Randomized controlled trial comparing the controlled rehabilitation with early ambulation and diet pathway versus the controlled rehabilitation with early ambulation and diet with preemptive epidural anesthesia/analgesia after laparotomy and intestinal resection

BACKGROUND: Multimodal postoperative care regimens accelerate recovery after abdominal surgery. The benefit of thoracic epidural (TE) analgesia over patient-controlled analgesia (PCA) remains unproven when used with a fast-track postoperative care plan. METHODS: Fifty-six patients undergoing major intestinal resection, and on a fast-track postoperative care plan, were randomized to preemptive TE or PCA. Patients were evaluated at standard time points for pain score, quality of life (Short Form-36), and complications. Oral analgesia was substituted for TE and PCA on the second postoperative day. Discharge criteria were identical for both groups. RESULTS: Six patients (20.6%) had a failed epidural. There was no difference in length of stay (5.8 versus 6.2 days, TE versus PCA, P = .55), total length of stay (including readmissions), pain scores, quality of life, complications, or hospital costs at any time point. CONCLUSION: TE offers no advantage over PCA for patients undergoing major intestinal resections who are on a fast-track postoperative care plan using PCA.     

Clinically relevant concentrations of propofol but not midazolam alter in vitro dendritic development of isolated gamma-aminobutyric acid-positive interneurons

BACKGROUND: Recent laboratory studies showed that exposure to supraclinical concentrations of propofol can induce cell death of immature neurons. However, no data are available regarding the effects of clinically relevant concentrations of this agent on neuronal development. The authors addressed this issue by evaluating the effect of propofol on dendritic growth and arbor expansion of developing gamma-aminobutyric acid-positive (GABAergic) interneurons. METHODS: Immature neuroblasts were isolated from the newborn rat subventricular zone and differentiated into GABAergic interneurons in culture. In addition to cell death, the effects of increasing concentrations and durations of propofol exposure on neuronal dendritic development were evaluated using the following morphologic parameters: total dendritic length, primary dendrites, branching point, and Scholl analysis. RESULTS: The authors demonstrate that propofol induced cell death of GABAergic neurons at concentrations of 50 microg/ml or greater. As little as 1 microg/ml propofol significantly altered several aspects of dendritic development, and as little as 4 h of exposure to this agent resulted in a persistent decrease in dendritic growth. In contrast, application of midazolam did not affect neuronal development. CONCLUSION: Short-term exposure of immature developing GABAergic neurons to clinically relevant concentrations of propofol can induce long-term changes in dendritic arbor development. These results suggest that propofol anesthesia during central nervous system development could interfere with the molecular mechanisms driving the differentiation of GABAergic neurons and thus could potentially lead to impairment of neural networks.     

Salvage of post-traumatic arthritis following distal radius fracture

There are practical recommendations that can be drawn from the aforementioned results. Due to the minimal morbidity of the wrist denervation, patients with good but painful wrist motion following fracture of the distal radius should first be evaluated for wrist denervation unless formal resection of the dorsal interosseous nerve has clearly been included in the previous treatment. The evaluation is performed in a standardized manner before and after test infiltration of both interosseous nerves. This evaluation includes assessment of pain, strength, and working capacity. Whereas the grip strength often does not (cannot)increase more than 10% to 20%, the subjective pain relief can be remarkable, leading to higher repetition counts and increased dexterity. Inpatients with insufficient response to the anesthetic nerve blocks, other pain sources must be sought, especially on the ulnar side of the wrist.Patients with less than functional range are candidates for complete arthrodesis. A way for further evaluation with regard to the potential of partial and complete wrist arthrodesis is trial immobilization of the wrist in a light cast ora firm reinforced brace. Trial immobilization also allows anticipating the functional deficit from loss of range of wrist motion. Due to the still-unrestricted pronation and supination, ulnar-sid-ed wrist pain may persist and will need adequate follow-up adjunct treatment. Patients who have good pain relief but are not willing to completely lose their wrist motion should be evaluated fluoroscopically or receive lateral radiographs in full flexion and extension to measure their mid-carpal joint mobility and anticipate the potential residual motion after radiocarpal fusion. Patients without pain relief from test anesthesia, trial immobilization, and no apparent distal radioulnar joint pathology are poor candidates for further operative treatment.In evaluating different salvage procedures,among all diagnoses, painful arthritis following fracture of the distal radius is the most difficult to treat and yields the poorest results. Emphasis must therefore be on better initial fracture treatment and earlier secondary reconstructive interventions. The current salvage procedures must allow further improvement or alternatives must be developed. Prosthetic replacement merits serious consideration, especially when it can be adapted to the specific post-traumatic setting. This situation is not worse than rheumatoid arthritis because the clinician is dealing with healthy and strong intact bone stock, tendons, and ligaments,and most important, complete absence of a progressive disease.     

The expression of inflammatory cytokines,TAM tyrosine kinase receptors and their ligands is upregulated in venous leg ulcer patients: a novel insight into chronic wound immunity

The systemic host defence mechanisms, especially innate immunity, in venous leg ulcer patients are poorly investigated. The aim of the current study was to measure Candida albicans killing activity and gene expressions of pro‐ and anti‐inflammatory cytokines and innate immune response regulators, TAM receptors and ligands of peripheral blood mononuclear cells separated from 69 venous leg ulcer patients and 42 control probands. Leg ulcer patients were stratified into responder and non‐responder groups on the basis of wound healing properties. No statistical differences were found in Candida killing among controls, responders and non‐responders. Circulating blood mononuclear cells of patients overexpress pro‐inflammatory (IL‐1α, TNFα, CXCL‐8) and anti‐inflammatory (IL‐10) cytokines as well as TAM receptors (Tyro, Axl, MerTK) and their ligands Gas6 and Protein S compared with those of control individuals. IL‐1α is notably overexpressed in venous leg ulcer treatment non‐responders; in contrast, Axl gene expression is robustly stronger among responders. These markers may be considered as candidates for the prediction of treatment response among venous leg ulcer patients.     

Association between serum resistin level and outcomes in kidney transplant recipients

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio‐demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition‐Inflammation in Transplant—Hungary Study (MINIT‐HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6‐year follow‐up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow‐up period (median [IQR]: 22[15–26] vs. 19[14–22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16–1.54) and 1.21(1.01–1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.     

LCT 13910 C/T polymorphism, serum calcium, and bone mineral density in postmenopausal women

Summary  LCT 13910 CC genotype is associated with lactose intolerance, a condition often resulting in reduced milk intake. Women with the CC genotype were found to have decreased serum calcium and reduced bone mineral density. Introduction  The CC genotype of the 13910 C/T polymorphism of the LCT gene is linked to lactose intolerance and low calcium intake. Methods  We studied 595 postmenopausal women, including 267 osteoporotic, 200 osteopenic, and 128 healthy subjects. Genotyping, osteodensitometry, and laboratory measurements were carried out. Results  Frequency of aversion to milk consumption was 20% for CC genotype and 10% for TT + TC genotypes (p = 0.03). The albumin-adjusted serum calcium was 2.325 ± 0.09 mmol/L for CC genotype and 2.360 ± 0.16 mmol/L for TT + TC genotypes (p = 0.031). Bone mineral density (BMD; Z score) was lower in the CC than TT + TC genotypes, respectively, at the radius (0.105 ± 1.42 vs 0.406 ± 1.32; p = 0.038), at the total hip (−0.471 ± 1.08 vs −0.170 ± 1.09; p = 0.041), and at the Ward’s triangle (−0.334 ± 0.87 vs −0.123 ± 0.82; p = 0.044). Conclusion  LCT 13910 C/T polymorphism is associated with decreased serum calcium level and lower BMD in postmenopausal women. Péter Lakatos and Gábor Speer contributed equally to this work.     

Regulatory role of host CD8+ T lymphocytes in experimental graft-versus-host disease across a single major histocompatibility complex class II incompatibility

BACKGROUND: CD8+ T cells are known to regulate type 2 helper T cell (Th2) alloreactive immune responses but their mode of activation is unclear. We investigated the role of host CD8+ T cells in experimental Th2-type graft-versus-host disease (GVHD) where donor/recipient disparity is restricted to a single major histocompatibility complex (MHC) class II antigen. METHODS: Immunoglobulin (Ig) E serum levels, eosinophilia and lymphoid tissue hyperplasia were compared after injection of bm12 CD4+ T cells in either wild-type or CD8+ T cell-deficient (CD8-/-) C57BL/6 mice. In vitro, we explored effects of the addition of CD8+ T cells from wild-type or IFN-gamma-/- mice in mixed leukocyte cultures prepared with beta2 microglobulin-deficient (beta2m-/-) CD4+ T cells as responders or beta2m dendritic cells as stimulators. RESULTS: HyperIgE resolved after 3 weeks in wild-type hosts whereas it persisted for 6 weeks in CD8-/- hosts. Eosinophil infiltrates in lymph nodes were significantly enhanced in CD8-/- hosts. Increased serum levels of IL-5 and IL-13 in CD8-/- hosts confirmed the enhancement of Th2-type responses in the context of recipient CD8+ T cell deficiency. Hyperplasia of lymph nodes and spleen were similar in both groups, as well as in vivo proliferation of donor CD4+ T cells. In vitro, CD8+ T cell regulation of the alloreactive Th2 response depended on their production of IFN-gamma and did not require expression of beta2m on CD4+ T cells or antigen-presenting cells. CONCLUSIONS: Host CD8+ T cells regulate alloreactive Th2 responses during graft-versus-host disease through an IFN-gamma dependent pathway, independently of the recognition of beta2m-associated MHC class I molecules.     

Repetitive transarterial chemoembolization (TACE) of liver metastases from gastric cancer: Local control and survival results

Objective

To evaluate the local tumor control and survival data after transarterial chemoembolization with different drug combinations in the palliative treatment of patients with liver metastases of gastric cancer.

Materials and methods

The study was retrospectively performed. 56 patients (mean age, 52.4) with unresectable liver metastases of gastric cancer who did not respond to systemic chemotherapy were repeatedly treated with TACE in 4-week intervals. In total, 310 chemoembolization procedures were performed (mean, 5.5 sessions per patient). The local chemotherapy protocol consisted of mitomycin alone (30.4%), mitomycin and gemcitabine (33.9%), or mitomycin, gemcitabine and cisplatin (35.7%). Embolization was performed with lipiodol and starch microspheres. Local tumor response was evaluated by MRI according to RECIST. Survival data from first chemoembolization were calculated according to the Kaplan–Meier method.

Results

The local tumor control was: complete response in 1.8% (n = 1), partial response in 1.8% (n = 1), stable disease in 51.8% (n = 29) and progressive disease in 44.6% (n = 25) of patients. The 1-, 2-, and 3-year survival rate from the start of chemoembolization were 58%, 38%, and 23% respectively. The median and mean survival times were 13 and 27.1 months. A Statistically significant difference between patients treated with different chemotherapy protocols was noted (ρ = 0.045) with the best survival time in the mitomycin, gemcitabine and cisplatin group.

Conclusion

Transarterial chemoembolization is a minimally invasive therapy option for palliative treatment of liver metastases in patients with gastric cancer.     

Brain metastasis

Background and purpose

This study was performed to evaluate the prognostic role for survival of the number and the type of involved extracranial organs in patients with brain metastasis.

Material and methods

The data of 1146 patients who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been retrospectively analyzed. In addition to the number of involved extra cranial organs, seven potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type, number of brain metastases, and the interval from cancer diagnosis to WBRT. Additionally, subgroup analyses were performed for patients with involvement of one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations) extracranial organs.

Results

The 6-month survival rates for the involvement of 0, 1, 2, 3, and ≥?4 extracranial organs were 51, 30, 16, 13, and 10?%, respectively (p?<?0.001). On multivariate analysis, the number of involved extracranial organs maintained significance (risk ratio 1.26; 95?% confidence interval 1.18–1.34; p?<?0.001). According to the multivariate analysis, age (p?<?0.001), gender (p?=?0.002), and KPS (p?<?0.001) were also independent prognostic factors for survival. In the subgroup analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the extracranial organ involved.

Conclusion

The number of involved extracranial organs proved to be an independent prognostic factor in patients with brain metastasis, regardless of the organs involved. The number of involved extracranial organs should be considered in future trials designed for patients with brain metastasis.