Neoquadruple induction with antithymocyte globulin/azathioprine/cyclosporine/prednisolone in simultaneous pancreas and kidney transplant recipients: 8.5-year results

Ten years ago therapy with antithymocyte globulin or OKT3, azathioprine, cyclosporine, and prednisolone was the most common induction treatment for simultaneous pancreas/ kidney (SPK) recipients. Although immunosuppression was started after surgery, there was a high incidence of acute rejection episodes. In 1995, we modified the application of antithymocyte globulin and prednisolone by starting prior to reperfusion. Between 1995 and 1996, 30 patients underwent a first SPK. Prior to reperfusion, antithymocyte globulin (4-6 mg/kg body weight) and 250 mg prednisolone were administered. Intraoperatively, another 250 mg prednisolone were administered as well as intravenous azathroprine 3 mg/kg. After surgery up to 10 doses of antithymocyte globulin were administered and cyclosporine trough levels targeted to 200 to 250 ng/mL. Prednisolone was reduced gradually. After a median period of 8.5 years (range: 7.8-9.5 years) patient, pancreas, and kidney graft survival were 93.3%, 70%, and 76.7%, respectively. Sixteen acute rejection episodes were diagnosed in 11 patients (36.7%), who were treated with prednisolone bolus (n = 4), prednisolone with OKT3 (n = 8), prednisolone with antithymocyte globulin (n = 1), cyclosporine to tacrolimus conversion (n = 2), or plasmapheresis (n = 1). Two recipients died after SPK due to severe infection or carcinoma with functioning grafts. Seven further pancreas grafts were lost. Five kidney losses were observed besides the two recipients who died with functioning grafts. While previous protocols yielded a rejection incidence after SPK between 50% and 80%, we observed 60% of patients with no rejection episode during an 8.5-year median follow-up.     

Operative Treatment and Soft Tissue Management of Open Distal Tibial Fractures – Pitfalls and Results

Open tibial fractures usually result from high-energy trauma. Severe soft-tissue injuries are often combined with open fractures of the distal tibia. A consecutive series of 42 patients with open extraarticular distal tibial fractures (Gustilo I–IIIc) operated on between July 2006 and February 2009 were included in the study reported here. We performed open reduction and internal fixation for the Gustilo I cases. Soft tissue was closed directly after antibiotic beads had been temporarily applied. For the Gustilo II and III cases, our treatment protocol included soft-tissue debridement of all devitalized soft tissue and bone fragments, pulsatile jet irrigation, and external stabilization. Soft tissue was temporarily closed with Epigard_ after the application of antibiotic beads. A second-look operation was scheduled after 3–5 days. Gustilo II patients needed an average of 1.1 (0–3) revisions until wound closure, compared to the average of 2.1 revisions necessary for the Gustilo III patients. It took 5.6 (0–16) days to obtain definitive wound closure in the Gustilo II patients and 9.9 (3–28) days in the Gustilo III patients. Skin grafting was sufficient for definitive softtissue closure in ten cases, local flaps in eight cases, and free musculocutaneous flaps were needed in six cases. Gustilo II patients with primary wound closure remained hospitalized for 11 days, while patients with secondary wound closure stayed in hospital for an average of 20 days. Our early results concerning infection rate, number of reoperations, and time to bony consolidation can be compared with other studies. Functional results will have to be evaluated at clinical follow-up.     

Near-infrared spectroscopic cerebral oxygenation reading in neonates and infants is associated with central venous oxygen saturation

BACKGROUND: The aim of the study was to elucidate easily determinable laboratory and vital parameters in clinical practice to explain variability of near-infrared spectroscopic cerebral oxygenation readings in critically ill newborns and infants using the NIRO 300 spectrometer. METHODS: Near-infrared spectroscopy (NIRS) cerebral tissue oxygenation index (cTOI) was measured on the forehead of critically ill neonates and infants with existing arterial and/or central venous access. We recorded patient characteristics and simultaneously determined sedation state, hemodynamic, respiratory and laboratory data, such as arterial blood gas analysis, electrolytes, hemoglobin and arterial lactate concentration, blood glucose and central venous oxygen saturation. Data were compared using linear, multiple and forward stepwise regression analysis (P < 0.05). RESULTS: A total of 155 neonates and infants aged from 0 to 365 days (median 12 days) were studied. cerebral tissue oxygenation index (cTOI) values ranged from 32.1 to 91.0% (60.5 +/- 11.5%). Simple linear regression analysis revealed significant associations between cTOI and arterial oxygen saturation (r = 0.254, P = 0.001), transcutaneously measured arterial oxygen saturation (r = 0.320, P < or = 0.0001), central venous oxygen saturation (r = 0.489, P < 0.0001), arteriovenous oxygen extraction (r = 0.445, P < 0.0001) and presence of a cardiac shunt (r = 0.250, P = 0.024). Multiple regression analysis and forward stepwise regression revealed two independent, significant predictors for cTOI, namely SvO2 (P < 0.0001) and presence or absence of a cardiac shunt (P = 0.003). SvO2 alone explained 23.9% of the variability of cTOI. The addition of the variable 'cardiac shunt' improved the model to 33%. CONCLUSIONS: Based on our study results cerebral tissue oxygenation readings by the NIRO 300 near-infrared spectrometer is influenced by central venous oxygen saturation, which partially explains intersubject variability of NIRS cerebral oxygenation readings.     

The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials

To comprehend the results of a randomized, controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this paper incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Discussion. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from four stages of trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, for each intervention group, that are included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.     

HLA-haploidentical blood progenitor cell transplantation in osteopetrosis

Infantile osteopetrosis (OP) carries an extremely poor prognosis unless treated early by hematopoietic stem cell transplantation. We explored the use of purified blood progenitor cells from HLA-haploidentical parents in 7 patients lacking suitable matched donors. Blood progenitor cells were purified by positive selection and by additional T-cell depletion using rosette formation. For conditioning, patients received busulfan, thiotepa, and either cyclophosphamide (5 patients) or fludarabine (2 patients). Stable donor engraftment developed in 6 of 7 patients. Graft-versus-host disease was not observed. Three of the 7 patients had no major complications and 4 of 7 had both veno-occlusive disease and respiratory failure. Five of 7 patients survive with complete cure of OP at a median of 4 years. Patients with OP lacking HLA-matched donors can be successfully treated by transplantation of purified blood progenitor cells from HLA-haploidentical donors.     

Relationship between body fat mass,carbohydrate tolerance and iri response during glucose infusion in subjects with early diabetes

Summary We have studied the interrelationship of total body fat mass, carbohydrate tolerance and IRI response in 17 non-obese and obese subjects, who were suspected of having early diabetes. We carried out an i.v. glucose infusion test consisting of a priming injection of 0.33 g/kg followed by constant glucose infusion of 12 mg/kg/min in all persons. Total body fat mass was estimated by the tritium dilution method. There was a positive correlation of body fat mass, fasting glucose concentration and blood glucose concentration at 150 min as well as a strong correlation between body fat mass and BG area 60–120 min as parameters of carbohydrate tolerance in all subjects, i.e. the degree of carbohydrate intolerance was directly related to the quantity of total body fat mass. A similar correlation was found when the non-obese and obese groups were analyzed separately. In neither group did total body fat mass correlate with parameters of IRI response. In obese subjects with pathological carbohydrate tolerance, however, a positive correlation of basal IRI concentration and total body fat mass was found. Furthermore, a close relation between basal IRI level and parameters of carbohydrate tolerance could be demonstrated in obese subjects. The present study failed to demonstrate any correlation of parameters of carbohydrate tolerance and glucose-induced IRI response in either group. Thus, the significant relationship between body fat mass and degree of carbohydrate intolerance indicates that total body fat mass plays an important role in the disturbance of blood glucose homeostasis in early diabetes with and without obesity. Investigation performed within the medical research project ‘Diabetes mellitus and disturbances of lipid metabolism’, Ministry of Health, GDR.     

Variability and evolution of Kaposi's sarcoma-associated herpesvirus in Europe and Africa. International Collaborative Group.

OBJECTIVE: To study the evolution of Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 in Europe and Africa. DESIGN AND METHODS: PCR and sequence analysis of the variable viral membrane glycoprotein gene K1 in 58 tumour and peripheral blood samples from patients with AIDS-related Kaposi's sarcoma (KS), 'classic' (HIV-negative) KS, transplant KS, Multicentric Castleman's Disease, other lymphoproliferative disorders, and healthy KSHV-infected individuals from the UK, Denmark, Sweden, Italy, Spain, Iceland, The Faroe Islands, Greece, The Gambia and Uganda. RESULTS: Three major groups of K1 sequences were found: A, B and C, as defined previously. The K1 gene has evolved, both within and between these three groups, under positive selection. KSHV group B strains predominate in Africa and are more distant from groups A and C, found in Europe, than A and C are from each other. Within group C two subgroups, C' and C", can be identified. Subgroup C" is more closely related to group A in a region of the K1 protein and appears to be phylogenetically close to the branchpoint between A and C. Group A and C strains are currently found in both HIV-1-infected and -uninfected Europeans, and were already present in Europe before the start of the AIDS epidemic. We found some examples of closely related K1 sequences in Italy and Denmark, but in general KSHV strains in Europe did not cluster geographically. CONCLUSION: KSHV strains in East and West Africa are closely related but phylogenetically distant from those in Europe. The two major KSHV groups in Europe are more closely related, with some strains adopting an intermediate phylogenetic position. In Europe, KSHV strains may have been disseminated at least several decades ago. Variability in the K1 region is driven by selection and does not correlate with different KSHV-related pathologies or geographic regions where clinically more aggressive HIV-negative KS ('endemic' KS) is more common.     

Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid Ineffective Conservative Long-term Therapy

Purpose

Chronic leg ulcers can be a challenge to treat and long-term therapy a significant cost factor in western public health budgets. Objective wound assessment assays enabling selection of appropriate wound therapy regimes would be desirable. Oxygenation status in ulcer tissue has obtained increased attention as a relevant factor in wound healing. To increase oxygenation in wounds, a topical hemoglobin spray was developed. Although favorable results have been noted, the link between clinical efficacy and the mode of action has not been demonstrated. The aims were to determine if changes in tissue oxygenation can be measured after topical application of hemoglobin on chronic wounds and to evaluate the findings in terms of therapy strategies.

Procedures

Photoacoustic imaging was used to measure the local oxygen saturation (StO₂) in leg ulcers before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was histopathologically graded and the change in wound size was documented in a follow-up examination.

Results

Measuring 49 patients, an increase in StO₂ after topical hemoglobin application from on average 66.1 to 71 % (p = 0.017) after 20 min was observed. Depending on the increase in StO₂ (>10 % or <10 %) patients were stratified into a Responder and a Non-Responder group. Wound size significantly decreased in the Responder Group (p = 0.001), while no significant difference in the Non-Responder group (p = 0.950) was noted.

Conclusion

Our findings suggest that the likelihood of wound healing under conservative therapy can be predicted by measuring changes in StO₂ after topical hemoglobin application. This assay may reduce treatment time and costs by avoiding ineffective conservative long-term therapy.

Trial Registration

German Clinical Trials Register: DRKS00005993