Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.

BACKGROUND: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. METHODS: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. RESULTS: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). CONCLUSIONS: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.

Osteosarcoma pre-diagnosed as another tumor: a report from the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: The course of osteosarcoma patients primarily treated as such has been well described. Little, however, is known about patients who were primarily treated assuming a different tumor diagnosis. METHODS: The database of the Cooperative Osteosarcoma Study Group COSS was searched (4.435 primary high-grade central osteosarcomas registered prior to 01/01/21). A different tumor entity had to have been assumed for at least one month after the initial diagnostic procedure before the correct diagnosis of osteosarcoma was finally made. Identified patients were analyzed for demographic, tumor-, and treatment-related factors as well as for survival outcomes. RESULTS: 37 patients were identified. They were a median of 19.7 (2.7-60.4) years old at first presentation and were more likely to be females than males (23:14). Bone cysts (n = 8), giant cell tumor of bone (n = 6), and osteoblastoma (n = 6) were the most frequent of 29/37 (78%) benign, chondrosarcoma and its variants (n = 6) the most frequent of 8/37 (22%) malignant original diagnoses. Tumors affected the extremities in 23 (62%), the trunk in 11 (30%), and the craniofacial bones in 3 (8%). Only one patient received systemic treatment while assuming the different diagnosis (1/37, 3%). The median time until the correct diagnosis of osteosarcoma was made was 8 months (range: 1 month-14.1 years). At that time, 6/37 (16%) presented with metastatic disease. All patients went on to receive chemotherapy, 17/37 (46%) neo-adjuvantly. Histologic response was only evaluated in 13/17 (76%) patients and was good (< 10% viable tumor) in only 4/13 (31%) patients. In 31/37 (84%) patients, a surgically complete resection of all macroscopically identified tumor manifestations could be achieved. Five-year overall and event-free survival rates at 5 years were 50.2% (standard error: 8.6%) and 42.6% (8.5%), respectively. CONCLUSION: Osteosarcoma may initially be misdiagnosed and hence subjected to inappropriate treatment including misguided surgery. Once diagnosed correctly, some of the affected patients may still be cured if finally treated according to modern osteosarcoma standards.

Acromioclavicular Disk as a Potential Source of Pain in AC Joint Injuries.

BACKGROUND: Injuries of the acromioclavicular joint (ACJ) are common shoulder injuries that often lead to pain and dysfunction of the affected shoulder. Regardless of operative or nonoperative treatment, a relatively large number of patients remain symptomatic and experience pain. However, the specific source of persistent pain in the ACJ remains ambiguous. PURPOSE: To investigate the presence of sensory nerve fibers or pain-generating neurotransmitters within the intra-articular disk of the ACJ to determine its potential role as an independent pain generator in ACJ disorders. STUDY DESIGN: Descriptive laboratory study. METHODS: Twelve paired ACJs from 6 fresh human cadavers (mean age, 56 years; range, 41-82 years) were harvested and freed from surrounding soft tissues, leaving only the ACJ capsule intact. The specimens were placed in 4.5% formaldehyde fixative for a minimum of 48 hours. Coronal plane sections were obtained and demineralized in EDTA for a week, embedded in paraffin for 12 hours, and dehydrated overnight. With a rotation microtome, 2-µm sections were cut and stained with hematoxylin and eosin to investigate tissue architecture and confirm the presence of a fibrocartilaginous intra-articular disk. The sections were immunohistochemically stained with antisera against S100, neuropeptide Y (NPY), and substance P (SP) to detect for neural tissue. Additionally, a nerve fiber count per 10 high-power fields representing an area of 0.2 mm2 was conducted for S100 stains. All sections were examined for the presence of positive immunoreactivity to S100, NPY, and SP. RESULTS: The presence of a fibrocartilaginous intra-articular disk could be observed in all 12 examined ACJs. In all specimens, an immunoreactivity to S100, NPY, and SP could be observed within the superior peripheral region of the intra-articular disk. High-power field nerve counts of the S100 stains revealed a mean ± SD of 7.9 ± 2.28 nerves per 10 high-power fields (range, 4-12). CONCLUSION: The documented immunoreactivity to S100, NPY, and SP indicates the presence of somatic and autonomic nerve fibers within the intra-articular disk of the ACJ. CLINICAL RELEVANCE: Confirming the presence of nerve fibers within the intra-articular disk of the ACJ suggests that the disk itself could be an independent source of pain after injury and thus a possible explanation for recalcitrant pain after treatment.

Lethal Encephalopathy in an Infant with Hypophosphatasia despite Enzyme Replacement Therapy.

Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations in the biomineralization-associated alkaline phosphatase gene, encoding tissue-nonspecific alkaline phosphatase (TNSALP). Symptoms include skeletal hypomineralization and extra-skeletal manifestations such as pyridoxine (B6)-responsive seizures due to impaired cerebral B6 passage. Since the introduction of enzyme replacement therapy (ERT), skeletal manifestations and B6-responsive seizures were reported to improve significantly. Nevertheless, there is an increasing evidence of B6-independent neurological manifestation of HPP including HPP-associated encephalopathy. Here, we present for the first time the brain alterations of an infant with neonatal HPP who died of neurological complications at the age of 5 months despite early initiation of ERT. CSF analysis showed normal concentrations of biogenic amines reflecting sufficient intracellular B6 availability. Postmortem histopathology revealed severe, localized affection of the cerebral cortex including cortical lesions in layers 2 and 3 in direct proximity to TNSALP-expressing neurons and hippocampal sclerosis. Our findings confirm that TNSALP deficiency may lead to a severe encephalopathy. We hypothesize that HPP-associated encephalopathy resistant to currently available ERT may develop in addition and probably independently of typical B6-responsive seizures in some patients. Prospective, controlled studies with close neurological follow-up including brain imaging are needed to identify patients at risk for severe neurological symptoms despite ERT.

Extraosseous osteoblastoma: A rare cause of breast mass in a prepubertal girl.

Extraosseous osteoblastoma of the breast, a rare disease, was diagnosed in a prepubertal girl. After tumor excision, the patient recovered well and an optimal cosmetic result was achieved. Interdisciplinary discussions about the case are essential.

Avian extremity reconstruction via osseointegrated leg-prosthesis for intuitive embodiment.

For large avians such as vultures, limb loss leads to loss of ambulation and eventually death from malnutrition. Prosthetic devices may replace the limb, however, conventional prosthetic sockets are not feasible in feathered limbs and the extreme stress and strain of unreflected daily use in animals. Osseointegration is a novel technique, where external prosthetic parts are connected directly to a bone anchor to provide a solid skeletal-attachment. This concept provides a high degree of embodiment since osseoperception will provide direct intuitive feedback allowing natural use of the limb in gait and feeding. Here we demonstrate for the first time an osseointegrated bionic reconstruction of a limb in a vulture after a tarsometatarsal amputation with a longterm follow-up.

Ultrasound of horizontal instability of the acromioclavicular joint : A simple and reliable test based on a cadaveric study.

BACKGROUND: Horizontal instability influences the clinical outcome after acromioclavicular joint (ACJ) injuries and in joint degeneration. A standardized, dynamic examination of the horizontal instability has not been described before. This current study presents a sonographic method to analyze the dynamics between the clavicle and acromion in the horizontal plane. METHODS: The horizontal joint play, the ACJ space and the offset between clavicle and acromion were sonographically assessed by a 45° ventrally angulated longitudinal section. A total of four investigators with different experience in the field of musculoskeletal ultrasound examining 20 ACJs in 10 human cadavers. Measurements in the absence of any pressure and under standardized anterior and posterior pressure onto the clavicle were carried out in different ligament status intact acromioclavicular (AC) and coracoclavicular (CC) ligaments as well as in a Rockwood (RW) II and III model. A two-sided t­test was used to examine the differences between joint positions and ligament status. RESULTS: The horizontal joint play was 1.3 ± 0.9 mm with intact ligaments, 1.4 ± 1.2 mm by transecting the AC ligaments and 1.9 ± 1.3 mm after additionally transecting the CC ligament. The joint space was 3.3 ± 1.1 mm with intact ligaments, 4.1 ± 1.8 mm in an iatrogenic RW 2 injury, and 5.3 ± 3.3 mm in an iatrogenic RW 3 injury. Manipulating the clavicle by applying anterior or posterior pressure did not change the difference within one injury pattern. Interobserver reliability was 83.9%. CONCLUSION: Apart from evaluating the ligaments and the joint capsule, measurement of the dynamic horizontal instability is possible in a human cadaver model. The ultrasound-based measurement of horizontal instability dynamics avoids radiation exposure, is readily available and cost-efficient.

A comparative study of intraoperative frozen section and alpha defensin lateral flow test in the diagnosis of periprosthetic joint infection.

Background and purpose - For decision-making (aseptic vs. septic), surgeons rely on intraoperatively available tests when a periprosthetic joint infection (PJI) cannot be confirmed or excluded preoperatively. We compared and evaluated the intraoperative performances of the frozen section and the alpha defensin lateral flow test in the diagnosis of PJI. Patients and methods - In this prospective study, consecutive patients with indicated revision surgery after arthroplasty were included. Patients were classified as having PJI using the MusculoSkeletal Infection criteria. The presence of alpha defensin was determined using the lateral flow test intraoperatively. During revision surgery, tissue samples were harvested for frozen and permanent section. Analysis of diagnostic accuracy was based on receiver-operating characteristics. Results - 101 patients (53 hips, 48 knees) were eligible for inclusion. Postoperatively, 29/101 patients were diagnosed with PJI, of which 8/29 cases were definitely classified as septic preoperatively. Of the remainder 21 septic cases, the intraoperative alpha defensin test and frozen section were positive in 13 and 17 patients, respectively. Sensitivities of the alpha defensin test and frozen section were 69% and 86%, respectively. The area under the curves of both tests showed a statistically significant difference (p = 0.006). Interpretation - The frozen section showed a significantly higher performance compared with the alpha defensin test and a near perfect concordance with the definitive histology, and therefore remains an appropriate intraoperative screening test in diagnosing PJI. Although the sensitivity of the alpha defensin test was lower compared with that of frozen section, this test is highly specific for confirming the diagnosis of PJI.

Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort.

BACKGROUND: High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. The European and American Osteosarcoma Study (EURAMOS)-1 is a collaboration of four study groups aiming to improve outcomes of this rare disease by facilitating randomised controlled trials. METHODS: Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high-grade osteosarcoma in which case complete surgical resection at all sites was deemed to be possible. A three-drug combination with methotrexate, doxorubicin and cisplatin was defined as standard chemotherapy, and between April 2005 and June 2011, 2260 patients were registered. We report survival outcomes and prognostic factors in the full cohort of registered patients. RESULTS: For all registered patients at a median follow-up of 54 months (interquartile range: 38-73) from biopsy, 3-year and 5-year event-free survival were 59% (95% confidence interval [CI]: 57-61%) and 54% (95% CI: 52-56%), respectively. Multivariate analyses showed that the most adverse factors at diagnosis were pulmonary metastases (hazard ratio [HR] = 2.34, 95% CI: 1.95-2.81), non-pulmonary metastases (HR = 1.94, 95% CI: 1.38-2.73) or an axial skeleton tumour site (HR = 1.53, 95% CI: 1.10-2.13). The histological subtypes telangiectatic (HR = 0.52, 95% CI: 0.33-0.80) and unspecified conventional (HR = 0.67, 95% CI: 0.52-0.88) were associated with a favourable prognosis compared with chondroblastic subtype. The 3-year and 5-year overall survival from biopsy were 79% (95% CI: 77-81%) and 71% (95% CI: 68-73%), respectively. For patients with localised disease at presentation and in complete remission after surgery, having a poor histological response was associated with worse outcome after surgery (HR = 2.13, 95% CI: 1.76-2.58). In radically operated patients, there was no good evidence that axial tumour site was associated with worse outcome. CONCLUSIONS: In conclusion, data from >2000 patients registered to EURAMOS-1 demonstrated survival rates in concordance with institution- or group-level osteosarcoma trials. Further efforts are required to drive improvements for patients who can be identified to be at higher risk of adverse outcome. This trial reaffirms known prognostic factors, and owing to the large numbers of patients registered, it sheds light on some additional factors to consider.

High-Grade Osteosarcoma of the Foot: Presentation, Treatment, Prognostic Factors, and Outcome of 23 Cooperative Osteosarcoma Study Group COSS Patients.

Osteosarcoma of the foot is a very rare presentation of a rare tumor entity. In a retrospective analysis, we investigated tumor- and treatment-related variables and outcome of patients registered in the Cooperative Osteosarcoma Study Group (COSS) database between January 1980 and April 2016 who suffered from primary high-grade osteosarcoma of the foot. Among the 23 eligible patients, median age was 32 years (range: 6-58 years), 10 were female, and 13 were male. The tarsus was the most commonly affected site (n=16). Three patients had primary metastases. All patients were operated: 5 underwent primary surgery and 18 received surgery following preoperative chemotherapy. In 21 of the 23 patients, complete surgical remission was achieved. In 4 of 17 patients, a poor response to neoadjuvant chemotherapy was observed in the resected primary tumors. Median follow-up was 4.2 years (range: 0.4-18.5). At the last follow-up, 15 of the 23 patients were alive and 8 had died. Five-year overall and event-free survival estimates were 64% (standard error (SE) 12%) and 54% (SE 13%), which is similar to that observed for osteosarcoma in general. Event-free and overall survival correlated with primary metastatic status and completeness of surgery. Our findings show that high-grade osteosarcoma in the foot has a similar outcome as osteosarcoma of other sites.

Matrix-associated chondrocyte transplantation for reconstruction of articulating surfaces in the temporomandibular joint: a pilot study covering medium- and long-term outcomes of 6 patients.

OBJECTIVE: Matrix-associated chondrocyte transplantation is routinely used in joints of the extremities but not in the temporomandibular joint (TMJ). STUDY DESIGN: We report the first case series in 7 patients of a tissue engineering approach to regenerate severely degraded articulating surfaces in the TMJ by simultaneously completely resurfacing both the mandibular condyle and the articular eminence/glenoid fossa with a commercially available collagen sponge seeded with autologous cells stabilized within a fibrin matrix. To facilitate healing, we temporarily employed a silicone membrane to protect the engineered tissues. The indications for surgery were posttraumatic fibro-osseous ankylosis, ankylosing osteoarthritis, or late-stage osteoarthritis. RESULTS: Six of the patients were recalled for follow-up after 3 years 6 months to 12 years 1 month. The maximum incisal opening was 18.2 ± 9.2 mm (range, 9-33 mm) before and 31.2 ± 13.6 mm (range, 12-47 mm) at the latest follow-up. Histologic specimens taken at 4 months showed beginning differentiation of fibrocytes into chondrocytes, whereas at 3 and 11 years, mature hyaline cartilage-not typical for the TMJ-was present. CONCLUSIONS: We conclude that the reconstruction of TMJ surfaces by matrix-associated chondrocyte transplantation may become a routine method for cartilage regeneration in the TMJ in the future.

C-reactive protein: An independent predictor for dedifferentiated chondrosarcoma.

Dedifferentiated chondrosarcoma is a rare primary bone malignancy with a very poor prognosis. The aim of the study was to identify pretreatment serum markers as prognostic factors for the overall survival (OS) of patients with dedifferentiated chondrosarcoma. We retrospectively reviewed 33 patients with histologically confirmed dedifferentiated chondrosarcoma treated at our department from 1977 to 2015. Kaplan-Meier estimation, uni- and multivariable Cox proportional hazard model were performed to evaluate the association between serum markers such as the C-reactive protein and OS. In univariable analysis, CRP was strongly associated with OS (HR 1.35; 95%CI 1.13-1.61; p = 0.001). This association prevailed after adjustment for AJCC tumor stage (HR 1.31; 95%CI 1.02-1.57; p = 0.031) in multivariable analysis. In conclusion, our data gave evidence that baseline CRP is an independent predictor for OS in patients with dedifferentiated chondrosarcoma. CRP could be exploited for the clinical prediction of this disease in the future. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:2797-2801, 2018.

Increased zinc accumulation in mineralized osteosarcoma tissue measured by confocal synchrotron radiation micro X-ray fluorescence analysis.

Abnormal tissue levels of certain trace elements such as zinc (Zn) were reported in various types of cancer. Little is known about the role of Zn in osteosarcoma. Using confocal synchrotron radiation micro X-ray fluorescence analysis, we characterized the spatial distribution of Zn in high-grade sclerosing osteosarcoma of nine patients (four women/five men; seven knee/one humerus/one femur) following chemotherapy and wide surgical resection. Levels were compared with adjacent normal tissue. Quantitative backscattered electron imaging as well as histological examinations was also performed. On average, the ratio of medians of Zn count rates (normalized to calcium) in mineralized tumor tissue was about six times higher than in normal tissue. There was no difference in Zn levels between tumor fraction areas with a low fraction and a high fraction of mineralized tissue, which were clearly depicted using quantitative backscattered electron imaging. Moreover, we found no correlation between the Zn values and the type of tumor regression according to the Salzer-Kuntschik grading. The underlying mechanism of Zn accumulation remains unclear. Given the emerging data on the role of trace elements in other types of cancer, our novel results warrant further studies on the role of trace elements in bone cancer. Copyright © 2016 The Authors. X-Ray Spectrometry published by John Wiley & Sons Ltd.

Bacillary angiomatosis presenting with facial tumor and multiple abscesses: A case report.

BACKGROUND: The clinical manifestation of bacillary angiomatosis (BA) can be limited to one organ, most commonly the skin, but systemic courses can also occur. We report a human immunodeficiency virus (HIV)-positive patient with a systemic manifestation of BA caused by Bartonella quintana, diagnosed in Vienna, Austria. The pathogen was detected in multiple organs including a facial tumor which is an unusual finding for BA. Furthermore, infections with B quintana are rare in our area and no other autochthonous cases have been reported. METHODS AND RESULTS: The clinical manifestation included multiple papules and nodules on the entire body, several organic abscesses, and a facial tumor influencing the patient's view.The main laboratory finding indicated HIV infection combined with severe immunosuppression with 47 CD4 cells/µL. Contrast-enhanced computed tomography of the chest and the abdomen showed multiple and abscesses. Histological examination of the facial tumor confirmed inflammatory process. Bartonella quintana was detected by PCR in blood and in the facial tumor as well as by culture in the skin tissue. Antibiotic treatment with doxycycline and antiretroviral therapy resulted in clinical improvement. CONCLUSION: Our case shows that rare opportunistic, vector-borne infections, usually associated with poverty, can lead to diagnosis of HIV even in well-developed countries. Furthermore, we provide details on clinical manifestation and diagnostic work-up which might expand the knowledge on disseminated infections with B quintana. As far, tumorous deformations have rarely been reported as consequence of BA. In our patient the pathogen was detected in the facial tumor using PCR techniques.

Evaluation of six different airway devices regarding regurgitation and pulmonary aspiration during cardio-pulmonary resuscitation (CPR) - A human cadaver pilot study.

BACKGROUND: Chest compressions and ventilation are lifesaving tasks during cardio-pulmonary resuscitation (CPR). Besides oxygenation, endotracheal intubation (ETI) during CPR is performed to avoid aspiration of gastric contents. If intubation is difficult or impossible, supraglottic airway devices are utilized. We tested six different airway devices regarding their potential to protect against regurgitation and aspiration during CPR in a randomized experimental human cadaver study. METHODS: Five-hundred ml of 0.01% methylene-blue-solution were instilled into the stomach of 30 adult human cadavers via an oro-gastric tube. The cadavers were then randomly assigned to one of six groups, resulting in 5 cadavers in each group. Airway management was performed with either bag-valve ventilation, Laryngeal Tube, EasyTube, Laryngeal Mask (Classic), I-Gel, or ETI. Thereafter 5min of CPR were performed according to the 2010 Guidelines of the European Resuscitation Council. Pulmonary aspiration was defined as the presence of methylene-blue-solution below the vocal cords or the ETI cuff as assessed by fiber-optic bronchoscopy. RESULTS: Thirty cadavers were included (14 females, 16 males). Aspiration was detected in three out of five cadavers receiving bag-valve ventilation and in two out of five intubated with LMA or I-Gel. In cadavers intubated with the LT, aspiration occurred in one out of five cases. No aspiration could be detected in cadavers intubated with ETI and EasyTube. CONCLUSION: This study provides experimental evidence that, during CPR, ETI offers superior protection against regurgitation and pulmonary aspiration of gastric contents than supraglottic airway devices or bag-valve ventilation.

Multiple relapses in high-grade osteosarcoma: when to stop aggressive therapy?

The prognosis after relapse of high-grade osteosarcoma is poor and complete resection of all tumors is essential for survival. A 6-year old was diagnosed with high-grade osteosarcoma and treated according to the COSS-96 protocol. Within 5 years from initial diagnosis, five osteosarcoma relapses occurred and every time it was possible to achieve complete surgical remission. Additional treatments included chemotherapy and dendritic cell-based cancer immune therapy. Since the end of therapy of the 5th relapse, he is alive for 11½ years. Our experience further supports that aggressive surgery can help to achieve long-term survival even in patients with multiple osteosarcoma relapses.

Non-occlusive mesenteric ischaemia: the prevalent cause of gastrointestinal infarction in patients with severe burn injuries.

BACKGROUND: Gastrointestinal complications occur frequently in intensive care patients with severe burns. Intestinal infarction and its deleterious consequences result in high mortality despite rapid surgical intervention. Our objective was to evaluate the aetiology of gastrointestinal infarction in intensive care patients with severe burns. STUDY DESIGN: We retrospectively evaluated all of the severe-burn victims at the burn unit of the Medical University of Vienna from 01/2002 to 06/2012 for whom a gastrointestinal infarction was diagnosed during their inpatient stay on computed-tomography, in the context of acute laparotomy, or upon autopsy by aetiology. RESULTS: After a severe thermal injury, 17 patients suffered a gastrointestinal infarction during their stay. In 82% of those patients, non-occlusive mesenteric ischaemia (NOMI) was identified as the cause of the gastrointestinal infarction. Patients with an embolic infarction tended to be older (78.0years embolism vs. 53.4 NOMI, mean, p<0.01), with a lower abbreviated burn severity index (8.7 embolism vs. 10.4 NOMI, mean, p<0.02) and a smaller total body surface area burned (20% embolism vs. 48% NOMI, mean, p<0.01) than those with a non-occlusive mesenterial ischaemia. No patients with an embolic infarction or any of the females in the entire gastrointestinal infarction group survived this event, resulting in a mortality rate of 100% for the embolic infarction group and female group. The decisive factor for surviving a NOMI was age (median age: male survivors 28years vs. nonsurvivors 66years (of this median, males=72years and females=60years), p<0.02). CONCLUSION: The results of our study clearly demonstrate that in severe-burn intensive care patients, non-occlusive mesenteric ischaemia is the most frequent cause of gastrointestinal infarction and that the decisive factor for survival is the patient's age.

Tumour response of osteosarcoma to neoadjuvant chemotherapy evaluated by magnetic resonance imaging as prognostic factor for outcome.

PURPOSE: This study evaluated the feasibility of computed magnetic resonance imaging (MRI) volumetry in conventional osteosarcomas. Secondly, we investigated whether computed volumetry provides new prognostic indicators for histological response of osteosarcomas after neoadjuvant chemotherapy. METHODS: In a retrospective cohort study, data from the Vienna Bone Tumour Registry was used. MR images from 14 patients (male:female = 1.8, mean age 19 years) were analysed prior to and after neoadjuvant chemotherapy according to current therapy regimens. Histological response to chemotherapy was graded according to the Salzer-Kuntschik classification. Computed volumetry was performed for the intraosseous part, as well as the soft-tissue component and the tumour as a whole. RESULTS: In a setting of appropriate radiological equipment, the method has been considered to be well implementable into clinical routine. The mean tumour volume prior to chemotherapy was 321 (±351) ml. In good responders (n = 6), overall tumour volume decreased by 47% (p = 0.345), whereas poor responders (n = 8) showed a 19% decrease (p = 0.128). Neoadjuvant multidrug therapy remarkably changed the tumour composition. This is seen in a decrease of the mean ratio of soft-tissue to intraosseous tumour volume from 8.67 in poor responders and 1.15 in good responders to 1.26 and 0.45 (p = 0.065), respectively. Interestingly, the bony compartment of good responders showed a volume increase during neoadjuvant chemotherapy (p = 0.073). However, we did not find prognostic markers for histological tumour response to pre-operative chemotherapy. CONCLUSIONS: Separated volumetry of tumour segments revealed interesting insights into therapy-induced growth patterns. If verified in a larger study population, these results should be taken into account when planning ablative surgery.

Vacuum inversion and securing of distal colonic pseudodiverticula with novel spiked O-rings.

BACKGROUND: Diverticular disease is increasingly prevalent in Western societies and is associated with significant morbidity. OBJECTIVE: Two-stage endoscopic device development for inversion and secured ligation of colonic diverticula; first, human cadaver studies were performed to measure forces required for diverticular inversion; second, a novel set of devices (elastic spiked O-ring with delivery system) was tested in animals. DESIGN: Prospective, observational study of human cadavers and prospective, interventional study of a porcine model. SETTING: University hospital pathology laboratory and animal facility. INTERVENTION: Full-thickness inversion of the colonic wall with a pipelike delivery instrument to produce an inverted pseudodiverticulum that was secured with a spiked O-ring. MAIN OUTCOME MEASUREMENTS: The forces required for diverticular inversion, the secured closure of inverted pseudodiverticula, and the time until necrotic tissue falls off. RESULTS: A total of 248 of 248 of cadaveric sigmoid diverticula could be inverted by means of vacuum or forceps. The forces required for inversion ranged from 0.28 to 0.47 N (median, 0.37 N). Twenty-four spiked O-rings were delivered in 6 living pigs to produce 24 inverted pseudodiverticula. One animal died the day after the procedure of a pulmonary thromboembolism. In the remaining 5 pigs, all delivered spiked O-rings remained in place for 7 to 22 days. At necropsy, none of the inverted sites showed signs of perforation but rather full-thickness reparative scarring with ingrowth of connective tissue. LIMITATIONS: Animal model, stiff pipelike delivery instrument, variations in diverticular location, diameter, and size. CONCLUSIONS: Endoluminal inversion and securing of colonic diverticula induces tissue necrosis, diverticular sloughing, and full-thickness scarring.