[Epidemiology of postpartum hemorrhages in the Umbrian population in the years 2006-2017.] / Epidemiologia delle emorragie post partum nella popolazione umbra nel periodo 2006-2017.

INTRODUCTION: Postpartum haemorrhage (PPH) is one of the main causes of mortality and severe maternal morbidity and its incidence is increasing also in Western countries. Aim of this study is to estimate the incidence and the trend of PPH in the Umbrian population using the validated Umbrian health database and to identify possible determinants for the development of PPH. METHODS: The source of the data was the regional Healthcare Database of the Umbria Region. The population of interest was represented by women who gave birth in Umbria between 2006 and 2017. The PPH was identified from the hospital data using the ICD-9-CM 666.x codes. Demographic data, principal and secondary diagnoses and data on maternal morbidity and blood component transfusion were collected. The incidence of PPH was calculated taking into account cases of PPH over the total number of births. The determinants of PPH, the associated morbidity and the variation in the severity of the PPH over time have been identified by logistic regression models. RESULTS: In Umbria, between 2006 and 2017, 93,403 births were registered (69% by vaginal delivery and 31% by caesarean section) and the rate of caesarean sections decreased by about 4%. The incidence of PPH increased three-fold during this period with an increase (p<0.001) of women with PPH who received transfusions. Regarding the caesarean sections, the PPH trend increased by 53% (p=0.3), while in the vaginal deliveries the PPHs increased by 233% (p<0.001). Logistic regression analysis showed that possible risk factors for the occurrence of PPH are maternal morbidity (OR 22.8, 95% CI 18.5-30.0), twin birth (OR 2.0, 95% CI 1.3-3.2) and antepartum haemorrhage (OR 5.7, 95% CI 3.1-10.4). CONCLUSIONS: The incidence of PPH has increased in recent years, while the morbidity associated with PPH has remained substantially unchanged. The study identified several risk factors responsible for PPH that can be used in the monitoring of pregnant women and for planning prevention strategies such as Patient Blood Management.

[Postpartum haemorrhage in Umbria: accuracy of the regional health information system for the code ICD-9-CM 666.x.] / Emorragia post partum in Umbria: accuratezza del sistema informativo sanitario regionale per il codice ICD-9-CM 666.x.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of morbidity and mortality for pregnant women. Administrative databases are useful sources of information for the assessment of PPH and related outcomes, once the corresponding ICD-9-CM code is validated. The objective of the present study is to evaluate the accuracy of the ICD-9-CM code related to PPH. MATERIAL AND METHODS: Source of the data was the Regional Healthcare Database of the Umbria Region. The population of interest were women with at least 20 weeks of gestation that delivered in any hospital in the Umbria Region during 2012-2016. Cases of interest were identified using the ICD-9-CM 666.x code. For validation purposes, both cases (women who delivered and developed PPH) and non-cases (women who delivered without occurrence of PPH) were considered and algorithms proposed. The basic criterion used for the validity of ICD-9-CM codes was the presence of bleeding ≥500 ml. Additional criteria based on values of haemoglobin or transfusion of red blood cells were considered. Sensitivity, specificity and predictive values were calculated. RESULTS: Medical charts of 422 cases and 200 non-cases were examined. Accuracy results for code 666.x related to the presence of bleeding ≥500 ml were: sensitivity 97% (95% CI, 96-99%), specificity 70% (65-76%), positive predictive value (PPV) 79% (76-82%) and negative predictive value (NPV) 95% (91-97%). The best algorithm was the one that, in addition to the basic criterion, considered both the haemoglobin values and red blood cell transfusion: sensitivity 93% (90-95%), specificity 85% (80-90%), PPV 92% (89-94%) and NPV 86% (81-90%). ICD-9 subcodes showed a higher specificity and PPV for immediate bleeding (666.0, 666.1) than delayed or secondary haemorrhage (666.2). CONCLUSIONS: The accuracy data from the present study confirm that the Regional Healthcare Database of the Umbria Region can be used as a reliable source for the evaluation of epidemiological studies relating to PPHs, in order to improve the quality of maternity care.

Oral iron-based interventions for prevention of critical outcomes in pregnancy and postnatal care: An overview and update of systematic reviews.

OBJECTIVE: The aim of this work was to summarize and update the evidence concerning oral iron-based interventions compared to placebo or no iron-based interventions to prevent critical outcomes in pregnancy or treat critical outcomes in the postpartum phase. METHOD: Published systematic reviews (Feb 2018) and primary studies (from 2015 to March 2018) retrieved from MEDLINE, EMBASE, and the Cochrane Library were examined. The AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool was used to assess the quality of reviews. GRADE was used to rate the quality of the evidence for critical outcomes. RESULTS: Antenatal care: Compared to placebo/no treatment, iron-based therapies reduced maternal anemia at term by 59% (seven trials at low risk of bias, RR 0.41, 95% CI 0.23-0.73; I2  = 86%; moderate-quality evidence) and maternal iron deficiency anemia by 67% (RR 0.33, 95% CI 0.16-0.69; I2  = 49%). There was no evidence of difference between iron-based therapies vs control in terms of side effects (RR 1.42, 95% CI 0.91-2.21), preterm delivery (13 studies: RR 0.93, 95% CI 0.84-1.03; low-quality evidence), low birthweight (RR 0.94, 95% CI 0.79-1.13; low-quality evidence) and infant mortality (RR 0.93, 0.72-1.20; low-quality evidence). POSTNATAL CARE: There was insufficient evidence to determine whether iron-based therapies can reduce postpartum anemia. CONCLUSION: Iron supplementation is effective in preventing maternal anemia at term but not low birthweight, preterm delivery or infant mortality.

Diagnostic, preventive and therapeutic evidence in obstetrics for the implementation of patient blood management: a systematic review protocol.

INTRODUCTION: Patientblood management (PBM) is defined as the application of evidence-based diagnostic, preventive and therapeutic approaches designed to maintain haemoglobin concentration, optimise haemostasis and minimise blood loss in an effort to improve patient outcome. We propose a protocol for the assessment of the evidence of diagnostic, preventive and therapeutic approaches for the management of relevant outcomes in obstetrics with the aim to create a framework for PBM implementation. METHODS AND ANALYSIS: Diagnostic, preventive and therapeutic tools will be considered in the gynaecological conditions and obstetrics setting (antenatal care, peripartum care and maternity care). For each condition, (1) clinical questions based on prioritised outcomes will be developed; (2) evidence will be retrieved systematically from electronic medical literature (MEDLINE, EMBASE, the Cochrane Library, Web of Science, and CINAHL); (3) quality of the reviews will be assessed using the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist; quality of primary intervention studies will be assessed using the risk of bias tool (Cochrane method); quality of diagnostic primary studies will be assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies); (4) the Grading of Recommendations Assessment, Development and Evaluation method will be applied to rate the quality of the evidence and to develop recommendations. ETHICS AND DISSEMINATION: For each diagnostic, preventive or therapeutic intervention evaluated, a manuscript comprising the evidence retrieved and the recommendation produced will be provided and published in peer-reviewed journals. Ethical approval is not required.

FISH analysis reveals frequent co-occurrence of 4q24/TET2 and 5q and/or 7q deletions.

We investigated TET2 deletion in 418 patients with hematological malignancies. Overall interphase FISH detected complete or partial TET2 monoallelic deletion (TET2(del)) in 20/418 cases (4.7%). TET2(del) was very rare in lymphoid malignancies (1/242 cases; 0.4%). Among 19 positive myeloid malignancies TET2(del) was associated with a 4q24 karyotypic abnormality in 18 cases. In AML, TET2(del) occurred in CD34-positive hematopoietic precursors and preceded established genomic abnormalities, such as 5q- and -7/7q-, which were the most frequent associated changes (Fisher's exact test P=0.000).

NPM1 deletion is associated with gross chromosomal rearrangements in leukemia.

BACKGROUND: NPM1 gene at chromosome 5q35 is involved in recurrent translocations in leukemia and lymphoma. It also undergoes mutations in 60% of adult acute myeloid leukemia (AML) cases with normal karyotype. The incidence and significance of NPM1 deletion in human leukemia have not been elucidated. METHODOLOGY AND PRINCIPAL FINDINGS: Bone marrow samples from 145 patients with myelodysplastic syndromes (MDS) and AML were included in this study. Cytogenetically 43 cases had isolated 5q-, 84 cases had 5q- plus other changes and 18 cases had complex karyotype without 5q deletion. FISH and direct sequencing investigated the NPM1 gene. NPM1 deletion was an uncommon event in the "5q- syndrome" but occurred in over 40% of cases with high risk MDS/AML with complex karyotypes and 5q loss. It originated from large 5q chromosome deletions. Simultaneous exon 12 mutations were never found. NPM1 gene status was related to the pattern of complex cytogenetic aberrations. NPM1 haploinsufficiency was significantly associated with monosomies (p<0.001) and gross chromosomal rearrangements, i.e., markers, rings, and double minutes (p<0.001), while NPM1 disomy was associated with structural changes (p=0.013). Interestingly, in complex karyotypes with 5q- TP53 deletion and/or mutations are not specifically associated with NPM1 deletion. CONCLUSIONS AND SIGNIFICANCE: NPM1/5q35 deletion is a consistent event in MDS/AML with a 5q-/-5 in complex karyotypes. NPM1 deletion and NPM1 exon 12 mutations appear to be mutually exclusive and are associated with two distinct cytogenetic subsets of MDS and AML.

A NUP98-positive acute myeloid leukemia with a t(11;12)(p15;q13) without HOXC cluster gene involvement.

We report a case of adult acute myeloid leukemia with a new t(11;12)(p15;q13) underlying a NUP98 rearrangement without HOXC cluster gene involvement. We designed a specific double-color double-fusion FISH assay to discriminate between this t(11;12)(p15;q13) and those producing NUP98-HOXC11 or NUP98-HOXC13. Our fluorescence in situ hybridization (FISH) showed that putative candidate partners mapping 600 kilobases centromeric to HOXC were RARG (retinoic acid receptor gamma), MFSD5 (major facilitator superfamily domain containing 5), and ESPL1 (extra spindle pole bodies homolog 1). It is noteworthy that so far only ESPL1 has been implicated in human cancers. This FISH assay is useful for diagnostic screening of NUP98-positive leukemias.

Sustained ventricular tachycardia in a thalidomide-treated patient with primary plasma-cell leukemia.

BACKGROUND: A 68-year-old man diagnosed with primary plasma-cell leukemia was given thalidomide maintenance treatment for his disease. He had previously failed induction therapy with cyclophosphamide, vincristine, adriamycin, and dexamethasone, but achieved complete remission after melphalan therapy. Multiple syncopal episodes started to occur during thalidomide treatment, and a Holter electrocardiogram showed multiple abnormalities, with an episode of sustained ventricular tachycardia. INVESTIGATIONS: Blood tests, peripheral blood smear, bone-marrow biopsy and aspirate, Holter electrocardiogram. DIAGNOSIS: Sustained ventricular tachycardia possibly owing to thalidomide treatment. MANAGEMENT: Thalidomide withdrawal, dexamethasone maintenance therapy, monthly oral courses of combined melphalan and prednisone, salvage therapy with bortezomib.