Arthrofibrosis of the knee in pediatric orthopedic surgery.

Arthrofibrosis is a challenging complication associated with knee injuries in both children and adults. While much is known about managing arthrofibrosis in adults, it is necessary to understand its unique aspects and management strategies in the pediatric population. This paper provides an overview of arthrofibrosis in pediatric orthopedic surgery, focusing on its causes, implications, classifications, and management. This paper is a comprehensive review of the literature and existing research on arthrofibrosis in pediatric patients. Arthrofibrosis is characterized by excessive collagen production and adhesions, leading to restricted joint motion and pain. It is associated with an immune response and fibrosis within and around the joint. Arthrofibrosis can result from various knee injuries in pediatric patients, including tibial spine fractures, ACL and PCL injuries, and extra-articular procedures. Technical factors at the time of surgery play a role in the development of motion loss and should be addressed to minimize complications. Preventing arthrofibrosis through early physical therapy is recommended. Non-operative management, including dynamic splinting and serial casting, has shown some benefits. New pharmacologic approaches to lysis of adhesions have shown promise. Surgical interventions, consisting of arthroscopic lysis of adhesions (LOA) and manipulation under anesthesia (MUA), can significantly improve motion and functional outcomes. Arthrofibrosis poses unique challenges in pediatric patients, demanding a nuanced approach that includes prevention, early intervention with non-operative means, and improvements in surgical techniques. Modern pharmacological interventions offer promise for the future. Customized interventions and research focused on pediatric patients are critical for optimal outcomes.

La artrofibrosis es una complicación difícil asociada con lesiones de rodilla tanto en niños como en adultos. Si bien se sabe mucho sobre el manejo de la artrofibrosis en adultos, es necesario comprender sus aspectos únicos y estrategias de manejo en la población pediátrica. Este documento proporciona una visión general de la artrofibrosis en la cirugía ortopédica pediátrica, centrándose en sus causas, implicaciones, clasificaciones y manejo. Este documento es una revisión completa de la literatura y la investigación existente sobre artrofibrosis en pacientes pediátricos. La artrofibrosis se caracteriza por una producción excesiva de colágeno y adherencias, lo que conduce a un movimiento articular restringido y dolor. Se asocia con una inmunorrespuesta y fibrosis dentro y alrededor de la articulación. La artrofibrosis puede ser el resultado de varias lesiones de rodilla en pacientes pediátricos, incluyendo fracturas de columna tibial, lesiones de LCA y LCP, y procedimientos extraarticulares. Los factores técnicos en el momento de la cirugía desempeñan un papel en el desarrollo de la pérdida de movimiento y deben abordarse para minimizar las complicaciones. Se recomienda prevenir la artrofibrosis a través de la fisioterapia temprana. La gestión no operativa, incluyendo el empalme dinámico y la fundición en serie, ha mostrado algunos beneficios. Los nuevos enfoques farmacológicos a la lisis de adherencias han demostrado ser prometedores. Las intervenciones quirúrgicas, consistentes en lisis artroscópica de adherencias (LOA) y manipulación bajo anestesia (MUA), pueden mejorar significativamente el movimiento y los resultados funcionales. La artrofibrosis plantea desafíos únicos en los pacientes pediátricos, exigiendo un enfoque matizado que incluye prevención, intervención temprana con medios no operatorios y mejoras en las técnicas quirúrgicas. Las intervenciones farmacológicas modernas ofrecen una promesa para el futuro. Las intervenciones e investigaciones personalizadas centradas en pacientes pediátricos son fundamentales para obtener resultados óptimos.

[The Development of Quality Standards for the Psychosocial Outpatient Care of Cancer Patients - Results of a Delphi Survey]. / Die Entwicklung von Qualitätsstandards für die ambulante psychosoziale Krebsberatung ­ Ergebnisse einer Delphibefragung.

BACKGROUND: The psychosocial outpatient care of cancer patients and their families is a central element of oncological care. To date, the provision of care to this group is very heterogeneous in terms of the spectrum of services offered and quality of care. The aim of this study was to develop a multidimensional classification of quality standards for psychosocial outpatient cancer counseling. METHOD: We conducted a study using the Delphi method. 97 experts from more than 10 different fields of action or institutional contexts (e. g. mental health care professionals, cancer societies, self-help groups) were included in 3 rounds of Delphi assessment. Finally, 134 single criteria within 9 quality areas (e. g. staff, range of services, documentation) were generated and evaluated for their relevance, clarity, comprehensiveness and level of obligation. RESULT: A total of 119 individual criteria (88.8%) achieved consensus within the 3 Delphi rounds. Hereof, 94 were basic criteria (79%) and 25 optional criteria (21%). The highest number of individual criteria referred to the service spectrum (26 individual criteria), documentation (21) as well as staff and accessibility (16 each). Fifteen criteria (11.2%) achieved no consensus and were removed. CONCLUSION: For the first time, criteria for assessing the quality of psychosocial outpatient cancer counseling with expert consensus are available, facilitating the evaluation of psychosocial outpatient cancer counseling.

Molecular substrates of schizophrenia: homeostatic signaling to connectivity.

Schizophrenia (SZ) is a devastating psychiatric condition affecting numerous brain systems. Recent studies have identified genetic factors that confer an increased risk of SZ and participate in the disease etiopathogenesis. In parallel to such bottom-up approaches, other studies have extensively reported biological changes in patients by brain imaging, neurochemical and pharmacological approaches. This review highlights the molecular substrates identified through studies with SZ patients, namely those using top-down approaches, while also referring to the fruitful outcomes of recent genetic studies. We have subclassified the molecular substrates by system, focusing on elements of neurotransmission, targets in white matter-associated connectivity, immune/inflammatory and oxidative stress-related substrates, and molecules in endocrine and metabolic cascades. We further touch on cross-talk among these systems and comment on the utility of animal models in charting the developmental progression and interaction of these substrates. Based on this comprehensive information, we propose a framework for SZ research based on the hypothesis of an imbalance in homeostatic signaling from immune/inflammatory, oxidative stress, endocrine and metabolic cascades that, at least in part, underlies deficits in neural connectivity relevant to SZ. Thus, this review aims to provide information that is translationally useful and complementary to pathogenic hypotheses that have emerged from genetic studies. Based on such advances in SZ research, it is highly expected that we will discover biomarkers that may help in the early intervention, diagnosis or treatment of SZ.

Microwave cavity-enhanced transduction for plug and play nanomechanics at room temperature.

Following recent insights into energy storage and loss mechanisms in nanoelectromechanical systems (NEMS), nanomechanical resonators with increasingly high quality factors are possible. Consequently, efficient, non-dissipative transduction schemes are required to avoid the dominating influence of coupling losses. Here we present an integrated NEMS transducer based on a microwave cavity dielectrically coupled to an array of doubly clamped pre-stressed silicon nitride beam resonators. This cavity-enhanced detection scheme allows resolving of the resonators' Brownian motion at room temperature while preserving their high mechanical quality factor of 290,000 at 6.6 MHz. Furthermore, our approach constitutes an 'opto'-mechanical system in which backaction effects of the microwave field are employed to alter the effective damping of the resonators. In particular, cavity-pumped self-oscillation yields a linewidth of only 5 Hz. Thereby, an adjustement-free, all-integrated and self-driven nanoelectromechanical resonator array interfaced by just two microwave connectors is realised, which is potentially useful for applications in sensing and signal processing.

Propagation of spin information at the supramolecular scale through heteroaromatic linkers.

We report an in-depth study on how spin information propagates at supramolecular scale through a family of heteroaromatic linkers. By density-functional theory calculations, we rationalize the behavior of a series of Cr7Ni dimers for which we are able to systematically change the aromatic linker thus tuning the strength of the magnetic interaction, as experimentally shown by low temperature micro-SQUID and specific heat measurements. We also predict a cos2 dependence of the magnetic coupling on the twisting angle between the aromatic cycles in bicyclic linkers, a mechanism parallel to charge transport on similar systems [L. Venkataraman et al., Nature (London) 442, 904 (2006)].

Hepatic failure as the presenting manifestation of malignant lymphoma.

Fulminant hepatic failure carries a high mortality regardless of etiology. Liver transplantation may be lifesaving. Hepatic invasion by malignant lymphoma is a rare cause of liver failure, but one that is potentially responsive to treatment. Lymphoma (non-Hodgkin's or Hodgkin's) should be included in the differential diagnosis of fulminant hepatic failure so that liver transplantation is avoided and appropriate therapy can be instituted. The findings and clinical course of 4 patients with liver failure due to hepatic lymphoma, who were referred to our institution for liver transplant evaluation, are presented and discussed. Medical records, imaging studies, and histological material were examined. Review of the literature revealed less than 40 cases of lymphoma presenting as fulminant hepatic failure. The diagnosis of malignant lymphoma may be difficult. The presenting symptoms and signs are indistinguishable from other causes of fulminant hepatic failure. Early liver biopsy with adequate tissue and immunologic studies is mandatory for diagnosis. This condition may be reversible and may respond to chemotherapy if the diagnosis is made prior to multiorgan system failure. The presence of malignant lymphoma is considered a contraindication to liver transplantation, although firm data are lacking.

Recurrent primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis after transplantation.

1. Recurrent primary biliary cirrhosis (PBC) after transplantation is controversial, but most studies support disease recurrence within the graft. 2. Granulomatous destructive cholangitis should be present, and exclusion of acute and chronic rejection, graft-versus-host disease, biliary obstruction, viral hepatitis, and drug effects is mandatory before making a diagnosis of recurrent PBC. 3. Recurrent primary sclerosing cholangitis (PSC) after transplantation is difficult to diagnose because of the lack of a diagnostic gold standard. 4. Well-defined cholangiographic and histological criteria should be present, and exclusion of preservation injury, blood group type incompatibility between donor and recipient, chronic rejection, hepatic arterial occlusion, and viral infection is mandatory before making a diagnosis of recurrent PSC. 5. Most studies support recurrent autoimmune hepatitis (AIH) after transplantation based on clinical, biochemical, serological, and histological criteria. Exclusion of rejection, viral infection, drug effects, and biliary obstruction is mandatory before making a diagnosis of recurrent AIH. 6. Intermediate-term patient and graft survival are excellent for patients with recurrent autoimmune liver diseases within the transplanted liver, but additional studies are required to address the impact of disease recurrence on long-term patient and graft survival.

The novel IMPDH inhibitor VX-497 prolongs skin graft survival and improves graft versus host disease in mice.

VX-497 is the first inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor generated in a structure-based drug design program specifically addressing the tolerability problems of currently available immunosuppressive drugs. The pharmacological activity of the compound has been examined in murine skin transplantation and graft versus host disease (GVHD) models. In the skin transplant study, trunk skin grafts from Balb/c mice were grafted onto C57Bl/6 mice. Mice were administered vehicle or VX-497 twice daily until day 10. Mean survival of skin grafts on vehicle-treated animals was 9.9 +/- 0.9 days. Graft survival was prolonged significantly in animals treated with VX-497 to 13.2 +/- 1.2 (p < 0.001, Kaplan Meier Log-Rank test) days in the 50 mg/kg group and 13.9 +/- 1.0 (p < 0.001) days in the 85 mg/kg group. In the GVHD study, 150 x 10(6) nonadherent splenocytes from B6 mice were injected intravenously into the F1 hybrid strain B6DBA/2. Groups of animals (n = 6) were administered vehicle or 50 or 100 mg/kg VX-497 b.i.d for 8 days. Animals were sacrificed and spleen weights and interferon-gamma (IFN-gamma) serum levels were determined by enzyme-linked immunosorbent assay. In addition, spontaneous spleen cell proliferation was measured using a 3H-thymidine uptake assay. Isografted F1 animals served as controls. GVHD developed in the vehicle-treated allografted F1 mice and treatment with VX-497 improved all manifestations of the disease significantly. The 2.9-fold increase in spleen weight in allografted animals was reduced to a 1.6-fold increase in the VX-497-treated mice. Serum IFN-gamma levels were increased 54-fold in the vehicle group while there was a 7.4-fold increase in VX-497-treated animals. Spontaneous spleen cell proliferation was increased 9.9-fold in the absence of VX-497 and there was a 3.5-fold increase in its presence. Thus, VX-497 has been shown to be effective in both a skin transplantation and a GVHD model in the mouse. The demonstrated pharmacological activity of VX-497 in these murine transplantation models warrants further evaluation of the drug in transplantation indications.

Hepatic angiosarcoma: an unusual cause of congestive heart failure.

Hepatic angiosarcoma is a rare form of liver cancer. The history, physical examination, and liver biopsy are nonspecific. As a result, diagnosis of angiosarcoma can be challenging. We report the case of an elderly woman with congestive heart failure caused by a hepatic angiosarcoma. The massive tumor burden created extensive arteriovenous shunting and a high-cardiac-output state.

Recurrent primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis after transplantation.

Viral hepatitis and malignancy frequently recur after transplantation, but recurrence of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis is controversial. Differences in study design, number of patients, immunosuppressive treatment, length of follow-up, and criteria for recurrence account for discrepant results. Most patients with suspected recurrent disease are asymptomatic after transplantation. In patients transplanted for PBC, antimitochondrial antibodies frequently persist and do not correlate with disease recurrence; liver biopsy remains the gold standard for diagnosis. Exclusion of other disorders that can mimic PBC is paramount prior to making a diagnosis of recurrent disease. The effects of immunosuppression may modify or delay disease expression within the graft. If PBC recurs, intermediate-term patient and graft survival is excellent, but long-term studies will be necessary to address the impact of disease recurrence on the allograft. Due to lack of a diagnostic gold standard, a diagnosis of recurrent PSC after transplantation is difficult to make. An accurate diagnosis of PSC recurrence requires well-defined cholangiographic and histologic criteria. Other disorders that can produce biliary strictures after transplantation should be excluded. As with PBC, the effects of immunosuppression may modify or delay disease expression within the graft; medium-term patient and graft survival is excellent. Recurrence of autoimmune hepatitis is based on clinical, biochemical, serologic, and histologic criteria. As in patients transplanted for PBC and PSC, other conditions that can mimic autoimmune hepatitis require exclusion prior to making a diagnosis of recurrence. Most adult recipients respond to an increase in immunosuppression, whereas pediatric recipients do not respond as well. A cautious approach to withdrawal of immunosuppression is warranted in all patients transplanted for autoimmune hepatitis and the consequences of recurrent disease within the graft will require prolonged follow-up. Future studies should focus on preventive and therapeutic strategies for recurrent autoimmune diseases after transplantation.

Modern immunosuppression.

The current treatment of posttransplant lymphoproliferative disease (PTLD) includes prophylaxis at the time of transplant, decreasing or stopping immunosuppresion and initiation of antiviral therapy in patients with polymerase chain reaction or clinical evidence of PTLD, and judicial reintroduction of immunosuppression in patients who have cleared their PTLD and have begun to have rejection. The pharmacology, pharmacokinetics, notable side effects, and toxicities of the immunosuppressive agents are described in this article. At the conclusion of each section the author's current practice with these agents and treatment strategies are described.

The role of the transjugular intrahepatic portal-systemic shunt in the management of variceal bleeding.

For patients who present with variceal bleeding refractory to endoscopic and pharmacologic methods, TIPS is a new and effective therapy. Stents are used in selected patients with decompensated liver disease and those who anticipate liver transplantation within 6 to 12 months. Surveillance of TIPS with ultrasound, with or without venography, is recommended to diagnose and treat stenosis or occlusion before variceal hemorrhage recurs. Hepatic encephalopathy may develop in a subset of patients, but it is usually well controlled with conservative measures. Child-Pugh and APACHE scores are predictive of patient survival after TIPS. Randomized controlled trials will be necessary to assess whether TIPS is useful, safe, and cost effective for the management of variceal bleeding in patients with end stage liver disease.

Interleukin-1 beta converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice.

To IL-1 beta is a principal mediator in the pathogenesis of inflammatory disease. The IL-1 beta-converting enzyme (ICE), a novel cysteine protease, is required for processing of the 31 kDa IL-1 beta precursor to generate the 17 kDa proinflammatory mature form. We investigated the effect of two irreversible peptidyl ICE inhibitors, VE-13,045 and VE-16,084, on IL-1 production in vitro and in vivo in acute and chronic inflammatory disease models. In vitro, VE-13,045 and VE-16084 inhibited IL-1 beta secretion by LPS-stimulated human adherent mononuclear cells (IC50's of 0.4 microM and 2.0 microM, respectively) and murine splenic monocytes (IC50's of 10 microM and 1.3 microM, respectively). Both VE-13,045 and VE-16,084 also inhibited LPS stimulated IL-1 alpha secretion, although with reduced potency. In vivo, a single intraperitoneal dose of VE-13,045 (50 mg/kg) administered to mice 60 to 75 minutes after a 40 mg/kg LPS challenge significantly reduced IL-1 beta serum levels by 50 to 70%. In the DBA/1J mouse model of Type II collagen-induced arthritis, prophylactic treatment with VE-13,045 (50 and 100 mg/kg/day) significantly delayed the onset of inflammation, with a 60% overall reduction in disease severity. VE-13,045 was more effective than either indomethacin (2 mg/kg/day) or methyl prednisolone (10 mg/kg/day). VE-13,045 was also effective in reducing inflammation and progression of arthritis when administered to mice with established disease. Histological analysis of wrist joints showed a reduction in synovial membrane damage, inflammatory cell infiltration and fibrosis, and cartilage erosion in VE-13,045-treated animals. This is the first demonstration of efficacy for an ICE inhibitor in a chronic disease model and suggests that ICE is an important target for design of anti-inflammatory or disease modifying drugs.

Gastric and duodenal mucosal prostaglandin concentrations in gastric or duodenal ulcer disease: relationships with demographics, environmental, and histological factors, including Helicobacter pylori.

We measured gastric and duodenal mucosal prostaglandin concentrations in 69 patients with active or inactive duodenal or gastric ulcer disease and 26 non-ulcer controls. Each underwent endoscopy enabling us to obtain multiple biopsies from the gastric body and antrum and from the duodenal bulb and postbulbar duodenum for measurement of mucosal prostaglandin concentrations, as well as a single biopsy from each region for mucosal histology. Using a multivariate linear regression model, we found that neither gastric nor duodenal ulcer disease significantly affected gastric or duodenal mucosal prostaglandin concentrations. Mucosal prostaglandin concentrations were similar at the edge of the ulcer and in the adjacent non-ulcerated mucosa. Neither gender symptoms, smoking, use of H2-receptor antagonists, disease activity, nor Helicobacter pylori infection had an independent effect on mucosal prostaglandins in any region. Gastritis in the body of the stomach was associated with significantly higher prostaglandins, while older age was associated with significantly lower gastric and duodenal prostaglandins. Gastroduodenal mucosal prostaglandins are thus not altered in patients with active or inactive peptic ulcer disease, even when multiple demographic and histologic variables are taken into consideration.

Effects of aspirin on gastric mucosal prostaglandin E2 and F2 alpha content and on gastric mucosal injury in humans receiving fish oil or olive oil.

Gastric mucosal prostaglandin E2 and F2 alpha content was evaluated in healthy human subjects who received either fish oil or olive oil (control) daily for 3 wk before exposure to aspirin or no aspirin. Two hours after aspirin administration, when mean serum salicylate concentration was approximately 12 mg/dl, gastric mucosal prostaglandin E2 and F2 alpha content was reduced by greater than 95% in the fundus and antrum (p less than 0.001) and there was endoscopic evidence of gastric mucosal damage (erosions, submucosal hemorrhages). Fish oil feeding had no significant effect on mucosal prostaglandin E2 or F2 alpha content or on the damaging effect of aspirin on the stomach, despite the fact that fish oil reduced serum triglyceride concentrations significantly. These studies indicate that the damaging effects of aspirin on the gastric mucosa are not influenced by dietary fish oil.

Effects of fish oil on gastric mucosal 6-keto-PGF1 alpha synthesis and ethanol-induced injury.

Fundic mucosal content and synthesis of 6-ketoprostaglandin F1 alpha, the major prostanoid in the rat gastric mucosa, were determined after rats had ingested a diet containing 10% fish oil or 10% corn oil for 4 wk. 6-Ketoprostaglandin F1 alpha content and synthesis in rats fed a fish oil-supplemented diet were reduced significantly compared with rats receiving a corn oil-supplemented diet (P less than 0.05). However, rats receiving 10% fish oil for 8 wk sustained significantly less gastric mucosal injury after intragastric challenge with 15% and then with absolute ethanol than rats receiving 10% corn oil or regular chow for 8 wk (P less than 0.05). Thus fish oil ingestion protected the gastric mucosa even though fish oils reduced mucosal prostaglandin synthesis.