Calreticulin (CALR) mutations were recently described in JAK2 and MPL unmutated primary myelofibrosis (PMF) and essential thrombocythemia. In the current study, we compared the clinical, cytogenetic ...and molecular features of patients with PMF with or without CALR, JAK2 or MPL mutations. Among 254 study patients, 147 (58%) harbored JAK2, 63 (25%) CALR and 21 (8.3%) MPL mutations; 22 (8.7%) patients were negative for all three mutations, whereas one patient expressed both JAK2 and CALR mutations. Study patients were also screened for ASXL1 (31%), EZH2 (6%), IDH (4%), SRSF2 (12%), SF3B1 (7%) and U2AF1 (16%) mutations. In univariate analysis, CALR mutations were associated with younger age (P<0.0001), higher platelet count (P<0.0001) and lower DIPSS-plus score (P=0.02). CALR-mutated patients were also less likely to be anemic, require transfusions or display leukocytosis. Spliceosome mutations were infrequent (P=0.0001) in CALR-mutated patients, but no other molecular or cytogenetic associations were evident. In multivariable analysis, CALR mutations had a favorable impact on survival that was independent of both DIPSS-plus risk and ASXL1 mutation status (P=0.001; HR 3.4 for triple-negative and 2.2 for JAK2-mutated). Triple-negative patients also displayed inferior LFS (P=0.003). The current study identifies 'CALR(-)ASXL1(+)' and 'triple-negative' as high-risk molecular signatures in PMF.
Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms with variable risk of evolution into post-PV and post-ET myelofibrosis, from now on referred to as secondary ...myelofibrosis (SMF). No specific tools have been defined for risk stratification in SMF. To develop a prognostic model for predicting survival, we studied 685 JAK2, CALR, and MPL annotated patients with SMF. Median survival of the whole cohort was 9.3 years (95% CI: 8-not reached-NR-). Through penalized Cox regressions we identified negative predictors of survival and according to beta risk coefficients we assigned 2 points to hemoglobin level <11 g/dl, to circulating blasts ⩾3%, and to CALR-unmutated genotype, 1 point to platelet count <150 × 10
/l and to constitutional symptoms, and 0.15 points to any year of age. Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM) allocated SMF patients into four risk categories with different survival (P<0.0001): low (median survival NR; 133 patients), intermediate-1 (9.3 years, 95% CI: 8.1-NR; 245 patients), intermediate-2 (4.4 years, 95% CI: 3.2-7.9; 126 patients), and high risk (2 years, 95% CI: 1.7-3.9; 75 patients). Finally, we found that the MYSEC-PM represents the most appropriate tool for SMF decision-making to be used in clinical and trial settings.
In a multi-institutional collaborative project, 1473 patients with myeloproliferative neoplasms (MPN) were screened for isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations: 594 essential thrombocythemia ...(ET), 421 polycythemia vera (PV), 312 primary myelofibrosis (PMF), 95 post-PV/ET MF and 51 blast-phase MPN. A total of 38 IDH mutations (18 IDH1-R132, 19 IDH2-R140 and 1 IDH2-R172) were detected: 5 (0.8%) ET, 8 (1.9%) PV, 13 (4.2%) PMF, 1 (1%) post-PV/ET MF and 11 (21.6%) blast-phase MPN (P<0.01). Mutant IDH was documented in the presence or absence of JAK2, MPL and TET2 mutations, with similar mutational frequencies. However, IDH-mutated patients were more likely to be nullizygous for JAK2 46/1 haplotype, especially in PMF (P=0.04), and less likely to display complex karyotype, in blast-phase disease (P<0.01). In chronic-phase PMF, JAK2 46/1 haplotype nullizygosity (P<0.01; hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7-5.2), but not IDH mutational status (P=0.55; HR 1.3, 95% CI 0.5-3.4), had an adverse effect on survival. This was confirmed by multivariable analysis. In contrast, in both blast-phase PMF (P=0.04) and blast-phase MPN (P=0.01), the presence of an IDH mutation predicted worse survival. The current study clarifies disease- and stage-specific IDH mutation incidence and prognostic relevance in MPN and provides additional evidence for the biological effect of distinct JAK2 haplotypes.
We have previously identified sole +9, 13q- or 20q-, as 'favorable' and sole +8 or complex karyotype as 'unfavorable' cytogenetic abnormalities in primary myelofibrosis (PMF). In this study of 433 ...PMF patients, we describe additional sole abnormalities with favorable (chromosome 1 translocations/duplications) or unfavorable (-7/7q-) prognosis and also show that other sole or two abnormalities that do not include i(17q), -5/5q-, 12p-, inv(3) or 11q23 rearrangement are prognostically aligned with normal karyotype, which is prognostically favorable. These findings were incorporated into a refined two-tired cytogenetic-risk stratification: unfavorable and favorable karyotype. The respective 5-year survival rates were 8 and 51% (hazard ratio (HR): 3.1, 95% confidence interval (CI): 2.2-4.3; P<0.0001). Multivariable analysis confirmed the International Prognostic Scoring System (IPSS)-independent prognostic value of cytogenetic-risk categorization and also identified thrombocytopenia (platelets <100 × 10(9)/l) as another independent predictor of inferior survival (P<0.0001). A similar multivariable analysis showed that karyotype (P=0.001) and platelet count (P=0.04), but not IPSS (P=0.27), predicted leukemia-free survival; the 5-year leukemic transformation rates for unfavorable versus favorable karyotype were 46 and 7% (HR: 5.5, 95% CI: 2.5-12.0; P<0.0001). This study provides the rationale and necessary details for incorporating cytogenetic findings and platelet count in future prognostic models for PMF.
Background: The NuvaRing®, a hormonal vaginal contraceptive device, has gained widespread usage due to its favourable efficacy and safety profiles. Exceedingly rare instances of unintended ...misplacement in the bladder have been reported. This study presents a review of the literature and the first video report illustrating the extraction of an intravesical NuvaRing®, discussing diagnostic and therapeutic approaches. Objective: To illustrate an effective method for intravesical NuvaRing® retrieval and raise awareness about this unusual complication. Materials and Methods: A 27-year-old patient with low urinary tract symptoms related to NuvaRing® misplacement underwent diagnostic procedures, including ultrasound and diagnostic cystoscopy. A cystoscopic extraction under general anaesthesia was performed. Main Outcome Measures: The effectiveness of pelvic ultrasound for diagnosing an intravesical foreign body, successful cystoscopic removal of NuvaRing® from the bladder, and symptom resolution were assessed. Results: The intravesical NuvaRing® was identified through pelvic ultrasound. During cystoscopy, the ring was detected inside the bladder. Multiple attempts with cystoscopic alligator graspers were made; the NuvaRing® was eventually extracted using transurethral Heiss forceps. The patient experienced minimal blood loss and was discharged the following day, reporting relief from symptoms. Conclusions: Unintentional NuvaRing® placement in the bladder is an extremely rare event that healthcare providers should consider when patients present with urinary symptoms and pelvic pain. Pelvic ultrasound is an efficient diagnostic tool, possibly averting the need for further imaging techniques. Cystoscopy remains the preferred method for diagnosis and treatment. This video report illustrates an effective technique for NuvaRing ® extraction, especially when appropriate graspers are unavailable. Adequate instruction on NuvaRing® insertion should always be emphasised.
Background
Pelvic organ prolapse (POP) is a dynamic disorder that affects the entire pelvic diaphragm. POP may often involve multiple organs. Abdominal sacrocolpopexy is considered the gold standard ...to treat female anterior and apical prolapse. Abdominal ventral mesh rectopexy has gained increasing acceptance as an effective treatment for rectal prolapse. The aim of the present study was to assess the safety, feasibility and 1-year outcomes of laparoscopic sacrocolpopexy plus ventral rectopexy as a combined treatment of multicompartment POP.
Methods
All female patients at our institution with anterior and apical prolapse with symptoms of obstructed defecation were examined by an urogynecologist and a colorectal surgeon, and were judged suitable for the study. Patients with Pelvic Organ Prolapse Quantification (POP-Q) system stage III and IV and concomitant rectal prolapse were treated by laparoscopic sacrocolpopexy plus ventral rectopexy. After surgery, 1- and 12-month follow-up was performed and the data were retrospectively analyzed. Patients’ symptoms were evaluated using the Female Sexual Distress Scale (FSDS), Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12), and Wexner–Agachan constipation score.
Results
A total of 98 patients underwent surgery. No intraoperative or postoperative morbidity occurred. At the time of follow-up, all women expressed great satisfaction with the surgical treatment: all the patients had at most POP-Q Stage 1 and 78.8% had a Patient Global Impression of Improvement (PGI-I) score < 3. Significant improvement of symptoms related to POP and to obstructed defecation syndrome, as shown by the FSDS, PISQ-12, and Wexner–Agachan constipation score, was observed in all patients at follow-up
Conclusions
Laparoscopic sacrocolpopexy with ventral rectopexy is a feasible and safe procedure for the combined surgical management of anterior, apical, and posterior prolapse, and provides excellent objective and subjective outcomes.
The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with 'myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In ...all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age >or=70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or >or=2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations.
Marfan Syndrome (MS) is a dominantly inherited connective tissue disorder with consequences on the strength and resilience of connective tissues that may predispose to Pelvic Organ Prolapse (POP). ...Literature lacks studies investigating POP surgery in patients affected by MS that might help surgical management decisions.
The objective of this paper is to describe the surgical procedure of laparoscopic sacral hysteropexy (LSHP) in a 37 years old woman affected by MS with symptomatic POP.
We performed a nerve-sparing laparoscopic sacral hysteropexy without complications and looked for anatomical and subjective outcomes. The patient completed The Female Sexual Distress Scale (FSDS), Pelvic Floor Disability Index (PFDI-20), and Wexner questionnaires preoperatively and postoperatively.
The patient stated a complete resolution of all POP related symptoms and there was a total correction of the descensus. Furthermore, no perioperative and postoperative complications were noted.
LSHP could be an effective and safe procedure for the treatment of POP in women affected by MS and this case report is the first to describe a reconstructive procedure in this category of patients.
The literature lacks studies investigating POP surgery in women with MS, that might help surgeons, thus we present this case to describe surgical and functional outcomes in this patient category, underlying the higher risk of complications and relapses related to the weakness of connective tissue. This case report may represent the basis of future studies to confirm the safety, efficacy and feasibility of LSHP and sacral colpopexy in patients with MS.
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