New rat to mouse xenograft transplantation of endometrium as a model of human endometriosis

BackgroundEndometriosis can lead to infertility. Since there is no definitive treatment for endometriosis, animal modelling seems necessary to examine the possible treatments. Mouse endometrium cannot be separated for endometriosis induction. In addition, transplantation of uterus into the abdominal viscera to induce endometriosis causes organ damage. In this study, we defined a new model of endometriosis leading to separability of endometrium and a safe anatomical region for transplantation.MethodsForty female mice were allocated to 5 groups: 1, sham; 2, allograft uterus transplantation of mice to anterior abdominal wall of mice; 3, allograft uterus transplantation of mice to mesentery of mice; 4, xenograft endometrial transplantation of rat to anterior abdominal wall of mice; 5, xenograft endometrial transplantation of rat to mesentery of mice. Adult female rats with a previous pregnancy experience were selected and placed in the vicinity of male rats for 2 weeks to induce estrogen secretion and increase endometrial thickness.ResultsIn the 4th group of animals, compared to sham, the peritoneal concentrations of VEGF‐A, TNF‐α, NO, MDA, and serum levels of CA‐125 and IL‐37 were increased and total body weight was decreased, while weight and size of endometrial lesions were increased significantly (P < .05). Genes expression of HOXA10 and HOXA11 were decreased significantly (P < .05) in groups 2 and 4 compared to sham.ConclusionsXenograft transplantation of endometrium from rat to anterior abdominal wall of mice can potentially mimic human endometriosis morphologically, histologically, and genetically.     

Exploring the expectation-actuality discrepancy: a systematic review of the impact of preoperative expectations on satisfaction and patient reported outcomes in spinal surgery

Quality in healthcare is increasingly graded through a patient-centric lens, using reports of satisfaction and self-perceived outcome. Preestablished expectations have been recognized to influence these measures. With this review, we aim to examine the impact of expectations on satisfaction and patient-reported outcomes (PRO) for individuals undergoing elective spine surgery. We systematically searched MEDLINE, EMBASE, CINAHL, and Cochrane Library electronic databases from inception to July 2015 for studies examining the relationship between expectations and satisfaction/PROs in the context of elective spinal surgery. Qualitative synthesis centered around three key questions: (1) Does the magnitude of preoperative expectations impact patient satisfaction and/or PRO after surgery? (2) Does the underlying spinal pathology influence this relationship? (3) What is the impact of unmet expectations on satisfaction? A total of 1489 citations were retrieved. Nineteen met our inclusion criteria. These comprised 3383 patients; 3200 had lumbar and only 183 had cervical spine surgery. Three findings prevailed: (1) high preoperative expectations appear to be associated with higher satisfaction and PROs after surgery for focal lumbar disc herniation, but not for lumbar spinal stenosis; (2) patient expectations frequently exceed actual outcome, creating an “expectation-actuality discrepancy” (E-AD); and (3) high-quality studies suggest a larger E-AD portends lower satisfaction. Limitations to the data include heterogeneous study populations and surgical indications, along with the use of non-validated assessment tools, particularly for satisfaction. Our findings highlight the potential importance of establishing realistic expectations prior to surgery and may serve to direct future research efforts.     

Targeted next-generation sequencing in chronic lymphocytic leukemia: a high-throughput yet tailored approach will facilitate implementation in a clinical setting

Next-generation sequencing has revealed novel recurrent mutations in chronic lymphocytic leukemia, particularly in patients with aggressive disease. Here, we explored targeted re-sequencing as a novel strategy to assess the mutation status of genes with prognostic potential. To this end, we utilized HaloPlex targeted enrichment technology and designed a panel including nine genes: ATM, BIRC3, MYD88, NOTCH1, SF3B1 and TP53, which have been linked to the prognosis of chronic lymphocytic leukemia, and KLHL6, POT1 and XPO1, which are less characterized but were found to be recurrently mutated in various sequencing studies. A total of 188 chronic lymphocytic leukemia patients with poor prognostic features (unmutated IGHV, n=137; IGHV3-21 subset #2, n=51) were sequenced on the HiSeq 2000 and data were analyzed using well-established bioinformatics tools. Using a conservative cutoff of 10% for the mutant allele, we found that 114/180 (63%) patients carried at least one mutation, with mutations in ATM, BIRC3, NOTCH1, SF3B1 and TP53 accounting for 149/177 (84%) of all mutations. We selected 155 mutations for Sanger validation (variant allele frequency, 10–99%) and 93% (144/155) of mutations were confirmed; notably, all 11 discordant variants had a variant allele frequency between 11–27%, hence at the detection limit of conventional Sanger sequencing. Technical precision was assessed by repeating the entire HaloPlex procedure for 63 patients; concordance was found for 77/82 (94%) mutations. In summary, this study demonstrates that targeted next-generation sequencing is an accurate and reproducible technique potentially suitable for routine screening, eventually as a stand-alone test without the need for confirmation by Sanger sequencing.     

Epstein–Barr virus and skin manifestations in childhood

Epstein–Barr virus (EBV) is a human B‐lymphotropic herpes virus and one of the most common viruses in humans. Specific skin signs related to EBV infection are the exanthem of mononucleosis, which is observed more frequently after ingestion of amoxicillin, and oral hairy leukoplakia, a disease occurring mostly in immunocompromised subjects with HIV infection. Other more uncommon cutaneous disorders that have been associated with EBV infection include virus‐related exanthems or diseases such as Gianotti–Crosti syndrome, erythema multiforme, and acute genital ulcers. Other skin manifestations, not correlated to virus infection, such as hydroa vacciniforme and drug‐induced hypersensitivity syndrome have also been linked to EBV. The putative involvement of EBV in skin diseases is growing similarly to other areas of medicine, where the role of EBV infection is being investigated in potentially debilitating inflammatory diseases. The prognosis of EBV infection in healthy, immunocompetent individuals is excellent. However, lifelong infection, which is kept in check by the host immune system, determines an unpredictable risk of pathologic unpredictable scenarios. In this review, we describe the spectrum of non‐tumoral dermatological manifestations that can follow EBV primary infection or reactivation of EBV in childhood.     

Biomechanical stability of an arthroscopic anterior capsular shift and suture anchor repair in anterior shoulder instability: a human cadaveric shoulder model

It was hypothesized that an arthroscopic Bankart repair with suture anchors supplies sufficient anterior shoulder stability, which cannot be improved by an additional capsular shift. In an experimental biomechanical human cadaver study, we tested ten fresh human cadaver shoulders in a robot-assisted shoulder simulator. External rotation and glenohumeral translation were measured at 0° and 80° of glenohumeral abduction. All measurements were performed under the following conditions: on the non-operated shoulder; following the setting of three arthroscopic portals; following an arthroscopic anterior capsular shift; following a simulated Bankart lesion; and following an arthroscopic Bankart repair. The application of three arthroscopic portals resulted in a significant increase of the anterior (P = 0.01) and antero-inferior translation (P = 0.03) at 0° and 80° abduction, as well as an increase in external rotation at 80° abduction (P = 0.03). Capsular shift reduced external rotation (P = 0.03), but did not significantly decrease translation. Simulating anterior shoulder instability, glenohumeral translation significantly increased, ranging from 50 to 279% of physiological translation. Arthroscopic shoulder stabilization resulted in a decrease of translation in all tested directions to approximately physiologic levels. External rotation in 0° abduction was thus decreased significantly (P = 0.003) to an average of 19°. The study proved that an arthroscopic anterior capsular shift in a cadaveric model decreases external rotation without a significant influence on glenohumeral translation. Arthroscopic shoulder stabilization with suture anchors thus sufficiently restores increased glenohumeral translation, but also decreases external rotation in neutral abduction. An anatomic reconstruction of the Bankart lesion without overconstraining of the antero-inferior capsule should therefore be the aim in arthroscopic anterior shoulder stabilization.     

Cigarette smoking and associated risk of multiple sclerosis in the Iranian population

Exposure to cigarette smoke is emerging as an environmental risk factor for multiple sclerosis (MS). We investigated the possible association between environmental tobacco smoke, its cumulative exposure, and MS risk. We used data from the Iranian Multiple Sclerosis Registry to identify a case-control of 662 patients who had MS and a comparison group of 394 patients. Information regarding current smoking status, including the number of cigarettes smoked per day, duration, and smoking pack-years indicative of cumulative dose of tobacco smoked was obtained. We analyzed the incidence of MS among ever–smokers who had been smokers during their disease course and prior to disease onset in comparison with never–smokers who had never been exposed by calculating the odds ratio (OR) with a 95% confidence interval (CI) employing logistic regression. Of the 662 MS patients, there were 523 women (79.0%) and 139 men (21.0%), with a mean age of 31 ± 10.0 years at disease onset. The risk for MS was increased among ever–smokers (OR = 1.78, 95% CI = 1.22–2.59, p = 0.03) compared to never–smokers. As compared with never smokers, the OR for patients with 6–10 pack years was 2.91 for men (95% CI = 1.11–9.47, p = 0.03) and 1.69 for women (95% CI = 1.02–6.45, p = 0.04). Our results demonstrate that cigarette smoking is significantly associated with an increased risk for MS. The risk effects of smoking were more noticeable in male patients and at higher tobacco doses.     

Rapid determination of anti-heparin/platelet factor 4 antibody titers in the diagnosis of heparin-induced thrombocytopenia

PURPOSE: Heparin-induced thrombocytopenia is mediated by antibodies directed against the heparin-platelet factor 4 (heparin/PF4) complex. Our aim was to investigate whether rapid measurement of anti-heparin/PF4 antibodies could improve the diagnostic workup of patients with suspected heparin-induced thrombocytopenia. METHODS: We examined 148 consecutive patients in our laboratory between January 1995 and June 2001 for suspected heparin-induced thrombocytopenia. Clinical data allowed retrospective assessment of the likelihood of heparin-induced thrombocytopenia. Antibodies against the heparin/PF4 complex were detected by a rapid particle gel immunoassay. RESULTS: Anti-heparin/PF4 antibodies were detected in 69 (47%) of the 148 patients, at dilution titers from 1 to 256. Clinically "likely" or "very likely" heparin-induced thrombocytopenia was significantly more common in patients with titers >or=4 (95% [39/41]) than in those with undetectable antibodies (13% [9/70]; P <0.0001), a titer of 1 (18% [4/22]; P <0.0001), or a titer of 2 (33% [2/6]; P = 0.001). All 19 samples with a positive platelet aggregation test had anti-heparin/PF4 antibody titers of at least 4, including 15 samples with titers >or=32. Thromboembolic complications in heparin-treated patients were significantly more prevalent in patients with titers >or=4 (63% [26/41]) than in those with undetectable antibodies (8% [6/79]; P <0.0001) or a titer of 1 (9% [2/22]; P <0.0001). Of the 11 patients with a titer of 1 who were maintained on heparin, none developed worse thrombocytopenia or thromboembolic complications. CONCLUSION: Anti-heparin/PF4 antibody titers, which can be measured rapidly and reproducibly using a particle gel immunoassay, can be used as a confirmatory test to complement a clinical likelihood score among patients with suspected heparin-induced thrombocytopenia.     

Pseudo-angiomatous hyperplasia of mammary stroma: a case with gigantomastia

Pseudo-angiomatous hyperplasia of mammary stroma (PASH) is a histopathological entity which is a microscopic fortuitous finding in mammary biopsies performed for different reasons. It may be symptomatic and appears then as a palpable lump. The term pseudo-angiomatous emphasizes the characteristic aspect of the stroma simulating a vascular tumor. We report a case of PASH in a 71 year-old woman who presented a recurring breast mass with rapid swelling of the mammary gland (70 x 60 x 20 cm) treated by mastectomy. PASH must be distinguished from a well-differentiated angiosarcoma. It is ruled out by immunohistochemistry.     

Identification of a Klebsiella pneumoniae strain associated with nosocomial urinary tract infection.

To differentiate between relapse of infection and reinfection of the urinary tract due to Klebsiella pneumoniae, 33 K. pneumoniae isolates collected from 20 patients with spinal cord injury (SCI) over 2 years were typed by genomic fingerprinting by repetitive-element PCR. Clinical isolates obtained from the same patients with recurrent episodes of urinary tract infection (UTI) revealed identical genomic fingerprints indicating relapse of UTI due to K. pneumoniae, despite appropriate antibiotic therapy. Seventeen isolates obtained from 8 of the 20 SCI patients shared a common genotype, termed RD6. Among non-SCI patients residing in other nursing units, the RD6 genotype was found in 5 of 10 patients with K. pneumoniae UTI but in only 1 of 20 patients with K. pneumoniae infection that did not involve the urinary tract, suggesting a strong association of this genotype with UTI. All RD6 isolates exhibited strong adherence (> or =50 adherent bacteria per cell) to HEp-2 cells, whereas other K. pneumoniae isolates generally did not adhere to or adhered very weakly to HEp-2 cells (< or =5 adherent bacteria per cell). Adherence was inhibited either by 4% D-mannose or by anti-type 1 fimbrial rabbit serum. These results suggest that the capacity of K. pneumoniae RD6 isolates to cause UTI may be mediated by its striking adherence to mammalian cells.     

Mitotic Index is an Independent Predictor of Recurrence‐Free Survival in Meningioma

While World Health Organization (WHO) grading of meningioma stratifies patients according to recurrence risk overall, there is substantial within‐grade heterogeneity with respect to recurrence‐free survival (RFS). Most meningiomas are graded according to mitotic counts per unit area on hematoxylin and eosin sections, a method potentially confounded by tumor cellularity, as well as potential limitations of accurate mitotic figure detection on routine histology. To refine mitotic figure assessment, we evaluated 363 meningiomas with phospho‐histone H3 (Ser10) and determined the mitotic index (number of mitoses per 1000 tumor cells). The median mitotic indices among WHO grade I (n = 268), grade II (n = 84) and grade III (n = 11) tumors were 1, 4 and 12. Classification and regression tree analysis to categorize cut‐offs identified three subgroups defined by mitotic indices of 0–2, 3–4 and ≥5, which on univariate analysis were associated with RFS (P < 0.01). In multivariate analysis, mitotic index subgrouped in this manner was significantly associated with RFS (P < 0.01) after adjustment for Simpson grade, WHO grade and MIB‐1 index. Mitotic index was then examined within individual WHO grade, showing that for grade I and grade II meningiomas, mitotic index can add additional information to RFS risk. The results suggest that the use of a robust mitotic marker in meningioma could refine risk stratification.