Experimental SARS-CoV-2 Infection of Bank Voles

After experimental inoculation, severe acute respiratory syndrome coronavirus 2 infection was confirmed in bank voles by seroconversion within 8 days and detection of viral RNA in nasal tissue for up to 21 days. However, transmission to contact animals was not detected. Thus, bank voles are unlikely to establish effective transmission cycles in nature.     

In vivo imaging of apoptosis by 99mTc-Annexin V scintigraphy: visual analysis in relation to treatment response.

BACKGROUND AND PURPOSE: Anticancer therapy induces apoptosis in a dose- and time-dependent fashion. (99m)Tc-Hynic-rh-Annexin V scintigraphy (TAVS) enables non-invasive in vivo imaging of treatment-induced apoptosis. We identified the visual patterns of (99m)Tc-Hynic-rh-Annexin V tumour uptake and related these to treatment response. PATIENTS AND METHODS: Thirty-three patients with malignant lymphoma (n=26), leukaemia (n=1) NSCLC (n=5), H&NSCC (n=1), scheduled for radiotherapy (n=27), platinum-based chemotherapy (n=5) or concurrent chemoradiation (n=1), underwent TAVS before and early after the start of treatment. Planar and SPECT images were visually examined to assess changes in tumour (99m)Tc-Hynic-rh-Annexin V uptake. Twenty-nine patients were eligible for further analysis. Annexin V uptake before (U(baseline)) and early after (U(post)) the start of treatment was graded using a four-step scale: 0, absent; 1, weak; 2, moderate and 3, intense. The difference between these values (Delta U) was calculated and correlated to tumour response after therapy (Spearman rank correlation test). RESULTS: Weak to moderate U(baseline) was detected in 13/15 patients with a complete response and U(post) was markedly increased in all these cases (Delta U range 1-3). Partial response (n=7) was associated with weak to moderate U(baseline) and a moderately increased U(post) (Delta U range 1-2). In patients with stable disease (n=5), U(baseline) was predominantly weak, without considerable changes in uptake after the start of treatment (Delta U range 0-1). Finally, in case of progressive disease (n=2), either no tumour uptake or a decrease in U(post) was detected (Delta U=-1). A statistically significant correlation was found between changes in (99m)Tc-Hynic-rh-Annexin V tumour uptake and clinical response (correlation coefficient=0.62; P<0.001). CONCLUSIONS: Complete or partial tumour response was associated with a marked increase of (99m)Tc Hynic-rh-Annexin V accumulation early during treatment compared to baseline values. In case of stable or progressive disease, pretreatment scans demonstrated predominantly low (99m)Tc Hynic-rh-Annexin V tumour uptake and no significant increase early after treatment. These results indicate that TAVS might be useful as a predictive test for treatment response.     

Mast cells and tumour angiogenesis: new insight from experimental carcinogenesis

Histopathologic examination and clinical observations of solid and haematological malignancies indicates mast cells as key host cells in the tumour infiltrate, with important consequence on tumour-associated angiogenesis and tumour growth. Data suggest indeed that tumour-infiltrating mast cells may exert a prominent function in the angiogenic "switch", which is essential for the progression of early tumours. The experimental approach has substantially increased our understanding of the role of tumour-infiltrating mast cells in the process of angiogenesis that accompanies tumour development. This review will focus on the crucial contribution of mast cells in promoting tumour neovascularization as it emerges from the most recent observations of experimental carcinogenesis in in vivo and in vitro models.     

Accuracy and initial stability of open- and closed-wedge high tibial osteotomy: a cadaveric RSA study

We analyzed the difference in angle-correction accuracy and initial stability between open-wedge (OWO) and closed-wedge tibial valgus osteotomy (CWO). Five fresh-frozen pairs of human cadaver lower limbs were used; their bone mineral density (BMD) was measured with DEXA and a planned 7° valgus osteotomy was performed, either with an open (right knees) or closed (left knees) technique. All knees for osteotomy were fixed with a rigid locked plate. In OWO, tricalcium phosphate (TCP) wedges were inserted. The knees were subjected to an increasing cyclic axial load until failure, while measuring the relative displacement of the bony segments with roentgen stereophotogrammetric analysis. The mean postoperative valgus correction angle was 9.5°±2.8° for CWO (over-correction of 2.5°) and 6.2°±2.0° for OWO (under-correction of 0.8°) (P =0.08). The data of displacement under load bearing showed no significant differences in rotations and translations in any direction. No significant correlation between BMD and the moment of failure was found (P =0.27). This study has shown that both methods gave an acceptable correction with a high variation of postoperative correction angles. There was a tendency for over-correction in the CWO group but no significant difference was found. There was no difference in initial stability between CWO and OWO with a rigid locked-plate fixation.     

Impact of blood source and component manufacturing on neurotrophin content and in vitro cell wound healing

BackgroundWe evaluated neurotrophin (NF) levels and their impact on in vitro cell wound healing in eye drops from differently prepared blood sources (cord blood [CB], and peripheral blood [PB]) in the same donor, to avoid intrasubject biological variability.Materials and methodsTwenty healthy adult donor PB samples, and twenty CB samples acquired at the time of delivery were processed to obtain serum (S), platelet-rich plasma (PRP), platelet-poor plasma (PPP), and S retrieved from PRP after activation with Ca-gluconate (PRP-R). The levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) were assessed with a Luminex xMAP (Luminex Corporation), and by using multikine kits from R&D system, and were statistically analysed in the eight different preparations. The impact of S, PRP, PPP, PRP-R from both sources on a cell line responding to NF supplementation (MIO-M1, UCL Institute of Ophthalmology, London, UK) was tested with a scratch wound assay, and analysed by IncuCyte S3 equipment.ResultsAll the preparations from CB showed higher NF levels, except for BDNF where no difference was found as compared to PB. PRP showed higher NF levels with respect to S, PPP and PRP-R in this decreasing order. Younger donors in PB contributed with higher NF levels. The scratch assay showed different cell migration results, with a complete wound closure only recorded with the supplementation of CB-S, and a progressive reduction by using PRP, PRP-R, and PPP from both sources.DiscussionProtocols of preparation and choice of blood source determine different NF levels in the final products. The therapeutic use of a natural neurotrophin pool from blood sources might have a clinical impact in several different settings. Efforts are needed to standardise the manufacturing and the product content in order to establish and modulate the posology of the final supplementation.     

Endoscopic management of anastomotic hemorrhage from pancreatogastrostomy

Background  Hemorrhage from pancreatic-enteric anastomosis after pancreaticoduodenectomy (PD) is a critical condition due to its difficult accessibility and delicate condition, and therefore remains a major challenge for the surgeon in charge. Objective  This study analyzed presentation and management of pancreatogastrostomy hemorrhage (PGH) after PD to determine the respective roles of endoscopy and surgery. Patients and methods  Patients who underwent PD with pancreatogastrostomy between 1989 and January 2008 were identified from a pancreatic resection database and analyzed with regards to PGH, treatment strategy and outcome, and incidence of postoperative complications. Results  Out of 265 consecutive patients with PD, 10 patients (3.7%) experienced an episode of PGH, detected on average on postoperative day 5. No patient with PGH died during hospital stay as opposed to a mortality rate of 2.7% in patients without PGH. Morbidity rates were 50% versus 48% and length of hospital stay was 23 versus 21 days for patients with and without PGH, respectively, with no statistical differences between the groups. Endoscopic approach to control PGH was successful in nine patients. Pancreatogastrostomies were not compromised regarding procedure or air insufflations and no concomitant development of pancreatic fistula was observed. Open surgery was inevitable in one patient with recurrent PGH in order to achieve hemostasis, but resulted in pancreatic fistula and protracted hospital stay. Conclusions  The present study demonstrates a feasible endoscopic approach for the management of PGH with high success rate and no concomitant procedure-related morbidity. Medical illustrations: Lothar Knorn, Bonn.     

Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome

Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

     

Oesophageal echocardiography

Summary The diagnostic value of oesophageal echocardiography is most striking in patients in whom precordial studies are of inadequate quality or fail to establish a definitive diagnosis. Oesophageal studies have excellent image quality, can be completed within 10 minutes without complications and, in most instances, enables the clinical question to be answered. In 50 patients referred for suspected thoracic aorta pathology, oesophageal echocardiography correctly excluded or diagnosed the type of aortic dissection, aortic aneurysm or the site of coarctation. Of 35 patients referred with suspected infective endocarditis, oesophageal echocardiography revealed complications in 18 patients, including vegetation, mycotic aneurysm, abscess or chordal rupture. Oesophageal echocardiography is extremely helpful to visualize intracardiac mass lesions. In 27 patients with a history of systemic or pulmonary embolism, the technique confirmed the presence, size and position of a mass lesion in 11 patients. Oesophageal color Doppler flow imaging further expands the diagnostic capabilities, particularly in patients with mitral valve prosthesis. Our experience indicates that oesophageal echocardiography significantly extends the diagnostic potential of echocardiography. Detailed knowledge of cardiothoracic anatomy and its pathologic sequelae is, however, a prerequisite for the efficient and safe application of this method.