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Chronic hemorrhagic diathesis in patients showing normal levels of plasmatic clotting factors strongly suggests for congenital platelet disorders. We report on a pediatric patient (male, 3 years, D1) with mild bleeding. A sibling (D2), his mother (D3) and father (D4) were included for laboratory investigation. Platelet counts in D1, D2 and D4 indicated mild thrombocytopenia (100 Gpt/L). D1 and D3 platelets showed significantly diminished aggregation response on arachidonic acid and U46619 stimulation. Immunostaining for platelet proteins on blood smears of D1 and D2 indicated defects in ß1-tubulin. Exon sequencing of TBXA2R and TUBB1 revealed heterozygosity for the novel TBXA2R*c.908T>C (p.L303P) mutation in D1 and D3. TUBB1 was either wild type (D2, D3) or heterozygous (D1, D4) for the common polymorphism TUBB1*c.920G>A (rs6070697; p.R307H). In conclusion, the bleeding phenotype of the index patient can be explained by a diminished platelet function caused by the TBXA2R*c.908T>C mutation inherited from the mother and a mild thrombocytopenia with unknown molecular basis that is inherited from the father.

Background: Obesity surgery has proven successful for weight loss and the resolution of comorbidities. There is, however, little evidence on its success and the risk of complications when considering age of onset of obesity (AOO), years of obesity (YOO), preoperative body mass index (BMI), Edmonton obesity staging system (EOSS) score, and age as possible predictors of weight loss, the resolution of comorbidities, and the risk of complications. Methods: Patients who underwent Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) from a prospective database were analyzed. Multiple regression analyses were used to predict comorbidities and their resolution, percentage excess weight loss (%EWL) and total weight loss (%TWL) 12 months after surgery, and the risk of complications using the predictors AOO, YOO, age, EOSS, and BMI. Results: 180 patients aged 46.8 ± 11.1 years with a preoperative BMI 49.5 ± 7.5 were included. The number of preoperative comorbidities was higher with older age (β = 0.054; p = 0.023) and a greater BMI (β = 0.040; p = 0.036) but was not related to AOO and YOO. Patients with AOO as a child or adolescent were more likely to have an EOSS score of ≥2. Greater preoperative BMI was negatively associated with %EWL (β = –1.236; p < 0.001) and older age was negatively associated with %TWL (β = –0.344; p = 0.020). Postoperative complications were positively associated with EOSS score (odds ratio [OR] 1.147; p = 0.042) and BMI (OR 1.010; p = 0.020), but not with age. AOO and YOO were not related to postoperative outcome. Conclusion: Greater BMI was associated with a lower %EWL and age was associated with a low %TWL. YOO and AOO did not influence outcome. Age, BMI, and EOSS score were the most important predictors for risk and success after obesity surgery. Surgery should be performed early enough for optimal outcomes.

Objective: Obesity surgery provides sustainable weight loss, improvement of comorbidities, and improved quality of life (QOL). There is few evidence on the patient perspective and goals. This study compared expected and achieved weight loss, body shape, and QOL. Methods: Patients completed the Moorehead-Ardelt QOL questionnaire (MAQOL) and questionnaires on actual and expected weight loss and body shape, comorbidities, and goals of obesity surgery preoperatively and within 24 months postoperatively. Results: 44 patients completed questionnaires pre- and postoperatively. BMI, MAQOL and comorbidities significantly improved postoperatively. Patients’ expected weight loss goal corresponded to a postoperative BMI of 32.6 ± 5.6 kg/m2 and was not different from their achieved BMI within 24 months after surgery (33.9 ± 6.3 kg/m2, p = 0.276). Self-reported body shape improved but did not reach preoperatively expected goals. During the weight loss period, patients adapted their weight loss and body shape goals to higher levels. Patients attributed a higher part of their success in weight loss to surgery postoperatively (79.5 ± 22.0 vs. 89.1 ± 18.4%, p = 0.028). Conclusion: Patients lost as much weight as they had expected and later modified the goals to even greater weight loss. Body shape improved but did not reach expected levels. QOL improved independently from weight loss and body shape. Patients attributed successful weight loss predominantly to surgery.

Abstract Background Insertion of a Totally Implantable Access Port (TIAP) can be performed either via Central Vein Puncture (CVP) or Brachiocephalic Vein Cut-down (venous section-VS). The primary success rate of TIAP implantation using VS rarely ever achieves 100%. The objective of this study was to describe a modified VS approach using a hydrophilic coated wire (TVS). Methods From 01.01.2015 to 31.12.2015, all patients receiving TIAP implantations were screened. During this time, all patients in whom the primary VS procedure was found to be unsuccessful were analysed. Results In 2015, 1152 patients had TIAP implantations performed by 24 different surgeons. Of these, 277 patients needed a second line rescue strategy either by CVP (n = 69) or TVS (n = 208). There were no statistically significant differences regarding demographics or indication for TIAP implantation between CVP and TVS. The operation time and the qualification of the operating surgeon between CVP and TVS did not differ significantly. After the introduction of the guidewire with a hydrophilic coated wire, the need for CVP decreased significantly from 12.7% to 8.8% (p

[This corrects the article DOI: 10.1371/journal.pone.0139547.].

Mesh augmentation seems to reduce recurrences following laparoscopic paraesophageal hernia repair (LPHR). However, there is an uncertain risk of mesh-associated complications. Risk-benefit analysis might solve the dilemma.A systematic literature search was performed to identify randomized controlled trials (RCTs) and observational clinical studies (OCSs) comparing laparoscopic mesh-augmented hiatoplasty (LMAH) with laparoscopic mesh-free hiatoplasty (LH) with regard to recurrences and complications. Random effects meta-analyses were performed to determine potential benefits of LMAH. All data regarding LMAH were used to estimate risk of mesh-associated complications. Risk-benefit analysis was performed using a Markov Monte Carlo decision-analytic model.Meta-analysis of 3 RCTs and 9 OCSs including 915 patients revealed a significantly lower recurrence rate for LMAH compared to LH (pooled proportions, 12.1% vs. 20.5%; odds ratio (OR), 0.55; 95% confidence interval (CI), 0.34 to 0.89; p = 0.04). Complication rates were comparable in both groups (pooled proportions, 15.3% vs. 14.2%; OR, 1.02; 95% CI, 0.63 to 1.65; p = 0.94). The systematic review of LMAH data yielded a mesh-associated complication rate of 1.9% (41/2121; 95% CI, 1.3% to 2.5%) for those series reporting at least one mesh-associated complication. The Markov Monte Carlo decision-analytic model revealed a procedure-related mortality rate of 1.6% for LMAH and 1.8% for LH.Mesh application should be considered for LPHR because it reduces recurrences at least in the mid-term. Overall procedure-related complications and mortality seem to not be increased despite of potential mesh-associated complications.

Autologous stem cell transplantation has greatly improved the prognosis of systemic recurrent non-Hodgkin’s lymphoma. However, no prospective data are available concerning the feasibility and efficacy of this strategy for systemic lymphoma relapsing in the central nervous system. We, therefore, we performed an international multicenter retrospective study of patients with a central nervous system recurrence of systemic lymphoma to assess the outcome of these patients in the era of stem cell transplantation. We collected clinical and treatment data on patients with a first central nervous system recurrence of systemic lymphoma treated between 2000 and 2010 in one of five centers in four countries. Patient- and treatment-related factors were analyzed and compared descriptively. Primary outcome measures were overall survival and percentage of patients transplanted. We identified 92 patients, with a median age of 59 years and a median Eastern Cooperative Oncology Group/World Health Organization performance status of 2, of whom 76% had diffuse large B-cell histology. The majority (79%) of these patients were treated with systemic chemotherapy with or without intravenous rituximab. Twenty-seven patients (29%) were transplanted; age and insufficient response to induction chemotherapy were the main reasons for not being transplanted in the remaining 65 patients. The median overall survival was 7 months (95% confidence interval 2.6–11.4), being 8 months (95% confidence interval 3.8–5.2) for patients ≤ 65 years old. The 1-year survival rate was 34.8%; of the 27 transplanted patients 62% survived more than 1 year. The Memorial Sloan Kettering Prognostic Index for primary central nervous system lymphoma was prognostic for both undergoing transplantation and survival. In conclusion, despite the availability of autologous stem cell transplantation for patients with central nervous system progression or relapse of systemic lymphoma, prognosis is still poor. Long-term survival is, however, possible and more likely in patients able to undergo stem cell transplantation.

The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established so far. In a prospective multicenter phase II study, we evaluated a potentially curative chemotherapy-only regimen in these patients. Adult immunocompetent patients 65 years of age or under received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m2 intravenously (i.v.) Day 1, ifosfamide 2 g/m2 i.v. Days 3– 5 and liposomal cytarabine 50 mg intrathecally (i.th) Day 6) and AraC/TT/DEP (cytarabine 3g/m2 i.v. Days 1–2, thiotepa 40 mg/m2 i.v. Day 2 and i.th. liposomal cytarabine 50 mg i.th. Day 3) followed by high-dose chemotherapy with carmustine 400 mg/m2 i.v. Day −5, thiotepa 2×5 mg/kg i.v. Days −4 to −3 and etoposide 150 mg/m2 i.v. Days −5 to −3, and autologous stem cell transplantation Day 0 (HD-ASCT). Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24), there was a complete remission in 15 (63%), partial remission in 2 (8%) and progressive disease in 7 (29%) patients. Myelotoxicity was the most adverse event with CTC grade 3/4 infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%±19 for all patients and 58%±22 for patients completing HD-ASCT. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients.(ClinicalTrials.govIdentifier NCT01148173)

Background The t(9;22) and t(4;11) chromosomal translocations, which generate the BCR-ABL and MLL-AF4 fusion genes, define high-risk subtypes of acute lymphoblastic leukemia in adults. However, the prognostic impact of other rarer fusion genes is less well established in adult acute lymphoblastic leukemia than in the childhood form.Design and Methods In the context of the German Multicenter Therapy Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) we used reverse transcriptase polymerase chain reaction to investigate 441 cases of BCR-ABL- and MLL-AF4-negative B-precursor acute lymphoblastic leukemia for the TCF3-PBX1 (E2A-PBX1) and ETV6-RUNX1 (TEL-AML1) fusion transcripts generated by the t(1;19)(q23;p13.3) and t(12;21)(p13;q22) translocations. Both are well-known molecular alterations in pediatric acute lymphoblastic leukemia in which they have favorable prognostic implications.Results We identified 23 adult patients with TCF3-PBX1 and ten with ETV6-RUNX1. In contrast to previous reports we found no significant difference in overall survival between TCF3-PBX1-positive and -negative patients. At 2 years after diagnosis all the ETV6-RUNX1-positive patients were alive and in continuous complete remission, but their long-term outcome was negatively affected by late relapses. TCF3-PBX1-positive patients exhibited a characteristic CD34−/CD33− and mostly cyIg+ immunophenotype. ETV6-RUNX1 only occurred in patients under 35 years old and was associated with a significantly lower white blood count.Conclusions In contrast to previous suggestions, adult patients with TCF3-PBX1-positive acute lymphoblastic leukemia do not appear to have a worse outcome than their negative counterparts. ETV6-RUNX1-positive patients had a very favorable performance status during the first few years but their long-term survival was negatively affected by late relapses. Both groups of patients are characterized by distinct clinicobiological features which facilitate their diagnostic identification.

Background Expression of CD56 has been associated with poor prognosis in acute myeloid leukemia and aggressive lymphoma.Design and Methods We analyzed the impact of CD56 expression in a cohort of 452 newly diagnosed adult T-cell acute lymphoblastic leukemia (T-ALL) patients; clinical data were available for 306 patients. Treatment was according to the GMALL study protocols 06/99 and 07/03 stipulating stratification into standard (thymic T-ALL) and high risk (pre- and mature T-ALL) groups.Results CD56 expression was detected in 63/452 (13.9%) patients. CD56+ T-ALL were predominantly of non-thymic (pre-T 35%, mature 41%) immunophenotypic subtypes, whereas 53% of the CD56− cases were thymic T-ALL (p=0.00002). CD13, CD33, CD34 and HLA-DR were significantly more frequently expressed. A clonal T-cell receptor rearrangement was detected in 22/23 CD56+ ALL. No major clinical differences were observed at presentation. Treatment of CD56+ ALL resulted in a lower rate of complete remissions (70% vs. 88%) (p=0.001) and a higher rate of resistant disease (21% vs. 8%) (p=0.004). CD56 expression had no significant influence on overall (48% vs. 59%) and disease free survival (67% vs. 57%) at three years.Conclusions CD56 is expressed on a subset of adult T-ALL with distinct immunophenotypical features and higher resistance to therapy. Most CD56+ ALL were treated in the high-risk arm of the GMALL study protocols owing to their non-thymic phenotype. Thus after risk adapted treatment a prognostic impact of CD56 expression was not detectable.