Up to 9-day survival and control of thrombocytopenia following alpha1,3-galactosyl transferase knockout swine liver xenotransplantation in baboons

Kim K, Schuetz C, Elias N, Veillette GR, Wamala I, Varma M, Smith RN, Robson SC, Cosimi AB, Sachs DH, Hertl M. Up to 9‐day survival and control of thrombocytopenia following GalT‐KO swine liver xenotransplantation in baboons. Xenotransplantation 2012; 19: 256–264.. © 2012 John Wiley & Sons A/S. Abstract: Background:  With standard miniature swine donors, survivals of only 3 days have been achieved in primate liver‐transplant recipients. The recent production of alpha1,3‐galactosyl transferase knockout (GalT‐KO) miniature swine has made it possible to evaluate xenotransplantation of pig organs in clinically relevant pig‐to‐non‐human primate models in the absence of the effects of natural anti‐Gal antibodies. We are reporting our results using GalT‐KO liver grafts. Methods:  We performed GalT‐KO liver transplants in baboons using an immunosuppressive regimen previously used by our group in xeno heart and kidney transplantation. Post‐operative liver function was assessed by laboratory function tests, coagulation parameters and histology. Results:  In two hepatectomized recipients of GalT‐KO grafts, post‐transplant liver function returned rapidly to normal. Over the first few days, the synthetic products of the donor swine graft appeared to replace those of the baboon. The first recipient survived for 6 days and showed no histopathological evidence of rejection at the time of death from uncontrolled bleeding, probably caused by transfusion‐refractory thrombocytopenia. Amicar treatment of the second and third recipients led to maintenance of platelet counts of over 40 000 per μl throughout their 9‐ and 8‐day survivals, which represents the longest reported survival of pig‐to‐primate liver transplants to date. Both of the last two animals nevertheless succumbed to bleeding and enterococcal infection, without evidence of rejection. Conclusions:  These observations suggest that thrombocytopenia after liver xenotransplantation may be overcome by Amicar therapy. The coagulopathy and sepsis that nevertheless occurred suggest that additional causes of coagulation disturbance must be addressed, along with better prevention of infection, to achieve long‐term survival.     

Sagittal spinopelvic parameters in children with achondroplasia: identification of 2 distinct groups

Imatinib mesylate has become the treatment of choice for gastrointestinal stromal tumors (GISTs) and has made a revolutionary impact on survival rates. Bone marrow necrosis is a very rare adverse event in malignant GIST. Bone metastases are also rarely encountered in the setting of this disease. The authors report on a patient with malignant GIST who developed a bone lesion, mimicking spinal metastasis on both MR imaging and FDG-PET/CT. Corpectomy and anterior fusion was performed, but the pathology report was consistent with bone marrow necrosis. Radiological and clinical similarities made the distinction between metastasis and bone marrow necrosis challenging for the treating physicians. Instead of radical surgical excision, more conservative methods such as percutaneous or endoscopic bone biopsies may be more useful for pathological confirmation, even though investigations such as MR imaging and FDG-PET/CT indicate metastatic disease.     

Distant metastases of adenoid cystic carcinoma of the salivary glands and the value of diagnostic examinations during follow-up

BACKGROUND: Adenoid cystic carcinoma (ACC) accounts for approximately 10% of all neoplasms of the salivary glands. Late distant metastases and local recurrences are responsible for a rather low long-term survival rate. AIM: To study the metastasizing pattern of ACC of the salivary glands in 51 patients. METHOD: Fifty-one patients with an ACC in the intraoral/sublingual salivary glands (n = 30), parotid gland (n = 8), submandibular gland (n = 2), maxillary sinus (n = 6), and nasal cavity (n = 5) have been studied. The male-female ratio was 1:1, the mean age was 54.3 (range, 19-81) years. In 30 cases treatment consisted of surgery and radiotherapy. In 13 cases surgery alone was carried out. The average follow-up time was 117.8 (range, 1-171) months. RESULTS: In 28 cases (54.9%) distant metastases occurred, and in 3 patients (5.8%) regional lymph node metastases occurred. In 12 of the 28 patients with distant metastases (42.8%), only the lungs were involved, whereas in 5 of the 28 patients (17.8%), the distant metastases occurred in other organs (eg, bones and brain). In 11 of the 28 patients (39.2%) metastases were found both in the lungs and other organs. Twenty-four of the 51 patients (47.0%) died because of their tumor. The average time between the occurrence of lung metastases and death was 32.3 months and between the occurrence of metastases elsewhere and death 20.6 months. CONCLUSION: Distant metastases of ACC of the salivary glands occur most often in the lungs. Although these lung metastases are the first to occur, these patients die later than patients with distant metastases in other organs. The value of annual chest films or other tests for the presence of distant metastases during follow-up after surgical removal of an ACC seems rather questionable.     

Bile-pancreatic juice exclusion promotes Akt/NF-kB activation and chemokine production in ligation-induced acute pancreatitis

Using a unique surgical model (the donor rat model), we showed previously that duodenal replacement of bile-pancreatic juice, obtained fresh from a donor rat, ameliorates ligation-induced acute pancreatitis. We hypothesize that bile-pancreatic juice exclusion from gut exacerbates Akt/nuclear factor-kB (NF-kB) pathway activation and induces chemokine production in ligation-induced acute pancreatitis. We compared rats with bile-pancreatic duct ligation to those with duodenal bile-pancreatic juice replacement fresh from a donor rat beginning immediately before duct ligation. Sham control rats had ducts dissected but not ligated. Rats were killed 1 or 3 hours after operation (n=7/group). Akt activation (immunoblotting, immune-complex kinase assay, and ELISA), inhibitory protein I-kB (I-kB) activation (immunoblotting), and production of chemokines MCP-1 and RANTES (ELISA) were measured in pancreatic homogenates. NF-kB was quantitated in nuclear fractions using electrophoretic mobility shift assay. Duct ligation produced significant increases in pancreatic Akt, IkB, and NF-kB activation and production of MCP-1 and RANTES. Activation of the Akt/NF-kB pathway and increased MCP-1 and RANTES production in response to duct ligation were significantly reduced by bile-pancreatic juice replacement (ANOVA, P<0.05). Bile-pancreatic juice exclusion stimulates Akt/NF-kB pathway activation and increases chemokine production in ligation-induced acute pancreatitis. Presented at the annual meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 16, 2005 (poster).     

Analysis of Risk Factors for Gunshot Wound Infection in a Nigerian Civilian Trauma Setting

Background

Survivors of firearm injury are at risk of wound infection. On average, civilian gunshot wound infection rates in developing countries are relatively high and almost on a par with infection rates in war trauma settings. Overall, there are limited data on civilian gunshot wound infection and its predisposing factors. The aim of this study was to determine the risk factors for gunshot wound infection in a civilian trauma setting of a developing nation.

Materials and method

This was a retrospective analysis of data on the entire patients who presented in Federal Teaching Hospital Abakaliki with firearm injury from January 2005 to December 2014.

Results

There were 196 patients, and wound infection was a complication in 58 (29.6 %) of them. The significant factors for high wound infection rate in univariate analysis were perforating wound (p < 0.001), high velocity injury (p < 0.001), haematocrit <30 % (p < 0.001), presence of fracture (p < 0.001), hollow viscus injury (p < 0.001) and injury to hospital arrival interval later than 6 h (p < 0.014). Anatomical site of injury correlated with infection rate (p < 0.001), highest rate (40.6 %) in lower extremity and least (9.1 %) in head and neck wounds. Multivariate logistic regression analysis identified haematocrit (p < 0.001), perforating wound (p < 0.021), presence of fracture (p < 0.043) and hollow viscus injury (p < 0.039) as independent predictors of gunshot wound infection.

Conclusion

The independent predictors of infection identified in this study call for judicious replacement of blood loss and high priority accorded to perforating wound, fractures and hollow viscus injury in interventions aimed at reducing gunshot wound infection rate.

     

Bilirubin appears to be the only independent variable affecting mortality on liver transplant waiting list if waiting time exceeds 1 year

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score has been shown to be the best predictor of short-term mortality on the liver transplant waiting list in the United States but waiting time often exceeds 1 year in many countries. We wanted to identify the factors affecting mortality on the liver transplant waiting list in Singapore where waiting time for liver transplant exceeds 1 year. PATIENTS AND METHODS: All patients who were listed on the liver transplant waiting list in Singapore from January 1997 to December 2003 excluding those who were transplanted were analyzed. MELD was calculated according to the United Network for Organ Sharing formula. Univariate analysis was performed to identify factors affecting mortality on the waiting list and multivariate analysis by logistic regression. Categorical and continuous variables were compared with the chi-square and Mann-Whitney U tests. RESULTS: There were 48 patients in the study. We found that on univariate analysis, bilirubin, INR, MELD score, and Child's score significantly influenced mortality on the waiting list but on multivariate analysis, bilirubin was the only independent prognostic indicator of mortality on the waiting list (LR = 1.97; 95% confidence interval = 1.08 to 3.61). INR was found to be significantly correlated to bilirubin with Pearson correlation (R = 0.63, P < .001). CONCLUSION: Bilirubin is the only independent factor affecting mortality on the liver transplant waiting list where waiting time exceeds 1 year.     

Optical spectroscopic determination of human meniscus composition

This study investigates the correlation between the composition of human meniscus and its absorption spectrum in the visible (VIS) and near infrared (NIR) spectral range. Meniscus samples (n = 24) were obtained from nonarthritic knees of human cadavers with no history of joint diseases. Specimens (n = 72) were obtained from three distinct sections of the meniscus, namely; anterior, center, posterior. Absorption spectra were acquired from each specimen in the VIS and NIR spectral range (400–1,100 nm). Following spectroscopic probing, the specimens were subjected to biochemical analyses to determine the matrix composition, that is water, hydroxyproline, and uronic acid contents. Multivariate analytical techniques, including principal component analysis (PCA) and partial least squares (PLS) regression, were then used to investigate the correlation between the matrix composition and it spectral response. Our results indicate that the optical absorption of meniscus matrix is related to its composition, and this relationship is optimal in the NIR spectral range (750–1,100 nm). High correlations (R²_uronic = 86.9%, R²_water = 83.8%, R²_{hydroxyproline} = 81.7%, p < 0.0001) were obtained between the spectral predicted and measured meniscus composition, thus suggesting that spectral data in the NIR range can be utilized for estimating the matrix composition of human meniscus. In conclusion, optical spectroscopy, particularly in the NIR spectral range, is a potential method for evaluating the composition of human meniscus. This presents a promising technique for rapid and nondestructive evaluation of meniscus integrity in real‐time during arthroscopic surgery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:270–278, 2016.