Cytomegalovirus infection and new-onset post-transplant diabetes mellitus.

We analyzed data from all consecutive kidney transplant patients at our institution between April 2003 and October 2006. We found 15 cases of late-onset cytomegalovirus (CMV) infection, two of which developed concurrent post-transplant diabetes mellitus (PTDM). In these two cases, PTDM was transient and normal glucose tolerance was achieved after an eight-wk therapeutic course of oral valganciclovir. These findings suggest that CMV infection after organ transplantation may be associated with concurrent PTDM. The distinct causative relationship is yet to be determined.

Segmental bioelectrical impedance analysis to assess perioperative fluid changes.

OBJECTIVES: Perioperative fluid accumulation determination is a challenge for the clinician. Bioelectrical impedance analysis (BIA) is a noninvasive method based on the electrical properties of tissues, which can assess body fluid compartments. The study aimed at assessing their changes in three types of surgery (thoracic, abdominal, and intracranial) requiring various regimens of fluid administration. DESIGN: Prospective descriptive trial. PATIENTS: A total of 26 patients scheduled for elective surgery were separated into three groups according to site of surgery: thoracic (n = 8), abdominal aortic (n = 8), and brain surgery (n = 10). SETTING: University teaching hospital. INTERVENTION: None. MEASUREMENTS: Whole body, segmental (arm, trunk, and legs) BIA at multiple frequency (0.5, 50, 100 kHz) was used to assess perioperative fluid accumulation after surgery. The fluid balances were calculated from the charts. RESULTS: The patients were aged 62+/-4 yrs. Fluid balances were 4.8+/-1.0 L, 4.1+/-0.5 L, and 1.9+/-0.3 L, respectively, in the three groups. In trunk surgery patients, fluid accumulation was detected as a drop in impedance in the operated area at all frequencies. In the operated area, there was an expansion of both intra- and extracellular compartments. A reduction in high frequencies' impedance in the legs was only detected after aortic surgery. Fluid accumulation and trunk impedance changes were strongly correlated. Neurosurgery only induced minor body fluid changes. CONCLUSIONS: Segmental BIA is able to detect and localize perioperative fluid accumulation. It may become a bedside tool to quantify and to localize fluid accumulation.

Impaired early visual response modulations to spatial information in chronic schizophrenia.

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia.

Improved virological outcome in White patients infected with HIV-1 non-B subtypes compared to subtype B.

BACKGROUND: Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ~10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important. METHODS: The effect of HIV-1 subtype B and non-B on the time to virological failure while taking combination antiretroviral therapy (cART) was analyzed. Other studies that have addressed this question were limited by the strong correlation between subtype and ethnicity. Our analysis was restricted to white patients from the Swiss HIV Cohort Study who started cART between 1996 and 2009. Cox regression models were performed; adjusted for age, sex, transmission category, first cART, baseline CD4 cell counts, and HIV RNA levels; and stratified for previous mono/dual nucleoside reverse-transcriptase inhibitor treatment. RESULTS: Included in our study were 4729 patients infected with subtype B and 539 with non-B subtypes. The most prevalent non-B subtypes were CRF02_AG (23.8%), A (23.4%), C (12.8%), and CRF01_AE (12.6%). The incidence of virological failure was higher in patients with subtype B (4.3 failures/100 person-years; 95% confidence interval [CI], 4.0-4.5]) compared with non-B (1.8 failures/100 person-years; 95% CI, 1.4-2.4). Cox regression models confirmed that patients infected with non-B subtypes had a lower risk of virological failure than those infected with subtype B (univariable hazard ratio [HR], 0.39 [95% CI, .30-.52; P < .001]; multivariable HR, 0.68 [95% CI, .51-.91; P = .009]). In particular, subtypes A and CRF02_AG revealed improved outcomes (multivariable HR, 0.54 [95% CI, .29-.98] and 0.39 [95% CI, .19-.79], respectively). CONCLUSIONS: Improved virological outcomes among patients infected with non-B subtypes invalidate concerns that these individuals are at a disadvantage because drugs have been designed primarily for subtype B infections.

Evidence for multiple B- and T-cell epitopes in Plasmodium falciparum liver-stage antigen 3.

Liver-stage antigen 3 (LSA-3) is a new vaccine candidate that can induce protection against Plasmodium falciparum sporozoite challenge. Using a series of long synthetic peptides (LSP) encompassing most of the 210-kDa LSA-3 protein, a study of the antigenicity of this protein was carried out in 203 inhabitants from the villages of Dielmo (n = 143) and Ndiop (n = 60) in Senegal (the level of malaria transmission differs in these two villages). Lymphocyte responses to each individual LSA-3 peptide were recorded, some at high prevalences (up to 43%). Antibodies were also detected to each of the 20 peptides, many at high prevalence (up to 84% of responders), and were directed to both nonrepeat and repeat regions. Immune responses to LSA-3 were detectable even in individuals of less than 5 years of age and increased with age and hence exposure to malaria, although they were not directly related to the level of malaria transmission. Thus, several valuable T- and B-cell epitopes were characterized all along the LSA-3 protein, supporting the antigenicity of this P. falciparum vaccine candidate. Finally, antibodies specific for peptide LSP10 located in a nonrepeat region of LSA-3 were found significantly associated with a lower risk of malaria attack over 1 year of daily clinical follow-up in children between the ages of 7 and 15 years, but not in older individuals.

Sudden cardiac arrest associated with early repolarization.

BACKGROUND: Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest. METHODS: We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects. RESULTS: Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008). CONCLUSIONS: Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.

A novel tool for the assessment of pain: validation in low back pain.

BACKGROUND: Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology. METHODS AND FINDINGS: Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%-97%) and specificity (97%; 95% CI 89%-100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs. CONCLUSIONS: We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.

Surgery for ruptured thoracic and thoraco-abdominal aortic aneurysms.

OBJECTIVE: To assess the outcome of patients with ruptured descending thoracic and thoracoabdominal aortic aneurysms undergoing emergency repair, in comparison to elective surgery for chronic lesions. METHODS: A prospective study of 100 consecutive patients operated upon the descending aorta (1-8 segments) using proximal unloading and distal protection with partial cardiopulmonary bypass, heparin surface-coated perfusion equipment and low systemic heparinization (loading dose 100 IU/kg, activated coagulation time > 180 s), staged cross-clamping, sealed grafts and graft inclusion. RESULTS: Arteriosclerotic lesions were present in 53/100 patients (53%) for all, 30/53 (56%) for chronic, and 21/33 (63%) for ruptured, aneurysms (NS). Dissecting lesions were found in 38/100 patients (38%) for all, 20/53 (38%) for chronic, and 8/33 (24%) for ruptured aneurysms (NS). Preoperative hematocrit was 38 +/- 6% for all, 40 +/- 5% for chronic, and 33 +/- 5% for ruptured aneurysmal patients (P < 0.001 ruptured versus chronic). The extent of aortic repair (1-8 segments) was 3.3 +/- 1.6 for all, 3.5 +/- 1.5 for chronic, and 3.2 +/- 1.4 for ruptured, aneurysms (NS). Transdiaphragmatic repair was performed in 51/100 (51%) of all, 28/53 (53%) of chronic, and 17/33 (51%) of ruptured aneurysms (NS). Aortic cross-clamp time was 38 +/- 21 min for all, 39 +/- 24 min for chronic, and 38 +/- 17 min for ruptured, aneurysmal patients (NS). The amount of red cells washed and autotransfused was 2792 +/- 2239 ml in all, 3143 +/- 2531 ml in chronic, and 2074 +/- 1350 ml in ruptured, aneurysmal patients (P < 0.025). The amount of packed red cells required was 2181 +/- 1830 ml for all, 1736 +/- 1333 ml for chronic, and 2947 +/- 2395 ml for ruptured aneurysmal patients (P < 0.010). Thirty-day mortality was 9/100 (9%) for all, 3/53 (6%) for chronic, and 5/33 (15%) for ruptured aneurysmal patients (NS). Parapareses/plegias occurred in 9/100 (9%) of all, 6/53 (11%) of chronic, and 3/33 (9%) of ruptured, aneurysmal patients (NS). Stepwise regression analysis identified aortic cross-clamp time as a predictor of early mortality (P = 0.002) and parapareses and paraplegias (P = 0.001). Age (P = 0.001), extent of repair (P = 0.008) and preoperative hematocrit (P = 0.001) were predictors for homologous transfusion requirements. CONCLUSION: Emergency repair of ruptured descending thoracic and thoracoabdominal aortic aneurysms can be achieved with acceptable results.

Is the diagnostic yield of upper GI endoscopy improved by the use of explicit panel-based appropriateness criteria?

BACKGROUND: Increasing the appropriateness of use of upper gastrointestinal (GI) endoscopy is important to improve quality of care while at the same time containing costs. This study explored whether detailed explicit appropriateness criteria significantly improve the diagnostic yield of upper GI endoscopy. METHODS: Consecutive patients referred for upper GI endoscopy at 6 centers (1 university hospital, 2 district hospitals, 3 gastroenterology practices) were prospectively included over a 6-month period. After controlling for disease presentation and patient characteristics, the relationship between the appropriateness of upper GI endoscopy, as assessed by explicit Swiss criteria developed by the RAND/UCLA panel method, and the presence of relevant endoscopic lesions was analyzed. RESULTS: A total of 2088 patients (60% outpatients, 57% men) were included. Analysis was restricted to the 1681 patients referred for diagnostic upper GI endoscopy. Forty-six percent of upper GI endoscopies were judged to be appropriate, 15% uncertain, and 39% inappropriate by the explicit criteria. No cancer was found in upper GI endoscopies judged to be inappropriate. Upper GI endoscopies judged appropriate or uncertain yielded significantly more relevant lesions (60%) than did those judged to be inappropriate (37%; odds ratio 2.6: 95% CI [2.2, 3.2]). In multivariate analyses, the diagnostic yield of upper GI endoscopy was significantly influenced by appropriateness, patient gender and age, treatment setting, and symptoms. CONCLUSIONS: Upper GI endoscopies performed for appropriate indications resulted in detecting significantly more clinically relevant lesions than did those performed for inappropriate indications. In addition, no upper GI endoscopy that resulted in a diagnosis of cancer was judged to be inappropriate. The use of such criteria improves patient selection for upper GI endoscopy and can thus contribute to efforts aimed at enhancing the quality and efficiency of care. (Gastrointest Endosc 2000;52:333-41).

Inter-informant agreement and prevalence estimates for substance use disorders: direct interview versus family history method.

OBJECTIVES: Family studies typically use multiple sources of information on each individual including direct interviews and family history information. The aims of the present study were to: (1) assess agreement for diagnoses of specific substance use disorders between direct interviews and the family history method; (2) compare prevalence estimates according to the two methods; (3) test strategies to approximate prevalence estimates according to family history reports to those based on direct interviews; (4) determine covariates of inter-informant agreement; and (5) identify covariates that affect the likelihood of reporting disorders by informants. METHODS: Analyses were based on family study data which included 1621 distinct informant (first-degree relatives and spouses) - index subject pairs. RESULTS: Our main findings were: (1) inter-informant agreement was fair to good for all substance disorders, except for alcohol abuse; (2) the family history method underestimated the prevalence of drug but not alcohol use disorders; (3) lowering diagnostic thresholds for drug disorders and combining multiple family histories increased the accuracy of prevalence estimates for these disorders according to the family history method; (4) female sex of index subjects was associated with higher agreement for nearly all disorders; and (5) informants who themselves had a history of the same substance use disorder were more likely to report this disorder in their relatives, which entails the risk of overestimation of the size of familial aggregation. CONCLUSION: Our findings have important implications for the best-estimate procedure applied in family studies.

Anaplastic astrocytoma in adults.

Anaplastic astrocytoma is an uncommon disease in the adult population. Prognosis is influenced by age, symptom duration, mental status and Karnofsky performance status. A truly complete resection, which is a recognized independent prognostic factor, is not possible and recurrence in the surgical cavity is common. Based on randomized data available, chemotherapy has consistently failed to improve the outcome of patients with anaplastic astrocytoma, while a meta-analysis showed a small, but significant improvement in survival favouring the use of chemotherapy. Outside a clinical trial, postoperative radiotherapy (30 x 2 Gy) remains the standard adjuvant therapy for most patients. For elderly patients, the application of treatment is usually based on performance status and neurological function. In recurrent disease, chemotherapy with temozolomide has been proven to be active and well-tolerated in phase II trials, but no comparative phase III trials of other cytotoxic drugs have been conducted.

Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.

PURPOSE: The aim of this study was to determine whether tumor location proximal or distal to the splenic flexure is associated with distinct molecular patterns and can predict clinical outcome in a homogeneous group of patients with Dukes B (T3-T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and distal colorectal cancer may arise through different pathogenetic mechanisms. Although p53 and Ki-ras gene mutations occur frequently in distal tumors, another form of genomic instability associated with defective DNA mismatch repair has been predominantly identified in the proximal colon. To date, however, the clinical usefulness of these molecular characteristics remains unproven. METHODS: A total of 126 patients with a lymph node-negative sporadic colon or rectum adenocarcinoma were prospectively assessed with the endpoint of death by cancer. No patient received either radiotherapy or chemotherapy. p53 protein was studied by immunohistochemistry using DO-7 monoclonal antibody, and p53 and Ki-ras gene mutations were detected by single strand conformation polymorphism assay. RESULTS: During a mean follow-up of 67 months, the overall five-year survival was 70 percent. Nuclear p53 staining was found in 57 tumors (47 percent), and was more frequent in distal than in proximal tumors (55 vs. 21 percent; chi-squared test, P < 0.001). For the whole group, p53 protein expression correlated with poor survival in univariate and multivariate analysis (log-rank test, P = 0.01; hazard ratio = 2.16; 95 percent confidence interval = 1.12-4.11, P = 0.02). Distal colon tumors and rectal tumors exhibited similar molecular patterns and showed no difference in clinical outcome. In comparison with distal colorectal cancer, proximal tumors were found to be statistically significantly different on the following factors: mucinous content (P = 0.008), degree of histologic differentiation (P = 0.012), p53 protein expression, and gene mutation (P = 0.001 and 0.01 respectively). Finally, patients with proximal tumors had a marginally better survival than those with distal colon or rectal cancers (log-rank test, P = 0.045). CONCLUSION: In this series of Dukes B colorectal cancers, p53 protein expression was an independent factor for survival, which also correlated with tumor location. Eighty-six percent of p53-positive tumors were located in the distal colon and rectum. Distal colon and rectum tumors had similar molecular and clinical characteristics. In contrast, proximal neoplasms seem to represent a distinct entity, with specific histopathologic characteristics, molecular patterns, and clinical outcome. Location of the neoplasm in reference to the splenic flexure should be considered before group stratification in future trials of adjuvant chemotherapy in patients with Dukes B tumors.

Complication of carotid stenting: incomplete misdeployment of the stent in the femoral artery.

OBJECTIVES: The presence of intravascular foreign bodies is underreported in the literature and is more commonly encountered in clinical practice. We report on a case where an attempt to position a carotid stent resulted in misdeployment of the stent in the femoral artery and its surgical removal. METHODS: A 63-year-old patient admitted to hospital for cerebral stroke underwent thrombolysis for occlusive dissection of right carotid artery and was transferred to our hospital for additional thrombo-aspiration and carotid stenting. RESULTS: The carotid stent was misdeployed incompletely in the femoral artery and had to be removed surgically. CONCLUSIONS: Appropriate knowledge of intravascular migration and deployment failure management should be considered as important as the optimal device deployment.