Admission Circulating Cell-Free DNA Levels as a Prognostic Factor in Pediatric Burns.

Background: Burn injuries in children are a major physical and psychological trauma, often a severe condition with long-term consequences. Current methods of assessing the extent of burn injuries on admission are inaccurate. Circulating cell-free DNA (cfDNA) is a potential marker of tissue damage that may be useful in burn care. Objective: To explore the use of cfDNA admission levels as a prognostic marker of pediatric burn severity and outcome. Methods: cfDNA levels of 38 pediatric burn patients (otherwise healthy) and 12 matched pediatric controls (minor elective surgery patients) admitted to our center were quantified by a direct fluorometric assay. Results: We found significantly higher admission cfDNA levels in the patient group (median 724 ng/ml, range 44-4405), compared to the control group (median 423 ng/ml, range 206-970, Mann-Whitney, P = 0.03) and a significant difference between cfDNA levels of partial-thickness burns (median 590 ng/ml, range 44-2909) and full-thickness burns (median 2394 ng/ml, range 528-4405, Mann-Whitney, P = 0.01). We also found significant correlations between cfDNA levels and hospitalization duration (Spearman, R = 0.42, P < 0.01) and undergoing surgical procedures (Spearman, R = 0.40, P < 0.01). PICU admission did not correlate to cfDNA levels (Spearman, R = 0.14, P = NS). Discussion. Admission cfDNA levels may be a valuable objective tool for assessing the severity of pediatric burn injuries on admission, including correlations with the length of hospitalization and surgical burden. Conclusion: Admission cfDNA levels may be a promising novel pediatric burn assessment method. Further investigation of cfDNA levels in healthy children standardized to age and larger cohorts are needed to establish cfDNA as a valuable prognostic factor for pediatric burn injury.

Desmoid Tumor and Silicone Breast Implant Surgery: Is There Really a Connection? A Literature Review.

BACKGROUND: Desmoid tumors are borderline tumors of the connective tissue, arising in the musculo-aponeurotic stromal elements. A desmoid tumor (DT) has an infiltrative and locally aggressive growth pattern and usually does not metastasize; however, it has a high recurrence and complication rate. DT located in the breast (BDT) represents a rare extra-abdominal form. Recently, the presence of breast silicone implants was suggested by several researchers as a risk factor for developing BDT. OBJECTIVES: The goal of this review is to investigate the possible correlation between BDT and breast implant surgery. METHODS: We conducted a literature review of BDT-reported cases, associated with breast implant surgery. RESULTS: The search revealed 36 cases of BDT associated with silicone breast implants. CONCLUSIONS: Based on the reviewed data, the incidence of BDT following breast implant surgery is lower than BDT in the general population. At the moment, a possible association between breast implants and the development of breast desmoid tumors cannot be unequivocally confirmed. A world registry with accurate documentation of each case of BDT associated with breast implant surgery should be performed for future investigation. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Facial reconstruction after pre maxillary resection in a bilateral cleft lip and palate patient - a case report Technologies for resection and reconstruction of mandibular lesions.

Loss of the premaxilla is a rare event while treating patients with bilateral cleft lip and palate. Its resection is no longer an acceptable method of treatment in modern practice. Nowadays, most cases of premaxillary loss are secondary to treatment and manipulation of the premaxilla, and not due to intentional resection. In the following case presentation we present the treatment of a seven years old boy, presented to our institution after being treated for bilateral cleft lip and palate by resection of the premaxilla. Through a series of operations including bone grafting, distraction of the maxilla, and cartilaginous graft we managed to reconstruct a proper facial habitus, a convex facial profile and nasal projection. Restoring the bony structure of the face is a significant challenge. Due to the complex three dimensional anatomy, the presence of critical structures and the variety and uniqueness of each deficiency it is essential to form the optimal surgical plan and to execute it precisely. Development of computer aided manufacturing (CAD/ CAM - computer assisted design / computer assisted manufacturing) and advances in manufacturing technologies and material science brought a whole array of options and tools for the purpose of planning and performing computer assisted surgery. CAD/CAM technology allow for various application: Manufacturing of a physical anatomical model, Using the 3D model for hardware pre-bending, Manufacturing of cutting jigs and intraoperative fixation templates, Manufacturing of custom made implants. The surgeon may choose which of the application to use in any specific case or combine all of these abilities according to the complexity of the case. Two cases presenting the applications of these technologies will be reviewed.

Wound 'dechronification' with negatively-charged polystyrene microspheres: a double-blind RCT.

OBJECTIVE: To compare the efficacy and safety of negatively-charged polystyrene microspheres (NCM)with controls (saline soaks) in the treatment of hard-to-heal wounds of various aetiologies. METHOD: Patients with one or more hard-to-heal wounds, defined as refractory to healing for at least 4 weeks, or those with exposed bone, tendon or ligament, were eligible for inclusion and were randomised to either NCM (PolyHeal; MediWound Ltd.) or controls, both applied twice daily for 4 weeks. Patients were monitored bi-weekly for an additional 8 weeks, while treated by standard wound care, at the investigators' discretion, and were re-evaluated 2 years after inclusion. The primary endpoint was defined as coverage of> 75% of the wound area by light-red granulation tissue after 4 weeks of treatment. RESULTS: Fifty-eight patients completed the study, 32 in the NCM group and 26 in the control group. The two most common wound types were those with primary etiologies of venous insufficiency and postoperative/post trauma. In the NCM group 47% of patients achieved > 75% light red granulation tissue after 4 weeks compared with 15% of patients in the control group (p=O.O I). The mean wound surface area in the NCM group was reduced by 39.0% after 4 weeks compared with 14.9% in the control group (p=0.02).The achievement of> 75% light red granulation tissue and reduction of mean wound surface area was also observed in the two main sub-groups (venous insufficiency and postoperative/post trauma), although it was not statistically significant, possibly due to the small sample size in each sub-group. CONCLUSION: This study demonstrates that compared to control treatment, NCM treatment of hard to-heal and chronic wounds improves formation of healthy granulation tissue and reduces wound size thus in fact 'kick-starting' the healing process and 'dechronifying' chronic wounds.

Capsular flap: new applications.

UNLABELLED: Breast augmentation with silicone implants is one of the most commonly performed procedures for women seeking improvement in their body image. Because the number of breast augmentation operations is growing, the number of subsequent reoperations is increasing. Causes for repeated operative procedures include infection, capsular contracture, silicone implant replacement, and breast reaugmentation. As the average volume of silicone implants used is steadily growing according to patients' wishes and fashion requirements, the plastic surgeon often is asked to replace the silicone implants with larger implants. Replacing breast implants with a similar sized implant is a relatively simple operation, but insertion of larger implants may present a challenge due to insufficient soft tissue coverage of the lower pole of the larger breast implant, especially in thin subjects. Total coverage of the breast implant can be achieved by use of tissue substitutes (TS), such as acellular dermal matrices. Usage of TS, however, is prone to complications and very costly, and these factors influence the implementation of TS in a private practice setup. This report describes a capsular flap used to cover the lower pole of breast implants. The flap guarantees multilayered stable wound closure and prevents displacement of the inframammary fold. The capsular flap also was used to correct an inferiorly displaced inframammary fold as a consequence of the breast augmentation. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Utilization of Inferiorly Based Dermofat Flap in Breast Reconstruction after Simple Mastectomy due to Gigantomastia.

Gigantomastia (GM) is a rare disabling condition characterized by excessive breast tissue growth. To date, there is no universal classification and definition of GM. At present, GM is determined as weight over 1.5 kg per breast (Dancey et al., 2008) or 3% or more of the patient's total body weight (Dafydd et al., 2011). The lack of generally acknowledged approach regarding GM is expressed by the different methods of its treatment ranging from hormonal prescription to mastectomy and subsequent complex breast reconstruction (Shoma et al., 2011). We describe a treatment approach, including simple mastectomy and immediate breast reconstruction by an inferiorly based dermofat flap with silicone implants and nipple grafting.

Distribution of hepatitis C virus in circulating blood components from blood donors.

BACKGROUND AND OBJECTIVES: Current nucleic acid tests (NAT) for blood donor screening use plasma as the test sample and, consequently, cannot detect virions bound to blood cells of infected donors. Hepatitis C virus (HCV) RNA and infectious virions have been detected in association with the cellular components of blood of patients with active liver disease; however, studies comparing HCV viral loads in whole blood and plasma have generated contradictory results. The aim of this study was to investigate the distribution of HCV in different compartments of the peripheral blood from HCV-infected blood donors, which may differ from that observed in patients with HCV-associated liver disease. MATERIALS AND METHODS: Hepatitis C virus-positive donor specimens were identified by NAT and antibody testing. HCV RNA was extracted from samples of whole blood and their corresponding components (RBC and plasma). Viral RNA was quantified by real-time qRT-PCR. RESULTS: Hepatitis C virus was present in all blood components from infected donors from which RNA could be amplified. For the majority of samples, plasma (34/46) had the highest detectable concentration of HCV RNA, and RBC (37/46) had the lowest. Specimens with negative NAT and positive antibody assays also produced qRT-PCR negative results. CONCLUSION: These results indicate that including the RBC fraction in the tested sample will not increase assay sensitivity. Although 10% of the specimens had a higher viral load in whole blood, there was no significant overall increase in sensitivity to justify changes in the specimen format. Thus, plasma specimens are well suited for blood donor screening for HCV.

Buffering and dilution in red blood cell storage.

BACKGROUND: Red blood cell (RBC) storage solutions work in a narrow pH range between 7.2 and 6.4. While keeping RBC within that pH range, ATP production can be increased by buffering or dilution. STUDY DESIGN AND METHODS: In the first study, 12 units of packed CP2D RBCs were pooled in groups of four, re-aliquoted, and added to one of four additive solutions (ASs): AS-3, 110 mL; EAS-61, 170 mL; EAS-78, 170 mL; or EAS-81, 110 mL. EAS-78 and -81 contain bicarbonate. Units were sampled approximately weekly for 10 weeks for biochemical measures. In the second study, 12 volunteers donated RBCs for measures of (51)Cr in vivo recovery after 6 or 8 weeks of storage in EAS-81. RESULTS: RBCs stored in the higher-volume or buffered ASs had higher RBC ATP concentrations. The combination had an additive effect. Hemolysis was reduced in dilute ASs and less so with buffering. RBCs stored for 8 weeks (n=6) in EAS-81 exhibited 87+/- 2 percent 24-hour (51)Cr in vivo recovery and 0.4+/- 0.2 percent hemolysis. CONCLUSIONS: It is possible to store RBCs for 8 weeks in buffered conventional volume ASs. Combining buffering and increased AS volume improves stored RBC characteristics further.

Use of grating theories in integrated optics.

Recently [Opt. Lett. 25, 1092 (2000)], two of the present authors proposed extending the domain of applicability of grating theories to aperiodic structures, especially the diffraction structures that are encountered in integrated optics. This extension was achieved by introduction of virtual periodicity and incorporation of artificial absorbers at the boundaries of the elementary cells of periodic structures. Refinements and extensions of that previous research are presented. Included is a thorough discussion of the effect of the absorber quality on the accuracy of the computational results, with highly accurate computational results being achieved with perfectly matched layer absorbers. The extensions are concerned with the diversity of diffraction waveguide problems to which the method is applied. These problems include two-dimensional classical problems such as those involving Bragg mirrors and grating couplers that may be difficult to model because of the length of the components and three-dimensional problems such as those involving integrated diffraction gratings, photonic crystal waveguides, and waveguide airbridge microcavities. Rigorous coupled-wave analysis (also called the Fourier modal method) is used to support the analysis, but we believe that the approach is applicable to other grating theories. The method is tested both against available numerical data obtained with finite-difference techniques and against experimental data. Excellent agreement is obtained. A comparison in terms of convergence speed with the finite-difference modal method that is widely used in waveguide theory confirms the relevancy of the approach. Consequently, a simple, efficient, and stable method that may also be applied to waveguide and grating diffraction problems is proposed.

Painful osteoblastic metastases: the role of nuclear medicine.

Although bone pain from osteoblastic metastases can be ameliorated 50% to 80% of the time by use of intravenously or orally administered radiopharmaceuticals, we cannot accurately predict who will or will not respond. The radiopharmaceuticals containing phosphorus-32, strontium-89 (Metastron), rhenium-186, samarium-153 lexidronam (Quadramet), and tin-117m are effective, but we do not know which of these is the most efficacious or the safest. Toxicity includes mild-to-moderate pancytopenia and an occasional brief flare of pain, and treatment of patients with disseminated intravascular coagulation must be avoided because it may predispose the patient to severe thrombocytopenia. Treatment may be repeated at approximately 8- to 12-week intervals, depending on the time of return to normal leukocytes and platelet counts. Tumoricidal effects are probably not the sole mechanism of pain relief.

Neutralization of hepatitis A virus (HAV) by an immunoadhesin containing the cysteine-rich region of HAV cellular receptor-1.

Hepatitis A virus (HAV) infects African green monkey kidney (AGMK) cells via the HAV cellular receptor-1 (havcr-1), a mucin-like type 1 integral-membrane glycoprotein of unknown natural function. The ectodomain of havcr-1 contains an N-terminal immunoglobulin-like cysteine-rich region (D1), which binds protective monoclonal antibody (MAb) 190/4, followed by an O-glycosylated mucin-like threonine-serine-proline-rich region that extends D1 well above the cell surface. To study the interaction of HAV with havcr-1, we constructed immunoadhesins fusing the hinge and Fc portion of human IgG1 to D1 (D1-Fc) or the ectodomain of the poliovirus receptor (PVR-Fc) and expressed them in CHO cells. These immunoadhesins were secreted to the cell culture medium and purified through protein A-agarose columns. In a solid-phase assay, HAV bound to D1-Fc in a concentration-dependent manner whereas background levels of HAV bound to PVR-Fc. Binding of HAV to D1-Fc was blocked by treatment with MAb 190/4 but not with control MAb M2, which binds to a tag epitope introduced between the D1 and Fc portions of the immunoadhesin. D1-Fc neutralized approximately 1 log unit of the HAV infectivity in AGMK cells, whereas PVR-Fc had no effect in the HAV titers. A similarly poor reduction in HAV titers was observed after treating the same stock of HAV with murine neutralizing MAbs K2-4F2, K3-4C8, and VHA 813. Neutralization of poliovirus by PVR-Fc but not by D1-Fc indicated that the virus-receptor interactions were specific. These results show that D1 is sufficient for binding and neutralization of HAV and provide further evidence that havcr-1 is a functional cellular receptor for HAV.

RBC storage for 11 weeks.

BACKGROUND: Increasing the length of RBC storage can increase both RBC availability and quality. This work addresses 11-week RBC storage in experimental ASs (EASs). STUDY DESIGN AND METHODS: Three studies were performed. In the first, 24-hour in vivo recovery of (51)Cr-labeled autologous RBCs was measured in nine volunteers after storage of their RBCs for 11 weeks in EAS 67. In the second study, 4 units of blood were divided and stored in aliquots with an EAS containing 0, 15, 30, or 45 mmol per L of mannitol; then hemolysis, RBC morphology, and microvesicle protein were measured. In the third study, 6 full units were stored for 12 weeks in the EAS containing 30 mmol per L of mannitol, with weekly sampling for morphologic and biochemical measures of RBC quality. RESULTS: RBCs stored for 11 weeks in EAS-67 had a mean 24-hour in vivo recovery of 79 +/- 5 percent, but the hemolysis was 1.35 +/- 0.68 percent. Increasing mannitol content of the EAS reduced hemolysis but increased microvesiculation. EAS-76, with 30 mmol per L of mannitol allowed 11-week storage with 0.48 +/- 0.10 percent hemolysis at 11 weeks and 0.62 +/- 0.14 percent hemolysis at 12 weeks. CONCLUSION: It is possible to store RBCs for 11 weeks in EAS with greater than 75 percent recovery and less than 1 percent hemolysis.

Therapeutic 131I in outpatients: a simplified method conforming to the Code of Federal Regulations, title 10, part 35.75.

UNLABELLED: The Code of Federal Regulations, title 10, part 35.75 (10CFR35.75), provides greater latitude and flexibility in the dosing and management of outpatients treated with therapeutic 131I than did preceding regulations. Prescribing physicians should consider applying these new regulations to enhance patient convenience and lower the cost of managing appropriate outpatients. Managed care organizations and third-party payers may require that all eligible patients be treated as outpatients or that justification for hospital admission be specifically documented. To facilitate application of the code and guidelines, maximum 131I doses for patients undergoing thyroid remnant ablation, therapy for metastatic or recurrent thyroid cancer, or therapy for hyperthyroidism have been calculated and summarized in tables. METHODS: A model was developed that calculates the maximum dose of 131I that may be dispensed to an outpatient. This model complies with 10CFR35.75. The maximum dose is calculated as a function of 5 variables: the occupancy factors for 3 periods after dose administration, the fractional uptake of 131I by residual thyroid tissue or metastasis, and the duration of constrained activity. Occupancy factor, a key new concept in the regulatory guidelines, is a physician estimate of the time that a treated patient will be near the individual with whom the patient will spend the most time after treatment. The model also considers 3 constants: the effective half-life of 131I during the preequilibrium period, and the effective half-lives of 131I in both the thyroidal component and the extrathyroidal component during the equilibrium period. Tables for maximum allowable patient 131I doses were derived on the basis of this model. RESULTS: Through dosing charts, maximum 131I therapy doses may easily be calculated. Most outpatients undergoing thyroid remnant ablation, therapy for metastatic or recurrent thyroid cancer, or therapy for hyperthyroidism may be treated with 7400 MBq (200 mCi) 131I or more. CONCLUSION: If the prescribing physician understands the concept of occupancy factor and how to use the dosing charts, our model facilitates application of and adherence to 10CFR35.75.

Twelve-year survival after the diagnosis of locally advanced carcinoma of the pancreas: A case report.

The long-term survival rate of patients with carcinoma of the pancreas is low. Even more so, long-term survival of patients with metastatic pancreatic carcinoma is extremely rare. In this case report, we describe a patient with an unusual course of disease. This patient was diagnosed with locoregional carcinoma of the pancreas and therefore underwent gastroenterostomy and cholecystojeojenostomy without resection of the primary tumor. Later he was treated with radiotherapy and chemotherapy and survived 12 years, during 11 of which he had no evidence of disease. He died 12 years after the initial diagnosis from peritoneal dissemination of poorly differentiated carcinoma complicated with obstructive jaundice and sepsis. To our knowledge, this patient had the longest reported survival with locally advanced pancreas carcinoma that was not resected. The case is presented and discussed in this article.

Systemic radiopharmaceutical therapy of painful osteoblastic metastases.

Bone pain from osteoblastic metastases can be ameliorated 40% to 80% of the time. Although we can predict nonresponders, we cannot predict responders; however, patients with a better performance scale may have a better chance of pain relief. Radiopharmaceuticals containing phosphorus 32, strontium 89, samarium 153, rhenium 186, and tin 117m are effective, but we do not know which is the most efficacious and the safest. Toxicity includes the flare phenomenon and mild to moderate pancytopenia, but disseminated intravascular coagulation can cause severe, life-threatening thrombocytopenia. This treatment may be repeated at about 9- to 12-week intervals, perhaps earlier with (153)Sm lexidronam, (186)Re etidronate, and (117m)Sn pentetate, with a success rate approaching that of the initial injection. The duration of action of pain reduction ranges from 2 weeks to many months. Tumorical effects are probably not the only mechanism of pain relief.

Successful storage of RBCs for 9 weeks in a new additive solution.

BACKGROUND: This study explored the effect of storing packed RBCs suspended in 200 mL of an alkaline, hypotonic, experimental additive solution (EAS 61). STUDY DESIGN AND METHODS: Packed RBC units prepared from RBCs collected from healthy donors in CPD were stored for 8 (n = 10) and 9 (n = 10) weeks under blood bank conditions after the addition of 200 mL of EAS 61 (adenine, 2 mM:; dextrose, 110 mM:; mannitol, 55 mM:; NaCl, 26 mM:; Na(2)HPO(4), 12 mM:). Standard methods were used for in vitro assays. The 24-hour in vivo autologous recoveries were measured with (51)Cr. RESULTS: Mean +/- SD recoveries at 8 and 9 weeks were 81 +/- 7 and 77 +/- 7 percent. After 9 weeks, the ATP of the RBCs was 81 percent of the initial value, hemolysis was 0.35 percent, supernatant potassium was 46 mEq per L, and the morphologic index was 94.1. CONCLUSION: Packed RBCs suspended in 200 mL of EAS 61 can be stored satisfactorily for 9 weeks. Longer RBC storage should reduce outdating, increase availability of transfusions in remote locations, and improve the efficiency of autologous donor programs.