Clinical application of the 21-gene oncotype recurrence score in an older cohort: A single center experience

BackgroundIn early luminal breast cancer, the Oncotype DX® Recurrence Score (RS) prognostic and predictive value with regards to chemotherapy (CHT) application benefit has been broadly validated. In older patients its value has not been deeply addressed. This study aimed to evaluate the benefits of RS testing and to look at differences in treatment allocation for these patients when compared with younger ones.MethodsWe included data from consecutive patients with early luminal HER2-negative breast cancer, treated between 2010 and 2022 at the University Hospital Basel and Cantonal Hospital Baselland, Switzerland. The older cohort included 63 (19%) patients aged ≥70, and the younger cohort 263 (81%) patients aged <70.ResultsOlder breast cancer patients had more co-morbidities (N = 36, 57% vs. N = 92, 35%, p = 0.002) and a higher clinical risk status (N = 49, 78% vs. N = 155, 59%; p = 0.01) when compared to younger patients. Histopathologic characteristics were significantly different between the two cohorts. Although older patients had a higher clinical risk status (78% vs. 59%) (p = 0.01), most of them (74%) received no CHT. Specifically, adjuvant CHT was administered less frequently in older than in younger patients (13% vs. 22%; p = 0.01). Moreover, older patients were less likely to complete CHT (>4 cycles: 78% vs. 97%).ConclusionBreast cancer patients aged ≥70 have higher clinical risk status, more co-morbidities, higher clinical stage (driven by larger tumor size), and more often RS ≥26. However, they receive fewer adjuvant RT and CHT than those aged <70. RS maintains its independent prognostic value in older patients. However, assessing the predictive value of additional CHT benefit remains challenging due to significant differences in CHT administration. Although therapy decision-making in older patients with breast cancer still follows RS-based guidelines, clinical practice indicates an individualized treatment approach.     

Clinical Evaluation of BRCA1/2 Mutation in Mexican Ovarian Cancer Patients

Ovarian cancer (OC) is an important cause of gynecologic cancer-related deaths. In Mexico, around 4700 new cases of OC are diagnosed per year and it represents the second cause of gynecological cancer mortality with more than 2700 deaths. Germline mutations in BRCA1/2 genes are present in 13–18% of OC cases. Few studies have evaluated the presence of mutations in BRCA genes in a population of OC Mexican patients and their relationship with clinical response and survival rates.A total of 179 OC patients were studied by molecular testing for BRCA1/2 through next-generation sequencing and multiplex ligation-dependent probe amplification. Recurrence-free survival (RFS) was estimated by the Kaplan–Meier method. BRCA mutation was detected in 33% of patients. A percentage of 66.1% were BRCA1 mutated and 33.9% were BRCA2 mutated. BRCA1 mutation carriers had a worst RFS compared with BRCA2 mutation carriers (37.6 [29–46.2] vs 72.7 [38.4–107.2]; P = 0.030). The most common mutation for BRCA1 was ex9-12del (28.2%) (Mexican founder mutation). The Mexican founder mutation had a better RFS than other BRCA1 mutations (86.1 [37.2–135.1] vs 34.5 [20.7–48.2]; P = 0.033). The presence of BRCA2 mutations in the ovarian cancer cluster region (OCCR) had a significantly better RFS than mutations in breast cancer cluster regions (BCCR) and not-related risk region (NRR) (NR vs 72.8 [39–106.6] vs 25.8 [8.3–43.2]; P = 0.013). These results demonstrate that the prevalence of BRCA1/2 positive patients in OC Mexican patients are the highest reported. Patients with mutations in BRCA2 have a better prognosis than those mutated in BRCA1. The Mexican founder mutation has an important role in clinical outcomes. These results highlight the importance to test all the HGSP (high-grade serous papillary) OC patients with or without cancer family history (CFH) in Mexican population.     

Complicaciones y pronóstico de pacientes ancianos diagnosticados de meningioma intracraneal

ObjectSurgical treatment in patients older than 70 years old with intracranial meningioma is still subject to controversy. The benefit/risk ratio of this surgery has not been assessed due to the lack of objective criteria. The aim of this study is to assess the surgical complications and outcomes in elderly patients in our centre.MethodA retrospective analysis was performed on patients with intracranial meningioma between January 2010 and March 2014. The incidence of post-surgical complications, as well as their associated risk factors, was also analysed. Functional outcomes were compared with Glasgow Outcome Scale and Karnofsky index with those who underwent surgery and those with conservative management. Finally, a comparison was made between patients younger than 70 years old operated on for intracranial meningioma.ResultsA total of 48 patients diagnosed with intracranial meningioma older than 70 years old, of which 37 were operated on and 11 were followed up with conservative management. There were no differences between the groups in neurological status at discharge (Glasgow Outcome Scale 5 67.6 vs. 72.2%, respectively). No differences were observed in functional outcome during 6 months of follow up in the Karnofsky index between surgical and non-surgical patients (P = .486). In the comparison between older and younger than 70 years old, there were no differences in the incidence of surgical complications (P = .64 in early complications and P = .23 in late complications).ConclusionThe results of the present study suggest that age should not be a limitation in surgical indications in patients older than 70 years old with intracranial meningioma. No statistical differences were found in functional status compared with conservative management or in surgical complications between younger and elderly patients.     

Mutation and Expression of Gene YY1 in Pancreatic Neuroendocrine Tumors and Its Clinical Significance

ObjectiveThe clinical significance of the YY1 gene mutation and expression in pancreatic neuroendocrine tumors (PNETs) remains unknown. Therefore, this study aimed to comprehensively analyze the somatic mutation of YY1 in the different subtypes of PNETs.MethodsA total of 143 PNETs were assessed by Sanger sequencing to identify the somatic mutation of YY1 gene in various subtypes of PNETs. YY1 protein expression was examined in 103 PNETs by immunohistochemical staining and western blot. Gene mutation and its protein expression were correlated with clinicopathologic features.ResultsA recurrent mutation (chr14:100743807C>G) in the YY1 gene was identified in 15 of 83 insulinomas (18%) and in only 1 of 60 noninsulinoma PNETs (1.7%) (P = .0045). The YY1 mutation was not found in MEN1-associated insulinomas. The YY1 mutation in insulinomas was correlated with older age and lower serum glucose levels (age, 57 vs 42.5 years, P = .006; blood glucose, 25.2 vs 33.6 mg/dL, P = .008). YY1 protein expression was found in 100 of 103 PNETs, although expression was weaker in metastases than in localized tumors (P = .036). The stronger expression of YY1 protein was associated with favorable disease-free survival of patients with PNETs (log-rank, P = .011; n = 70). Multivariable statistical analysis showed that YY1 protein expression could be an independent predictor of prognosis.ConclusionThe hotspot YY1 mutation mostly occurred in insulinomas and rarely in noninsulinoma PNETs. The stronger YY1 protein expression was correlated with the better prognosis of PNETs patients.     

The impact of left common pulmonary vein on cryoballoon ablation of atrial fibrillation. A meta-analysis

IntroductionConflicting results regarding the impact of left common pulmonary vein (LCPV) on clinical outcome of atrial fibrillation (AF) ablation with cryoballoon technology have been reported.MethodsWe systematically searched PubMed and Cochrane library for articles that compared the arrhythmia recurrence rate after cryoballoon ablation between patients with normal pattern PVs and patients with LCPV. Studies of first ablation for persistent and paroxysmal AF using the 28 mm Arctic Front Advance, Medtronic cryoballoon (CB-A) reporting clinical success rates at a mean follow-up of ≥12 months were included. Data were analyzed by applying a random effects model.ResultsA total of 5 studies with a total of 1178 patients met our predefined inclusion criteria. After a mean follow-up of 18.4 months, the overall success rate of CB-A ablation among patients with persistent and paroxysmal AF was 57%; in the LCPV group the success rate was 46% and in the normal anatomical pattern group it was 61%. No significant heterogeneity was noted among the studies (I² = 35.8%; Q (df = 3) = 6.23 p-value = 0.18). Arrhythmia recurrence after CB-A ablation was not statistically significant between the two groups (LogOR 0.24; 95% CI [-0.16-0.63]; p-value = 0.23). No significant difference in PNI was observed between the two groups (p-value = 0.693).ConclusionThe presence of LCPV does not affect the long-term outcome of paroxysmal and persistent atrial fibrillation ablation with 28 mm CB-A compared to normal left PVs pattern.     

Copper,selenium and zinc levels after bariatric surgery in patients recommended to take multivitamin-mineral supplementation

BackgroundBariatric surgery is widely performed to improve obesity-related disorders, but can lead to nutrient deficiencies. In this study we examined serum trace element concentrations before and after bariatric surgery.MethodsWe obtained serum trace element concentrations by inductively coupled plasma-mass spectrometry (ICP-MS) method in 437 patients (82% women, median preoperative body-mass index 46.7 kg/m² [interquartile range 42–51]) undergoing either gastric banding (22.7%), sleeve gastrectomy (20.1%), or gastric bypass (57.3%) procedures. Trace element data were available for patients preoperatively (n = 44); and 3 (n = 208), 6 (n = 174), 12 (n = 122), 18 (n = 39), 24 (n = 44) and 36 months (n = 14) post-operatively. All patients were recommended to take a multivitamin-mineral supplement after surgery.ResultsCopper deficiency was found in 2% of patients before surgery; and after surgery deficiency rates ranged from 0 to 5% with no significant change in median concentrations during follow-up (p = 0.68). Selenium deficiency was reported in 2% of patients before surgery; and after surgery deficiency rates ranged from 11 to 15% with a near-significant change in median concentrations (p = 0.056). Zinc deficiency was reported in 7% before surgery; and after surgery deficiency rates ranged from 7 to 15% with no significant change in median concentrations (p = 0.39).ConclusionsIn bariatric surgery patients recommended to take multivitamin-mineral supplements, serum copper, zinc and selenium concentrations were mostly stable during the first years after bariatric surgery. There was a possible tendency for selenium concentrations to decline during the early postoperative period.     

Évaluation par la TEMP–TDM des lésions classées indéterminées en scintigraphie osseuse chez les patients de cancérologie

The aim of the present study was to investigate the contribution of the single photon emission computed tomography/computed tomography (SPECT/CT) in cancer patients and to evaluate its ability to correctly classify indeterminate lesions on planar bone scintigraphy (PBS).MethodsFrom November 2006 to August 2007, all patients with confirmed malignancy, whose PBS showed indeterminate lesions, underwent without delay a SPECT/CT. The study included 120 patients (67 men, 53 women), with a mean age of 69 ± 12 years (range 42–96 years). The patients with obvious metastases, important pains or who did not accept the examination were excluded from the study. The location of the lesions was described either as precise, probable or indeterminate. The lesions were classified either as definitely malignant, definitely benign or indeterminate.ResultsBreast, prostate, lung and kidney neoplasms represented approximately 80% of all cancers. The PBS highlighted 267 lesions of location either as precise (n = 29), probable (n = 129) or indeterminate (n = 109), classified either as definitely malignant (n = 28), definitely benign (n = 27) or indeterminate (n = 212). The SPECT/CT revealed 440 lesions, of location either as precise (n = 353), likely (n = 39) or indeterminate (n = 48), classified either as definitely malignant (n = 84), definitely benign (n = 305) or indeterminate (n = 51). Thoracic and lumbar spine and pelvis were the locations of 79% of the scintigraphic lesions and of 88% of the osseous metastases. SPECT/CT modified the final report of 80 patients, by excluding from metastases (n = 2), by showing metastases (n = 23) and by showing the benign character of indeterminate lesions (n = 55). Moreover, 69 patients out of 120 (> 57%) had an evolution confirmed with 35 true positives, 31 true negatives, one false negative and two patients with indeterminate lesions on SPECT/CT, without osseous metastasis.ConclusionThe assessment of the indeterminate scintigraphic lesions of oncologic patients benefits from the SPECT/CT. The lesion-based analysis showed that the SPECT/CT detected more lesions (+64%) and correctly classified 88% of the detected lesions. The patient-based analysis highlighted that SPECT/CT modified the final report for more than 66% of the patients. The follow-up showed that SPECT/CT correctly classified for more than 95% of the patients.     

Chlamydia trachomatis and Anti-MUC1 Serology and Subsequent Risk of High-Grade Serous Ovarian Cancer: A Population-Based Case–Control Study in Northern Sweden

BACKGROUND: Chlamydia trachomatis salpingitis causes inflammatory damage to the fallopian tube and could potentially cause initiation and progression of high-grade serous ovarian cancer (HGSC). Furthermore, C. trachomatis infection may stimulate mucin 1 (MUC1) protein production, possibly affecting anti-MUC1 antibody levels. The aim of this study was to examine if serology indicating past infection with C. trachomatis as well as anti-MUC1 production was associated with subsequent risk of HGSC. MATERIALS AND METHODS: In a prospective nested case–control study within the Northern Sweden Health and Disease Study and the Northern Sweden Maternity Cohort, the prevalence of chlamydial and anti-MUC1 antibodies was analyzed in blood samples drawn more than one year before diagnosis from 92 women with HGSC and 359 matched controls. Matching factors were age, date at blood draw, and sampling cohort. Plasma C. trachomatis IgG was analyzed using commercial micro-immunofluorescence test; chlamydial Heat Shock Protein 60 IgG (cHSP60) and anti-MUC1 IgG were analyzed with ELISA technique. RESULTS: The prevalence of C. trachomatis IgG and cHSP60 IgG antibodies, as well as the level of anti-MUC1 IgG was similar in women with HGSC and controls (16.3% vs. 17.0%, P = 0.87; 27.2% vs. 28.5%, P = 0.80; median 0.24 vs. 0.25, P = 0.70). Anti-MUC1 IgG and cHSP60 IgG levels were correlated (r = 0.169; P < 0.001). CONCLUSIONS: The findings of this prospective nested case–control study did not support an association between C. trachomatis infection, as measured by chlamydial serology, or anti-MUC1 IgG antibodies, and subsequent risk of HGSC.     

Genetic polymorphisms in AURKA,BRCA1, CCNE1 and CDK2 are associated with ovarian cancer susceptibility among Chinese Han women

IntroductionCentrosome aberrations and cell-cycle deregulation have important implications for ovarian cancer development. The AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation.MethodsUsing a haplotype-based analysis, this study aimed to investigate whether genetic polymorphisms in these four genes may contribute to ovarian cancer susceptibility. A total of 22 single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 287 cases of ovarian serous cystadenocarcinomas and 618 age-matched cancer-free controls from the Chinese Han population, and then haplotype blocks were reconstructed according to our genotyping data and linkage disequilibrium (LD) status of these SNPs.ResultsFor AURKA, we found that haplotype GA [rs6064391 (T→G) + rs911162 (G→A)] was strongly associated with decreased ovarian cancer risk (adjusted OR = 0.31, 95% CI = 0.15–0.63, P = 0.0012). For BRCA1, we found that haplotype CGTAG was associated with decreased ovarian cancer risk (adjusted OR = 0.64, 95% CI = 0.41–0.98, P = 0.0417). Moreover, women harboring homozygous GA/CGTAG haplotypes showed the lowest risk (OR = 0.12, 95% CI = 0.02–0.94, P = 0.0438). In CCNE1, the SNPs rs3218035 and rs3218042 were significantly associated with increased ovarian cancer risk (rs3218035: adjusted OR = 5.20, 95% CI = 1.85–14.52, P = 0.0017; rs3218042: adjusted OR = 4.98, 95% CI = 1.75–14.19, P = 0.0027). For CDK2, no significant association was found.ConclusionsThis study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may affect ovarian cancer susceptibility in Chinese Han women.     

Digital Health and Shared Decision-Making in Diabetes Care – A Survey Initiative in Patients and Clinicians

ObjectiveTo assess the landscape of digital health resources in the United States, better understand the impact of the digital health on shared decision-making, and identify potential barriers and opportunities for progress in the care of persons with diabetes.MethodsThe study consisted of two phases: A qualitative phase in which one-on-one interviews were conducted virtually with 34 physicians (endocrinologists {Endos}: n = 15; primary care physicians {PCPs}: n = 19) between February 11, 2021 and February 18, 2021, and a quantitative phase in which two online, email-based surveys in the English language were conducted between April 16, 2021 and May 17, 2021: one with healthcare professionals (HCP) (n = 403: n = 200 Endos and n = 203 PCPs), and one with persons with diabetes (n = 517: patients with type 1 diabetes, n = 257; patients with type 2 diabetes, n = 260).ResultsDiabetes digital health tools were found to be helpful in shared decision-making, but leading barriers include cost, coverage, and lack of time by healthcare professionals. Among diabetes digital health tools, continuous glucose monitoring (CGM) systems were used most commonly and viewed as most effective in improving quality of life and facilitating shared decision-making. Strategies for increasing use of diabetes digital health resources included lower cost, integration into electronic health records, and increased simplicity of tools.ConclusionThis study revealed that both Endos and PCPs feel that diabetes digital health tools have an overall positive impact. Integration with telemedicine and simpler, lower cost tools with increased patient access can further facilitate shared decision-making and improved diabetes care and quality of life.     

Effect of Bisphosphonates on Fracture Incidence in Young Adults With Low Bone Density

ObjectiveTo assess the effect of bisphosphonates on fracture incidence in young adults over a 5-year follow-up period.MethodsBased on the Kaiser Permanente electronic health record, this retrospective study investigated patients aged 19 to 40 years with abnormal bone density (either any Z-score of ≤−2 standard deviation [SD] or any T-score of ≤−2.5 SD). The incidence and time to fracture between the control (patients with <6 months of bisphosphonate exposure) and treatment (patients with ≥6 months of bisphosphonate use within 4 years of their first dual energy x-ray absorptiometry scan) groups were compared. Comparisons were analyzed with Χ² test for categorical variables and Wilcoxon rank sum test for continuous variables.ResultsA total of 422 patients met the inclusion and exclusion criteria. Fractures occurred in 18 patients (5.0%) of the control group (n = 358) and 5 patients (7.8%) of the treatment group (n = 64; P = .37). T-scores were significantly lower in the treatment group (−2.53 ± 0.58 SD) than those in the control group (−2.30 ± 0.80 SD; P = .002) but did not correlate with fracture risk. No significant differences were found in total fracture incidence (hazard ratio = 1.54; 95% confidence interval, 0.26-6.26). Similarly, no correlation was noted between the length of bisphosphonate therapy and fracture incidence (odds ratio = 0.99; 95% confidence interval, 0.966-1.026).ConclusionIn summary, we did not find a clear correlation of fracture incidence with the use of bisphosphonates in young adults. Further research into the pathophysiology, specific etiologies, and treatment options in this population is needed.     

Differing patterns of peripheral blood leukocyte telomere length in rheumatologic diseases

Telomeres progressively shorten with repeated somatic tissue cell division, their length being an indicator of cellular ageing. Telomeric dysfunction may be implicated in a variety of diseases. We measured mean telomere length in peripheral blood leukocytes (PBL) from patients with various rheumatologic diseases. Mean PBL telomere length was measured using real-time quantitative polymerase chain reaction (Q-PCR) assay in a control population (n = 130; age range: 3–94 years) and in subjects diagnosed with rheumatoid arthritis (RA; n = 86; age range: 31–82 years), psoriatic arthritis (PA; n = 56; age range: 26–79 years) and ankylosing spondylitis (AS; n = 59; age range: 21–75 years). These diseases are associated with chronic systemic inflammatory activity. Telomere length was also quantified in subjects with osteoarthritis (OA; n = 34; age range: 43–82 years) and osteoporosis (OP; n = 35; age range: 59–95 years), diseases without a chronic systemic inflammatory component. Telomere length in OA showed no differences from age-matched controls (p = 0.234), but was significantly shorter in OP (p = 0.001). Telomere length was significantly longer than controls in RA (p = 0.015), PA (p < 0.001) and AS (p < 0.001). Different patterns in telomere length from PBL are evidenced in rheumatologic pathologies, possibly dependent on the presence or absence of chronic systemic inflammation.     

Liquid chromatography–tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid

BackgroundAnalysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography–tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was validated.MethodsThe method utilized a simple sample-preparation procedure of protein precipitation for FSA and acid hydrolysis for TSA. Negative electrospray ionisation was used to monitor the transitions m/z 308.2 → 87.0 (SA) and m/z 311.2 → 90.0 (¹³C₃-SA). Conjugated sialic acid (CSA) was calculated by subtracting FSA from TSA. We established reference intervals for FSA, TSA and CSA in CSF in 217 control subjects. The method has been applied to patients’ samples with known differences in SA metabolites like meningitis (n = 6), brain tumour (n = 2), leukaemia (n = 5), and Salla disease (n = 1).ResultsLimit of detection (LOD) was 0.54 μM for FSA and 0.45 μM for TSA. Intra- and inter-assay variation for FSA (21.8 μM) were 4.8% (n = 10) and 10.4% (n = 40) respectively. Intra- and inter-assay variation for TSA (35.6 μM) were 9.7% (n = 10) and 12.8% (n = 40) respectively. Tested patients showed values of TSA above established reference value.ConclusionThe validated method allows sensitive and specific measurement of SA metabolites in CSF and can be applied for clinical diagnoses.     

Oxidative stress evaluation in patients with chronic Chagas disease

IntroductionChagas disease (CD), caused by protozoan Trypanosoma cruzi (T. cruzi), is a neglected disease that affects millions of people worldwide. The parasite clearance by the immune cells is accomplished by the activation of inflammation and production of reactive oxygen species, including nitric oxide (NO) that can lead to tissue injury and DNA damage. On the other hand, to balance the oxidative environment and decrease free radicals, there is an antioxidant system composed of enzymes and vitamins. The aim was to evaluate oxidative stress parameters in symptomatic and asymptomatic patients with Chagas disease.MethodsParticipants were divided into three groups: indeterminate CD (asymptomatic, n = 8), CD with cardiac/digestive involvement (symptomatic, n = 14), and Control healthy individuals (n = 20). The following parameters were analyzed: DNA damage, NO serum levels, hydrophilic antioxidant capacity (HAC) and vitamin E.ResultsSymptomatic patients showed increased DNA damage and NO levels and lower HAC and vitamin E levels compared to asymptomatic patients and control subjects.ConclusionsIt is possible to conclude that CD patients with clinical symptoms have higher oxidative stress, characterized by increased DNA damage and NO levels, and reduced antioxidant capacity and vitamin E levels.     

Evaluación de la utilidad diagnóstica de la biopsia ungueal en las onicomicosis

BackgroundOnychomycosis affects between 2% to 30% of the world population. Nail biopsy may help in making a diagnosis and can distinguish between invasion and colonisation.AimsTo evaluate the diagnostic usefulness of nail biopsy with Periodic acid–Schiff (PAS) staining for onychomycosis, compared to direct KOH examination, culture and its combination in a reference laboratory in Colombia.MethodsThe study included 66 patients in whom a blind and independent reading of the three tests was performed. The usefulness was defined based on the validity (sensitivity, specificity, Youden's index, likelihood ratios), performance (predictive values) efficiency (proportion of correctly diagnosed patients), and reproducibility (kappa coefficient).ResultsThe mean age of the patients was 55 ± 16 years, and included 76% women. The direct tests with KOH were positive in 66.7% (n = 44), 62.1% (n = 41) were positive with culture, and 56.1% (n = 37) with the biopsy. The main causal agents were non-dermatophytes moulds in 36.4% (n = 24). The most frequent species were Neoscytalidium dimidiatum (n = 11), Trichophyton rubrum (n = 11), and Candida parapsilosis (n = 13). The sensitivity of nail biopsy, when compared to the standard (KOH and/or culture), was 71%, specificity 83%, Youden's index 0.54, positive likelihood ratio 4.25, negative likelihood ratio 0.35, positive predictive value 92%, negative predictive value 52%, efficiency 74% and kappa coefficient 0.45. When biopsy was evaluated only in patients with onycholysis of the nail plate greater than 50%, all the parameters of diagnostic usefulness increased.ConclusionsThe overall usefulness of the biopsy was moderate for patients with more severe symptomatology, which makes its use advisable in cases of extensive onycholysis, and when discriminating colonisation from invasion is required.     

Evaluation of Factors Associated With Fracture and Loss of Bone Mineral Density Within 1 Year After Liver Transplantation

ObjectiveOrthotopic liver transplant recipients are at high risk of fragility fractures both in pre-liver transplant (pre-LT) and in the immediate posttransplant (post-LT) period. The aims of this study were to identify risk factors associated with post-LT fracture and identify factors that contribute to changes in bone mineral density (BMD) in post-LT as they relate to the risk of fracture in the immediate post-LT period.MethodsWe conducted a retrospective cohort study of first-time LT recipients who had BMD testing within 2-year pre-LT and 1-year post-LT. We assessed factors associated with immediate post-LT fracture using logistic regression models and linear regression models.ResultsNew fractures occurred in 41/286 (14.3%) of LT recipients during the first year following LT. In multivariate analysis, we noted an increased odds of fracture for patients with prior history of fracture (P < .001), patients who were older (P = .03), patients with higher end-stage liver disease score (P = .03), and patients with lower BMD. After adjustment for multiple testing, only a history of prior fracture was statistically significant.ConclusionOur study demonstrated that prior fracture at any site was associated with developing a new fracture in the first year post-LT.     

La TEP au 18F-FDG dans le diagnostic et le suivi évolutif des plasmocytomes solitaires

AimTo assess the role of [¹⁸F]FDG-PET in solitary plasmacytoma with regards to staging, therapeutic follow-up and monitoring.Patients and methodsTwenty consecutive patients were included in the present study when following conditions were met: (i) solitary plasmacytoma histologically confirmed (bone, n = 16; extramedullary, n = 4); (ii) [¹⁸F]FDG-PET scan from July 2004 to April 2009. The clinical follow-up was over than 2 years for 13 patients. Ten patients underwent a post-therapy PET scan. PET scans were visually analysed.ResultsPET scan enabled confirmation of all main lesions (sensitivity: 100%) and also detected infra-clinical lesions in eight cases. Follow-up for more than 2 years showed a progression disease into myeloma in five from six cases (83%) with infraclinical lesions at the baseline PET scan. Among 10 patients who underwent post-therapeutic PET scan, six experienced a complete response at the main lesion site and four experienced a partial response.ConclusionFDG-PET may play an important role in plasmacytoma staging and enables detection of smaller lesions (otherwise undetected).     

Comparing the effects of Dextran 70 and Hydroxyethyl starch in an intestinal storage solution

IntroductionOur lab has developed a novel strategy for intestinal preservation involving the intraluminal delivery of a nutrient-rich preservation solution. The aim of this study was to compare the effectiveness of two impermeant agents for use in our solution: Dextran 70 (D70; Mw = 70 kDa) and Hydroxyethyl starch (HES; Mw = 2200 kDa).MethodsRat intestines were procured, including an intravascular flush with University of Wisconsin solution followed by a ‘backtable’ intraluminal flush with: UW solution (group 1, UW), or an amino acid-based nutrient-rich preservation solution (AA solution) containing either 5% D70 (group 2, AA-D70) or HES (group 3, AA-HES). Tissue samples (n = 6) were taken at 2, 4, 8, and 12 h cold storage; histology, energetic, end-product, and oxidative parameters were assessed. In separate groups (n = 4), D70 and HES were fluorescently labeled with fluorescein isothiocyanate (FITC) in order to directly observe mucosal penetration of the starch and dextran.ResultsOver the 12 h storage time-course, direct visualization of the fluorescently labeled D70 showed penetration of the mucosal layer as early as 2 h and progressively continued to do so throughout the 12 h period. In contrast, HES did not cross the mucosal barrier and remained captive within the lumen. As time of storage progressed, grade of injury increased in all groups, however, at 4 and 12 h the AA-HES treated tissues exhibited significantly less injury compared to UW and AA-D70, P < 0.05. AA-HES group showed on moderate villus clefting (median grade 2; P < 0.05) while the AA-D70 group exhibited complete villus denudation (grade 4) and the UW group had extensive injury into the regenerative cryptal regions (grade 6). Metabolic parameters revealed a preferential maintenance of ATP and Energy Charge; increases in lactate, alanine and ammonium supported the involvement of aerobic and anaerobic pathways for energy production.ConclusionThe results of this study challenge the idea that oncotic support is not a fundamental requirement of static organ storage. Furthermore, our data suggests that HES is an effective oncotic agent for use in our intraluminal nutrient-rich preservation solution, while Dextran 70 is not.