Presence of Epstein-Barr virus latent membrane protein 1 gene in the nasopharyngeal swabs from patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common head and neck malignancy in southeastern China and Taiwan. Early detection of the local disease followed immediately by proper treatment is essential to increase the cure and survival rates. Because every NPC tumor cell carries Epstein-Barr Virus (EBV) genomes, detection of EBV genomic DNA such as latent membrane protein 1 gene (LMP1) might indicate the presence of NPC. We developed a simple and noninvasive technique of nasopharyngeal swabbing to acquire nasopharyngeal cells for detecting the presence of EBV genome. The aim of this study was to investigate the feasibility and reliability of this technique. METHODS: We collected nasopharyngeal cells by means of a nasopharyngeal swabbing technique and detected the presence of EBV LMP1 with polymerase chain reaction (PCR). Thirty-eight swab specimens were obtained from patients with NPC who were newly diagnosed or were just beginning radiotherapy. Two groups of control subjects were recruited, including 20 patients with other head and neck cancers and eight family members of the NPC patients. An additional group of 65 NPC patients were enrolled in the course of regular follow-up after definitive radiotherapy. RESULTS: All of the samples yielded sufficient DNA for PCR amplification. Thirty-six of 38 NPC swab samples were positive for EBV LMP1, and all the control subjects had swab sample results negative for EBV. All five patients with suspected local recurrence exhibited positive EBV test results. CONCLUSIONS: Demonstration of EBV LMP1 in the nasopharyngeal swab specimens detected NPC with a sensitivity of 94.7% and specificity of 100%. This study confirms the reliability and feasibility of nasopharyngeal swab in the predicting and screening of NPC.     

One-year posttransplant renal function is a strong predictor of long-term kidney function: results from the Neoral-MOST Observational Study

BACKGROUND: Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study--Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. RESULTS: Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 micromol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. CONCLUSIONS: Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.     

EB病毒阳性晚期鼻咽癌患者行TCR-T治疗的护理

目的 总结EB病毒阳性晚期鼻咽癌患者行T细胞受体工程化T细胞(TCR-T)治疗的护理经验,为临床护理提供借鉴.方法 对13例行TCR-T治疗的EB病毒阳性晚期鼻咽癌患者,做好TCR-T治疗的预处理护理、TCR-T输注护理;密切观察病情,及早发现异常及时有效处置;做好随访等.结果 13例均顺利完成TCR T治疗,治疗后2...     

Poor response to recombinant erythropoietin is associated with loss of T-lymphocyte CD28 expression and altered interleukin-10 production.

BACKGROUND: Recombinant erythropoietin (Epo) therapy is well established as an effective treatment for the anaemia of end-stage renal disease. However, 5-10% of such patients do not respond adequately and an important contributory factor to this is chronic inflammation. METHODS: The present study compares the circulating T-cell phenotypes of haemodialysis patients who respond poorly to Epo with those who respond well, along with normal controls. Isolated peripheral blood mononuclear cells were labelled with immunofluorescent monoclonal antibodies to surface antigens and analysed by flow cytometry. In vitro mononuclear cell cytokine secretion was also studied in the three subject groups. The cells were cultured for 48 h either without stimulus, with lipopolysaccharide or with monoclonal antibodies to CD3 and CD28. RESULTS: C-reactive protein levels were increased in poor responders to Epo (18.6 +/- 20.7 mg/l) compared with good responders (8.7 +/- 8.0 mg/l) and normal controls (3.8 +/- 1.1 mg/l). Patients responding poorly to Epo had increased circulating levels of CD4+/CD28- and CD8+/CD28- T-cells compared with patients responding well to Epo and normal controls. Unstimulated mononuclear cells from poor responders showed increased in vitro generation of interleukin-10 (IL-10) compared with both patients responding well to Epo and normal controls. Additionally, IL-10 generation stimulated by monoclonal antibodies to CD3 and CD28 was increased in poor responders compared with normal controls. CONCLUSIONS: These findings suggest that patients responding poorly to Epo may show enhanced immune activation as manifest by changes in both T-cell function and phenotype.     

Risk of lymphoid neoplasia after cardiothoracic transplantation. a cohort study of the relation to Epstein-Barr virus

BACKGROUND: Organ transplantation is associated with a greatly increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD), which is often fatal. There has been little epidemiological analysis, however, of the risk factors for LPD in transplant patients and none on whether the risks of non-EBV-associated lymphoid neoplasms are also increased. METHODS: The risk of lymphoid neoplasia was assessed in a cohort of 1563 patients who underwent cardiothoracic transplantation at Harefield Hospital, UK from 1980 to 1994 and were followed until December 1995. EBV antibody was assessed in the patients before transplantation, and lymphoid neoplasms were assessed for EBV RNA and latent EBV gene expression. RESULTS: Thirty cases of LPD occurred during follow-up. One lymphoma of unknown EBV status occurred. There were also six cases of EBV-negative non-Hodgkin's lymphoma (EBV-negative NHL), a highly significant excess over expectations from the general population rates of NHL (standardized incidence ratio 10.2 [95% confidence interval, 4.6-22.8]). The risk of LPD was significantly 10-fold raised in individuals who were EBV seronegative before transplantation; independently of this, it decreased steeply with age at transplantation and was greatest in the first year after transplantation. The risk was significantly raised in young seronegative recipients if the donor was older than the recipient. EBV-negative NHL occurred entirely in men 45 years old and older who were EBV seropositive before transplantation, and risk was not related to duration since transplantation. CONCLUSIONS: The risk factors found for LPD accord with EBV etiology and with greater hazard from primary infection than from reactivation. A second non-Hodgkin's lymphoid neoplasm, not related to EBV, seems also to be a consequence of transplantation and immunosuppression but is unlikely to be due to first infection by a ubiquitous agent. Its etiology and prevention need investigation separately from LPD.     

Prospective randomized study of conversion from tacrolimus to cyclosporine A to improve glucose metabolism in patients with posttransplant diabetes mellitus after renal transplantation

Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) compared with cyclosporine A (CYC). The present 12‐month, multicenter, investigator‐driven, prospective, randomized study was designed to assess whether conversion from tacrolimus to CYC can reverse PTDM after renal transplantation. Predominantly white patients with PTDM according to the 2005 American Diabetes Association criteria were randomized to either replacement of TAC with CYC or continuation of their TAC‐based regimen after stratification for type of glucose‐lowering therapy, steroid therapy, and hepatitis C status. At 12 months, 14 of 41 patients with complete data in the CYC arm (34%; 95%CI 19%‐49%) were free of diabetes, whereas this was the case in only 4 of 39 patients (10%; 95%CI 3%‐20%) in the TAC arm (P = .01). At 12 months, 39% of patients in the CYC arm were off glucose‐lowering medication vs 13% of patients in the TAC arm (P = .01). The CYC group decreased glycated hemoglobin level during the 12‐month follow‐up, resulting in significantly lower levels compared with the TAC group (6.0 ± 0.9% vs 7.1 ± 1.7% at 12 months; P = .002). In conclusion, replacement of TAC with CYC significantly improves glucose metabolism and has the potential to reverse diabetes during the first year after conversion. (EU Clinical Trials Register No. 2006‐001765‐42)     

Reactivations of cytomegalovirus, human herpes virus 6, and Epstein-Barr virus differ with respect to risk factors and clinical outcome after hematopoietic stem cell transplantation

One hundred two recipients of hematopoietic stem cell transplants (HSCTs) 45, from siblings and 57 from matched unrelated donors, were followed for cytomegalovirus (CMV), human herpes virus (HHV) 6, and Epstein-Barr Virus (EBV) reactivation by quantitative polymerase chain reaction in the context of immunologic reconstitution and posttransplantation complications. CMV, EBV, and HHV6 DNA copies (>100 copies/10(5) cells) were detected in 34%, 27%, and 26% of patients, respectively. The presence of 100 copies of EBV or CMV was associated with posttransplant complications: 29/66 versus 6/36 (P<.01) or 24/66 versus 4/36 (P=.01). CMV reactivation was more frequent among patients with acute graft-versus-host disease grade≥I: 17/35 versus 18/67 (P<.05). Older patient age of adults>16 year (2/16 versus 33/86; P<.05) and, to a lesser extent, CMV IgG positivity before HSCT (34/84 versus 1/10; P=.08) or an HLA-mismatched graft (9/16 versus 26/86; P=.08) constituted risk factors for CMV reactivation, which resulted in a higher rate of bacterial pneumonia (7/11 versus 28/91; P=.04). EBV reactivation risk was associated with donor EBV IgG seropositivity (28/84 versus 0/10; P=.03) and donor female gender (18/47 versus 10/55; P=.03). In contrast to EBV and CMV, EBV reactivation itself was associated with encephalitis (5/8 versus 23/94; P=.013), which was also seen as a trend among HHV6 reactivations (8/8 versus 46/94; P=.08). Multivariate analysis demonstrated that these factors play independent roles in the reactivation of the investigated herpes viruses.     

The impact of age on the response of patients with superficial bladder cancer to intravesical immunotherapy

PURPOSE: We determined the influence of age on response to intravesical immunotherapy in patients with superficial bladder cancer. MATERIALS AND METHODS: Data from a national phase II multicenter trial for BCG plus IFN-alpha intravesical therapy for superficial bladder cancer were analyzed. Recurrence-free survival 2 years after the initiation of therapy was examined in patients by incremental age decade. BCG-N patients received 81 mg BCG and 50 MU IFN-alpha, while patients who had previously been treated with BCG received a third of the BCG dose with 50 MU IFN-alpha and those who were BCG intolerant received a tenth of the BCG dose with 100 MU IFN-alpha. Kaplan-Meier survival curves were obtained. RESULTS: In all patients the largest difference in response was between the 289 who were 61 to 70 years old and the 123 who were older than 80 years with a 22% difference in cancer-free survival at a median followup of 24 months (61% vs 39%, p = 0.0002). When we assessed BCG-N and BCG treated patients separately in the 2 age groups, patients older than 80 years had a persistently lower response rate than younger patients 61 to 70 years old. Of BCG-N patients those older than 80 and younger than 50 years had the lowest cancer-free survival at a median followup of 24 months (47% and 45%, respectively). On multivariate analysis age was an independent risk factor for response. CONCLUSIONS: Aging appears to be associated with a decreased response to intravesical immunotherapy and is particularly apparent in patients older than 80 years. A potential explanation could be their depressed baseline immune status and consequent inability to mount an immune reaction to BCG or IFN-alpha.     

Early quality of recovery according to QoR-15 score is associated with one-month postoperative complications after elective surgery

Study objectiveThe QoR-15 scale is a validated tool to assess the quality of postoperative recovery (QoR). Our objective was to assess the association between the early QoR-15 values and the occurrence of one-month postoperative complications.DesignWe used the data from a prospective single-centre cohort study conducted in the Angers University Hospital from July 2019 to February 2020 that validated the French version of the QoR-15 (FQoR-15).SettingPreoperative room, ward, and home.Patients363 French-speaking adult patients, undergoing elective surgery, were enrolled (217 (59,8%) men, median age 60 (range 44 to 71) years old), including 139 (38.3%) ambulatory surgeries.InterventionPatients completed the QoR-15 scale the day before, at 24 and 48 h after surgery.MeasurementsPostoperative complications were recorded according to the PostOperative Morbidity Survey (POMS) classification till 30 days after surgery. The QoR was classified as excellent (QoR-15 > 135), good (122 ≤ QoR-15 ≤ 135), moderate (90 ≤ QoR-15 ≤ 121) or poor (QoR-15 < 90). Days alive and out of hospital up to 30 days after surgery was also recorded.Main resultsAccording to the POMS classification, 176 (48.5%) patients had at least one complication up to 30 days after surgery. Among the 69 (19.0%) patients with a poor recovery at H24, 58 (84.1%) had at least one complication up to 30 days after surgery compared to 10 (23.8%) among the 42 (11.6%) in the excellent recovery group (p < 0.0001). The QoR-15 score at H24 allowed suitable discrimination of the occurrence of at least one complication up to 30 days after surgery (AUC 0.732 (95% CI 0.680 to 0.784)).ConclusionThe early QoR-15 scale after surgery is moderately associated with the occurrence of postoperative complications up to 30 days after elective surgeries (i.e. it has predictive validity).     

Application of Epstein-Barr virus serology to the diagnosis and staging of North American patients with nasopharyngeal carcinoma

From 1978 to 1981, 151 patients with nasopharyngeal carcinoma (NPC) were enrolled in a prospective, collaborative study of North American patients, most of them white. Thirty-seven had World Health Organization (WHO) type 1 tumors, and 114 had WHO types 2 and 3 tumors. The anti-Epstein-Barr virus (EBV) profile of elevated antibody titers directed against viral capsid antigen and early antigen was seen in 85% of the patients with WHO types 2 and 3 tumors but in only 16% of the patients with WHO type 1 tumors. Geometric mean titers tended to be higher in higher stages of the disease in several staging systems. Low antibody-dependent cellular cytotoxicity at diagnosis appears to reflect a poorer prognosis, and the determination of antibody titers by this assay may prove to be useful for identifying persons in whom recurrent disease is likely to develop after conventional therapy. Anti-EBV titers can aid in diagnosis and treatment planning in patients with NPC, particularly those with occult primary NPC.     

加速康复外科的临床意义不仅仅是缩短住院日

加速康复外科(ERAS)已在我国开展近10年,其包含的围术期镇痛方案和目标导向性液体治疗等干预措施不断得到优化.ERAS理念在外科领域得到了广泛应用和推广,它不仅缩短患者的住院时间、还能减少患者术后并发症、提高器官功能、减轻手术应激反应、改善肿瘤患者预后及延长患者的生存时间.ERAS是一门方兴未艾的学科,推动ERAS的多学科培训及教育计划,补充高质量的研究证据,以及进一步转化临床实践应用将是其未来发展的方向.因此,加深对ERAS本质的研究及理解具有重要意义.     

Oxandrolone induced lean mass gain during recovery from severe burns is maintained after discontinuation of the anabolic steroid

Weight loss and lean mass loss from burn induced catabolism can be more rapidly restored when the anabolic steroid oxandrolone is added to optimum nutrition compared to nutrition alone. Our purpose in this study was to determine whether the regained lean body mass (LBM) is retained 6 months after stopping oxandrolone.

Forty-five severe burn patients, entering the recovery phase were randomized into a nutrition group alone or with the addition of oxandrolone, 20 mg per day upon admission to the acute burn rehabilitation (RH) unit. Oxandrolone was discontinued after at least 80% of the involuntary weight loss occurring in the acute burn period, was restored. Body composition was measured using bioelectric impedence analysis (BIA).

We found that patients receiving oxandrolone, in the rehabilitation unit, regained weight and lean mass two to three times faster than with nutrition alone. The difference was statistically significant (P<0.05). All patients were discharged from RH on a nutrition and exercise program and monitored in the outpatient burn center.

After 6 months, body weight and body composition were again measured. We found that the body weight and lean mass which was restored during RH, was maintained 6 months after discontinuation of oxandrolone. Lost lean mass was not yet restored in the nutrition alone group.

We can conclude that body weight and lean mass which is lost, due to burn induced catabolism, can be effectively restored in the post-burn recovery period with oxandrolone. The body weight and lost lean mass which is regained, is maintained 6 months after stopping the drug.     

Retinal injury as an early manifestation of posttransplant thrombotic microangiopathy: recovery with plasma exchanges and conversion to sirolimus--case report and review of the literature

Thrombotic microangiopathy (TMA) remains a serious event. We report a case of occurrence of TMA in the immediate postoperative period after a living-related renal transplantation. A distinguished feature of the case was major, early involvement of the retina with marked by decreased visual acuity along with thrombocytopenia and renal functional impairment. The syndrome was reversible with plasma exchange and conversion from tacrolimus to sirolimus. The patient's renal function is excellent at 11 months after transplantation. Decreased visual acuity and cotton wool exudates may be the first manifestation of posttransplant TMA.     

Recovery of erectile function after radical prostatectomy is quantitatively related to the response to intraoperative cavernous nerve stimulation

OBJECTIVE

To correlate the results of intraoperative cavernous nerve stimulation (CaNS) at radical prostatectomy (RP), with preoperative erectile function (EF) and to determine the significance of the results of stimulation after RP in predicting the recovery of EF.

PATIENTS AND METHODS

The study included 183 potent men who had not received neoadjuvant therapy, and who had RP without nerve grafting, with intraoperative CaNS, between July 1998 and April 2002. Follow‐up International Index of Erectile Function (IIEF) questionnaires were returned at a median (range) of 25 (1–51) months. Age, preoperative EF, neurovascular bundle (NVB) status, pathological stage and CaNS results were evaluated as independent predictors of the recovery of EF, as assessed by the IIEF, using Cox proportional hazards analysis.

RESULTS

CaNS strength before RP correlated with the level of preoperative potency (P = 0.023). CaNS strength after RP correlated with that before RP (P < 0.001) and the degree of NVB preservation (P = 0.007). Only age and maximum percentage change in penile girth after RP were significant independent predictors of the recovery of EF. For each 1‐year increase in age, men were 4%, 6% and 5% less likely to achieve erections, defined as an IIEF EF domain score of ≥17, ≥22 and ≥26, respectively. For each 1% increase in maximum percentage change in penile girth after RP with CaNS, men were 26% (95% confidence interval 7–48%), 22% (0–49%), and 47% (17–83%) more likely to achieve erections, with an IIEF EF score of ≥17, ≥22 and ≥26, respectively. There was a significant false‐negative rate, with 15% of patients with a minimal CaNS response normalizing their EF score and 35% recovering scores of ≥22.

CONCLUSIONS

While CaNS results after RP correlated strongly with the degree of NVB preservation, the degree of penile girth change, rather than degree of surgeon‐documented NVB preservation, was independently predictive of the recovery of EF.     

Polymorphisms of the human NRAMP1 gene are associated with response to bacillus Calmette-Guerin immunotherapy for superficial bladder cancer

PURPOSE: Superficial bladder tumors have a high recurrence rate and 10% to 20% of recurrences progress to invasive cancer. Recurrence and progression can best be prevented by nonspecific immunotherapy using intravesical BCG instillations. The NRAMP1 gene has been implicated in susceptibility to infectious and autoimmune diseases, and in response to BCG in murine models. We evaluated the association of 5 NRAMP1 gene polymorphisms with the risk of superficial bladder cancer recurrence and response to immunotherapy. MATERIALS AND METHODS: The (GT)n, 274 C/T, 469 + 14 G/C, 1465-85 G/A and D534N polymorphisms were tested on peripheral blood DNA of individuals from three cohorts: 37 bladder tumor patients treated by transurethral resection and without recurrence after up to eight years, 67 patients at high risk of recurrence of their bladder tumors and treated with BCG and 109 controls, using restriction fragment length polymorphisms or microsatellite analysis following PCR amplification. RESULTS: The D543N G:A genotype was found more frequently in patients at high risk of recurrence (8 of 67 or 12%) than in controls (2 of 109 or 2%) (p = 0.007). Patients with nonrecurrent tumors showed no difference with controls (1 of 37 or 3%) (p = 1.0). Moreover, in multivariate and survival analyses, both D543N and (GT)n polymorphisms showed association with recurrence-free survival in the cohort of patients at high risk of recurrence, following BCG treatment. CONCLUSIONS: These data suggest the implication of the NRAMP1 gene in bladder cancer recurrence and response to BCG immunotherapy.     

Diffuse large B-cell lymphoma in a renal allograft associated with Epstein-Barr virus in the recipient: a case report and a review of lymphomas presenting in a transplanted kidney

Abstract:  The purpose of this review was to evaluate the case reports with lymphoproliferative disorders exclusively localized in the allograft transplanted kidney. We also report a rare case of diffuse large B-cell lymphoma originated from the lymphocytes of the recipient with exclusive localization in the kidney allograft. We searched the medical literature for case reports of this condition. We found only 16 cases of lymphoma presenting in the kidney allograft without systemic affectation. The most frequent clinical manifestations were graft dysfunction and fever. In the majority of patients included in this review, the diagnosis was established from the tissue of explanted allograft. Seven patients were diagnosed with B-cell lymphoma, and the relationship with Epstein-Barr virus could only be demonstrated in four patients. However, the outcome was satisfactory in all cases, except in one case in which death was not related with the lymphoma etiology. Health care providers should be aware of this clinical entity and heightened index of suspicion should be used so as not to delay diagnosis and not to lose the allograft.