Reconstruction of the proximal femur with a modular resection prosthesis

Background

Various megaprostheses are currently available for reconstruction of the proximal femur after tumor resection. This study evaluates the survival and complications of a modular megaprosthesis for reconstruction of the proximal femur.

Materials and methods

We studied the medical files of 109 tumor patients (age range 16–86 years) who underwent proximal femoral reconstruction with the MRP^® megaprosthesis from 2002 to 2011. There were 70 patients with metastases, 34 patients with bone sarcomas, and five patients with hematological malignancies; 82 were primary and 27 were revision reconstructions. Mean follow-up was 2.5 years; 31 patients had a minimum five-year follow-up. We evaluated the survival and function of the patients, and the survival and complications of the megaprostheses.

Results

Survival was significantly higher for the patients with bone sarcomas compared to those with metastases and hematological malignancies. Mean MSTS functional score was similar between patients with bone sarcomas and those with hematological malignancies and metastases, and between patients with primary and those with revision reconstructions. Overall survival of the MRP^® megaprostheses was 74 % at 5 and 9 years. Fourteen (13.6 %) major complications occurred at a mean period of 1.4 years (range 3 months to 4.5 years); these included infection (5.8 %), dislocation (3.9 %), local recurrence (2.9 %), and acetabular fracture (1 %).

Conclusion

MRP^® megaprostheses are a valuable reconstruction option after tumor resection of the proximal femur.

     

Intraperitoneal mesh prosthesis metastasis from pancreatic cancer,after laparoscopic hernia repair

Introduction There are very few case reports of metastasis on a mesh prosthesis following laparoscopic hernia repair in the literature and its incidence is completely unknown.

Case report A 76-year-old male patient presented in December 2013 with a suspicious malignant lesion of the pancreatic tail on the MRI. He was also complaining of a painful mass in the right para-rectal area. An exploratory laparoscopy performed in December 2013 revealed microscopic whitish peritoneal implants in the left hypochondrium and a massive metastasis involving a mesh prosthesis placed é years before in the right para-rectal area. The pathology report of biopsies of the mesh confirmed a metastasis compatible with a pancreatic tumor.

Discussion Possible modes of metastasis and limited published data to date on mesh prosthesis metastasis are presented. This situation can be assimilated to port-site metastasis after laparoscopy.

Conclusion A mesh prosthesis metastasis after laparoscopic hernia repair is very rare.     

Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia

In β-thalassemia, the mechanism driving ineffective erythropoiesis (IE) is insufficiently understood. We analyzed mice affected by β-thalassemia and observed, unexpectedly, a relatively small increase in apoptosis of their erythroid cells compared with healthy mice. Therefore, we sought to determine whether IE could also be characterized by limited erythroid cell differentiation. In thalassemic mice, we observed that a greater than normal percentage of erythroid cells was in S-phase, exhibiting an erythroblast-like morphology. Thalassemic cells were associated with expression of cell cycle–promoting genes such as EpoR, Jak2, Cyclin-A, Cdk2, and Ki-67 and the antiapoptotic protein Bcl-X_L. The cells also differentiated less than normal erythroid ones in vitro. To investigate whether Jak2 could be responsible for the limited cell differentiation, we administered a Jak2 inhibitor, TG101209, to healthy and thalassemic mice. Exposure to TG101209 dramatically decreased the spleen size but also affected anemia. Although our data do not exclude a role for apoptosis in IE, we propose that expansion of the erythroid pool followed by limited cell differentiation exacerbates IE in thalassemia. In addition, these results suggest that use of Jak2 inhibitors has the potential to profoundly change the management of this disorder.     

Liver frailty and all-cause mortality in the older participants of the Salus in Apulia Study

The liver contribution to the biological network underlying physical frailty in aging is underestimated. How best to measure this contribution magnitude and impact on health risk trajectories in frail individuals is not yet entirely clear. We analyzed the association of a novel liver frailty phenotype with the risk of death in older participants of the Salus in Apulia Study cohort. Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1929 older adults (65?+). Physical frailty was classified by Cardiovascular Health Study criteria, and liver fibrosis risk by fibrosis-4 (FIB-4). The liver frailty phenotype was defined as physical frailty plus high-risk liver fibrosis (score?>?2.67). Physical frailty, high-risk liver fibrosis, and liver frailty subjects were compared to subjects without these conditions (non-frail). Proportional Cox regression tested the adjusted association between liver frailty and all-cause mortality for each category. The liver frailty prevalence was relatively low (3.8%), but higher in men (58.1%). Compared to non-frail older subjects, liver frailty subjects were significantly older (effect size (ES)???1.11, 95% confidence interval (CI)???1.35 to???0.87), with a lower education (ES 0.48, 95%CI 0.24 to 0.71) and higher multimorbidity (ES 15.81, 95%CI 4.20 to 27.41). Cox multivariate analyses showed a two-fold increased risk of overall mortality (hazard ratio 2.09, 95%CI 1.16–3.74) even after the adjustment for age, sex, education, and alcohol consumption. The liver frailty phenotype runs twice the risk of overall mortality compared with the non-frail population. This clinical tool, validated in a Southern Italian population, is based on simple sets of measures that can conveniently be assessed also in the primary care setting.

     

Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome

MED13L haploinsufficiency has recently been described as responsible for syndromic intellectual disability. We planned a search for causative gene variants in seven subjects with intellectual disability and overlapping dysmorphic facial features such as bulbous nasal tip, short mouth and straight eyebrows. We found two de novo frameshift variants in MED13L, consisting in single-nucleotide deletion (c.3765delC) and duplication (c.607dupT). A de novo nonsense variant (c.4420A>T) in MED13L was detected in a further subject in the course of routine whole-exome sequencing. By analyzing the clinical data of our patients along with those recently described in the literature, we confirm that there is a common, recognizable phenotype associated with MED13L haploinsufficiency, which includes intellectual disability and a distinctive facial appearance. Congenital heart diseases are found in some subjects with various degree of severity. Our observation of cleft palate, ataxia, epilepsy and childhood leukemia observed in single cases broadens the known clinical spectrum. Haploinsufficiency for MED13L should be considered in the differential diagnosis of the 1p36 microdeletion syndrome, due to overlapping dysmorphic facial features in some patients. The introduction of massive parallel-sequencing techniques into clinical practice is expected to allow for detection of other causative point variants in MED13L. Analysis of genomic data in connection with deep clinical evaluation of patients could elucidate genetic heterogeneity of the MED13L haploinsufficiency phenotype.     

Interchangeability of biosimilar and biological reference product: updated regulatory positions and pre- and post-marketing evidence

Introduction: Since 2006, biosimilars have been available in several countries worldwide, thus allowing for potential savings in pharmaceutical expenditure. However, there have been numerous debates about the interchangeability of biosimilars and reference products based on concerns of immunogenicity by switching between biological products, which may cause lack of effect and toxicity.

Areas covered: The authors provide the reader with an overview of the different positions of regulatory authorities on the interchangeability and automatic substitution of biosimilars and reference products. Presently, the FDA allows automatic substitution without prescriber intervention if the biosimilar is interchangeable with reference products, while the European Medicines Agency delegate to each single EU member state.

Expert opinion: Different approaches in defining interchangeability and automatic substitution call for harmonization to increase confidence of healthcare professionals and patients about the clinical impact of switching. Networks of electronic healthcare records and administrative databases, potentially linkable to clinical charts and registries may rapidly assess frequency and benefit-risk profile of different switching patterns in routine care at different levels, thus integrating and strengthening pre-marketing evidence.     

Non-coronary cardiac events,younger age,and IVIG unresponsiveness increase the risk for coronary aneurysms in Italian children with Kawasaki disease

Clinical Rheumatology - Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for...     

Chronic rejection after liver transplantation: Opening the Pandora’s box

Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the “early” phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.