Thrombotic Micro‐Angiopathy with Sirolimus‐Based Immunosuppression: Potentiation of Calcineurin‐Inhibitor‐Induced Endothelial Damage?

Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration.     

Cochlear implant benefits in deafness rehabilitation: PET study of temporal voice activations.

Cochlear implants may improve the medical and social prognosis of profound deafness. Nevertheless, some patients have experienced poor results without any clear explanations. One correlate may be an alteration in cortical voice processing. To test this hypothesis, we studied the activation of human temporal voice areas (TVA) using a well-standardized PET paradigm adapted from previous functional MRI (fMRI) studies. METHODS: A PET H(2)(15)O activation study was performed on 3 groups of adult volunteers: normal-hearing control subjects (n = 6) and cochlear-implanted postlingually deaf patients with >2 y of cochlear implant experience, with intelligibility scores in the "Lafon monosyllabic task" >80% (GOOD group; n = 6) or <20% (POOR group; n = 6). Relative cerebral blood flow was measured in 3 conditions: rest, passive listening to human voice, and nonvoice stimuli. RESULTS: Compared with silence, the activations induced by nonvoice stimuli were bilaterally located in the superior temporal regions in all groups. However these activations were significantly and similarly reduced in both cochlear implant groups, whereas control subjects showed supplementary activations. Compared with nonvoice, the voice stimuli induced bilateral activation of the TVA along the superior temporal sulcus (STS) in both the control and the GOOD groups. In contrast, these activations were not detected in the POOR group, which showed only left unilateral middle STS activation. CONCLUSION: These results suggest that PET is an adequate method to explore cochlear implant benefits and that this benefit could be linked to the activation of the TVA.     

Initial clinical results for breath-hold CT-based processing of respiratory-gated PET acquisitions

Purpose  Respiratory motion causes uptake in positron emission tomography (PET) images of chest structures to spread out and misregister with the CT images. This misregistration can alter the attenuation correction and thus the quantisation of PET images. In this paper, we present the first clinical results for a respiratory-gated PET (RG-PET) processing method based on a single breath-hold CT (BH-CT) acquisition, which seeks to improve diagnostic accuracy via better PET-to-CT co-registration. We refer to this method as “CT-based” RG-PET processing. Methods  Thirteen lesions were studied. Patients underwent a standard clinical PET protocol and then the CT-based protocol, which consists of a 10-min List Mode RG-PET acquisition, followed by a shallow end-expiration BH-CT. The respective performances of the CT-based and clinical PET methods were evaluated by comparing the distances between the lesions’ centroids on PET and CT images. SUV_MAX and volume variations were also investigated. Results  The CT-based method showed significantly lower (p = 0.027) centroid distances (mean change relative to the clinical method = −49%; range = −100% to 0%). This led to higher SUV_MAX (mean change = +33%; range = −4% to 69%). Lesion volumes were significantly lower (p = 0.022) in CT-based PET volumes (mean change = −39%: range = −74% to −1%) compared with clinical ones. Conclusions  A CT-based RG-PET processing method can be implemented in clinical practice with a small increase in radiation exposure. It improves PET-CT co-registration of lung lesions and should lead to more accurate attenuation correction and thus SUV measurement.     

Sleeve lobectomy for bronchogenic cancers: factors affecting survival

BACKGROUND: Sleeve lobectomy is a parenchyma-sparing procedure that is particularly valuable in patients with cardiac or pulmonary contraindications to pneumonectomy. The purpose of this study is to report our experience with sleeve lobectomy for bronchogenic cancer and to investigate factors associated with long-term survival. METHODS: Between January 1981 and June 2001, 169 patients underwent sleeve lobectomy for non-small-cell lung cancer (n = 139) or carcinoid tumor (n = 30), including 61 with a preoperative contraindication to pneumonectomy. Mean age was 59 +/- 14 years (range, 19 to 82 years). Vascular sleeve resection was performed in 11 patients. The remaining bronchial stump contained microscopic disease in 7 patients. RESULTS: Major bronchial anastomotic complications occurred in 6 (3.6%) patients: one was fatal postoperatively, three required reoperation, and two were managed conservatively. In the non-small-cell lung cancer group, operative mortality was 2.9% (4 of 139), and overall 5-year and 10-year survival rates were 52% and 28%, respectively. Six patients experienced local recurrence after complete resection. By multivariate analysis, two factors significantly and independently influenced survival: nodal status (N0 or N1 versus N2; p = 0.01) and microscopic invasion of the bronchial stump (p = 0.02). In the carcinoid tumor group, there were no operative deaths, and overall 5-year and 10-year survival rates were 100% and 92%, respectively. CONCLUSIONS: Sleeve lobectomy achieves local tumor control and is associated with low mortality and bronchial anastomotic complication rates. Long-term survival is excellent for carcinoid tumors. For patients with non-small-cell lung cancer, N2 disease or incomplete resection is associated with a worse prognosis; outcome is not affected by presence of a preoperative contraindication to pneumonectomy.     

Outcomes of breast-conservation therapy for invasive lobular carcinoma are equivalent to those for invasive ductal carcinoma

BACKGROUND: Breast-conservation therapy (BCT), including wide local excision and postoperative irradiation, is considered standard treatment for early-stage invasive ductal carcinoma (IDC). The use of BCT in patients with invasive lobular carcinoma (ILC) has been questioned because of concerns regarding ipsilateral breast recurrence and risk of bilateral breast cancer. We evaluated our institutional experience with BCT and compared treatment outcomes for ILC with those for IDC. METHODS: A review of our BCT database revealed 84 patients with ILC and 1,126 with IDC with stage I or II disease treated with BCT and radiation between 1976 and 1999. We evaluated local-regional recurrence, disease-specific survival, and contralateral breast cancer rates in both groups. RESULTS: The 5- and 10-year local-regional recurrence rates for the ILC group were 1% and 7%, respectively, and 4% and 9%, respectively, for the IDC group (P = .70). There were no significant differences in the 5- and 10-year disease-specific survival rates between the groups. Contralateral breast cancer occurred in 11.3% of patients with IDC and 11.9% of patients with ILC. CONCLUSIONS: BCT achieves similar local-regional control and survival outcomes in selected patients with ILC or IDC. Breast-conservation therapy is an appropriate treatment strategy for patients with early-stage invasive lobular carcinoma.     

No effect of HLA‐C mismatch after allogeneic hematopoietic stem cell transplantation with unrelated donors and T‐cell depletion in patients with hematological malignancies

HLA‐C mismatch in unrelated donor's hematopoietic stem cell transplantation (HSCT) has been associated with poor patient outcome. However, the impact of HLA‐C mismatch in the context of HSCT combined with in vivo T‐cell depletion remains unclear. We therefore performed a single‐center, retrospective analysis of the clinical outcome on patients with hematological malignancies treated with allo‐HSCT, who underwent T‐cell depletion. The majority of the patients (n=276) received a HLA‐A, HLA‐B, HLA‐DRB1‐matched graft that were either also HLA‐C matched (n=260), or patients with the permissive HLA‐C*03:03/03:04 mismatch (n=16), while the remaining patients (n=95) received a HLA‐C‐mismatched graft (excluding HLA‐C*03:03/03:04 mismatches). We did not observe any significant differences between the HLA‐C‐matched patients (including the permissive HLA‐C*03:03/03:04 mismatch) and the HLA‐C‐mismatched patients regarding cumulative proportion surviving, graft failure, relapse‐free survival, relapse, or acute graft‐versus‐host disease. Our data suggest that in the context of high dose T lymphocyte‐depleting agents, HLA‐C matching is not essential for patients with hematological malignancies.     

C1q binding is not an independent risk factor for kidney allograft loss after an acute antibody‐mediated rejection episode: a retrospective cohort study

After kidney transplantation, C4d is an incomplete marker of acute antibody‐mediated rejection (AMR) and C1q‐binding donor‐specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q‐binding impact on allograft survival. We compared clinical, histological and serological features of C4d− and C4d+ AMR, C1q+ and C1q− DSA AMR and analysed C4d and C1q‐binding impact on allograft survival. Among 500 for‐cause kidney allograft biopsies, 48 fulfilled AMR criteria. C4d+ AMR [N = 18 (37.5%)] have significantly higher number class I DSA (P = 0.02), higher microvascular score (P = 0.02) and more transplant glomerulopathy (P = 0.04). C1q+ AMR [N = 20 (44%)] presented with significantly more class I and class II DSA (P = 0.005 and 0.04) and C4d+ staining (P = 0.01). Graft losses were significantly higher in the C4d+ group (P = 0.04) but similar in C1q groups. C4d+ but not C1q+ binding was an independent risk factor for graft loss [HR = 2.65; (1.11–6.34); P = 0.028]. In our cohort of clinical AMR, C4d+ staining but not C1q+ binding is an independent risk factor for graft loss. Allograft loss and patient survival were similar in C1q+ and C1q− AMR.     

Patient satisfaction after laparoscopic lateral suspension with mesh for pelvic organ prolapse: outcome report of a continuous series of 417 patients

Introduction and hypothesis

Sacropexy is considered the gold standard for the treatment of pelvic organ prolapse (POP) although dissection of the promontory may be challenging, particularly in obese women. Laparoscopic lateral suspension with mesh (LLS) could be an alternative.

Methods

LLS provides lateral attachment by fibrosis of a vesicovaginal mesh. Clinical evaluation was performed at 1 year using the simplified POP quantification system (POP-Q). Primary outcomes were objective and subjective cure at 1 year. After a mean of 7.2 years the rates of reoperation and complications were assessed as secondary outcomes. Patient satisfaction was evaluated by telephone interview using a ten-point-scale and the PGI-I scale. Factors predicting satisfaction were determined by logistic regression analysis.

Results

A total of 417 patients were treated between 2003 and 2011. At 1 year 78.4% of patients were asymptomatic and anatomic success rates were 91.6% for the anterior compartment, 93.6% for the apical compartment and 85.3% for the posterior compartment. The complication rate of Clavien-Dindo grade III or higher was 2.2%. The mesh exposure rate was 4.3% and the reoperation rate was 7.3%. Of the 417 patients, 214 participated in the telephone interview. Over 85% rated their situation as improved and satisfaction was associated with the absence of concomitant hysterectomy.

Conclusions

LLS is a safe technique with promising results in terms of a composite outcome, low complication rates and high long-term patient satisfaction. However, a randomized controlled trial is needed to establish the technique as an alternative to sacropexy in the treatment of POP in obese and high morbidity patients.

     

Main traumatic events in Europe: PTSD in the European study of the epidemiology of mental disorders survey

A potentially traumatic event (PTE) contributes to trauma through its frequency, conditional probability of posttraumatic stress disorder (PTSD), and experience of other PTEs. A cross-sectional survey was conducted, enrolling 21,425 adults nationally representative of six European countries. Using the WHO-Composite International Diagnostic Interview, 8,797 were interviewed on 28 PTEs and PTSD. Prevalence of 12-month PTSD was 1.1%. When PTSD was present, the mean number of PTEs experienced was 3.2. In a multivariate analysis on PTEs and gender, six PTEs were found to be more traumatic, and to explain a large percentage of PTSD, as estimated by their attributable risk of PTSD: rape, undisclosed private event, having a child with serious illness, beaten by partner, stalked, beaten by caregiver.     

HIV prevention: What have we learned from community experiences in concentrated epidemics?

Drawing on lessons learned from community experiences in concentrated epidemics, this paper explores three imperatives in the effort to reduce the sexual transmission of HIV: combat prevention fatigue, diversify HIV testing and combat stigma and discrimination. The paper argues for a non‐judgmental harm reduction approach to the prevention of sexual transmission of HIV that takes into account the interpretation of risk by diverse individuals and communities in the era of antiretroviral therapy. This approach requires greater attention to increasing access to opportunities to know one's serostatus, especially among key populations at greater risk. Novel approaches to diversifying HIV testing approaches at community level are needed. Finally, the paper makes a plea for bold measures to combat stigma and discrimination, which continues to represent a formidable barrier for access to services for affected populations and may contribute to HIV‐related risk behaviours. A “triple therapy” approach to address stigma and discrimination is discussed, which includes greater acceptance of people living with HIV and AIDS (PLWHA), improving relevant laws and policies, and involving prevention users‐ working with people rather than for people‐. Note: this paper corresponds to the plenary talk of Bruno Spire at the XVIIth World AIDS Conference, August 8th, Mexico city: http://www.kaisernetwork.org/health_cast/player.cfm?id=4383