Early Regenerative Response in the Intrathoracic Porcine Esophagus—The Impact of the Inflammation

In order to improve the treatment of children born with long‐gap esophageal atresia, a porcine model was developed for studying esophageal regrowth using a bridging graft composed of a silicone stented Biodesign mesh. The aim of the study was to investigate how leakage and contact between the native muscle and Biodesign mesh affected the early healing response. Resection of 3 cm of intrathoracic esophagus was performed in 10 newly weaned piglets. They were fed through a gastrostomy 8–10 days prior to sacrifice. In order to achieve nonleaking anastomoses, the silicone stent and suturing technique had to be adjusted between the first four and second six piglets. The technical adjustment decreased leakage. A nonleaking anastomosis could not be achieved when the native muscle layers were sewn less central on the bridging graft compared with the mucosa. If there was leakage, the inflammatory response increased, with islets of perivascular T‐lymphocytes and infiltration of macrophages in the native muscle layers. In the bridging area, new vessels were seen in the submucosa in 9 of 10 piglets between 4 and 10 days after surgery. Smooth muscle cells also appeared to move from the cut muscle edges of both the muscularis mucosa and the lamina muscularis and were seen as a layer of several cells under newly formed mucosa. Double staining of the basal membrane of the ingrowing vessels and the pericytes showed that the basal membrane was thinner over some of the pericytes, but there was no accumulation of immature‐looking cells in the submucosa of the bridging area. In this porcine model, where esophageal regrowth was studied by using a bridging graft composed of a silicone stented Biodesign mesh, we can conclude that leakage increased the inflammatory response in early healing. Ingrowth of new vessels was seen in the bridging area and movement of smooth muscle cells was found under newly formed mucosa.     

Laparoscopic Ladd's procedure for malrotation in infants and children is still a controversial approach

BackgroundOpen Ladd's procedure is the gold standard for the correction of intestinal malrotation and laparoscopic approach remains controversial. This study aimed to evaluate our experience in laparoscopic management of malrotation.MethodsSingle center retrospective study including patients who underwent a laparoscopic assessment of intestinal malrotation with correction if appropriate between 2007 and 2017.ResultsSixty-five patients (median age 7 months) had a laparoscopic assessment with and without correction of malrotation. Forty-five (69%) were symptomatic, including 16 (25%) with a midgut volvulus. The procedure was completed laparoscopically in 55 (86%) patients in 110 min (30–190). Conversions happened more frequently at the beginning of the experience. With a follow-up of 12.5 months (8 days–5.3 years), morbidity rate was 15% and 4 (6%) patients underwent a redo surgery, all in the first 5 months after surgery, compared with 3/53 (6%) in a contemporaneous group undergoing open Ladd's.ConclusionThis is the largest series reported so far of the laparoscopic management of malrotation. Laparoscopic Ladd's procedure is reliable but still exposes to open conversion which may be in part owing to a learning curve. A low conversion threshold is important in cases with volvulus. The redo rate is similar to that of the open procedure.Level of evidenceLevel III retrospective comparative treatment study.     

αv integrins play an important role in myofibroblast differentiation

Transforming growth factor-beta1 is a potent mediator of the differentiation of fibroblasts into myofibroblasts, which is characterized by the appearance of the cytoskeletal protein alpha-smooth muscle actin. The aim of this study was to investigate the role of integrin extracellular matrix receptors in transforming growth factor-beta1-induced myofibroblast differentiation. We show that blockade of the alphav and/or beta1 integrins prevents the transforming growth factor-beta1-induced myofibroblast differentiation, seen by the increased expression of alpha-smooth muscle actin and enhanced collagen gel contraction in three human fibroblast cell lines (from the mouth, skin, and kidney). Further, blockade of alphav specific integrins alphavbeta5 and alphavbeta3 suppressed myofibroblast differentiation in fibroblasts from the mouth and skin; however, in the kidney cells, the prevention of differentiation was seen only with blockade of alphavbeta5 integrin but not alphavbeta3. A possible reason for this result may be different degrees of responsiveness to transforming growth factor-beta1 treatment seen from different anatomical origins of the cell lines. These data indicate a novel role for alphav integrins in the differentiation of human fibroblasts from the mouth, skin, and kidney into myofibroblasts and suggest that there is a common differentiation pathway.     

Scaphoid (navicular) fractures of the wrist in children: attention to the impacted buckle fracture

We retrospectively analyzed the radiographic findings in 76 patients with proven scaphoid (navicular) fractures. The purpose of the study was to determine the incidence of the impacted buckle fracture of the scaphoid bone in children. Fourteen of the 76 patients (17%) demonstrated such a fracture, and all of the fractures occurred in the middle or distal third of the scaphoid bone. The mean age of this group of patients was 13.7 years, as compared to the mean age of 15.6 years in the patients with overt transverse fractures. One out of 14 of the patients with a buckle fracture was female. None developed complicating aseptic necrosis. The fractures were most clearly visualized on AP and oblique views of the wrist, and all cases demonstrated edematous thickening of the soft tissues and/or navicular fat pad obliteration adjacent to the scaphoid bone. The use of comparative views was extremely helpful in the detection of this fracture. Electronic Publication     

Clinical comparison of full-field digital mammography and screen-film mammography for detection of breast cancer

OBJECTIVE: The purpose of this work is to compare full-field digital mammography and screen-film mammography for the detection of breast cancer in a screening population. SUBJECTS AND METHODS: Full-field digital mammography was performed in addition to screen-film mammography in 6736 examinations of women 40 years old and older presenting for screening mammography at either of two institutions. Two views of each breast were acquired with each technique. The digital and screen-film mammograms were each interpreted independently. In addition to a clinical assessment, each finding was assigned a probability of malignancy for use in receiver operating characteristic analysis. In cases in which the digital and screen-film interpretations differed, a side-by-side analysis was performed to determine the reasons for the discrepancy. With few exceptions, findings detected on either technique were evaluated with additional imaging and, if warranted, biopsy. RESULTS: Additional evaluation was recommended on at least one technique in 1467 cases. These additional evaluations led to 181 biopsies and the detection of 42 cancers. Nine cancers were detected only on digital mammography, 15 were detected only on screen-film mammography, and 18 were detected on both. The difference in cancer detection is not statistically significant (p > 0.1). Digital mammography resulted in fewer recalls than did screenfilm mammography (799 vs 1007, p < 0.001). The difference between the receiver operating characteristic curve area for digital (0.74) and screen-film (0.80) mammography was not significant (p > 0.1). Reasons for discrepant interpretations of cancer were approximately equally distributed among those relating to lesion conspicuity, lesion appearance, and interpretation. CONCLUSION: No significant difference in cancer detection was observed between digital mammography and screen-film mammography. Digital mammography resulted in fewer recalls than did screen-film mammography.     

Brain‐derived neurotrophic factor prevents dendritic retraction of adult mouse retinal ganglion cells

We used cultured adult mouse retinae as a model system to follow and quantify the retraction of dendrites using diolistic labelling of retinal ganglion cells (RGCs) following explantation. Cell death was monitored in parallel by nuclear staining as ‘labelling’ with RGC and apoptotic markers was inconsistent and exceedingly difficult to quantify reliably. Nuclear staining allowed us to delineate a lengthy time window during which dendrite retraction can be monitored in the absence of RGC death. The addition of brain‐derived neurotrophic factor (BDNF) produced a marked reduction in dendritic degeneration, even when application was delayed for 3 days after retinal explantation. These results suggest that the delayed addition of trophic factors may be functionally beneficial before the loss of cell bodies in the course of conditions such as glaucoma.     

Recurrence of progressive multifocal leukoencephalopathy despite immune recovery in two HIV seropositive individuals

We present two cases of recurrent progressive multifocal leukoencephalopathy (PML) in patients with long standing virally suppressed human immunodeficiency virus (HIV) and normal CD4+ T cell count who were taking stable regimens of highly active antiretroviral therapy (HAART). This has significant implications for other patients with a past history of PML, not just those with HIV but also those on medications such as natalizumab or fumarates.     

A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast‐like cells

Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations in the NF1 gene. Patients often suffer from tissue‐specific lesions associated with local double‐inactivation of NF1. In this study, we generated a novel fracture model to investigate the mechanism underlying congenital pseudarthrosis of the tibia (CPT) associated with NF1. We used a Cre‐expressing adenovirus (AdCre) to inactivate Nf1 in vitro in cultured osteoprogenitors and osteoblasts, and in vivo in the fracture callus of Nf1^flox/flox and Nf1^flox/? mice. The effects of the presence of Nf1^null cells were extensively examined. Cultured Nf1^null‐committed osteoprogenitors from neonatal calvaria failed to differentiate and express mature osteoblastic markers, even with recombinant bone morphogenetic protein‐2 (rhBMP‐2) treatment. Similarly, Nf1^null‐inducible osteoprogenitors obtained from Nf1 mouse muscle were also unresponsive to rhBMP‐2. In both closed and open fracture models in Nf1^flox/flox and Nf1^flox/? mice, local AdCre injection significantly impaired bone healing, with fracture union being <50% that of wild type controls. No significant difference was seen between Nf1^flox/flox and Nf1^flox/? mice. Histological analyses showed invasion of the Nf1^null fractures by fibrous and highly proliferative tissue. Mean amounts of fibrous tissue were increased upward of 10‐fold in Nf1^null fractures and bromodeoxyuridine (BrdU) staining in closed fractures showed increased numbers of proliferating cells. In Nf1^null fractures, tartrate‐resistant acid phosphatase–positive (TRAP+) cells were frequently observed within the fibrous tissue, not lining a bone surface. In summary, we report that local Nf1 deletion in a fracture callus is sufficient to impair bony union and recapitulate histological features of clinical CPT. Cell culture findings support the concept that Nf1 double inactivation impairs early osteoblastic differentiation. This model provides valuable insight into the pathobiology of the disease, and will be helpful for trialing therapeutic compounds. © 2012 American Society for Bone and Mineral Research     

Efficacy and safety of emergency non-invasive pelvic ring stabilisation

BackgroundUrgent non-invasive pelvic ring stabilisation (pelvic binding, PB) in shocked patients is recommended by state and institutional guidelines regardless of the fracture pattern. The purpose of this study was to determine the adherence to the guidelines, efficacy of the technique and identification of potential adverse effects associated with PB.Patients and methodsA 41-month retrospective analysis of the prospective pelvic fracture database was undertaken at a level 1 trauma centre. High-energy pelvic fractures were included in the analysis with exclusion of the A type injuries (AO/OTA classification) and patients who were dead on arrival. Collected data included patient demographics, injury severity score, fracture classification, application and timing of PB, associated injuries, physiological parameters, resuscitation fluids and outcomes. Pre and post-PB radiographs were reviewed. The potential effects of the PB on soft tissue (femoral vessel, bladder and rectal injury) complications were assessed by independent experts.Results115 patients with high-energy B and C type pelvic ring injuries were included. Thirty-six (31%) patients presented in haemorrhagic shock on arrival. A total of 43 pelvic bindings were performed, 18 of them on shocked patients. The adherence to the guidelines was 50% (18/36) overall. Analysing fracture types of shocked patients the adherence was: B1 80%, B2 20%, B3 20%, C1 66%, C2 86%, C3 33%. The alignment of the pelvis was improved or perfect on post-PB radiographs in 68% and had not changed in 21%. In some cases of B2 and B3 type injuries the PB increased the deformity after application (11%). There were 10 deaths (8.7%) in the study group, with 4 deaths attributed to acute pelvic bleeding. Two of these had PB applied and two were identified as potential for improvement. One femoral artery injury, four bladder injuries and three rectum injuries were identified in patients who had PB applied. Association between the PB and these injuries is unlikely.ConclusionThe adherence to the guidelines should be improved with further education and system development. The good effect of the technique was evident on radiographs. Although in some lateral compression fracture patterns the deformity increased, no hazards were associated with the use of PB.     

Grade progression and regression in recurrent urothelial cancer

PURPOSE: Recurrent urothelial cancers are reported to have characteristics similar to those of the primary tumor, with 10% to 25% of low grade tumors recurring as high grade disease. We determined how often grade progression and regression occur and whether abnormalities in p53 protein expression in original tumors are preserved in recurrences. MATERIALS AND METHODS: Two groups of patients treated for recurrent stages Ta/T1 urothelial bladder cancers with at least 1 tumor-free examination between the index and recurrent tumors were reviewed. Group 1 included 115 patients in whom the first available tumor was compared with the last recurrence and group 2 included 42 in whom the initial tumor was compared with the first recurrence. Immunohistochemical analysis of p53 expression was performed on a subset of 34 tumor pairs. RESULTS: In group 1, 33 grade 3 tumors (45%) recurred as grade 1 or 2 tumors, while 9 of 82 grades 1 and 2 tumors (11%) recurred as grade 3 tumors. Five of 7 group 2 grade 3 tumors (71%) recurred as grade 1 or 2 disease, while 1 of 35 grades 1 and 2 tumors (3%) recurred as grade 3 disease. In the 34 pairs studied immunohistochemically 6 of 14 grade 3 tumors recurred at lower grades. Nuclear p53 over expression occurred in 21 index tumors (12 of 14 grade 3, 8 of 17 grade 2 and 1 of 3 grade 1) and in 9 recurrences (6 of 10 grade 3, 2 of 17 grade 2 and 1 of 7 grade 1). Only 7 of 21 p53 positive and 2 of 12 p53 negative index tumors were p53 positive on recurrence. CONCLUSIONS: While progression from low to high grade occurred in less than 15% of patients, grade regression was observed in almost 50%. The loss of p53 positivity in regressing tumors indicates that these recurrences are molecularly distinct from the corresponding initial tumor.