Hyponatremia: how much attention do we pay to it?

The objective is to describe hyponatremia in patients hospitalized in geriatric (GU) and Internal medicine units (IM), its characteristics and diagnostic approach in order to improve its management and treatment. It is a retrospective study. We collected data through the informatic system of the hospital, performing statistical analysis with SmallStata14. We analyzed patients admitted during 2015 who showed hyponatremia at admission or developed it in any moment during hospitalization. On 824 patients admitted to the Geriatric (n=351) and Internal Medicine (n=473) wards during 2015 (mean age 77.5\ub114.6 yrs; 56% males), 140 patients (17%) had hyponatremia. Hyponatremia was already present at admission in the emergency unit in 49 patients (74% mild; 14% moderate and 12% severe); 10 patients had hypernatremia but developed hyponatremia thereafter. More than half of the patients was taking at least one drug or had a comorbidity possibly causing hyponatremia. 78 patients (56%) developed it during hospitalization (82% mild, 17% moderate and 1% severe). The mean sodium nadir during hospitalization was 131.8\ub12.4mEq/l. Further analyses to improve the diagnostic accuracy were performed in a minority of cases (plasmatic osmolarity has never been measured, urinary osmolarity and sodium in only 3 and 14 patients respectively). At hospital discharge 48 (34%) patients were still hyponatremic (in 79% mildly) and 71 patients were still assuming at least one drug possibly causing hyponatremia. The hyponatremia was often neglected in the letter of discharge. Hyponatremia is a common observation in GU and IM and it can be due to several causes thus guidelines for its treatment are often useless. The lack of appropriate investigations often lead to improper management. Since even mild hyponatremia has been associated with bad clinical outcomes, more attention should be given, in order to improve the management. Further studies are ongoing

Exceedance of design actions in epicentral areas: insights from the ShakeMap envelopes for the 2016–2017 central Italy sequence

ShakeMap is the tool to evaluate the ground motion effect of earthquakes in vast areas. It is useful to delimit the zones where the shaking is expected to have been most significant, for civil defense rapid response. From the earthquake engineering point of view, it can be used to infer the seismic actions on the built environment to calibrate vulnerability models or to define the reconstruction policies based on observed damage vs shaking. In the case of long-lasting seismic sequences, it can be useful to develop ShakeMap envelopes, that is, maps of the largest ground intensity among those from the ShakeMap of (selected) events of a seismic sequence, to delimit areas where the effects of the whole sequence have been of structural engineering relevance. This study introduces ShakeMap envelopes and discusses them for the central Italy 2016–2017 seismic sequence. The specific goals of the study are: (i) to compare the envelopes and the ShakeMap of the main events of the sequence to make the case for sequence-based maps; (ii) to quantify the exceedance of design seismic actions based on the envelopes; (iii) to make envelopes available for further studies and the reconstruction planning; (iv) to gather insights on the (repeated) exceedance of design seismic actions at some sites. Results, which include considerations of uncertainty in ShakeMap, show that the sequence caused exceedance of design hazard in thousands of square kilometers. The most relevant effects of the sequence are, as expected, due to the mainshock, yet seismic actions larger than those enforced by the code for structural design are found also around the epicenters of the smaller magnitude events. At some locations, the succession of ground-shaking that has excited structures, provides insights on structural damage accumulation that has likely taken place; something that is not accounted for explicitly in modern seismic design. The envelopes developed are available as supplemental material

Serum and Cyst Fluid Tumor Marker Levels in the Differential Diagnosis of Benign Ovarian Cysts

Serum and cystic fluid levels of CA 125, CA 19.9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) were assayed in 74 consecutive women of median age 30 years (range 15 to 74 years) undergoing surgery for adnexal cysts of presumed benign nature. Median (range) serum levels of CA 125, CA 19.9, CEA and AFP were 46.5 IU/ml (4.3-406), 28.5 IU/ml (1-96.3), 1.4 ng/ml (0.5-3.5) and 2.4 ng/ml (1-9.9) in 44 endometriotic cysts; 22.5 (4.7-82), 4.9 (1-226),1.3 (0.7-4.8) and 4 (0.5-10.5) in 11 dermoid cysts, 14 (8.6-25.1), 3.2 (1-6), 1 (0.3-2.8) and 3.7 (1.9-6) in 9 mucinous cysts, and 6.9 (0.5-104), 18 (1-132), 0.8 (0.1-1.9) and 2.1(1-5.4) in 10 cases with mixed histotypes. Corresponding cystic fluid levels were 342,864 (1,418-3,404,682), 228,000 (117-2,500,000), 106 (0.5-2,908) and 1.3 (0.4-51) in endometriomas; 843,895 (10,842-1,676,948), 740,039 (77-1,280,000), 470 (61-880) and 2.5 (1-4) in dermoids; 3,485 (27.2-149,804), 9,007 (36.4-153,475), 1,631 (402-11,096) and 1 (0.5-2.5) in mucinous cysts, and 13,068 (5,300-43,767), 412 (1-142,700), 0.8 (0.4-5.3) and 2.3 (1-4) in the mixed histotype group. No significant between group differences were detected in serum marker levels. Patients in the mucinous cyst group had significantly lower CA 125 cystic fluid levels compared with women with endometriomas and dermoids (P<0.05). Fluid aspirate tumor marker measurements did not aid in the differential diagnosis of benign ovarian cysts, mainly due to the extremely wide scattering of values

The value of cyst puncture in the differential diagnosis of benign ovarian tumours

A prospective collection of serum samples and ovarian cyst fluid was used to assess the use of different tumour markers and cyst fluid cytology in combination with serum tumour markers for the differential diagnosis of benign ovarian cysts. A consecutive series of 108 women of median age 30 years (range 15-75) undergoing laparotomy or operative laparoscopy for presumedly benign ovarian cyst(s) were studied at a teaching hospital at the University of Milan, Italy. The main outcome measures were tumour markers CA 125, CA 19.9 and carcino-embryonic antigen (CEA) in serum and ovarian cyst fluid, oestradiol and progesterone concentrations in cyst fluid, and cytology of the sediment. The studied cysts were endometriotic (55 subjects), dermoid (16), mucinous (12), serous (10) or of miscellaneous histotype (15, including four follicular and one luteal). Serum CA 125 concentrations were significantly higher in the endometrioma patients than in the other groups. The sensitivity of CA 125 in the differentiation of endometriomas from other adnexal tumours was 61.8% and the specificity 94.3%; combining CA 125 and CA 19.9 assays yielded a sensitivity of 83.6% and specificity of 62.3%. Cyst fluid tumour markers values were extremely scattered with ample overlap between different cyst types. Oestradiol and progesterone concentrations were similar in the histological subgroups. Cyst fluid cytology was non-specific. We concluded that the aspiration of fluid from presumedly benign ovarian cysts appears to contribute little to the differential diagnosis of various tumours. The use of combining serum CA 125 and CA 19.9 assays in the diagnosis of endometriomas needs further confirmation

Human chorionic gonadotropin patterns after a single dose of methotrexate for ectopic pregnancy

Objective: The great variability in human chorionic gonadotropin (HCG) levels after a single dose of methotrexate (MTX) for ectopic pregnancy makes it difficult to predict treatment failure. We describe different patterns of HCG levels. Study design: Fifty patients were injected i.m. with 50 mg/m2 of MTX for an ectopic pregnancy. Venous blood samples for HCG detection were obtained on the day of treatment (day 0), day 3 and day 7 and weekly until values were undetectable. Patients were classified as: group 1, persistent pathology (n = 11); group 2, complete resolution with a decrease of HCG levels at day 3 (n = 30); group 3, complete resolution after a rise of HCG values at day 3 (n = 9). Statistical analysis was performed using the Mann-Whitney non-parametric test with 95% confidence intervals. Results: Values of day 0 were similar for all the groups. HCG levels of group 3 decreased rapidly after day 3 and at day 7 they were significantly different from levels of group 1. Differences in HCG levels between groups 2 and 3 became indistinguishable from day 21. Conclusion: The observation of patients undergoing resolution after an initial increase of HCG levels justify an expectant management for 1 week in clinically stable patients. The strategy to separate HCG curves in patients undergoing resolution may shed light on the different clinical responses to therapy for ectopic pregnancies. However, the phenomenon of the immediate rise of HCG should be better investigated

Use of the concomitant serum dosage of CA 125, CA 19-9 and interleukin-6 to detect the presence of endometriosis : Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions

Background: Recent studies have proposed the measurement of CA 19-9 and IL-6 as an alternative to CA 125 as markers for endometriosis. This study was performed in order to verify the clinical value of serum CA 125, CA 19-9 and IL-6 levels, either by themselves or combined, in the detection of the disease. Methods: In a prospective cohort study, serum concentrations of CA 125, CA 19-9 and IL-6 were measured in a consecutive series of 80 women of reproductive age who underwent laparoscopy for benign gynaecological pathologies. Results: Endometriosis was documented in 45 women (stage I-II in 14 cases and stage III-IV in 31 cases). Patients with endometriosis had significantly higher levels of CA 125 than controls [23.4 IU/ml (13.3-37.6) versus 11.4 IU/ml (9.1-18.5), P < 0.001)]. Conversely, women with and without the disease were shown to have similar levels of both IL-6 pg/ml [0.6 (undetectable-1.4) versus 1.0 pg/ml (0.4-1.9), P = 0.09] and CA 19-9 [9.8 IU/ml (4.5-20.8) versus 7.4 IU/ml (2.8-11.5), P = 0.11]. The area under the receiver operating characteristics curve resulted in a statistically significant difference from the null hypothesis only for CA 125 (P < 0.001). Sensitivity and specificity of CA 125 were 27 and 97% respectively and were higher than those related to CA 19-9 and IL-6. Concomitant use of the three dosages led to a sensitivity and a specificity of 42 and 71% respectively. Conclusions: The concomitant dosage of CA 125, CA 19-9 and IL-6 does not add significant information in respect to the CA 125 test alone in diagnosing either early or advanced stages of endometriosis

NESS v1.0: A worldwide collection of strong-motion data to investigate near source effects

The availability of high-quality waveforms recorded in epicentral areas of moderate-to-strong earthquakes is a key factor for investigating ground-motion characteristics close to the seismic source. In this study, near-source strong-motion waveforms (named NESS1) were collected from worldwide public archives with the aim of building a flat file of high-quality metadata and intensity measures (IMs) of engineering interest. Particular attention was paid to the retrieval of reliable information about event sources, such as geometries and rupture mechanisms that are necessary to model near-source effects for engineering seismology and earthquake engineering applications. The accelerometric records are manually and uniformly processed, and the associated information is fully traceable. NESS1 consists of about 800 three-component waveforms relative to 700 accelerometric stations, caused by 74 events with moment magnitude larger than 5.5 and hypocentral depth shallower than 40 km, with Joyner-Boore distance up to 140 km. Ground-motion data were selected to have a maximum source-to-site distance within one fault length, defined through seismological scaling relations. About 40 records exhibit peak acceleration or peak velocity exceeding 1g or 120 cm=s, and they represent some of the largest ground motion ever recorded. Evidence of near-source effects was recognized in the NESS1 dataset, such as velocity pulses, large vertical ground motions, directional and hanging-wall amplifications and fling step. In particular, around 30% of the records was found to exhibit pulse-like characteristics that are possibly due to forward rupture directivity. Electronic Supplement: Table listing the main features of the selected events, including the references of fault geometry parameters and Figures showing further metadata and intensity measures distributions of the NESS1 flat file

Blood pressure and 10-year mortality risk in the Milan Geriatrics 75+ Cohort Study : role of functional and cognitive status

Background: optimal blood pressure targets in older adults are controversial.Objective: to investigate whether the relation of blood pressure with mortality in older adults varies by age, functional and cognitive status.Design: longitudinal geriatric outpatient cohort.Setting: Milan Geriatrics 75+ Cohort Study.Subjects: one thousand five hundred and eighty-seven outpatients aged 75 years and over.Methods: the relations of systolic (SBP) and diastolic blood pressure (DBP) with mortality risk were analysed using Cox proportional hazards models. Blood pressure, Mini-Mental State Examination (MMSE) and Basic Activities of Daily Living (ADL) were assessed at baseline. All analyses were adjusted for socio-demographic factors, co-morbidities and medications.Results: one thousand and forty-six patients died during 10-year follow-up. The relationships of SBP and DBP with mortality risk were U-shaped; SBP of 165 mmHg and DBP of 85 mmHg were associated with the lowest mortality. Patients with SBP < 120 mmHg and patients with SBP 120-139 mmHg had 1.64-fold (95% confidence intervals, CI 1.21-2.23) and 1.32-fold (95% CI 1.10-1.60) higher mortality risk than patients with SBP 160-179 mmHg (P values 0.001 and 0.004, respectively). In patients with SBP below 180 mmHg, higher SBP was associated with lower mortality in patients with impaired ADL and MMSE but not in those with preserved ADL and/or MMSE (P for interaction 0.033). Age did not modify the correlation of SBP with mortality.Conclusions: the correlations of SBP and DBP with mortality were U-shaped. Higher SBP is related to lower mortality in subjects with impaired ADL and MMSE. ADL and MMSE may identify older subjects who benefit from higher blood pressure

Thyroid Status and Mortality Risk in Older Adults With Normal Thyrotropin: Sex Differences in the Milan Geriatrics 75+Cohort Study

Pathophysiology, epidemiology and therapy of agein

Divergent Transcription of the Nkx2-5 Locus Generates Two Enhancer RNAs with Opposing Functions

Enhancer RNAs (eRNAs) are a subset of long noncoding RNA generated from genomic enhancers: they are thought to act as potent promoters of the expression of nearby genes through interaction with the transcriptional and epigenomic machineries. In the present work, we describe two eRNAs transcribed from the enhancer of Nkx2-5\u2014a gene specifying a master cardiomyogenic lineage transcription factor (TF)\u2014which we call Intergenic Regulatory Element Nkx2-5 Enhancers (IRENEs). The IRENEs are encoded, respectively, on the same strand (SS) and in the divergent direction (div) respect to the nearby gene. Of note, these two eRNAs have opposing roles in the regulation of Nkx2-5: IRENE-SS acts as a canonical promoter of transcription, whereas IRENE-div represses the activity of the enhancer through recruitment of the histone deacetylase sirtuin 1. Thus, we have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription