and externally rotated, what are the median and shortest distances between the entrance point of the subscapular nerves into subscapularis muscle and the myotendinous junction of this muscle? (2) What are those distances in other positions of the shoulder? (3) Did those measurements differ between specimen sexes or sides? METHODS: In 84 shoulders of 66 embalmed anatomic specimens, the distance from the myotendinous junction of the subscapularis muscle to the entrance points of the subscapular nerves into the subscapularis muscle was measured using an inelastic thread and a millimeter gauge with the arm abducted 60° and rotated externally. In 16 of 84 shoulders, which were selected randomly, after taking the measurements with the arm abducted 60° and rotated externally, arm positions were changed and further measurements were taken with the arm abducted 60° and rotated neutrally, abducted 60° and rotated internally, and abducted 90° and rotated externally. The positions of the entrance points were described with statistical parameters and compared between different sides, sexes, and joint positions. Measurements were verified using eight fresh-frozen shoulders, showing no difference in distances compared with embalmed specimens and confirming reproducibility of measurements. Absolute distances were used to minimize possible distortion when using correlations and for straightforwardness and clinical applicability. RESULTS: The median (range) distance was 43 mm (24 to 64) for the upper subscapular nerve and 38 mm (23 to 59) for the lower subscapular nerve with the arm rotated externally and abducted 60°. In the 16 subsamples, internal rotation decreased the distance to 34 mm (24 to 49) and 31 mm (15 to 43), respectively, and maximal external rotation and 90° of abduction increased it up to 49 mm (30 to 64) and 41 mm (27 to 56). Comparison of left and right sides yielded no difference. Comparison of sexes showed distances for the lower subscapular nerve of 36 mm (23 to 54) in females versus 39 mm (24 to 60) in males. CONCLUSION: In no specimen did the nerve come closer than 23 mm medial to the myotendinous junction with the arm rotated externally and abducted. Therefore, not exceeding a distance of 20 mm medial to the myotendinous junction with the arm rotated externally seems to provide sufficient protection from nerve injury during surgery. CLINICAL RELEVANCE: Based on the described zone of 20 mm medial to the myotendinous junction, the risk of nerve injury in a subscapularis split approach can be minimized.

Robotic Tissue Sampling for Safe Post-Mortem Biopsy in Infectious Corpses.

In pathology and legal medicine, the histopathological and microbiological analysis of tissue samples from infected deceased is a valuable information for developing treatment strategies during a pandemic such as COVID-19. However, a conventional autopsy carries the risk of disease transmission and may be rejected by relatives. We propose minimally invasive biopsy with robot assistance under CT guidance to minimize the risk of disease transmission during tissue sampling and to improve accuracy. A flexible robotic system for biopsy sampling is presented, which is applied to human corpses placed inside protective body bags. An automatic planning and decision system estimates optimal insertion point. Heat maps projected onto the segmented skin visualize the distance and angle of insertions and estimate the minimum cost of a puncture while avoiding bone collisions. Further, we test multiple insertion paths concerning feasibility and collisions. A custom end effector is designed for inserting needles and extracting tissue samples under robotic guidance. Our robotic post-mortem biopsy (RPMB) system is evaluated in a study during the COVID-19 pandemic on 20 corpses and 10 tissue targets, 5 of them being infected with SARS-CoV-2. The mean planning time including robot path planning is 5.72±167s. Mean needle placement accuracy is 7.19± 422mm.

Iatrogenic Tracheal Rupture Related to Prehospital Emergency Intubation in Adults: A 15-Year Single Center Experience.

OBJECTIVE: Iatrogenic tracheal rupture is an unusual and severe complication that can be caused by tracheal intubation. The frequency, management, and outcome of iatrogenic tracheal rupture due to prehospital emergency intubation in adults by emergency response physicians has not yet been sufficiently explored. METHODS: Adult patients with iatrogenic tracheal ruptures due to prehospital emergency intubation admitted to an academic referral center over a 15-year period (2004-2018) with consideration of individual risk factors were analyzed. RESULTS: Thirteen patients (eight female) with a mean age of 67 years met the inclusion criteria and were analyzed. Of these, eight tracheal ruptures (62%) were caused during the airway management of cardiopulmonary resuscitation (CPR). Stylet use and difficult laryngoscopy requiring multiple attempts were documented in eight cases (62%) and four cases (30%), respectively. Seven patients (54%) underwent surgery, while six patients (46%) were treated conservatively. The overall 30-day mortality was 46%; five patients died due to their underlying emergencies and one patient died of tracheal rupture. Three survivors (23%) recovered with severe neurological sequelae and four (30%) were discharged in good neurological condition. Survivors had significantly smaller mean rupture sizes (2.7cm versus 6.3cm; P <.001) and less cutaneous emphysema (n = 2 versus n = 6; P = .021) than nonsurvivors. CONCLUSIONS: Iatrogenic tracheal rupture due to prehospital emergency intubation is a rare complication. Published risk factors are not consistently present and may not be applicable to identify patients at high risk, especially not in rescue situations. Treatment options depend on individual patient condition, whereas outcome largely depends on the underlying disease and rupture extension.

Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid.

Diagnosing traumatic brain injury (TBI) from body fluids in cases where there are no obvious external signs of impact would be useful for emergency physicians and forensic pathologists alike. None of the previous attempts has so far succeeded in establishing a single biomarker to reliably detect TBI with regards to the sensitivity: specificity ratio in a post mortem setting. This study investigated a combination of body fluid biomarkers (obtained post mortem), which may be a step towards increasing the accuracy of biochemical TBI detection. In this study, serum and cerebrospinal fluid (CSF) samples from 30 acute lethal TBI cases and 70 controls without a TBI-related cause of death were evaluated for the following eight TBI-related biomarkers: brain-derived neurotrophic factor (BDNF), ferritin, glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), lactate dehydrogenase, neutrophil gelatinase-associated lipocalin (NGAL), neuron-specific enolase and S100 calcium-binding protein B. Correlations among the individual TBI biomarkers were assessed, and a specificity-accentuated threshold value analysis was conducted for all biomarkers. Based on these values, a decision tree modelling approach was performed to assess the most accurate biomarker combination to detect acute lethal TBIs. The results showed that 92.45% of acute lethal TBIs were able to be diagnosed using a combination of IL-6 and GFAP in CSF. The probability of detecting an acute lethal TBI was moderately increased by GFAP alone and considerably increased by the remaining biomarkers. BDNF and NGAL were almost perfectly correlated (p = 0.002; R2 = 0.944). This study provides evidence that acute lethal TBIs can be detected to a high degree of statistical accuracy using forensic biochemistry. The high inter-individual correlations of biomarkers may help to estimate the CSF concentration of an unknown biomarker, using extrapolation techniques.

Ultrasound in legal medicine-a missed opportunity or simply too late? A narrative review of ultrasonic applications in forensic contexts.

OBJECTIVES: Conventional autopsies remain the gold standard of postmortem healthcare quality assurance and help gathering extended knowledge on diseases. In answer to constantly declining autopsy rates non- or minimally invasive autopsy methods were introduced. Ultrasound is a well-established tool for imaging commonly used in clinical practice. This narrative review aims to summarize the current literature regarding the feasibility and validity of ultrasound in a forensic context. MATERIAL AND METHODS: A PubMed database search was carried out. Abstracts were scanned for pre-defined ex- and inclusion criteria, followed by a snowball search procedure applied to the primarily included articles. RESULTS: Forty-five publications met our inclusion criteria. The selected articles concern the feasibility of ultrasound in pre- or postmortem settings, forensic age estimation, and minimally invasive approaches. For imaging, ultrasound was deemed a reliable tool for the examination of epiphyses und superficial wounds, with limitations regarding internal organs and image quality due to postmortem changes. Ultrasound-guided minimally invasive approaches yielded higher success rates for adequate tissue sampling. Many investigations were carried out in low- and middle-income countries focusing on infectious diseases. CONCLUSION: Ultrasound seems a promising but underutilized imaging tool in legal medicine to date. Promising approaches on its feasibility have been conducted. Especially for minimally invasive methods, ultrasound offered significant improvements on qualified biopsy sampling and thus appropriate diagnostics. Moreover, ultrasonic evaluation of epiphyses for age estimation offered valuable results. Nevertheless, further assessment of ultrasonic feasibility in forensic contexts is needed.

Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators.

Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-ß1 and tumor necrosis factor-α, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.