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Wastewater reuse is one of the crucial water resources in Egypt due to the ongoing need to increase water resources and close the supply-demand gap. In this study, a new coagulant has been investigated before sand filters as an advanced wastewater treatment method. The sand filter pilot was run at a hydraulic loading rate of 0.75 m/h and two different dosages of three coagulants (Alum, FeCl 3 , and Ferrate VI) were selected using the jar tests. The sand filter without coagulant removed 12% of BOD 5 and 70% of turbidity. Applying in-line coagulation before the sand filter provided effluents with better quality, especially for turbidity, organics, and microorganisms. Ferrate provided the highest removal of turbidity (90%) and BOD 5 (93%) at very low dosages and lower costs compared with other coagulants, however, it adversely impacted both conductivity and dissolved solids. A significant effect on reducing bacteria was obtained with 40.0 mg/L of alum. According to the study's findings, the ferrate coagulant enhanced the sand filter's performance producing effluents with high quality, enabling it to meet strict water reuse regulations as well as aquatic environmental and health preservations., Competing Interests: The authors declare there is no conflict., (© 2024 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits copying, adaptation and redistribution, provided the original work is properly cited (http://creativecommons.org/licenses/by/4.0/).)

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year overall survival of 11%. The disease is usually diagnosed at advanced stages, and systemic chemotherapy is the standard-of-care treatment for the majority of patients with PDAC. Although novel treatment options, such as targeted therapy and immunotherapy, have achieved substantial progress leading to practice-changing results, with FDA approvals for several solid tumors so far, the progress achieved for PDAC is relatively limited. Recent studies uncovered potential therapeutic targets for patients with PDAC, and potential therapeutic opportunities are currently being further examined. Herein, we review recent advances in systemic therapy regimens, including cytotoxic agents, targeted therapies, immunotherapy, and novel therapeutic options for managing patients with PDAC. We also elaborate on molecular profiling to guide treatment and existing therapeutic opportunities that may further advance the clinical care of patients with this devastating disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: A 56-year-old woman presented with an extensive sarcoma requiring nearly total back resection. She had limited donor sites for reconstruction because of a previous laparotomy, but presented with a significantly larger, identical twin. Cancer has traditionally been considered a contraindication for vascularized composite allotransplantation; however, immunosuppression is potentially avoidable between monozygotic twins., Methods: A preoperative genetic workup revealed 10/10 human leukocyte antigen homozygosity. Despite substantial phenotypic divergence in size and facial features, the sisters were genotypically identical. A two-stage, double deep inferior epigastric perforator transplant was planned for delayed reconstruction. At the first stage following the resection, an arteriovenous loop was performed to provide recipient vasculature to the back. At a second stage, the transplantation was performed. In addition, bilateral lumbar artery perforator flaps were created to reduce the length of the defect. Intraoperative steroid bolus and a short taper alone were used for immunosuppression., Results: The resection resulted in a 22 × 29-cm specimen down to the spine. After a 4-day interval for permanent pathologic evaluation, the transplant was successfully transferred between twins. Two arteries and six veins were anastomosed to establish perfusion. Postoperatively, there have been no episodes of rejection or flap compromise at last follow-up (>36 months)., Conclusions: This case represents one of the few vascularized composite allotransplantations between monozygotic twins, and the only reported successful vascularized composite allotransplantation for a recurrent cancer diagnosis. Oncologic safety depended on 100 percent histocompatibility to avoid immunosuppression. Limited patient donor sites precluded total autologous coverage, and a substantial size discrepancy between the twins favored a transplant., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background: Obesity is a multifactorial metabolic disease resulting from behavioral and genetic factors. Obesity is linked to diabetes mellitus and hypertension, which are considered as major risk factors for chronic kidney disease (CKD); moreover, it has a direct effect on developing CKD and end stage renal disease (ESRD). Here was aimed to examine the association between uncoupling protein 2 (UCP2) gene expression and obesity in CKD patients., Methods: UCP2 gene expression was analyzed by real time polymerase chain reaction (RT-PCR) in 93 participants divided into three groups. The groups included 31 non-obese CKD patients, 31 obese CKD patients, and 31 healthy, age-matched, unrelated volunteers as a control group., Results: UCP2 gene expression was significantly relevant when comparing the non-obese CKD and obese CKD groups to the control group (p< 0.001). No significant association was found when the groups were compared by gender; Chi-square (X2) was 2.38 and p= 0.304. A significant negative correlation was found between UCP2 gene expression and BMI in CKD (p< 0.05)., Conclusion: These results indicate that UCP2 gene expression plays a significant role as a risk factor for obesity in CKD patients.

Immunosuppressant agents are essential in every transplant recipient's care yet walking the fine line of over- or under-immunosuppression is a constant struggle for both patients and transplant providers alike. Optimization and personalization of immunosuppression has been limited by the need for non-invasive graft surveillance methods that are specific enough to identify organ injury in real time. With this in mind, we propose a pilot study protocol utilizing both donor derived cell free DNA (dd-cfDNA, gene expression profiling (GEP), and machine learning (iBox), called KidneyCare, to assess the feasibility and safety in reducing immunosuppressant exposure without increasing the risk of clinical rejection, graft injury, or allograft loss. Patients randomized to the immunominimization arm will be enrolled in one of two protocols designed to eliminate one immunosuppressant and optimize the dose of the Calcineurin Inhibitors (CNIs) using the KidneyCare platform. All patients will be maintained on dual therapy of either steroids and a low dose CNI, or mycophenolate mofetil (MMF) and low dose CNI. Their outcomes will be compared to patients who have their immunosuppressants managed using standard clinical assessment and treatment protocols to determine the impact of immuno-optimization on graft function, complications, and patient reported outcomes.

Background: Autophagy is a catabolic process, utilized constitutionally by body cells to recycle nutrients and to remove unwanted/damaged intracellular constituents. It is enhanced during periods of stress, such as starvation and hypoxia, aiding in cell survival and it is linked to major cellular processes, such as apoptosis and antigen expression. The process has been extensively studied in vitro models or tumor tissue samples with rare application on human subjects., Methods: Plasma samples from 24 advanced solid tumor patients were collected at different time points before and after chemotherapy. Their exosomes were isolate and blotted for microtubule-associated protein-1 light chain-3 (LC-3B) protein as a marker for autophagy. All the subjects received a standard chemotherapy regimen of carboplatin- gemcitabine with chloroquine (CQ)/ hydroxychloroquine (HCQ) in chronic doses throughout their treatment period as an autophagy modulator. CQ/HCQ was given in 50 mg increments as guided by their tolerability to treatment., Results: A total of 267 plasma samples were obtained for the 24 patients and processed. Each sample corresponds to a single time point. The first group included 6 patients, all received 50 mg of CQ with chemotherapy. LC-3B I was detected in their isolated exosomes, while LC3-BII was not detected in their samples. The second cohort of patients included 3 subjects who re-ceived 100mg of HCQ. They demonstrated both LC3-BI and II on day 15 after chemotherapy in one patient, and on third cycle after 24 hours in the second patient. The third cohort included 3 subjects who received 150 mg of HCQ. All cases demonstrated LC3-BI and II on first cycle of treatment after less than 24 hours. The last cohort included 8 subjects, who received a fixed dose of 100 mg of HCQ with treatment. In this cohort, we were able to detect both LC3-B isoforms on advanced time points of second and third cycles., Conclusion: Detection of autophagy protein LC3-B in exosomes serves as a dynamic method to monitor autophagy. It can be utilized to study the effects of anti-neoplastic agents on autophagy and mechanisms of drug resistance, however, to standardize our results a larger specimen of patients should be included.

Objectives: Numerous studies addressed the effect of statin on cancer patients. The aim of this study is to define the effect of statin administration with chemotherapy on the patients’ outcomes. Methods: We retrospectively researched the database of the University of Cincinnati cancer to identify lung cancer patients who received statins (S+, n=41) during their treatment in our institute. We also, retrieved data for contemporaneously treated patients who did not receive statins (S-, n=159) as a control arm. Clinico-demographical data and overall survival (OS) were analyzed using Pearson’s Chi-square (χ2) test and Kaplan-Meier survival curves with Log-rank test. Adjustment using Cox proportional hazard ratios (HR) were done based on (age, gender, race and stage) to identify effect of statins on their outcomes. Results: The median age for S+ was 64y (IQR; 55-69) and 71.2% of the patients were white. Histopathology was 55.4% and 31.7% for adenocarcinoma and squamous cell carcinoma, respectively. Fifty-six percent were stage IV in each study arm and the median OS was14.9 m. Median OS was insignificantly lower in S–ve arm (13.7 vs 15.6 months; P=0.652, HR=0.91, 95%CI 0.52-1.57). Our results show that after different types of adjustments, S+ did not show survival advantage (P>0.05) compared to the control arm. Conclusion: While showing an increase in overall survival in patients with advanced lung cancer, the results of this study did not reach statistical significance. This could be due for the small sample size of this retrospective study.

Background: With antiprogrammed death receptor-1 (anti-PD-L1) therapy, a recent meta-analysis reported higher incidence of cutaneous, endocrine and gastrointestinal complications especially with dual anti-PD-L1 immunotherapy (IMM). Methods: Our primary outcome was assessment of all cardiotoxicity grades in IMM compared with different treatments, thus a systemic review and a meta-analysis on randomized clinical trials (RCTs) were done. Results: We included 11 RCTs with 6574 patients (3234 patients in IMM arm vs 3340 patients in the other arm). Three non-small-cell lung cancer RCTs, seven melanoma RCTs and only one prostatic cancer RCT met the inclusion criteria. There were five RCTs that compared monoimmunotherapy to chemotherapy "(n = 2631 patients)". No difference exists in all cardiotoxicity grades or high-grade cardiotoxicity (p > 0.05). Lung cancer exhibited a higher response rate and lower mortality in IMM. Conclusion: There was no reported statistically significant cardiotoxicity associated with anti-PD/PD-L1 use. Lung cancer subgroups showed better response and survival rates.

Hematological malignancies can manifest as extramedullary soft tissue masses in relatively rare cases. The rarity of it causes a diagnostic and therapeutic challenge. One of the rarest manifestations is myeloid sarcoma (MS). MS develops as part of acute myeloid leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome or at relapse, especially following allogeneic hematopoietic stem cell transplant. The tumor displays high myeloperoxidase expression, hence the color green, and is called chloroma. It most commonly appears in lymph nodes, skin and soft tissues, bone, testes, gastrointestinal tract, and peritoneum. Immunohistochemistry shows CD68-KP1 as the most commonly expressed marker, then myeloperoxidase, CD117, CD99, CD68/PG-M1, lysozyme, CD34, terminal deoxynucleotidyl transferase, CD56, CD61, CD30, glycophorin A, and CD4. Different chromosomal abnormalities including MLL rearrangement, t(8; 21), monosomy 7, trisomy 8, trisomy 11, trisomy 4, inversion (16), monosomy 16,16q deletion, 5q deletion, and 20q deletion were reported. Most of the literature about MS are case reports and small retrospective studies, thus there is limited clinical knowledge of the cases and their presentation and management plans. Here, we provide a review of what has been reported in the literature about MS in the light of our experiences., (© 2019 S. Karger AG, Basel.)

Large cell neuroendocrine cancer (LCNEC) of the lung exhibits morphological and immunohistochemical characteristics of both neuroendocrine and large cell carcinomas. No defined optimal therapy has been described for this subset of patients and the question of whether these patients should be treated with non-small cell lung cancer (NSCLC) treatment protocols, according to the National Comprehensive Cancer Network (NCCN) guidelines, or with small cell lung cancer (SCLC) due to histological and clinical similarities is still uncertain. We conducted a retrospective review of patients identified with diagnosis of LCNEC of the lung at the University of Cincinnati Cancer Center from the year 2002 to 2012 to determine which treatment approach resulted in improved outcomes in this rare category of disease. Patients who received chemotherapy whether NSCLC (group A) or SCLC (group B) protocols did not show significant changes in OS (P=0.911). Meanwhile, patients who underwent surgery (group C) had better OS compared to groups A and B (P= 0.027 and 0.024, respectively). This analysis reveals that outcomes for SCLC or NSCLC treatment strategies in LCNEC patients did not result in survival advantages and future research should be addressing it as a separate entity.

Clear cell carcinomas are common finding in renal, ovarian and uterine carcinomas. However, clear cell lung cancer (CCLC), first described by Liebow and Castleman in 1963, is considered an extremely rare variant of lung tumors. The 2011 WHO classification of lung tumors considered CCLC as a rare cytologic feature of squamous cell or adenocarcinomas. It is no longer recognized as a formal subtype, albeit it can be referred to in the pathological diagnosis as “with clear cell features” even with marginal fractions of the tumor cells. Such recognition is needed since the variation in clinical features and outcome in this subset of patients. The disease has a clinically vague natural history, is characterized by slight female predominance and is often seen in the elderly. As frequently encountered with rare diseases, its clinical course and treatment options have many questions still yet to be answered. In this paper, we review both the natural history and treatment options mentioned in literature, in the light of our experience by reporting a case series of four patients diagnosed with CCLC and highlight their aspects., (Creative Commons Attribution License)

Patients bridged to transplant (BTT) with continuous-flow left ventricular assist devices (CF-LVADs) have increased in the past decade. Decision support tools for these patients are limited. We developed a risk score to estimate prognosis and guide decision-making. We included heart transplant recipients bridged with CF-LVADs from the United Network for Organ Sharing (UNOS) database and divided them into development (2,522 patients) and validation cohorts (1,681 patients). Univariate and multivariate Cox proportional hazards models were performed. Variables that independently predicted outcomes (age, African American race, recipient body mass index [BMI], intravenous [IV] antibiotic use, pretransplant dialysis, and total bilirubin) were assigned weight using linear transformation, and risk scores were derived. Patients were grouped by predicted posttransplant mortality: low risk (≤ 38 points), medium risk (38-41 points), and high risk (≥ 42 points). We performed Cox proportional hazards analysis on wait-listed CF-LVAD patients who were not transplanted. Score significantly discriminated survival among the groups in the development cohort (6.7, 12.9, 20.7; p = 0.001), validation cohort (6.4, 10.1, 13.6; p < 0.001), and ambulatory cohort (6.4, 11.5, 17.2; p < 0.001). We derived a left ventricular assist device (LVAD) BTT risk score that effectively identifies CF-LVAD patients who are at higher risk for worse outcomes after heart transplant. This score may help physicians weigh the risks of transplantation in patients with CF-LVAD.

Objectives: To review the outcomes of treatment in patients with pulmonary sarcomatoid carcinoma (PSC) treated at the University of Cincinnati Medical Center (UCMC)., Results: There was no significant difference in survival of patients treated with chemotherapy alone (median, 256 days) compared to patients not undergoing treatment (median, 205.5 days). Patients who underwent surgery and adjuvant chemotherapy showed a trend in improvement of survival (median, 457.6 days). Patients requiring only surgery had the longest OS of 713.5 days., Conclusions: Systemic chemotherapy alone did not improve survival in patients with PSC. Surgery provides the greatest overall survival benefit and adjuvant chemotherapy may also improve survival., Methods: From 2000 to 2014, twenty-five patients with pathologically confirmed PSC were treated at UCMC. The outcomes were retrospectively analyzed by treatment with overall survival (OS) as the endpoint., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest exists.

Background: Vimentin belongs to an intermediate filament (IF) family of proteins, mainly present in mesenchymal cells and has a crucial role in maintaining cellular integrity. Vimentin can induce epithelial to mesenchymal transition, and thus increase migration and invasion capacity of the cells. It has been shown to be a useful and reliable diagnostic and prognostic marker in several cancers including colon cancers, breast and hepatocellular cancers. Recent studies suggest that it may have a role in distant metastasis of non-small cell lung cancer (NSCLC) accounting for poor survival [1]., Methods: The aim of the study is to assess the impact of vimentin testing as a diagnostic and prognostic marker in NSCLC. This is a case study of 12 NSCLC patients who had vimentin testing as a part of their work up over the past five years at the University of Cincinnati. A total of 12 patients with advanced lung cancer were included in this case study as they were found to have strong vimentin expression. This was correlated with overall survival of this group of patients., Results: Median survival of the patients was 4.66 months. This is 7.34 months less compared to the median survival of patients with stage IV NSCLC which is reported to be 12 months., Conclusions: More studies are warranted into the use of vimentin as an emerging useful marker for early diagnosis, aggressive transformation relapse, and prognostication of NSCLC. It may have therapeutic value in NSCLC as observed in other cancers.

Background: FLT3-ITD mutations are common in AML subgroups, particularly in Acute Promyelocytic Leukemia (APL). It infers poor prognosis in AML patients; however, its prognostic value in APL is still controversial. We aimed to assess the distribution and prognostic value of FLT3-ITD mutation within AML subgroups, focusing on APL., Methods: In NCI, Cairo University, 346 newly diagnosed AML patients were included. Morphological, immunophenotypic and cytogenetic analysis were done at presentation and fixed follow-up points with monitoring in follow up visits of patients. FLT3-ITD mutations were detected using RT-PCR., Results: FLT3-ITD mutations were detected in 18.5% of AML patients with significant higher incidence in M3 patients (35.5%, p = 0.027) in comparison to other types. There was significant negative association between FLT3ITD mutations and CD34 expression (p = 0.026). FLT3 wild patients had a significantly better response on Day 35 than the mutant group (p = 0.046). Overall Survival (OS) of the wild group was significantly better than that of the mutant group (p = 0.003). In APL patients, OS of wild-FLT3 patients was significantly better than of those with mutant FLT3 (p = 0.018). In non-APL patients, favorable cytogenetic changes - t(8;21) and inv(16) - are more common in FLT3 wild group (12.8%) than in FLT3 mutant group (6.3%). In non-APL patients, FLT3-ITD mutation retained its adverse prognostic effect (p = 0.016). CD34 expression affected survival in both FLT3 mutant and wild groups., Conclusions: We conclude that FLT3-ITD mutations infer poor prognostic effects both in AML patients generally and in the APL group specifically. CD34 may have a prognostic impact in FLT3-ITD mutant patients, which is to be further investigated.

Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains ("female brain" or "male brain"). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only "male" or only "female" features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the "maleness-femaleness" continuum are rare. Rather, most brains are comprised of unique "mosaics" of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain.

Concerns about adverse effects of calcineurin inhibitors (CNIs) have prompted development of protocols that minimize their use. Whereas previous CNI withdrawal trials in heterogeneous cohorts showed unacceptable rates of acute rejection (AR), we hypothesized that we could identify individuals capable of tolerating CNI withdrawal by targeting immunologically quiescent kidney transplant recipients. The Clinical Trials in Organ Transplantation-09 Trial was a randomized, prospective study of nonsensitized primary recipients of living donor kidney transplants. Subjects received rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplantation, subjects without de novo donor-specific antibodies (DSAs), AR, or inflammation at protocol biopsy were randomized to wean off or remain on tacrolimus. The intended primary end point was the change in interstitial fibrosis/tubular atrophy score between implantation and 24-month protocol biopsies. Serially collected urine CXCL9 ELISA results were correlated with outcomes. The study was terminated prematurely because of unacceptable rates of AR (4 of 14) and/or de novo DSAs (5 of 14) in the tacrolimus withdrawal arm. Positive urinary CXCL9 predated clinical detection of AR by a median of 15 days. Analyses showed that >16 HLA-DQ epitope mismatches and pretransplant, peripheral blood, donor-reactive IFN-γ ELISPOT assay results correlated with development of DSAs and/or AR on tacrolimus withdrawal. Although data indicate that urinary CXCL9 monitoring, epitope mismatches, and ELISPOT assays are potentially informative, complete CNI withdrawal must be strongly discouraged in kidney transplant recipients who are receiving standard-of-care immunosuppression, including those who are deemed to be immunologically quiescent on the basis of current clinical and laboratory criteria., (Copyright © 2015 by the American Society of Nephrology.)

Background: Asthma, a common lung disease in children, is caused by excessive immune responses to environmental antigens., Objective: Given the immuno-modulatory properties of vitamin D, the aim of the current study was to investigate the relationship between vitamin D levels and markers of asthma severity., Methods: This was investigated in a 70 Saudi children with and without asthma and were recruited from the King Abdul Aziz University Hospital, Jeddah, Saudi Arabia, over the period of 11 months (May 2011-April 2012). Childhood asthma control test instrument was employed to assess the level of asthma control among asthmatic patients. Anthropometric measurements were taken and interviewer-administrated questionnaire was completed for all study participants. Pulmonary function test was performed by recording changes in the peak expiratory flow. Venous blood samples were withdrawn for measurements of vitamin D, bone profile, cytokines profile (interleukin-10, tumor necrosis factor-alpha, platelets derived growth factor), and atopy markers (IgE and eosinophil count)., Results: Hypovitaminosis D is highly prevalent among asthmatic children with highly significant increase in several markers of allergy and asthma severity as compared with healthy control children. Significant correlations between several inflammatory and immunological markers and vitamin D levels were also found. Finally, lower 25-hydroxyvitamin D levels were associated with a higher asthma prevalence in multivariable analysis., Conclusion: Our study showed that hypovitaminosis D is highly prevalent in the whole population in addition to a highly significant increase in several markers of allergy and asthma severity among asthmatic children as compared with healthy control children.

Background: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease., Methods: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2)., Results: A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period., Conclusions: Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome. (Funded by Alexion Pharmaceuticals; C08-002 ClinicalTrials.gov numbers, NCT00844545 [adults] and NCT00844844 [adolescents]; C08-003 ClinicalTrials.gov numbers, NCT00838513 [adults] and NCT00844428 [adolescents]).

Background: The islets of Langerhans are micro-organs rich in blood vessels. The process of islet isolation and culture disrupts the vasculature of the islets. The reestablishment of an appropriate microvascular supply is an essential prerequisite for long-term survival and function of islet grafts. In this study, we examined the effects on the process of neovascularization of coating the islets with fibrin., Methods: Isolated human islets were stained using the dioctadecylindocarbocyanine (DII) dye. An aliquot of the human islets were embedded in 3-dimensional fibrin. Human islets (100 islets-equivalents) were transplanted into a mouse dorsal window model to evaluate angiogenesis over 17 days. Transplanted islets were divided into 2 groups: either free islets or islets coated with fibrin gel. Animals were imaged using intravital microscopy immediately and at 3, 4, 8, 11, and 17 days after surgery. The DII dye caused the islets to be fluorescent and visible using a rhodamine filter. Fluorescein isothiocyanate dextran was used to visualize vasculature structures surrounding the islets., Results: Human islets coated with fibrin demonstrated an early appearance of a network of immature blood vessels that produced a significantly higher density/unit area for neovascularization by day 8 after transplantation., Conclusion: Our preliminary data showed that fibrin played a role in early neovascularization and support to sustain development of new blood vessels. Fibrin formed a matrix that helped to maintain the 3-dimensional structure of, and therefore reducing the environmental stress on islets., (Published by Elsevier Inc.)

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.

Although arterio-venous fistulae (AVF) are currently considered to be the first choice of permanent vascular access for hemodialysis, there are some patients who are not candidates for fistulae and synthetic grafts provide other options. The Thoratec (Vectra) polyurethane vascular access graft is a new prosthetic graft that may be cannulated within days of insertion due to "self-sealing" properties. However, a tendency for kinking at the suture site due to the strong elasticity of this graft, leading to undesirable complications such as thrombosis, have been reported. We describe a surgical modification of the anastomosis by interposing a segment of expanded polytetrafluoroethylene graft (ePTFE, Venaflo) between the native vessels and the polyurethane graft sections in a pediatric patient. This modification may overcome the kinking complication associated with use of the polyurethane graft and the resulting thrombosis.

The effect of reaming velocity on the pressure distribution within the bone was investigated numerically by solving the full three-dimensional momentum equations together with the continuity equation using the finite element technique. Viscosity was also varied to obtain a pressure envelope. It was found that all the experimental data follow the same trends as the envelopes predicted by the finite element model. It was clear that an increase in either the implant insertion rate or the viscosity resulted in an increase in pressure in the intramedullary canal.

Context: Approximately 20% of liver transplant recipients develop posttransplant diabetes mellitus. Hepatitis C, a leading indication for liver transplantation, has been identified as a risk factor for posttransplant diabetes mellitus and is an observation that is not well described., Objective: To evaluate the incidence of posttransplant diabetes mellitus and risk factors associated with this condition., Design: A retrospective chart review., Setting: A large urban transplant center., Patients: One hundred fifteen liver transplant recipients who received a transplant between January 1, 1998, and August 31, 2001., Results: The rate of posttransplant diabetes mellitus, calculated at 3-month intervals in the first year after liver transplantation, ranged from 19.4% to 24.6%, which is similar to the averages reported in most published studies. The cumulative rate of posttransplant diabetes mellitus, which includes all patients who developed this condition during the time studied, was 31.3%. Clinical and demographic factors, including immunosuppression regimens, were similar between patients with and without posttransplant diabetes mellitus. Two risk factors for posttransplant diabetes mellitus were identified: hepatitis C, which was the leading indication for transplantation in this group (54.8%), and cytomegalovirus infection during the first year after transplantation. Other clinical and demographic variables, such as gender, age, ethnicity, rejection episodes, body mass index, and immunosuppression, were not identified as risk factors for posttransplant diabetes mellitus in liver transplant recipients.

Acute rejection after pancreas transplantation remains a significant problem and contributes to immunologic graft loss. No clinical markers of pancreas rejection have been universally accepted. Recent studies have identified several cytotoxic genes as possible markers of acute rejection in renal and islet cell transplant recipients. However, these markers of rejection have not been evaluated in pancreas transplant recipients. This study evaluated the differential expression of granzyme B, perforin, and human leukocyte antigen (HLA)-DRA in peripheral blood between patients with and without biopsy-proven pancreas rejection (n = 7 per group). Gene expression levels were analyzed using real time reverse transcriptase polymerase chain reaction assays. Expression of these genes in controls (n = 17) with and without type 1 diabetes was also analyzed. Patients with biopsy-proven pancreas rejection had higher levels of granzyme B, perforin, and HLA-DRA than patients who did not have rejection, although the difference was not statistically significant. Moreover, patients with biopsy-proven pancreas rejection had a significantly higher level of granzyme B than control subjects with type 1 diabetes (p

Purpose: Trigeminal neuralgia is the most common neurological cause for facial pain. Contemporary interventional treatment relies on surgical microvascular decompression or, alternatively, percutaneous interventions targeting the semilunar ganglion via the foramen ovale. For the latter approach, only free-hand punctures using fluoroscopy devices have been reported. Therefore, the present study aimed to evaluate a new fluoroscopy-based guidance device for transforaminal puncture., Methods: Two experienced examiners punctured the foramen ovale bilaterally free-hand, and using a guidance device in human cadavers (n = 9). The number of attempts for puncture was recorded. A new attempt was counted each time the needle had to be retracted for redirection., Results: As compared to the free-hand puncture of the foramen ovale (4.44 +/- 2.79), the new guidance device significantly reduced the number of trials needed (1.37 +/- 0.69)., Conclusion: The employment of a guidance device facilitated percutaneous transforaminal puncture and resulted in a significantly decreased number of puncture attempts as compared to free-hand techniques in human cadavers.

Soft tissue injuries with associated bone defects are difficult to manage and often require prolonged treatment with repeated interventions. Frequently, a free flap is applied as a first step and bone grafting is carried out in a second procedure. Ideally, these two procedures are combined in one operation, utilizing a soft tissue flap with an attached vascularized bone fragment. The lateral arm flap can provide such an osteoseptocutaneous flap and has been utilized clinically with success; however, the vascular anatomy of the flap, especially the humeral fragment, has not been described in detail previously, and there is broad disagreement concerning its innervation. In this study, the arteries and nerves of 24 fresh cadaver arms were dissected after injection of colored latex. The levels of origin of the periosteal arteries of the humerus were also documented. The lateral arm flap has a consistent arterial supply from three septocutaneous perforating branches that are arranged in a predictable pattern. The lateral supracondylar ridge of the humerus is vascularized by direct branches of the posterior branch of the radial collateral artery and by arteries that arise from muscular branches supplying adjacent muscles. The innervation of the lateral arm flap is by the inferior lateral cutaneous nerve of the arm. Knowledge of the consistent vascular anatomy of the lateral humerus and soft tissue of the donor site allows an osteoseptocutaneous flap to be raised safely with an appropriate technique. We recommend use of the lateral arm flap with a humeral fragment for the treatment of combined soft tissue and bone defects when a single step surgical solution is indicated., (Copyright 2003 Wiley-Liss, Inc.)

Image quality of storage phosphor radiographs acquired at different exposure levels was compared to define the minimal radiation dose needed to achieve images which allow for reliable detection of wrist fractures. In a study on 33 fractured anatomical wrist specimens image quality of storage phosphor radiographs was assessed on a diagnostic PACS workstation by three observers. Images were acquired at exposure levels corresponding to a speed classes 100, 200, 400 and 800. Cortical bone surface, trabecular bone, soft tissues and fracture delineation were judged on a subjective basis. Image quality was rated according to a standard protocol and statistical evaluation was performed based on an analysis of variance (ANOVA). Images at a dose reduction of 37% were rated sufficient quality without loss in diagnostic accuracy. Sufficient trabecular and cortical bone presentation was still achieved at a dose reduction of 62%. The latter images, however, were considered unacceptable for fracture detection. To achieve high-quality storage phosphor radiographs, which allow for a reliable evaluation of wrist fractures, a minimum exposure dose equivalent to a speed class of 200 is needed. For general-purpose skeletal radiography, however, a dose reduction of up to 62% can be achieved. A choice of exposure settings according to the clinical situation (ALARA principle) is recommended to achieve possible dose reductions.

Aim: To define the value of digital radiography with a clinical flat panel detector system for evaluation of wrist fractures in comparison with state of the art storage phosphor radiography., Material and Methods: Hard copy images of 26 fractured wrist specimens were acquired with the same exposure dose on a state of the art storage phosphor radiography system and a clinical flat panel detector. Image features like cortical bone surface, trabecular bone, soft tissues and fracture delineation were independently analysed by 4 observers using a standardised protocol. Image quality ratings were evaluated with an analysis of variance (ANOVA)., Results: Flat panel detector radiographs were rated superior with respect to cortical and trabecular bone representation as well as fracture evaluation, while storage phosphor radiographs produced better soft tissue detail., Conclusion: In some of the observed image quality aspects, the performance of caesium iodide/amorphous silicon flat panel detector exceeds state of the art storage phosphor radiography. This makes it well suited for skeletal imaging particularly in trauma as seen in the detection of wrist fractures., (Copyright 2002 The Royal College of Radiologists.)

Unlabelled: We conducted a randomized, controlled, crossover study to determine cervical spine motion for six airway management techniques in human cadavers with a posteriorly destabilized third cervical (C-3) vertebra. A destabilized C-3 segment was created in 10 cadavers (6-24 h postmortem). Cervical motion was recorded by continuous lateral fluoroscopy. The following airway management techniques were performed in random order on each cadaver with manual in-line stabilization applied: face mask ventilation (FM), laryngoscope-guided orotracheal intubation (OETT), fiberscope-guided nasal intubation (FOS-NETT), esophageal tracheal Combitube((R)) (Kendall-Sheridan, Neustadt, Germany) insertion (ETC), intubating laryngeal mask insertion with fiberscope-guided tracheal intubation (ILM-OETT), and laryngeal mask airway insertion (LMA). Afterward, maximum head-neck flexion (FLEX-MAX) and maximum head-neck extension (EXT-MAX) without manual in-line stabilization was performed to determine maximum motion. The maximum posterior displacement of C-3 and the maximum segmental sagittal motion of C2-3 were determined. There was a significant increase in posterior displacement for the FM (1.9 +/- 1.2 mm, P: < 0.01), OETT (2.6 +/- 1.6 mm, P: < 0.0001), ETC (3.2 +/- 1.6 mm, P: < 0.0001), ILM-OETT (1.7 +/- 1.3 mm, P: < 0. 01), LMA (1.7 +/- 1.3 mm, P: < 0.01), FLEX-MAX (3.7 +/- 1.9 mm, P: < 0.0001), EXT-MAX (1.8 +/- 1.7, P: < 0.01), however, not for FOS-NETT (0.1 +/- 0.7 mm). Posterior displacement was less for the ILM-OETT and LMA than for the ETC (both P: < 0.04). There were no significant increases in segmental sagittal motion with any airway manipulation other than with FLEX-MAX (-4.5 +/- 4.0 degrees, P: < 0.01). Posterior displacement was similar to FLEX-MAX for the OETT and ETC; however, it was less for the FM, FOS-NETT, ILM-OETT, and LMA (all P: < 0.01). Posterior displacement was similar to EXT-MAX for all airway manipulations other than for FOS-NETT (P: < 0.001). For cervical motion and the techniques tested, the safest method of airway management in a patient with a posteriorly destabilized C-3 segment is FOS-NETT. LMA devices may be preferable to the ETC., Implications: In the cadaver model of a destabilized third cervical vertebrae, significant displacement of the injured segment occurs during airway management with the face mask, laryngoscope-guided oral intubation, the esophageal tracheal Combitube (Kendall-Sheridan, Neustadt, Germany), the intubating and standard laryngeal mask airway; but not with fiberscope-guided nasal intubation. For cervical motion and the techniques tested, the safest airway technique with this injury is fiberscope-guided nasotracheal intubation. Laryngeal mask devices are preferable to the esophageal tracheal Combitube.

On September 19, 1991, at an altitude of 3,200 m (10,498 feet), the remains of a well-preserved, freeze-dried mummified body of a 3,000 BC, Late Stone Age man, was found on the Austrian-Italian border. Studies conducted at the University of Innsbruck have revealed that these are the remains of a 45-46-year-old male, 45 kg (99 lbs) (living weight) and 160 cm (5 feet, 2 inches) tall. Morphometric, pathophysiologic, paleobotanical, photogrammetric, anthropological, computer tomographic, and other studies have been conducted to determine the living conditions and possible causes of death of this Late Stone Age man.

The 5,200-year-old Tyrolean Ice Man discovered in 1991 in the Otztal Alps is the world's most ancient known human glacier mummy. Histological investigation was aimed at 1) optimizing specimen preparation and 2) documenting the preservation state of (sub)cellular components. Minute pieces of frozen tissue were removed endoscopically from rib bone and cartilage, major blood vessels, oral cavity and alimentary tract, liver, spleen, diaphragm, respiratory system, femoral muscle and nerve, sympathetic trunk, brain, and skin. Double fixation with glutaraldehyde followed by osmium tetroxide and embedding in Epon/Araldite epoxy resins proved to be the method of choice for both light and transmission electron microscopy combined with classical histochemistry. In particular, mild evacuation of the desiccated tissue was determined to be essential to ensure homogeneous infiltration with fixatives and resins; as a result, sections of excellent quality could be obtained with any kind of sample. With regard to the preservation degree of (sub)cellular components, distinct tissue-specific patterns were observed. There were highly intact skeletal and connective tissues proper, however, most interestingly, there were remarkably intact nervous tissue components as well. By contrast, epithelial, muscle, and reticular connective tissues as well as blood had generally disintegrated due to autolysis, freeze/thaw damage, and adipocere formation. For a tentative interpretation of these patterns, we considered general aspects of cryopreservation, such as physicochemical properties of subcellular constituents and tissue physiology.

The role of the periosteal and intraosseous blood supply to the femur and the proximal tibia was investigated to improve the operating technique for transplantation of allogenic vascularized femoral diaphyses and knee joints in humans. Altogether 48 limbs were injected with gelatin, red latex milk, or Revertex and macroscopically prepared; 41 limbs were studied for the variation and division of the truncus profundo-circumflexus. In 200 femurs and 200 tibias the location of the nutrient foramen was determined. The arteries supplying the periosteum of the distal femur and the proximal tibia have defined nutritive areas. The following technique should be followed: If the femoral artery alone is prepared as the vascular pedicle, the optimal section for resection of the femur in knee joint transplantations is 6 to 12 cm above the level of the femur condyles and 5 to 7 cm below the tibial plateau. For the transplantation of femoral diaphyses, the deep femoral artery can be used if the lateral femoral circumflex artery is protected. The Proximal line of resection is defined between the greater and lesser trochanter. For shorter grafts one must consider the number and location of nutrient foramens. For longer grafts the distal branches of the femoral artery must be respected as the intraosseous blood supply reaches distally down to the level of about 8 cm above the femoral condyles. In all these operations of the variation of the truncus profundo-circumflexus and the trifurcation of the popliteal artery must be considered.

Aim: The aim of this paper is to describe the adaption of 3D-navigation for interstitial brachytherapy. The new method leads to prospective and therefore improved planning of the therapy (position of the needle and dose distribution) and to the possibility of a virtual simulation (control if vessels or nerves are on the pathway of the needle)., Material and Methods: The EasyGuide Neuro navigation system (Philips) was adapted in the way, that needles for interstitial brachytherapy were made connectable to the pointer and correctly displayed on the screen. To determine the positioning accuracy, several attempts were performed to hit defined targets on phantoms. Two methods were used: "free navigation", where the needle was under control of the navigation system, and the "guided navigation" where an aligned template was used additionally to lead the needle to the target. In addition a mask system was tested, whether it met the requirements of stable and reproducible positioning. The potential of applying this method in clinical practice was tested with an anatomical specimen., Results: About 91% of all attempts lied within 5 mm. There were even better results on the more rigid table (94% < 4 mm). No difference could be seen between both application methods ("free navigation" and "navigation with template"), they showed the same accuracy., Conclusions: The accuracy of the phantom experiments and the confirmation by the experiment with the anatomical specimen showed that excellent results can be expected in clinical practice using rigid tables and patient supporting systems.

Background: The Iceman is a prehistoric, completely preserved, 5300-year-old male human mummy., Objective: To obtain the first biopsy specimens from inside the Iceman while meeting an extended standard of hygiene and following precise intraoperative guidance to the site of biopsy and keeping tissue damage to a minimum., Design: Biopsy specimens from the nose, the maxillary sinus, and the larynx of the Iceman were obtained. Special caution had to be taken while performing the biopsies to not contaminate the Iceman with heavy metals or remnants of microorganisms., Subject: The Iceman, a cadaver kept frozen in a glacier for 5300 years. The Iceman is in an excellent state of preservation and will allow fundamental histological, morphological, and molecular genetic insights into early man., Intervention: The biopsies were planned and executed with the aid of Interventional Video Tomography, a system that guides the surgeon to the target area by combining live video with existing imaging modalities. The system does not need mechanical fixation of the subject (the Iceman) and is barely in physical contact with the subject; thus, it was the ideal tool for guiding the surgeon to the site of the biopsy samplings through a tiny canal into the nose, the maxillary sinus, and the larynx of the Iceman., Results: We have obtained a number of tissue samples by precisely guided 3-dimensional navigation. Unnecessary tissue damage was avoided., Conclusions: Visual inspection of the extracted mucosa showed typical human cadaver tissue, despite its age, without clinical abnormalities. Currently, the samples are being investigated by various international scientific groups.

A soluble HLA ELISA for the detection of donor specific anti-HLA class I IgG antibodies was developed and compared with microlymphocytotoxicity. Donor sHLA was prepared from donor blood or purified blood lymphocytes and captured onto monoclonal antibody coated ELISA plates. After incubation of captured HLA with test serum, bound IgG antibodies were detected using a peroxidase-conjugated anti-human IgG antibody. Serum samples from patients on waiting lists to receive kidney transplants were tested by lymphocytotoxicity (AHG protocol) and/or sHLA ELISA in four different laboratories using HLA preparations from eight organ donors. Concordant crossmatch results were obtained for 854 (99%) of 864 ELISA crossmatches. In contrast, concordant results were obtained for 234 (91%) of 256 lymphocytotoxicity crossmatches. Interlaboratory reproducibility of ELISA results was 99%. In contrast, interlaboratory reproducibility of lymphocytotoxicity assay results was 78%. Endpoint titrations of serum specimens containing anti-HLA antibodies demonstrated equivalent sensitivity of ELISA and AHG lymphocytotoxicity crossmatch and similar sensitivity of ELISA and flow cytometry crossmatch. Specimens tested positive by lymphocytotoxicity without DTT treatment but negative with DTT treatment were tested negative by ELISA. Comparison of lymphocytotoxicity and ELISA crossmatch results showed an agreement of 94%. This demonstrates that detection of anti-donor HLA class I antibodies by ELISA is a reliable alternative to microlymphocytotoxicity testing.

The posterior cruciate ligament (PCL) can be anatomically divided into three bundles: anterolateral, posteromedial, and posterior oblique. The changes in distance between the femoral and tibial attachment sites of these three bundles were measured in 10 human knee specimens with intact ligamental structures. The femoral to tibial distance (and thus the length) of the posterior oblique bundle remained nearly the same throughout flexion between 0 degrees and 90 degrees. The femoral to tibial distance of the anterolateral and the posteromedial bundles distinctly changed throughout the same range of motion. For a truly functional replacement of the PCL, correct isometric placement of the transplant is especially important. Based on the results of the present study, an isometric reconstruction of the PCL is achieved by positioning the graft within the original attachment site of the posterior oblique bundle.

Renal function was studied in 2 groups of renal transplant recipients and their donors by technetium-99m diethylenetriamine pentaacetic acid and a gamma camera. The pediatric group (group A) comprised 40 children and their adult kidney donors. The adult group (group B) consisted of 112 consecutive adult renal transplant recipients and their adult donors. All patients received kidneys from living donors and were given the same immunosuppression protocol (PRED plus CSA). Donor glomerular filtration rate (GFR) was determined before nephrectomy and at a mean period of 30 (range 10-50) months after nephrectomy. The graft GFR was measured at 1, 3, 6, and 12 months and at the most recent follow-up visit. Moreover, the functional reserve of the graft was assessed by infusion of dopamine and an amino acid. The postnephrectomy GFR of donors in groups A and B were 74 +/- 18 and 72 +/- 20 ml/min/1.73 m2, respectively. The GFR of pediatric recipients was significantly lower than that of adult recipients at corresponding time points along the course of follow-up. The mean values of graft GFR were 47.6 +/- 20 and 63.8 +/- 29.6 ml/min/1.73 m2 for pediatric and adult recipients, respectively (P < 0.001). Moreover, the graft functional reserve was significantly lower in pediatric recipients. These data demonstrate that adult kidneys transplanted into pediatric recipients have lower GFR than those transplanted into adults, despite corrections for body surface area. Although the reason for this phenomenon is unknown, the observation may have important implications for management of pediatric recipients.

The morphological foundations of CT-imaging of the cruciate ligaments in 4 different positions of examination are presented comparing roughly identical anatomical sections with CT-scans. Several parts of the cruciate ligaments, such as origin, course and insertion can be viewed in different CT-planes.

The flexor tendons in the region of the palm obtain their blood supply from an arterial network in the peritenon, which is fed by the superficial palmar arch and its branches. Rarely this network is supplied by the deep palmar arch. The origin, course and number of the arterial branches supplying the flexor tendons are described in detail. At least one of these nutrient arteries must be preserved in flexor tendon surgery. An adequate arterial supply of the tendons in the digital sheath can only be ensured by preserving all vincula tendinum.

Degeneration of the knee joint and increase of anterior-posterior tibial displacement are resulting from total meniscectomy, especially in knees with anterior cruciate deficiency. Vascularisation of the meniscus was studied in 12 cadaver knees after latex injection of vessels. Vascularisation of the anterior and posterior horns was found to be much better than that of the body of meniscus. All vessels originated from the popliteal artery, but variably in importance, and formed the perimeniscal and subsynovial network. 11 peripheral meniscus tears (8 freshly injured, 3 ruptures older than 2 months) were repaired by refixation, followed by immobilisation for 6 weeks. Arthroscopy 3 months postoperatively showed complete healing of all tears. Clinical examinations--follow-up for 14 months--showed no signs of rerupture in any of the patients.