Francisella tularensis Transmission by Solid Organ Transplantation, 20171.

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor's residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation.

Radial head resection and hemi-interposition arthroplasty in patients with multiple hereditary exostoses: description of a new surgical technique.

Multiple hereditary exostoses (MHE) are a rare disorder characterized by the growth of bony protrusions. Elbow involvement is found in a considerable number of patients and varies from the presence of a simple osteochondroma to severe forearm deformities and radial head dislocation. Patients encounter a variety of symptoms, for example, pain, functional impairment, and cosmetic concerns. Several types of surgical procedures, therefore, can be offered, ranging from excision of symptomatic osteochondromas to challenging reconstructions. In this paper, we will discuss the essential basics of visualizing, planning, and treatment options of forearm deformities in MHE. In more detail, we will describe our current surgical technique as a salvage procedure for Masada type II forearm deformities in patients with MHE.

Multiple osteochondromas (MO) in the forearm: a 12-year single-centre experience.

Multiple osteochondromas (MO) are a rare autosomal dominant disorder characterized by the presence of osteochondromas located on the long bones and axial skeleton. Patients present with growth disturbances and angular deformities of the long bones as well as limited motion of affected joints. Forearm involvement is found in a considerable number of patients and may vary from the presence of a simple osteochondroma to severe forearm deformities and radial head dislocation. Patients encounter a variety of problems and symptoms e.g., pain, functional impairment, loss of strength and cosmetic concerns. Several surgical procedures are offered from excision of symptomatic osteochondromas to challenging reconstructions of forearm deformities. We describe visualizing, planning and treating these forearm deformities in MO and, in particular, a detailed account of the surgical correction of Masada type I and Masada type II MO forearm deformities.

Intraosseous atypical chondroid tumor or chondrosarcoma grade 1 in patients with multiple osteochondromas.

BACKGROUND: The autosomal dominant condition multiple osteochondromas, formerly called multiple hereditary exostoses, is associated with a risk of malignant progression of osteochondroma into secondary peripheral chondrosarcoma. Most patients with multiple osteochondromas have exostosin-1 or exostosin-2 gene mutations. To our knowledge, it has not been previously reported that patients may also harbor intraosseous (central) chondroid neoplasms, enchondromas, or atypical chondroid tumors or central chondrosarcomas. The combination of osteochondroma and enchondromas also exists in patients with metachondromatosis, a disorder associated with a protein tyrosine phosphatase non-receptor type 11 gene mutation. This study aims to establish any correlation between multiple osteochondromas and intraosseous cartilaginous neoplasms. METHODS: We retrospectively reviewed all histologically proven intraosseous atypical chondroid tumors or chondrosarcomas in our prospective nationwide Dutch tertiary referral multiple osteochondromas database. Demographic, clinical, radiographic, histological, and genetic data were recorded. The institutional medical ethics review board approved the study. RESULTS: From 195 adult patients, seven (3.6%) were identified with intraosseous atypical chondroid tumor or chondrosarcoma World Health Organization grade 1 and had a mean age of forty-two years; five of these patients were male. In all cases, radiographic and genetic findings were consistent with multiple osteochondromas, not metachondromatosis; three patients had an exostosin-1 mutation, four patients had an exostosin-2 mutation, and no patients had a protein tyrosine phosphatase, non-receptor type 11 mutation. Six patients underwent successful operative treatment without complications or recurrences after a mean follow-up duration of forty-eight months (range, twelve to 144 months). One patient was scheduled for surgery after biopsy and histologic confirmation. Of the seven patients, five (71%) also developed a peripheral chondrosarcoma in a known osteochondroma during the study period. CONCLUSIONS: Apart from osteochondromas or peripheral chondrosarcomas, multiple osteochondromas are also associated with intraosseous chondroid neoplasms, potentially resulting in central chondrosarcoma. Therefore, intraosseous lesions should not automatically be regarded as innocuous in this patient population.

Complex forearm deformities: operative strategy in posttraumatic pathology.

Complex posttraumatic forearm deformities have a significant impact on the integrity of the upper extremity leading to pain, instability in both the proximal and/or distal radioulnar articulation, and reduced range of forearm motion. Corrective osteotomy or more advanced procedures for malunited fractures or other posttraumatic deformities of the upper extremity, especially in the forearm are challenging procedures. In this review we will discuss the essential aspects of anatomy and pathomechanics, clinical and radiological assessment and the pathway from preoperative planning to the actual deformity correction surgery, either with one-stage correction or using gradual lengthening with external fixation ("callotasis techniques") and finally the functional outcome we can expect for our patients. In addition we will analyze the modern computer-assisted techniques available to date.

A randomized, multicenter study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C.

This randomized, prospective, multicenter trial compared the safety and efficacy of steroid-free immunosuppression (IS) to the safety and efficacy of 2 standard IS regimens in patients undergoing transplantation for hepatitis C virus (HCV) infection. The outcome measures were acute cellular rejection (ACR), severe HCV recurrence, and survival. The patients were randomized (1:1:2) to tacrolimus (TAC) and corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, and corticosteroids (arm 2; n = 72), or MMF, TAC, and daclizumab induction with no corticosteroids (arm 3; n = 146). In all, 295 HCV RNA-positive subjects were enrolled. At 2 years, there were no differences in ACR, HCV recurrence (biochemical evidence), patient survival, or graft survival rates. The side effects of IS did not differ, although there was a trend toward less diabetes in the steroid-free group. Liver biopsy samples revealed no significant differences in the proportions of patients in arms 1, 2, and 3 with advanced HCV recurrence (ie, an inflammation grade ≥ 3 and/or a fibrosis stage ≥ 2) in years 1 (48.2%, 50.4%, and 43.0%, respectively) and 2 (69.5%, 75.9%, and 68.1%, respectively). Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV, steroid sparing has no clear advantage in comparison with traditional IS.

Evolution of surgical treatment for sarcomas of proximal humerus in children: retrospective review at a single institute over 30 years.

BACKGROUND: Proximal humerus, although a common site for primary bone sarcomas, finds scant mention in literature as far as options and outcome of reconstruction in the skeletally immature skeleton are concerned. Reconstruction after resection of proximal humeral sarcomas in the immature skeleton poses specific challenges to the surgeon, and there has been a definite evolution of these techniques over the decades. We studied the evolution and compared the outcome of various techniques for such reconstruction over 3 decades at a single institution. METHODS: All 61 children younger than 13 years of age and treated for a primary sarcoma of the proximal humerus at Department of Musculoskeletal Oncology, Rizzoli Orthopedic Institute, from 1976 to 2006 were studied for techniques of resection and reconstruction, complications, surgical procedures needed during follow up, and functional and radiologic outcomes during and at final follow-up. The functional outcomes after various procedures were compared using the Musculoskeletal Tumor Society scoring system. RESULTS: A definite trend from amputation in the first decade, to the use of nonbiological reconstruction (endoprostheses, K nail cement spacer) in the second and biological reconstruction (vascular proximal fibula autograft, osteoarticular allograft, and allograft prosthesis composite) in the third decade was seen. There was a trend of improvement in the functional outcome over the 3 decades, although the complication rates and the need for repeated surgical procedures remained a major problem in all the techniques. CONCLUSIONS: Reconstruction of proximal humerus after resection for sarcomas is a challenging task. Although endoprostheses do have a definite role to play in reconstruction of proximal humerus in children, the use of biological techniques in well-selected patients is being carried out more often now than before, as is reflected in this series, with a potentially improved functional outcome. LEVEL OF EVIDENCE: Level III-Retrospective comparative study.

No haploinsufficiency but loss of heterozygosity for EXT in multiple osteochondromas.

Multiple osteochondromas (MO) is an autosomal dominant disorder caused by germline mutations in EXT1 and/or EXT2. In contrast, solitary osteochondroma (SO) is nonhereditary. Products of the EXT gene are involved in heparan sulfate (HS) biosynthesis. In this study, we investigated whether osteochondromas arise via either loss of heterozygosity (2 hits) or haploinsufficiency. An in vitro three-dimensional chondrogenic pellet model was used to compare heterozygous bone marrow-derived mesenchymal stem cells (MSCs EXT(wt/-)) of MO patients with normal MSCs and the corresponding tumor specimens (presumed EXT(-/-)). We demonstrated a second hit in EXT in five of eight osteochondromas. HS chain length and structure, in vitro chondrogenesis, and EXT expression levels were identical in both EXT(wt/-) and normal MSCs. Immunohistochemistry for HS, HS proteoglycans, and HS-dependent signaling pathways (eg, TGF-ß/BMP, Wnt, and PTHLH) also showed no differences. The cartilaginous cap of osteochondroma contained a mixture of HS-positive and HS-negative cells. Because a heterozygous EXT mutation does not affect chondrogenesis, EXT, HS, or downstream signaling pathways in MSCs, our results refute the haploinsufficiency theory. We found a second hit in 63% of analyzed osteochondromas, supporting the hypothesis that osteochondromas arise via loss of heterozygosity. The detection of the second hit may depend on the ratio of HS-positive (normal) versus HS-negative (mutated) cells in the cartilaginous cap of the osteochondroma.

Surgical compared with conservative treatment for acute nondisplaced or minimally displaced scaphoid fractures: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is a current trend in orthopaedic practice to treat nondisplaced or minimally displaced fractures with early open reduction and internal fixation instead of cast immobilization. This trend is not evidence-based. In this systematic review and meta-analysis, we pool data from trials comparing surgical and conservative treatment for acute nondisplaced and minimally displaced scaphoid fractures, thus aiming to summarize the best available evidence. METHODS: A systematic literature search of the medical literature from 1966 to 2009 was performed. We selected eight randomized controlled trials comparing surgical with conservative treatment for acute nondisplaced or minimally displaced scaphoid fractures in adults. Data from included studies were pooled with use of fixed-effects and random-effects models with standard mean differences and risk ratios for continuous and dichotomous variables, respectively. Heterogeneity across studies was assessed with calculation of the I(2) statistic. RESULTS: Four hundred and nineteen patients from eight trials were included. Two hundred and seven patients were treated surgically, and 212 were treated conservatively. Most trials lacked scientific rigor. Our primary outcome parameter, standardized functional outcome, which was assessed for 247 patients enrolled in four trials, significantly favored surgical treatment (p < 0.01). With regard to our secondary parameters, we found heterogeneous results that favored surgical treatment in terms of satisfaction (assessed in one study), grip strength (six studies), time to union (three studies), and time off work (five studies). In contrast, we found no significant differences between surgical and conservative treatment with regard to pain (two studies), range of motion (six studies), the rates of nonunion (six studies) and malunion (seven studies), and total treatment costs (two studies). The rate of complications was higher in the surgical treatment group (23.7%) than in the conservative group (9.1%), although this difference was not significant (p = 0.13). There was a nearly significantly higher rate of scaphotrapezial osteoarthritis in the surgical treatment group (p = 0.05). CONCLUSIONS: Based on primary studies with limited methodological quality, this study suggests that surgical treatment is favorable for acute nondisplaced and minimally displaced scaphoid fractures with regard to functional outcome and time off work; however, surgical treatment engenders more complications. Thus, the long-term risks and short-term benefits of surgery should be carefully weighed in clinical decision-making.

Hepatic and cardiac iron overload among patients with end-stage liver disease referred for liver transplantation.

BACKGROUND: Iron overload is associated with fatal cardiovascular events following liver transplantation. Myocardial iron deposits were observed post-mortem in patients who died of cardiac events after transplantation at our institution. This observation prompted testing to exclude cardiac iron in subsequent transplant candidates. AIMS: To assess the results of testing for iron overload in liver transplant candidates at our institution. METHODS: Ferritin, TIBC, and serum iron were measured in cirrhotics referred for transplantation. Patients with transferrin saturation ≥50% and ferritin ≥250 ng/mL underwent liver biopsy graded for iron. Patients with 3-4+ hepatic iron deposits underwent HFE mutation analysis and endomyocardial biopsy with iron staining. RESULTS: Eight hundred and fifty-six patients were evaluated for liver transplantation between January 1997 and March 2005. Two hundred and eighty-seven patients (34%) had transferrin saturation ≥50% and ferritin ≥250 ng/mL. Patients with markers of iron overload had more advanced liver disease than those with normal iron indices. One hundred and fifty-three patients underwent liver biopsy. Twenty-six patients (17%) had 3-4+ hepatic iron staining. One patient was a C282Y heterozygote. Endomyocardial biopsy was performed in 14 patients of whom nine had cardiac iron deposition. CONCLUSIONS: Non-HFE-related cardiac iron overload can occur in advanced liver disease We therefore recommend screening for cardiac iron prior to liver transplantation.

Public Policy and the Dynamics of Children's Health Insurance, 1986­1999.

The past 20 years have seen important changes in public policy with the potential for significant impacts on health insurance for children. These changes included both those explicitly intended to expand access to public insurance for children, including expansions in eligibility for Medicaid and the introduction of the State Children's Health Insurance Program (SCHIP), and other changes in antipoverty policy. Since health insurance coverage among children is entwined with parental welfare participation and employment, shifts in policy designed to encourage work in place of welfare participation--such as welfare reform and the expansion of the Earned Income Tax Credit (EITC)--may have secondary impacts on children's health insurance coverage. As parents leave welfare, with its guaranteed health insurance through Medicaid, for jobs that may or may not have health insurance coverage offered as a benefit, children may experience a change in the source of their health insurance coverage or may become uninsured. Similarly, changes in health care markets and economic conditions such as rising health care prices and cyclicality in the availability of employment may also affect children's coverage. Despite the potential importance of these factors for coverage, the fraction of children who are uninsured has remained largely constant, particularly through the 1990s. However, this relatively constant level of uninsurance may mask changes in the underlying dynamics of health insurance among children. In this paper, we use monthly data from the 1986­1996 panels of the Survey of Income and Program Participation (SIPP) to examine patterns of health insurance coverage among children during the period 1986­1999, focusing on transitions between public coverage, private coverage, and no coverage. Using these data, we find that over the 1990s the rate of transitions among all three insurance states--public insurance, private insurance, and no insurance--increased, with a particular increase in transitions involving public coverage. We investigate whether there is evidence of a relationship between insurance transitions and various policy and economic variables, focusing on the impacts of expansions in public coverage availability, the effects of other policies directed at the poor that affect employment and insurance coverage, and economic conditions. We find that several of the policy changes that took place over the 1990s had important effects on health insurance transitions for children.

Hepatitis C infection increases the risk of new-onset diabetes after transplantation in liver allograft recipients.

BACKGROUND: Recent evidence suggests that new-onset diabetes after transplant (NODAT) adversely affects orthotopic liver transplant (OLTX) patient and graft survival. The objective of this study is to evaluate the effect of hepatitis C infection on the natural history of NODAT. METHODS: A retrospective review of 492 OLTX recipients at a single center was conducted from January 1993 to January 2003. Patients were followed for a minimum of 12 months (range 12 months-10 years). The study population consisted of 444 OLTX recipients who were either HCV positive (n = 206) or HCV negative (n = 238). NODAT was defined by the need for antidiabetic medication for at least 7 days starting anytime after OLTX. Statistical analysis was performed by using the Student t test, Kaplan-Meier survival, and chi-square tests. RESULTS: The overall incidence of NODAT was 33% (146/444). There was a significant difference in the development of NODAT between the HCV-positive group (82/206, 40%) and the HCV-negative group (64/238, 27%) (P < .001). Other independent risk factors for development of NODAT were male gender and age >50 years. CONCLUSION: Hepatitis C infection contributes to the development of diabetes mellitus in OLTX recipients. The mechanisms behind HCV infection and associated NODAT in HCV-positive OLTX recipients warrant further investigation.

Adult living donor versus deceased donor liver transplantation: a 6-year single center experience.

No long-term (>3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported. This is a prospective, IRB approved, 6-year comparison of A2ALLTx to ADDLTx. Data include: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 6 years, 202 ADDLTx (74.5%) and 69 A2ALLTx (25.5%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (48.1% vs. 42%). Data regarding overall patient and graft survival, monetary charges and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (11.5% vs. 23.9%) and more biliary complications (26.1% vs. 11.4%). Overall, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.

Comparative analysis of outcome following liver transplantation in US veterans.

The purpose of this study was to evaluate whether there was a difference in mortality following orthotopic liver transplantation (OLT) in a US veteran (VA) population (n = 149) compared to a non-VA (university) population (n = 285) and what factors could explain this difference. Survival following OLT for 149 VA patients was compared with that of 285 university patients. By Kaplan-Meier survival analysis, VA patients had higher mortality than university patients with respective 1-year, 3-year, and 5-year survival of 82%, 75%, and 68% vs. 87%, 82%, and 78% (p = 0.006). Gender, etiology of end-stage liver disease (ESLD) and donor age (i.e. older than 34 years) also significantly influenced survival. However, when donor and recipient age, gender, model for end-stage liver disease (MELD) score, and etiology of liver disease were included with hospital status in a multivariate Cox proportional hazards model, the VA population did not have higher mortality. A final model to predict mortality following transplantation was derived for all 434 patients where individuals were assigned risk scores based on the equation R = 0.219 (gender) + 0.018 (donor age) + 0.032 (recipient age) + 0.021 (MELD), where recipient age, donor age, and MELD score are the respective continuous variables and gender = 1 (men) and 0 for women (c-statistic = 0.71).

Laparoscopic adjustable gastric banding in the treatment of obesity: a systematic literature review.

BACKGROUND: We attempted to compare the safety and efficacy of laparoscopic adjustable gastric banding with vertical-banded gastroplasty and gastric bypass. Morbid obesity presents a serious health issue for Western countries, with a rising incidence and a strong association with increased mortality and serious comorbidities, such as diabetes, hyperlipidemia, and cardiovascular disease. Unfortunately, conservative treatment options have proven ineffective. Surgical interventions, such as vertical-banded gastroplasty (stomach stapling), Roux-en-Y gastric bypass, and, more recently, laparoscopic gastric banding have been developed with the aim of providing a laparoscopically placed device that is safe and effective in generating substantial weight loss. METHODS: Electronic databases were systematically searched for references relating to obesity surgery by (1) laparoscopic adjustable gastric banding (LAGB), (2) vertical banded gastroplasty (VBG), and (3) Roux-en-Y gastric bypass (RYGB). RESULTS: Only 6 studies reported comparative results for laparoscopic gastric banding and other surgical procedures. One study reported comparative results for all 3 surgical procedures, and this study was only of moderate quality. In total, 64 studies were found that reported results for LAGB and 57 studies reported results on the comparative procedures. LAGB was associated with a mean short-term mortality rate of approximately 0.05% and an overall median morbidity rate of approximately 11.3%, compared with 0.50% and 23.6% for RYGB, and 0.31% and 25.7% for VBG. Overall, all 3 procedures produced considerable weight loss in patients up to 4 years in the case of LAGB (the maximum follow-up available at the time of the review), and more than 10 years in the case of the comparator procedures. CONCLUSIONS: The Australian Safety and Efficacy Register of New Interventional Procedures-Surgical Review Group concluded that the evidence base was of average quality up to 4 years for LAGB. Laparoscopic gastric banding is safer than VBG and RYGB, in terms of short-term mortality rates. LAGB is effective, at least up to 4 years, as are the comparator procedures. Up to 2 years, LAGB results in less weight loss than RYGB; from 2 to 4 years there is no significant difference between LAGB and RYGB, but the quality of data is only moderate. The long-term efficacy of LAGB remains unproven, and evaluation by randomized controlled trials is recommended to define its merits relative to the comparator procedures.

Treatment of Hepatocellular Carcinoma.

The incidence of hepatocellular carcinoma (HCC) is increasing in the United States. Several modalities are available for the treatment of HCC, and decisions regarding the optimal choice of therapy are based on tumor burden and severity of liver disease. Classification systems are helpful for prognostic purposes and to guide in the choice of therapy. Surgical resection is a mainstay of therapy for patients with solitary small tumors and preserved liver function (noncirrhotic or Child-Pugh class A cirrhotic patients without portal hypertension). Unfortunately, a minority of patients is eligible for resection, and postoperative recurrence or de novo HCC is common. Liver transplantation offers the best chance of curing HCC in cirrhotic patients. Patients with a solitary tumor less than 5 cm or no more than three tumors each 3 cm or less have a survival rate of 70% with less than 20% recurrence at 5 years. Access to liver transplantation is limited by organ availability, and tumor progression during the waiting period can lead to ineligibility. Ethanol injection and radiofrequency ablation are effective modalities to ablate small tumors (generally <5 cm) in patients who are not candidates for resection or liver transplantation. These modalities can also be used to treat HCC prior to liver transplantation. Transarterial chemoembolization is used to treat patients with multifocal or large HCC who are ineligible for other therapies. Chemotherapeutic agents are infused into the tumor via the hepatic artery along with embolic material in order to induce tumor necrosis. This technique should be used in selective patients with relatively preserved liver function, absence of portal vein thrombosis, or encephalopathy. Limited data exist to support the use of this modality as a primary treatment option for small HCC. Chemotherapeutic or hormonal therapies have a limited role in the management of patients with HCC. Despite mixed outcomes, we routinely use the somatostatin analog octreotide in advanced, multifocal HCC. Emerging therapies should focus on treatment of small tumors and targeted pharmacologic therapy for advanced disease.