In multivariate regression analysis, female gender , Sokal risk , type of transcript  and achievement of an early molecular response (EMR) at 3 months , retained statistical significance. These clinical and biologic features associated with the achievement of a stable deep molecular response should be taken into account at a time when treatment-free remission strategies are being actively pursued in the management of CML.Deep molecular response in chronic myeloid leukemia (CML) patients treated with imatinib is a prerequisite for possible discontinuation. We identify clinico-biologic features linked with the probability of reaching MR4.5 (BCR-ABL/ABL ≤ 0.0032% IS) as a stable response (confirmed on two or more consecutive determinations). In a series of 208 patients treated with imatinib first-line outside clinical trials, after a median follow-up of 7 years the incidence of stable MR4.5 was 34.6%, obtained in median time of 5.4 years. In univariate analysis, female gender ( The introduction of tyrosine kinase inhibitors (TKIs) into the pharmacologic armamentarium for the treatment of chronic myeloid leukemia (CML) has drastically changed the management and outcome of chronic phase patients . With imMore robust and standardized definitions of molecular response have been introduced and are universally accepted . PatientOverall, we retrospectively analyzed 208 patients; median age was 57.7 years range 21–90) with 65% of patients > 65 years old. Sokal risk stratification stratified 100 patients as low risk (48.1%), 83 as intermediate (39.9%) and 25 as high risk (12%). According to the European treatment and outcome study (EUTOS) stratification, 114 patients were low risk (54.8%) and 94 high-risk (45.2%). Overall, after 1 year the incidence of CCyR was 83%, whereas at 7 years the cumulative incidence of MR3 was 70% and of MR4 51.5%. The overall incidence of a stable MR4.5 was 34.6%  and median age . Moreover, we found a significant association between the Sokal risk stratification and the likelihood of obtaining a MR4.5: 32% in patients classified as low risk, 22% in intermediate risk patients and 11% in high risk patients (p = 0.01). The e14a2 type of transcript was associated with a significantly increased rate of MR4.5 (43%) compared to the e13a2 type . At 3 months, in the cohort who reached a stable MR4.5 only 1% of patients had not achieved an early molecular response (EMR or BCR-ABL1/ABL ratio < 10%), compared to 6% in the cohort that did not achieve a stable MR4.5 (p = 0.001). The rate of MR3 at 3 months was 15% in the cohort of patients who achieved stable molecular response vs 4% in the cohort who did not (p = 0.02). At 6 months, a MR3 was obtained by 43% of the patients who achieved a stable MR4.5 compared to only 19% in the cohort who did not reach this stable response (p = 0.01). At 12 months, this difference was again significant . None of the patients who achieved a stable MR4.5 developed resistance with an EFS of 100%, whereas the EFS in the cohort who never achieved a stable MR4.5 was 81% (p = 0.01). Indeed, as previously reported, fluctuations of the molecular residual disease at the level of MR4.5 did not influence EFS or OS [p = 0.001). We included in the analysis also drug dose, different schedules and median discontinuation time for intolerance, but all these factors did not results significant. The estimated 7-year OS was 96% in the cohort of patients with a stable MR4.5 and 89% in the cohort of patients who did not reach such a response, with a favorable trend that has so far not reached statistical significance (p = 0.087).We analyzed in univariate analysis the prognostic variables associated with the achievement of a stable MR4.5 Table : we idenP = 0.022), Sokal risk , type of transcript  and achievement of EMR at 3 months  were associated with a significantly higher probability of achieving MR4.5 during treatment at any time. Indeed, in multivariate analysis no association was reached for molecular responses obtained at 6 and 12 months, or for age.We then assessed prognostic associations in a Cox multivariate regression analysis Table : female We also estimated how many patients would satisfy criteria for discontinuation: according to Stop Imatinib trial (STIM), 29% of patients could attempt to treatment-free remission whereas according to European Stop Tyrosine Kinase Inhibitor study (EUROSKY) criteria, 42% of patients could be defined candidate [p < .001 for both). After 8 years 54.4% of women achieved a stable MR4.5 compared to 27.2% of men, with no differences in terms of Sokal risk, imatinib dose intensity or median age, being observed between sexes. The real reasons for this gender difference could not be defined and the phenomenon was attributed to possible pharmacokinetic differences, immune response or simply to a better adherence of females to long-term treatment [In this retrospective single center real life study outside of clinical trials, we could document that female gender, low vs intermediate/high Sokal risk, e14a2 type of transcript and achievement of EMR after 3 months of treatment represent prognostic factors significantly associated with a subsequent achievement of a stable MR4.5 in CML patients treated with imatinib first-line. Our results support and extend observations derived individually from clinical trials. Branford and colleagues  reportedreatment . We prevreatment . Sokal sreatment : after 4The type of transcript was investigated by the MD Anderson Cancer Center group that evaluated the impact of the e14a2 and e13a2 transcripts on responses and OS . PatientFinally, in our regression model, the achievement of an EMR at 3 months was associated with a long-term positive outcome. This evidence confirms the value of this early evaluation as reported by several groups and with different TKIs. In particular, the Australian group showed that patients who had achieved at 3 months a BCR-ABL1 ratio < 0.1% had a significantly higher cumulative incidence of stable MR4.5 after 8 years (78.2%) compared to patients with a ratio > 0.1% and < 1% (52.7%) or to patients who had a ratio > 1% up to 10% (29%). Patients who had not achieved an EMR at 3 months had the lowest percentage of stable MR4.5 after 8 years (8.6%) . The samA stable deep molecular response has become an endpoint for the majority of CML patients in order to attempt a possible treatment discontinuation. A long follow-up of the STIM1 study has shown that only about 40% of patients remained disease-free without imatinib after 65 months . The earA series of 208 chronic phase CML patients treated first-line with imatinib at our center outside of clinical trials and having a median follow-up of 7 years was analyzed. Patients were diagnosed and followed between January 2000 and December 2014. No patient had received interferon prior to imatinib treatment.The following response categories were analyzed using standard definitions: CCyR, major molecular response (MR3 or ratio BCR-ABL/ABL < 0.1% IS), MR4 (ratio BCR-ABL/ABL < 0.01% IS) and MR4.5 (ratio BCR-ABL/ABL < 0.0032% IS). Patients were monitored and stratified at each time point according to the 2013 European LeukemiaNet (ELN) recommendations . A stablp value < 0.05 that emerged from the univariate test was selected to construct a full multivariate Cox regression model to predict baseline prognostic factors for the entire study cohort. The full model was reduced to a final model using the stepwise selection method so that all factors remaining in the model were statistically significant. EFS was measured from the start of treatment to the occurrence of an event, considering loss of complete hematologic response (CHR) or major cytogenetic response, progression to advanced phase of disease (accelerated or blast phase), or death from any cause during treatment. OS was defined from the date of CML diagnosis to the date of death or last follow-up using the Kaplan Meyer method.The following features were included in the analysis aimed at identifying the probability of obtaining a stable deep molecular response: age, gender, Sokal and Eutos score, white blood cell count, hemoglobin level, platelet count, BCR-ABL transcript type, type of response at each time point according to the 2013 ELN recommendations . First,


CD73 dephosphorylates adenosine monophosphate to adenosine that is an anti-inflammatory molecule inhibiting immune activation and vascular leakage. Therefore, CD73 could be an interesting mediator both in sepsis and acute kidney injury (AKI). We aimed to explore the soluble CD73 (sCD73) levels and their evolution in critically ill patients with severe sepsis and, second, to scrutinize the potential association of sCD73 levels with AKI and 90-day mortality.post-hoc laboratory analysis of the prospective, observational FINNAKI study conducted in 17 Finnish ICU during 5 months in 2011–2012. Plasma samples of 588 patients admitted with severe sepsis/shock or with developing severe sepsis were analyzed at 0h (ICU admission) and 24h, and additionally, on day 3 or day 5 from a subset of the patients.This was a P<0.001. From 24h to Day 3 (n = 132) the sCD73 levels rose to 5.18 [2.98–8.83] ng/mL (P = 0.373) and from 24h to Day 5 (n = 224) to 5.52 [3.57–8.90] ng/mL (P<0.001). Patients with AKI had higher sCD73 values at 0h and at 24h compared to those without AKI. Non-survivors with severe sepsis, but not with septic shock, had higher CD73 levels at each time-point compared to survivors. After multivariable adjustments, sCD73 levels at 0h associated independently neither with the development of AKI nor 90-day mortality.The median [IQR] sCD73 levels at 0h were 5.11 [3.29–8.28] ng/mL and they decreased significantly from 0h to 4.14 [2.88–7.11] ng/mL at 24h, Compared to normal population, the sCD73 levels were generally low at 0h, showed a decrease to 24h, and later an increase by day 5. The sCD73 levels do not seem useful in predicting the development of AKI or 90-day mortality among patients with severe sepsis or shock. Severe sepsis is diagnosed up to a third of patients treated in intensive care units (ICUs) , 2. MultThe complex pathophysiology of severe sepsis involves both pro-inflammatory reactions to eliminate the invading pathogens and anti-inflammatory responses to limit local and systemic tissue injury . CD73 isCD73 is especially abundant on the cell surfaces in the kidneys . CD73 deIn humans, patients with more severe acute pancreatitis had decreased levels of plasma soluble CD73 (sCD73), and the activity of soluble form of CD73 showed prognostic value in predicting the development of severe acute pancreatitis . FurtherTherefore, CD73 is an interesting mediator both in sepsis and AKI and a potential target of therapeutic interventions. However, the sCD73 levels among critically ill patients with severe sepsis or AKI are currently unknown. We hypothesized that in severe sepsis and septic shock, the sCD73 concentrations would be decreased–one potential underlying mechanism being increased degradation. Thus, we decided to explore the sCD73 levels and their evolution in critically ill patients with severe sepsis. Moreover, we aimed to scrutinize the potential association of sCD73 levels with AKI and 90-day mortality.post-hoc laboratory study of the prospective, observational Finnish Acute Kidney Injury (FINNAKI) study  CD73 activity among these 42 patients was 730 [342–1416] nmol/mL/h.We found the DELFIA assay for the detection of sCD73 to be reliable, but the absolute values obtained by the DELFIA method were lower than that detected by the ELISA method  and therSamples from 588 consecutive patients were analyzed  were admitted with septic shock, 300 (51.0%) were admitted with severe sepsis and 179 (59.7%) of them developed septic shock within a median [IQR] of 2.9 [1.7–9.2] hours. Of the 98 (16.7%) patients admitted without fulfilling the criteria for severe sepsis/septic shock, 60 (61.2%) were diagnosed with septic shock after a median [IQR] of 5.4 [2.4–23.7] hours.P = 0.014. In comparisons according to the presence of other pre-existing comorbidities , no differences in sCD73 levels at 0h existed (data not shown).Among all patients, the median [IQR] sCD73 levels at 0h were 5.11 [3.29–8.28] ng/mL. P <0.001. From measurement at 24h to Day 3 (n = 132) the sCD73 levels rose to 5.18 [2.98–8.83] ng/mL (p = 0.373) and from 24h to Day 5 (n = 224) 5.52 [3.57–8.90] ng/mL (P <0.001). When patients were grouped in tertiles according to the change in sCD73 values from 0 to 24h, patients in the the lowest tertile (median [IQR] change -3.02 [-5.73–-2.28] ng/ml) had higher lactate and SOFA scores on day 1 compared to those in the highest tertile (median [IQR] change 0.26 [-0.05–1.17] ng/ml)  .P>0.999).P = 0.004, but not in other time-points .Patients with AKI diagnosed until day 5 in the ICU had higher sCD73 values at 0h and at 24h compared to those without AKI . When paOf the 588 patients, 164  were dead by day 90. The non-survivors had significantly higher sCD73 levels both at 0h and at 24h . The difIn this sub-cohort of critically ill septic patients from the prospective FINNAKI study we found that the sCD73 levels were generally low at 0h compared to previously reported data, showed a decrease to 24h, and an increase by day 5. Patients admitted with septic shock presented with the lowest concentrations. Moreover, patients with AKI and 90-day non-survivors with severe sepsis presented with slightly higher levels compared to non-AKI patients and 90-day non-survivors, but the sCD73 levels were not independently associated with the development of AKI or 90-day mortality.The origin of sCD73 measured in plasma is thought to be mainly from shedding from blood lymphocytes . CompareMajority of patients showed a decrease in sCD73 levels within the 24h in ICU. By day 5, we demonstrated an increase in sCD73 levels. The drop seen at 24h could be due to increased degradation of sCD73 or its leakage to the tissues. Unfortunately the lymphocyte levels were not measured so that we cannot comment on whether the initial drop seen in sCD73 levels would have been due to a reduction in circulating lymphocyte levels and decreased shedding of sCD73. Patients categorized according to the magnitude of change in sCD73 levels between 0 and 24h did not differ regarding fluid balance, and, thus, the observed drop is unlikely to be due to hemodilution. Alternatively, CD73 production may be diminished like reported to occur in leukocytes of patients with severe pancreatitis and low levels of sCD73 . As CD73Patients with AKI presented with higher sCD73 levels at 0h and 24h. This is surprising, as one could assume AKI to involve increased degradation of sCD73. Unfortunately, no studies examining the sCD73 levels and AKI in the critically ill exist for comparison. Potentially, endogenous mechanisms are working to increase the sCD73 levels given that work in mice has shown induction of CD73 to be protective in ischemia-reperfusion–related AKI . Decreasper se do not explain these findings. If sCD73 levels in plasma are solely from circulating lymphocytes [We found the non-survivors with severe sepsis but not with septic shock to have higher sCD73 levels compared to survivors. Patients with AKI also had higher sCD73 levels, which could potentially also associate with worse outcome. However, the difference between survivors and non-survivors regardless of the severity of sepsis was robust for exclusion of AKI patients, suggesting that decreased clearance due to AKI or AKI phocytes , then thThe encouraging results of using interferon-beta to increase the activity of CD73, and potentially, decrease the permeability of pulmonary capillaries, showed that among patients with ARDS the treatment increased the CD73 activity almost to three-fold during the dosing period . In a super se. Fourth, the differences between all groups in the sCD73 concentrations were generally small, and the clinical significance of these is unclear.The strengths of our analysis include detailed collection of clinical data and the multicenter design. Several limitations should be discussed, however. First, to study the trend in sCD73 levels, we analyzed samples from patients of whom both 0h and 24h plasma were available. Therefore, those who died or were discharged shortly after admission were excluded (9.8% of the severe sepsis FINNAKI cohort) [post-hoc laboratory analysis prospective, multicenter FINNAKI study among septic critically ill patients, we found that the sCD73 levels were generally low and showed a further decrease from 0h to 24h. Moreover, the sCD73 levels were higher in AKI versus non-AKI patients and in non-survivors with severe sepsis than in survivors, but were not independently associated either with the development of AKI or 90-day mortality. The sCD73 levels do not seem useful in predicting the outcome of patients with severe sepsis or shock.In conclusion, in this S1 Dataset(XLSX)Click here for additional data file.S1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S1 Text Material(PDF)Click here for additional data file.


Lumbosacral alignment is a crucial factor for an appropriate spinal function. Changes in spinal alignment lead to diminished body biomechanics. Additionally, lumbosacral alignment may affect quality of life, sagittal balance and fall risk in elderly. In this study, we aimed to compare lumbosacral alignment in geriatric and non-geriatric patients suffering from low back pain.A total of 202  patients who visited to physical medicine and rehabilitation clinic with low back pain between January 2017 and August 2017 were enrolled in this study. Standing lateral lumbar radiographs were obtained from the electronic hospital database. Lumbar lordosis angle, sacral tilt, lumbosacral angle and lumbosacral disc angle were calculated on lateral standing lumbar radiographs.The mean age of the non-geriatric group was 43.02 ± 13.20 years, the geriatric group was 71.61 ± 6.42 years. In geriatric patients, lumbar lordosis angle, sacral tilt and lumbosacral disc angle were significantly smaller . No significant differences were observed in lumbosacral angle between the groups (p = 0.508).Our study indicates the specific changes in lumbosacral alignment with aging. Identifying these changes in lumbosacral alignment in the geriatric population will enable to create proper rehabilitation strategies. The spine, pelvis, hip joints and lower extremities are continuously contact with each other to transmit the body weight to the ground with minimum energy and deformity. Lumbosacral alignment is one of the crucial factor for appropriate spinal function.9Aging is another important factor which changes lumbosacral alignment. The lumbar spine is constantly changing and reshaping throughout life. Takeda et al.In our study we aimed to compare lumbosacral alignment between geriatric and non-geriatric patients suffering low back pain. Secondary aim was to determine the additional effect of aging on lumbosacral alignment in low back pain cases. Discovering specific spinal changes in geriatric patients with low back pain will contribute to create suitable rehabilitation strategies.Patients who visited to our clinic with complaint of low back pain between January 2017 and August 2017 were included in this study. Standing lateral lumbar radiographs were obtained from the electronic hospital database. Total of 941 patients 18 years old or above were identified in the hospital database. Two groups were formed according to age: geriatric group (65 years or above), non-geriatric group (between 18 and 64 years). Patients who had spinal surgery, spinal infection, spinal trauma, spondyloarthritis, spinal tumour, scoliosis, excessive vertebral fracture were excluded. Additionally, patients whose radiographs were not appropriate were also excluded. Following the application of exclusion criteria, radiographs of 202 patients were included in this study.Measurement of the lumbosacral angles was evaluated on digitalized lateral radiographs by Enlil PACS System software. This software enables placing straight lines and calculating lumbosacral angles. Lumbosacral angle calculations were determined as mentioned below:Lomber lordosis angle (LLA) was measured from the intersection of two lines drawn from the upper edge of the L1 vertebra and the lower edge of the L5 vertebra.Sacral tilt (ST) was measured from the intersection of the lines tangent to the posterior sight of S1vertebra and the vertical line.Lumbosacral angle (LSA) was measured from the intersection of the lines drawn from superior endplate of S1 vertebra and the horizontal line.Lumbosacral disc angle (LSDA) was measured from the intersection of two lines drawn from the inferior end plate of L5 vertebra and the superior end plate of S1 vertebraStatistical analyses were evaluated with SPSS version 20.0 for Windows . All results are expressed as mean value and standard deviation, number, percentage. Normality of the variables was analyzed with Shapiro-Wilk test. Chi-square test was performed to evaluate differences in categorical variables. Determination of differences in continuous variables between two groups was assessed using independent samples t-test. Pearson correlation analysis was used to determine the correlations between findings. The statistical significance value was accepted as 0.05. Correlation analyses were classified as weak, moderate, strong or very strong correlation according to coefficient (r) values being 0–0.25, 0.25–0.50, 0.50–0.75 or 0.75–1.00, respectively.A total of 202 patients were enrolled in our study. 122 patients  were in non-geriatric group; 80 patients  were in geriatric group. Gender differences were not statistically significant between groups (p = 0.106). The mean age of the non-geriatric group was 43.02 ±13.20 years, the geriatric group was 71.61 ± 6.42 years.The mean values of the LLA, ST, LSA and LSDA were 40.25 ± 9.01, 40.62 ± 6.85, 38.39 ± 8.96 and 8.91 ± 2.51 in non-geriatric group. The mean values of the LLA, ST, LSA and LSDA were 37.73 ± 7.80, 38.32 ± 6.31, 37.50 ± 9.91 and 7.98 ± 2.89 in geriatric group. In the geriatric group, LLA, ST and LSDA were significantly smaller . Despite that, there was no significant difference between the groups in terms of LSA (p=0.508) .When non-geriatric and geriatric group were pooled and analyzed according to gender; the mean values of the LLA, ST, LSA and LSDA were 36.95 ± 7.84, 37.88 ± 6.21, 36.19 ± 9.01 and 8.14 ± 2.79 in male patients. The mean values of the LLA, ST, LSA and LSDA were 40.82 ± 8.80, 40.95 ± 6.79, 39.30 ± 9.38 and 8.81 ± 2.62 in female patients. LLA, ST and LSA were found to be significantly higher in female patients .No significant difference was observed between male and female patients in terms of LSDA (p=0.08).The mean values of the LLA, ST, LSA and LSDA were 39.01± 8.36, 38.29 ± 6.16, 37.03 ± 8.45 and 8.21 ± 2.34 in male patients. The mean values of the LLA, ST, LSA and LSDA were 40.94 ± 9.33, 41.93 ± 6.91, 39.16 ± 9.19 and 9.30 ± 2.54 in female patients. ST and LSDA was significantly higher in female patients (p=0.004 and p = 0.022). No significant difference was found between male and female patients in terms of LLA and LSA (p = 0.258 and p = 0.208) .The mean values of the LLA, ST, LSA and LSDA were 34.56 ± 6.51, 37.42 ± 6.33, 35.23 ± 9.65 and 8.05 ± 3.26 in male patients. The mean values of the LLA, ST, LSA and LSDA were 40.59 ± 7.83, 39.14 ± 6.25, 39.55 ± 9.82 and 7.92 ± 2.54 in female patients. LLA was significantly higher in female patients (p<0.001). However, there was no significant difference between male and female patients in ST, LSA and LSDA  .When the correlation of lumbosacral angles with each other were evaluated without dividing patients into two groups; LLA demonstrated a positive moderate correlation with ST . LSA showed a positive moderate correlation with LLA, ST and LSDA .When the correlation of lumbosacral angles in the non-geriatric group was analyzed; LLA showed a positive moderate correlation with ST . LSA was positively and strongly correlated with ST and LLA ; positively and weakly correlated with LSDA .When the correlation analyzes were evaluated in the geriatric group; LLA demonstrated a positive strong correlation with SIA . LSDA was positively and moderately correlated with ST and LSA .In our study, we analyzed lumbosacral alignment using lateral sagittal lumbosacral angles measurement. We compared measurements between two different groups; non-geriatrics and geriatrics. Additionally, differences were evaluated between male and female patients. All patients in our study had low back pain.LLA, ST and LSDA were significantly smaller in geriatric group . Furthermore, LSA was smaller in geriatric group but difference was not significant (p=0.508). Our results are consistent with previous studies. Takeda et al.Along with age, remarkable changes occur in the spinal column and curvatures. More evident changes were observed after the age of 60 years.Lumbosacral alignment LLA in particular, affects quality of life, sagittal balance and fall risk in geriatric population.25All our data were analyzed according to gender. LLA, ST and LSA were found to be higher in female patients. ST and LSDA were significantly higher in female patients in non-geriatric group and LLA was significantly higher in female patients in geriatric group. Our results have showed that female patients had a hyperlordotic posture. Similar to our results, Benlidayi et al.The relations of all these measurements with each other have an important role for maintaining proper spinal alignment. Any change in one of these parameters leads to a change in the others to provide functional and proper spino-pelvic unit. Thus, we evaluated the correlation analyses of lumbosacral angles. Boulay et al.Results of this study describe how lumbosacral angles change with age and differ between sexes. Our study provides a better understanding and valuable informations on lumbosacral alignment. It is important for the physicians to be aware of the differences in lumbosacral parameters between these unalterable demographic characteristics. This study might also set light to future researches on the interventions preventing from malalignment in geriatric population. We believe that our results might help improving the treatment strategies of patients with spinal deformity.It has a retrospective design. As a result of retrospective design, we could not evaluate the body mass index and occupation conditions. Hip joint, knee joint and ankle joint positions may influence the lumbosacral parameters. We could not evaluate these joints positions in our study. We could not assess the pain level and quality of life. Therefore, we could not identify clinical impacts of lumbosacral parameters. We could not compare the lumbosacral parameters between patients with acute low back pain and patients with chronic low back pain. We did not evaluate healthy controls. Our results must be confirmed with multi-centered prospective, longitudinal studies. Future longitudinal studies should clarify the association between lumbosacral alignment and clinical symptoms.This study has described the changes in lumbosacral alignment with aging. Our results are important for showing that age may influence the lumbosacral angles including LLA, ST and LSDA. LLA, ST and LSDA were smaller in geriatric patients. Variations in lumbosacral alignment have also been demonstrated among male and female patients. LLA, ST and LSA were higher in female patients. We consider that variations on lumbosacral alignment with aging and among sexes should be taken into account before the surgical plans and rehabilitation programmes. Strategies aiming to provide a good sagittal lumbosacral alignment need to be investigated. Studies with larger sample size in which standardized angle regions and methods are used are needed for determination of the changes in lumbosacral angles with age.BFK conceived, designed and did statistical analysis & editing of manuscript.BFK, EB did data collection and manuscript writing.BFK did review and final approval of manuscript.All the listed authors have approved the revised manuscript and is accountable for the integrity of this study.


The cardio-thoracic ratio (CTR) and the transverse cardiac diameter (TCD) on Plain chest radiography are the two parameters commonly used to diagnose cardiomegaly and heart disease. A CTR of greater than 50% on a PA film is abnormal and normally indicates cardiac or pericardial disease condition, whiles an increase of TCD from 1.5 to 2cm on two consecutive radiographs, taken at short interval, suggests possible cardiac pathology. The aim was to determine the suitability of using the same TCD and CTR to detect cardiomegaly for all age groups and genders respectively.A retrospective study involved the review of 1047 radiological images of adults aged 21 to 80 years, who had plain postero-anterior chest radiographs between January 2012 and November 2013 by 3 radiologists. Data recorded included the transverse cardiac, thoracic diameter and the cardiothoracic ratios. Descriptive analyses were carried out using the Microsoft excel 2010.The mean age and standard deviation for the study population was 35.1 ± 12.7. The mean and standard deviations for the transverse cardiac diameter, thoracic diameter, and the cardiothoracic ratios for male participants were 13.08cm ± 1.2, 29.7cm ± 2.7 and 46.6% ± 3.9; and 12.9 cm ± 1.3, 27.1 cm ± 2.6, and 47.8% ± 4.8 for females. An increase in TCD of 1cm resulted in a CTR of greater than 50.0% in all but the males aged 21-40 years.The study found that the same TCD and CTR values are not suitable in detecting cardiomegaly for all age groups and genders. The postero-anterior (PA) chest radiograph is a common and non-invasive way to radiologically assess the size of the heart for disease and patient response to treatment . There aPublications from the 1980s suggest that though the upper limit for CTR measurement is generally considered to be 50%, a ratio of 55% may be considered normal for Blacks and Asians , 5–7. NeA retrospective descriptive study was conducted by evaluating the radiology reports of 104A total of 1047 radiological images were reviewed. The CTR and TCD are common parameters used for the evaluation of cardiomegaly in the management of heart disease. The accuracy of these measurements in determining whether or not one has cardiac disease or not can therefore not be overemphasized. The study included adults comprising 397 (39.9%) females, and 650 (62.1%) males, with an age range of 21 to 80 years. The mean age of the study was 35.1 years ± 12.7. This study had a mean TCD of 13.8cm±1.2cm for males, and 12.9cm±1.3cm for females, and a CTR of 46.6% ± 3.9 for males, and 47.8% ± 4.8 for females .The value of the CTR as a means of evaluating heart size in an individual would depend on a constant TTD, to which the TCD can be compared. Studies have shown significant variations of TTD and hence, the CTR is regarded as an unreliable parameter by many authors –11. NotwThis study showed that an increase in TCD of 1cm instead of 1.5cm was significant, as it resulted in a CTR of greater than 50.0% in all but the males aged 21-40 years, where the CTR was 49.7%. A 1.5cm increase in TCD on the other hand, resulted in values of CTR ranging from 51.4% to 52.2% for men, and 51.9% to 57.2% for females. These results suggest that withholding treatment till the CTR difference reaches 1.5cm is likely to delay management and allow disease progression. The average CTR values from the study  showed tThe study found that the same TCD and CTR values are not suitable in detecting cardiomegaly for all age groups and genders. The differences in CTR and TCD increases noted in the study differ from those in existing publications, and appear to influence the threshold for deciding whether an individual has cardiomegaly and possibly, cardiac disease or a pericardial effusion. In diagnosing cardiomegaly or cardiac disease therefore, clinicians may have to take into consideration the local averages or normal values of the cardiac parameters, and how they compare to available published figures.A cardiothoracic ratio greater than 50% is considered abnormal and suggestive of cardiomegaly;Transverse cardiac diameters of 15.5cm for males and 14.5cm for females are considered as the normal upper limits respectively;An increase in the transverse cardiac diameter by 1.5cm on two consecutive chest radiographs taken at short intervals is considered abnormal, and a sign of cardiomegaly.The average cardiothoracic ratio differs for different age groups and genders;The average transverse cardiac diameter differs for different age groups and genders; hence an increase by 1.5cm does not always translate into an abnormal cardiothoracic ratio of greater than 50%;The average cardiothoracic ratio for females aged 41-60years, and older than 60years is 50.7% and 51% respectively. This implies these females may be regarded as having mild cardiomegaly when they may actually be normal.The authors declare no competing interest.


To assess the feasibility of computed tomography (CT)-guided localization using a specific long dual-barbed hookwire in resection of pulmonary nodules with the size of 20mm or less by video-assisted thoracoscopic surgery (VATS) and to discuss the necessity of early treatment of small pulmonary nodules by VATS.All the nodules were successfully localized with hook wire under CT guidance. The 34 nodules had a mean diameter of 8.9 ± 3.8 mm and a mean distance from the most superficial edge of the nodules to the visceral pleura of 21.4 ± 12.4 mm. The mean length of time for CT-guided percutaneous localization was 9.0 ± 3.8 minutes. Asymptomatic pneumothorax and parenchyma hemorrhage were observed in 1 patient (3.2%) and 5 patients (16.1%), respectively. VATS successfully resected all the lesions after localization. The mean VATS operation time was 2.6 ± 1.2 hours . 24 (70.6%) malignant nodules and 10 benign nodules were discovered after surgery.Between March 2012 and August 2014, 31 patients with 34 small pulmonary lesions underwent CT-guided hook wire localization and VATS resection. The efficacy of preoperative localization was evaluated in terms of procedure time, VATS success rate and associated complications of localization. And the pathology and imaging diagnosis of all nodules were recorded.The CT-guided Hook-wire localization for pulmonary nodules with the size of 20 mm or less is an effective and safe technique to assist VATS. Once small pulmonary nodules change in size or number, it is necessary to treat in an early and aggressive way with minimally invasive surgery. Recently, an increase in small pulmonary nodules (SPNs) has been identified by high resolution Computed Tomography (CT) in routine clinic, particularly in low dose CT screening of lung cancer for high-risk population . HoweverThere were a total of 34 pulmonary lesions with diameters of 20mm or less in the 31 patients selected,  with the mean age of 52.5 ± 11.1 years . 26 patients had a single nodule and 3 patients had two nodules in the same lung. 2 patients had multiple nodules in bilateral lungs, but we chose the largest one in the peripheral pulmonary parenchyma for wedge resection and diagnose. The 34 SPNs had a mean maximal long-axis diameter of 8.9 ± 3.8 mm , and a mean distance from the most superficial edge of the nodules to the visceral pleura of 21.4 ± 12.4 mm . While 7 lesions (20.6%) appeared to be ground glass nodule (GGN), 27 nodules (79.4%) displayed to be solid nodule in peripheral lung. The imaging diagnosis of 7 GGNs: 3 indeterminate lesions, 1 benign lesion and 3 malignant lesions were included. The imaging diagnosis of 27 solid nodules: 9 indeterminate nodules, 14 malignant nodules and 4 benign nodules were included. The characteristics of 34 SPNs in 31 patients were shown in Table All the 34 SPNs were successfully localized with 34 dual-barbed hookwires in the 31 patients. The mean length of time for CT-guided percutaneous localization was 9.0 ± 3.8 minutes , and the mean numbers of needle insertions or adjustments were 3.4 ± 1.4 times . Two hookwire placements were simultaneously performed in 3 patients with 2 target lesions  cases, which were successfully managed by closed thoracic drainage. Subcutaneous emphysema occurred in 2 (6.5%) cases.All 34 nodules in the 31 patients were completely removed by VATS. The mean VATS operation time was 2.6 ± 1.2 hours . Of the total 34 SPNs, there were 24 (70.6%) malignant nodules and 10 (29.4%) benign nodules. Histological results were diagnosed by experienced pathologists (as shown in Table There were 27 solid lesions including 9 (33.3%) benign lesions and 18 (66.7%) malignant lesions . As to the 27 solid lesions and the 7 GGNs, malignant nodules made up for 66.7% and 85.7%, respectively. These data illustrate the fact that these SPNs with the diameter of 20 mm or less have a high rate of malignancy. What's more, there were 9 indeterminate lesions and 5 misdiagnosed lesions among the 27 solid nodules. In the 9 indeterminate lesions, malignant nodules accounted for 55.6% (5/9). Of the 5 misdiagnosed solid nodules, 2 nodules, which had the imaging diagnoses of benign lesions, turned out to be malignant. Meanwhile, there were 3 indeterminate lesions and 1 misdiagnosed lesions among the 7 GGNs. In the 3 indeterminate GGNs, malignant nodules accounted for 66.7% (2/3). There was one misdiagnosed GGN, which had the imaging diagnoses of benign lesion, turned out to be malignant. As a result, it is urgency for us to make early and effective diagnoses and treat these SPNs with the diameter of 20 mm or less. Closely follow-up observation is recommended. And Once the small pulmonary nodule changes in size or number, it is necessary to treat SPNs in an early and aggressive way with minimally invasive surgery.Among all the 34 SPNs in this study, malignant lesions accounted for 70.6%  had SPNs and primary tumors in other parts of body at the same time. These two female patients both have cervical cancer as the primary cancer and a SPN simultaneously, and both received lobe wedge resection. The histopathological results were focal necrosis with calcification and tuberculosis, respectively. The clinical staging came out to be stage IB1 other than stage IV. These patients then received laparoscopic cervical cancer radical excision, sequentially. No further treatment was needed after surgery. Meanwhile, there were 6 patients  with SPNs having a history of malignant tumor. The primary tumors had all been removed surgically. For the first 4 patients, the SPNs were all diagnosed to be metastatic after lobe wedge resection  was used, with the simultaneous acquisition of 16 slices per full rotation. The technical parameters were: 120 kV, 250 mAs, collimation 6 × 2 mm, slice 1 mm, reconstruction increment 1 mm. The dual-barbed wire system  consisted of a 20-gauge, 10.7 cm long, calibrated cannula and a 20 cm long calibrated wire with two thorns . The cannula had stenciled marks every 10 mm on the outside of the needle shaft. Figure .With the previously available CT scans for guidance, patient was appropriately positioned, and improvised metal markers were used to determine if the puncture site was properly placed. CT scan was then performed to identify the suspicious nodule. Routine breathing instructions were not given during preliminary imaging or during localization procedure unless deemed necessary by the treating physician. An optimal access route was designed by measuring the distance from the skin to the superficial edge of SPNs and choosing an entry point. After disinfection of the skin and a subcutaneously local anesthesia (1% lidocaine hydrochloride) around the marked area, the cannula needle with the dual-barbed wire was gradually inserted through the pulmonary parenchyma into the nodule. While the outer cannula needle was withdrawn, the dual barb could be released. A postprocedure CT scan was performed to confirm the final position of the dual-barbed wire, and to assess for any existing complications. CT-guided localization was scheduled 2 hours before VATS surgery. The period of time patients spent from receiving a subcutaneously local anesthesia to the withdrawing of the outer cannula needle was regarded as the localization procedure time.VATS was performed under general anesthesia using single lung ventilation via a double-lumen endobronchial tube. In most cases, the thoracoscope was inserted through a 11.5 mm thoracic port in the seventh intercostal space on the midaxillary line. The procedure involved making another 11.5 mm thoracic port for the endoscopic stapler, and a 5.5 mm thoracic port for the lung forceps. The wire was easily pulled for tracing SPN in the pleural cavity without dislodging the hook-head when the lung collapsed. The lesion was sequentially resected. The resected wire and lung tissue were packed into surgical bags to prevent metastatic implantation of malignant disease and were withdrawn from the chest via an intercostal incision. All the resected lung specimens were immediately sent for frozen-section histopathological examination.A frozen-section specimen was removed from the pulmonary nodules for histopathological diagnosis. If the nodule was diagnosed to be benign or metastatic, no further resection was performed. The pleural cavity was douched with saline solution, and then a chest tube with underwater drainage system was placed. When the nodule was diagnosed to be primary lung cancer, VATS lobectomy and mediastinal lymph node cleaning-up were performed.SPSS for OS X, version 20.0 , was used to access all the statistical analyses. Data were presented as mean ± standard deviation (SD), unless otherwise indicated.In summary, the combination of CT-guided localization using a dual-barbed hookwire with VATS is a safe, convenient and efficient technique for early treatment of SPN that should be widely expanded in clinical practice. And we should draw our attention to the small pulmonary nodule with the diameter of 20 mm or less, and closely follow-up observation is recommended. Once the small pulmonary nodule changes in size or number, it is necessary to treat SPNs in an early and aggressive way with minimally invasive surgery.


Cesarean scar pregnancy (CSP) is a rare condition that occurs when the pregnancy implants in a cesarean scar. An early diagnosis and a proper management are fundamental to prevent maternal complications. We review and discuss the different treatment employed in our unit to reduce morbidity, preserve fertility, and predict possible complications. The reported treatment has been expectant management, operative hysteroscopy approach, and intramuscular injection of 50 mg methotrexate (MTX), followed by cervical dilation and manual vacuum aspiration (D&S) with a Karman cannula under ultrasound guidance, uterine artery embolization (UAE), and manual vacuum aspiration under ultrasound guidance and uterine artery embolization before surgical laparotomic resection. Complications were more frequent in women with a history of three or more cesarean section deliveries and with a myometrial thickness thinner than 2 mm. MTX and D&S treatment appear to be most effective and safe at the early age of pregnancy, while UAE and D&S are related to the highest risk of complication in any age of pregnancy. An appropriate preoperative diagnostic evaluation, the identification of cases at higher risk, and those eligible for a conservative treatment are fundamental to reduce complications. Cesarean scar pregnancy (CSP) is a rare occurrence consisting in the implantation of the gestational sac in the hysterotomy scar , 2. A reThe exact pathogenic mechanisms are still unclear but CSP is believed to occur when a blastocyst implants on fibrous scar tissue within a wedge-shaped myometrial defect in the anterior lower uterine segment, by the site of a prior cesarean scar.Due to the increase of CDs the incidence of CSP is rising. This condition can be dangerous for the women because of the related complications such as placenta previa or accreta, uterine rupture, and hemorrhage, leading to increased maternal morbidity and mortality. Therefore, an early diagnosis is crucial to improve the proper management. Several authors have reported sonographic criteria to aid in a diagnosis of CSP , 5, 11. Considering the lack of unique guidelines and management protocols, the aim of our study was to analyze the different methods of treatment for CSP offered by our team and identify the criteria on which to base the choice of the best approach for the women.This is a retrospective review of a case series of 45 pregnant women between 6 and 13 weeks, referred to our Department from 2013 to May 2017, with a diagnosis of CSP.All clinical and anamnestic data were extracted from medical records of the patients.The CSP was diagnosed by transvaginal ultrasound, according to diagnostic criteria as reported by several authors , 5, 11.The following eligibility criteria had to be met: (1) the ultrasound images confirming the diagnosis were available and the gestational/chorionic sac was clearly visible as well as the entire uterus with its fundic and cervical contour; (2) adequate follow-up period was tight and registered.All women gave written informed consent. All procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was not registered at the clinical trial registry and IRB approval was not obtained as it is a retrospective study that we did not change or experience but merely observed and collected data.In 12 cases, the ultrasound showed a very thin or absent myometrial layer (<2 mm) between gestational sac and bladder; these women underwent MRI with contrast medium for suspected placental invasion of the bladder.Expectant management (EM)Hysteroscopic resection of gestational tissue (HSC) performed under general anesthesia. The cervix was dilated up to 10 mm with Hegar's dilators, introducing a continuous flow 9 mm bipolar resectoscope with a 4 mm loop . The setting of the electrosurgical generator was Versapulse modality with 110 W and 80 DES. Saline solution was used for distention and irrigation of the uterine cavity and the intrauterine pressure was automatically controlled by Endomat Intramuscular injection of a single dose 50 mg of MTX, following 48 hours by cervical dilatation with 1 mg of vaginal Gemeprost dispensed 3 hours before the manual vacuum aspiration with a Karman cannula (D&S) under ultrasound guidance (MTXii + D&S)Uterine artery embolization (UAE) and manual vacuum aspiration (D&S) under ultrasound guidance following the procedure described above (UAE + D&S)UAE and surgical laparotomic resection (UAE + Surg).The treatment modalities in our experience are as follows:Complications, like uterine rupture or profuse bleeding, were treated by means of a Foley catheter inflated with 30–40 cc in the isthmus region for 24 hours. The severe bleeding was considered when we observed a drop in hemoglobin (Hb) levels greater than 5 units and/or a reduction of hematocrit (Hct) percentage greater than 10%. In the presence of Hb levels below 6 mg/dl and/or Hct under 20%, if necessary, blood cell transfusion was administered.All women treated with conservative management underwent clinical and instrumental follow-up one week and one month later.t-test or one-way analysis of variance (ANOVA) for continuous variables and χ2 test for categorical variables.All statistical analyses were performed with SPSS version 20.0 . Comparisons between unpaired groups were made by Student's p < 0.05 was considered statistically significant.Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to evaluate factors predicting treatment complication. Women' ages ranged from 26 to 42 years (mean: 33.68 ± 3.52 years). Clinical women's data in relation to treatment modalities are shown in All 45 women had an empty uterine cavity at ultrasound scan, and the gestational sac was detected in the hysterotomy scar, adjacent to the bladder. HCG levels were recorded.All women had a history of prior uterine surgery. As for the number of cesarean sections before the CSP, of the 45 women, 14 (31.1%) had had one, 17 (37.8%) had had two, 10 (22.2%) had had three, and 4 (8.9%) had had four CDs.Thirty-four patients (75.6%) showed a low gestational age (≤8 weeks) at the time of diagnosis and treatment.Class 1: myometrial thickness ≤ 2 mm and high vascular patternClass 2: myometrial thickness > 2 mm and high vascular patternClass 3: myometrial thickness > 2 mm and normal vascular pattern.According to ultrasound findings, which focused on the myometrial thickness and the presence of a vascular pattern of the cesarean section scar, we stratified patients into three risk classes (the first class results of high risk and class 3 results low risk):The color Doppler showed a rich vascular pattern in the cesarean section scar in 36 cases (80.00%) and a myometrial thickness ≤ 2 mm in 12 patients (26.7%), so that 12 patients (26.7%) were assigned to the first class risk group, 24 patients (53.33%) to risk class 2, and the last 9 patients (20.0%) to risk class 3.According to risk classes and gestational age, the modality treatment was summarized in In 4 cases (8.9%), the EM approach was adopted, in consideration of the low gestational age (6 weeks) with mean myometrial thickness > 3 mm and the absent rich vascular pattern ; during Five patients (11.1%) in risk class 3 and with gestational age < 8 weeks were treated with HSC. None of the complications were observed at follow-up in these patients.Nineteen women (42.2%) within <8 weeks gestational age, myometrial thickness > 2 mm, and rich vascular pattern were treated with intramuscular injection of 50 mg MTX and, after 48 hours, D&S under ultrasound guidance. No postoperative complications were observed at the 1-week and 1-month follow-up . AccordiEleven women (24.4%) were treated with UAE and D&S under ultrasound guidance; 6 of them had gestational age <8 weeks, myometrial thickness ≤ 2 mm, and a rich vascular pattern (risk class 1). Two patients presented with profuse vaginal bleeding and mechanical hemostasis with a Foley catheter for 24 hours was necessary. Three patients presented intrauterine haematoma 24 h after treatment with spontaneous resolution after about 40-day follow-up. In only one case, severe intraoperative bleeding caused haematoma and hemorrhagic myometrial infarction in the scar area, which was treated by urgent subtotal hysterectomy, prophylactic salpingectomy, and ovarian conservation .The other 5 patients performing UAE and D&S had gestational age ≥ 8 weeks with a rich vascular pattern and myometrial thickness > 2 mm (risk class 2). Two patients presented profuse vaginal bleeding and mechanical hemostasis with a Foley catheter for 24 hours was necessary, and one of them was treated with 2 units of red blood cells because hemoglobin levels were below 6 mg/dl. One patient presented intrauterine haematoma 24 h after treatment with spontaneous resolution after about 40-day follow-up.All women with more advanced gestational age showed an increased vascularization pattern at color Doppler evaluation independently from myometrial thickness, so that we have no patients with advanced gestational age belonging to class risk 3.Six women (13.3%) with gestational age > 8 weeks belonging to class risk 1 were treated with UAE and surgery. Four women underwent edge excision of CSP by laparotomic hysterotomy with successful repair of the myometrial scar. Two patients underwent hysterectomy with prophylactic salpingectomy and ovarian conservation for the absence of myometrial thickness at laparotomy. No further complications were observed in follow-up.β-hCG level, or vascular pattern of ultrasonographic findings ; UAE + D&S showed the highest percentage of complications.The occurrence of complication significantly differed from group . Five patients (11.1%) had profuse bleeding and another 5 women (11.1%) had haematoma, but in only one case we observed myometrial infarction. Only this woman was treated with radical surgery. In other cases, conservative management was effective.p < 0.005).ROC curve analysis and logistic regression were used to evaluate risk factors capable of predicting treatment complication, including number of previous cesareans, myometrial thickness, treatment modality, and class risk.p = 0.019; CI 95%: 0.57–0.92) : 0.54–0.91) : 0.54–0.93) (p = 0.04 CI (95%): 0.52–0.91) (The areas under curve (AUC), for the number of previous cesarean deliveries, treatment modality myometrial thickness, and class risk, were 0.75 (57–0.92) ; 0.72 (p54–0.91) ; 0.74 (p54–0.93) ; and 0.752–0.91) , respectp = 1.0; CI (95%): 0.30–0.71); CDs ≥ 2, 0.64 : 0.46–0.82); CDs ≥ 3, 0.75 : 0.57–0.93); and CDs ≥ 4, 0.51 : 0.30–0.71)  .p = 0.59; CI (95%): 0.34–0.77); 0.71 : 0.52–0.91); 0.61 : 0.43–0.80); and 0.46 : 0.25–0.68)  .p = 0.95; CI (95%): 0.30–0.71); for HSC 0.43 : 0.24–0.62); for MTX + D&S 0.23 : 0.09–0.36); for UAE + D&S 0.92 : 0.80–1.0); and for UAE + SURG 0.41 : 0.23–0.6) (The UAE + D&S was the major indicator of treatment complication occurrence. The AUCs for each treatment were for EM 0.51 (.23–0.6) .p = 0.04; CI (95%): 0.52–0.91); for risk class 2: 0.35 : 0.16–0.54); for risk class 3: 0.44 : 0.24–0.63)  .The four cuts off variables were also compared by ROC analysis .p ≤ 0.001)  .N = 35) of patients with CSP were successfully treated without any complications. Among patients who reported complications, only 1 had severe complications requiring destructive surgery, whereas in 90.0% of the cases the complication was manageable by mechanical hemostats and/or blood transfusion. Our complication rate is lower than the one reported in the literature. The selection method of patients, adopted in our institution, allows reducing treatment failure.In the present study, 77,8%  both in lower than in high gestational age. So, undergoing UAE + DS results in a specific significant risk factor in terms of complications.Our data confirm that the number of previous cesareans, the myometrial thickness, and the class risk are specific factors in complication's occurrence. On the other hand, our data lack in demonstrating that the gestational age and the presence of a rich vascular pattern are specific risk factors. This lack of evidence may be attributable to the fact that the evaluation of the vascular pattern, in our study, was subjective and not performed by VOCAL index so that may be overestimated. Moreover, this is a retrospective study and both gestational age and vascular pattern have been considered as selective criteria in the treatment modality limiting their effects on statistical analysis.However, color Doppler evidence of a high-speed peritrophoblastic flow and low resistance near the hysterotomy scar  has beenTo date, hysteroscopy represents a widely accepted method for the management of several gynecological conditions –20 or evIn this regard, several authors in recent years have described the successful hysteroscopic treatment of CSPs in combination with another surgical approach  or medicIn our study group, we have no complication after hysteroscopic approach, so this treatment appears safe and effective. Taking into account that we have reported only 5 cases considered of low-risk class, another study should confirm our data.Some studies report , 28 the However, in a recent review, Birch Petersen et al. recommended five approaches for treating CSP depending on availability, the severity of symptoms, and surgical skills. In this paper, the authors support an interventional rather than a medical approach. They have reported the use of laparoscopic surgical treatment as effective in selected cases and when performed by laparoscopist surgeons with specific expertise in the subject . In our Among the most important diagnostic criteria to evaluate the risk of complications, there are myometrial thickness and the numbers of previous CDs , 34. In The combination of MTX + D&C appears to be the most effective and safe treatment for women in the early stages of pregnancy, whereas UAE and D&S result in a significant specific risk factor for complication independent of gestational age.In conclusion, our study shows an overall complication rate of 22.2%, lower than that reported in the literature (44.1%) . The comThe standard treatment has not been established in the management of scar pregnancy yet. However, the correct diagnosis and the personalized evaluation of risk factors could support physicians in making the best choice in terms of safety and efficacy.


P = 0.223; P = 0.06). 2D TVUS has sensitivity, specificity, and positive and negative predictive values of 54%, 84.7%, 75%, and 68.5%, respectively. Endometrial thickness of >7.5 mm has sensitivity, specificity, positive and negative predictive values, and overall accuracy of 82%, 37.3%, 52.6%, 71%, and 57.8%, respectively. Endometrial volume of >1.2 mL has sensitivity, specificity, positive and negative predictive values, and overall accuracy of 90%, 42.4%, 57%, 83.3%, and 64.2%, respectively. 3D VOCAL may be used as a noninvasive method for the diagnosis of EP in premenopausal women with AUB.The aim is to compare hysteroscopy, two-dimensional transvaginal ultrasound (2D TVUS), and three-dimensional (3D) Virtual Organ Computer-aided AnaLysis™ (VOCAL) to detect endometrial polyps (EPs) in premenopausal women with abnormal uterine bleeding (AUB). This prospective study was done at Ain Shams Maternity Hospital, Egypt, from March 5, 2015, to December 30, 2015, enrolling 118 premenopausal women with AUB. 2D TVUS, 3D VOCAL, and hysteroscopy were done. 109 patients reached final analysis. 36 women (33%) were diagnosed with EP by 2D TVUS. 50 (45.9%) had EP by hysteroscopy. Endometrial thickness was 10.1 mm by 2D TVUS and endometrial volume was 4.92 mL by VOCAL in women with EP by hysteroscopy compared to 9.9 mm and 3.50 mL in women with no EP, respectively ( Endometrial polyps (EPs) are benign growths of the endometrium appearing as a localized swelling protruding into the uterine cavity. Histologically, an endometrial polyp consists of endometrial glands surrounded by stroma and covered by epithelium . It is aVarious tools for diagnosis are two-dimensional transvaginal ultrasound (2D TVUS), sonohysterography, hysteroscopy, and curettage followed by histopathology. Hysteroscopy is the gold standard for the confirmation of the diagnosis enabling the gynecologist not only to detect the EP, its site, and number but also to remove it in the same setting , 6.Endometrial polyps may appear as a thick regular endometrium by 2D TVUS or as focal masses within the endometrial canal. Conventional 2D TVUS is useful in providing information about the uterus through axial and sagittal cuts, yet quite limited in the coronal plane. On the other hand, 3D TVUS overcomes this limitation by reconstructing the coronal plane of the uterus, providing more accurate diagnosis of uterine anomalies and higher definition of endometrial delineation, hence higher accuracy of localization of endometrial polyps, fibroids, and intrauterine devices , 8. HoweMeasurement of endometrial volume by Virtual Organ Computer-aided AnaLysis (VOCAL) has been widely studied –16; howeThe current study is the first to date addressing the use of VOCAL imaging program to measure endometrial volume for improving the accuracy of diagnosing EPs in symptomatic premenopausal women with AUB over the conventional 2D TVUS in comparison to hysteroscopy.NCT02300805. Institutional review board approval was obtained on 10 November 2014 and all women signed written informed consent at recruitment.This prospective study was carried out at Ain Shams Maternity Hospital, Cairo, Egypt, from 5 March 2015 to 30 December 2015. 118 premenopausal women complaining of abnormal uterine bleeding in the form of menorrhagia, metrorrhagia, or both were recruited. Menopausal women, women with general causes of bleeding like bleeding disorders and liver diseases, and women on drugs like hormonal contraception and anticoagulants were excluded; so were patients with fibroids and fibroid polyps. This study conforms to the Declaration of Helsinki and was registered on clinicaltrials.gov with registration number Two-dimensional transvaginal ultrasound, Virtual Organ Computer-aided AnaLysis (VOCAL) imaging program, and diagnostic hysteroscopy were done for all women for detection of endometrial polyps.Two-dimensional transvaginal ultrasound was done using Voluson E6  S-VDW 5–8 MHz transvaginal probe to measure endometrial thickness after obtaining longitudinal plane of the uterus and to detect the presence of endometrial polyps.VOCAL imaging program was used for all patients to measure endometrial volume. Voluson E6  three-dimensional (3D) system with RIC 5-9 D transvaginal probe was used. A longitudinal view of the uterus was obtained and “Volume Analysis” on the touch panel was selected, and then VOCAL was selected. “Reference Image: A” was activated. The endometrium was adjusted to fit within green arrows and manually traced by using trackball/pointer. For a valid trace, the trace pointer had to cross the rotation axis line twice. The pointer was moved to the edge of the endometrium and then moved to a new area to be traced. Six traces were drawn by rotating at 30°. Sequence was repeated for all traces. On the final trace, “Done” and then “Accept Region of Interest (ROI)” were selected to obtain endometrial volume in milliliters. All ultrasound scans were done by a single highly experienced operator (fifth author).Outpatient office hysteroscopy was done 1 to 3 days after the ultrasonography. It was performed using a 2.9 mm telescope with a 30° fore oblique lens  inserted in a continuous flow 4 mm sheath . Isotonic saline was used as distension medium in all cases. Introduction was by the nontouch vaginoscopic technique without anesthesia in most cases, inspecting the vagina, cervix, and uterine cavity. Cases with difficult vaginoscopic entry were done conventionally using Collin's speculum and tenaculum. If polyps were found, they were simultaneously excised using 5 Fr. hysteroscopic scissors  or a bipolar electrode needle .The required sample size was estimated using the Power Analysis and Sample Size software version 11.0.10 . According to a previous study , the pret-test. Skewed numerical variables were presented as median (interquartile range) and between-group differences were compared using the Mann–Whitney test. Categorical data were presented as number (%) and between-group differences were compared using Fisher's exact test. Ordinal data were compared using the chi-squared test for trend. Receiver-operating characteristic (ROC) curve analysis was used to examine the value of endometrial thickness as estimated with 2D TVUS or endometrial volume as estimated with VOCAL in differentiating between patients with or without histopathologically diagnosed endometrial polyps. The DeLong method was used to compare the area under the ROC curve versus that of random prediction. P value <0.05 was considered statistically significant.Data were analyzed using IBM SPSS Statistics version 22 . The Shapiro-Wilk test was used to examine the normality of numerical data distribution. Normally distributed numerical data were presented as mean ± SD and intergroup differences were compared using the unpaired 118 patients were recruited but data of 109 patients reached final statistical analysis. Five patients were excluded because of diagnosis of multiple uterine fibroids by initial 2D TVUS and another four women were excluded because of failure of visualization of the uterine cavity during hysteroscopy because of excessive uterine bleeding.The average age of participants was 35 years (interquartile range between 29.8 and 44 years). Their parity ranged from nullipara to para 7. 36 women (33%) were initially diagnosed with endometrial polyps by 2D TVUS . 50  . AverageOut of the 50 women confirmed to have EP by hysteroscopy, 40 women (80%) had single polyp; 7 women (14%) had 2 or 3 polyps; and 3 women (6%) had more than 3 polyps. Mean size of the polyps was 11.8 mm (range from 7.3 mm to 19.6 mm). Histopathology results showed that 9 women (18%) had functional polyps; 18 women (36%) had hyperplastic polyps; 14 women (28%) had mucous polyps; and 9 women (18%) had proliferative polyps.P = 0.435 and P = 0.282, resp.). Average endometrial thickness by 2D TVUS was 10.1 mm in women diagnosed with endometrial polyp using hysteroscopy compared to 9.9 mm in women with no endometrial polyp (P = 0.223) (P = 0.062)  . Endomet= 0.062) .Diagnostic accuracy of 2D TVUS to detect endometrial polyps compared to hysteroscopy which is the gold standard diagnostic tool is shown in P = 0.219). An endometrial thickness of >7.5 mm has a sensitivity of 82.0%, a specificity of 37.3%, and an overall accuracy of 57.8%. Positive and negative predictive values are 52.6% and 71%, respectively.P = 0.060). Endometrial volume of >1.2 mL has a sensitivity of 90%, a specificity of 42.4%, and an overall accuracy of 64.2%. Positive and negative predictive values are 57% and 83.3%, respectively.P = 0.219). This endometrial thickness had a sensitivity and specificity of 82% and 37% with overall accuracy of 58%. PPV and NPV were 53% and 71%, respectively. On the other hand, cut-off value for endometrial volume measured by VOCAL of more than 1.2 mL was still statistically insignificant (P = 0.06) for AUC of 0.604. Sensitivity and specificity were 90% and 42% with overall accuracy of 64%, while PPV and NPV were 57% and 83%, respectively, which are superior to 2D TVUS.In the current study, an endometrial volume of more than 1.2 mL to predict endometrial polyps proved to be better than diagnosis by 2D TVUS and endometrial thickness of more than 7.5 mm. Sensitivity and specificity of 2D TVUS to diagnose endometrial polyps were 54% and 85%, respectively, while positive and negative predictive values were 75% and 69%, respectively. In comparison, cut-off value for endometrial thickness of more than 7.5 mm measured by 2D TVUS showed AUC of 0.568 which was statistically insignificant (De Godoy Borges et al.  studied 3 were 63%, 70%, 27%, and 92% and 39%, 88%, 36%, and 90%, respectively; when combining both parameters, ultrasound diagnostic accuracy improved to 66%, 89%, 50%, and 94%. In the current study, cut-off values for endometrial thickness and volume were different from those of Fang et al.; the latter study has recruited women with infertility rather than abnormal uterine bleeding with an 11% incidence of EP in Fang et al.'s study sample compared to 46% incidence of EP in the sample of the current study.Fang et al.  enrolledOne strength of the current study is that it is the first to date addressing the diagnostic accuracy of VOCAL in prediction of endometrial polyps specifically in premenopausal women with AUB. Furthermore, it is the first study to provide a cut-off value for endometrial volume in premenopausal women with AUB. In addition, a single experienced sonographer performed all 2D and 3D TVUS which was done prior to hysteroscopy to avoid bias in diagnosis by ultrasound.3D VOCAL has better diagnostic accuracy for EP in premenopausal women with AUB compared to 2D TVUS. 3D VOCAL may be used as a noninvasive preliminary method for diagnosis of premenopausal women complaining of AUB with EP who are in need for further uterine cavity assessment by hysteroscopy.


To determine whether periodic supportive supervision after a training course improved the quality of paediatric hospital care in Kyrgyzstan, where inappropriate care was common but in-hospital postnatal mortality was low.In a cluster, randomized, parallel-group trial, 10 public hospitals were allocated to a 4-day World Health Organization (WHO) course on hospital care for children followed by periodic supportive supervision by paediatricians for 1 year, while 10 hospitals had no intervention. We assessed prospectively 10 key indicators of inappropriate paediatric case management, as indicated by WHO guidelines. The primary indicator was the combination of the three indicators: unnecessary hospitalization, increased iatrogenic risk and unnecessary painful procedures. An independent team evaluated the overall quality of care.P < 0.0001 for all). Overall quality of care improved significantly in intervention hospitals.We prospectively reviewed the medical records of 4626 hospitalized children aged 2 to 60 months. In the intervention hospitals, the mean proportion of the primary indicator decreased from 46.9%  at baseline to 6.8% (95% CI: 1.1 to 12.1) at 1 year, but was unchanged in the control group . At 1 year, the risk ratio for the primary indicator in the intervention versus the control group was 0.09 (95% CI: 0.06 to 0.13). The proportions of the other nine indicators also decreased in the intervention group (Periodic supportive supervision for 1 year after a training course improved both adherence to WHO guidelines on hospital care for children and the overall quality of paediatric care. HospitaDoctors in charge of children from the intervention hospitals attended a 4-day, WHO training course on WHO’s guidelines on hospital care for children.Pocket book of hospital care for children;Hospital care for children: quality assessment and improvement tool (The primary aim of the study was to determine whether or not case management was inappropriate when compared with guidelines in WHO’s ent tool .24 Our pent tool . At eachAt the baseline assessment (i.e. time point T1), health staff, data collectors, patients and data analysts were all blinded to the study allocation group. During the intervention (i.e. T2 to T6), neither hospital staff nor the supportive supervision team could be blinded but they were not involved in data collection or data analysis. Data collectors knew the allocation group but were not involved in data analysis. However, children and their families were blinded to both the allocation group and the characteristics of the intervention.Hospital care for children: quality assessment and improvement tool  field-tested the template used for collecting data on indicators of inappropriate case management, which included an explicit definition of each indicator, before being used in the study; (ii) field-tested data collectors’ performance before the study and their understanding was reinforced, if necessary, to ensure consistency; (iii) rotated data collectors among hospitals to reduce the influence of subjectivity; (iv) determined the reliability of the data collectors in evaluating medical records by comparing their evaluations with those of a team of independent international paediatricians at time points T1, T2 and T6 ; and (v)The ethical committees of the Kyrgyz State Medical Institute of Postgraduate and Continuous Training and of the Institute for Maternal and Child Health IRCCS Burlo Garofolo in Italy approved the study. In addition, the director of each participating hospital gave informed consent. The privacy of children and their families was protected by collecting data anonymously. Data are reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement for cluster randomized controlled trial,Using data from the baseline assessment study, we calculated the sample size required by taking into account: (i) the fixed number of clusters; (ii) the intracluster correlation coefficient determined at the baseline assessment; (iii) the expected effect of the intervention; and (iv) the desired power of the study.χ2 test, as appropriate, to compare categorical variables and t test and the mean difference to compare quantitative variables. Trends in proportions were compared using the Cochran–Armitage χ2 test. All statistical tests were two-sided and a P-value less than 0.05 was considered statistically significant. We analysed data using Stata version 12  and OpenEpi version 2.3.1 .We present categorical variables as absolute numbers, proportions and risk ratios (RRs) with 95% confidence intervals (CIs) and quantitative variables as means and standard deviations. We used Fisher’s exact test or Yates’s corrected P for trend < 0.0001) in the intervention hospitals. No significant change was observed in control hospitals, 45.5% (95% CI: 25.2 to 67.9) at T1 to 64.7% (95% CI: 43.3 to 86.1) at T6 (P for trend > 0.05). At T6, the RR for the primary indicator in the intervention versus the control group was 0.09 (95% CI: 0.06 to 0.13). The mean proportion of unnecessary hospitalization also decreased over time in the intervention group from 47.6% (95% CI: 27.5 to 67.7) at T1 to 13.1% (95% CI: 5.0 to 21.2) at T6 (P for trend < 0.001), but remained stable in the control group . Similarly, the mean proportion of an incorrect diagnosis decreased significantly in the intervention group from 49.7% (95% CI: 29.9 to 69.5) at T1 to 14.7% (95% CI: 7.0 to 22.4) at T6 (P for trend < 0.0001), but not in the control group . The mean proportion of incorrect treatment decreased significantly only in the intervention group, from 77.9% (95% CI: 57.6 to 98.2) at T1 to 15.7% (95% CI: 7.4 to 24.0) at T6 (P for trend < 0.0001); the RR in the intervention group at T6 was 0.16 (95% CI: 0.12 to 0.29). A similar pattern was observed for the other six indicators and the RR in the intervention versus the control group was: 0.16 (95% CI: 0.13 to 0.21) for an inconsistency between diagnosis and treatment; 0.14 (95% CI: 0.11 to 0.19) for increased iatrogenic risk; 0.15 (95% CI: 0.12 to 0.20) for unnecessary painful procedures; 0.09 (95% CI: 0.07 to 0.13) for inadequate monitoring; 0.05 (95% CI: 0.03 to 0.08) for failure to assess nutritional status; and 0.03 (95% CI: 0.02 to 0.06) for inadequate use of fluids.During the study period, similar trends were observed for all indicators . In partHospital care for children: quality assessment and improvement tool.At baseline, there was no significant difference between intervention and control hospitals in quality-of-care summary scores for the 17 subsections of WHO’s –We found that a standard, 4-day, WHO training course followed by periodic supportive supervision from national, trained paediatricians every 2 months for 1 year significantly reduced inappropriate case management of hospitalized children and improved the overall quality of paediatric care. Our findings add to the existing literatureOur study was a pragmatic trial because it was conceived as part of an implementation project rather than being performed in a so-called pure study setting. Nevertheless, the supportive supervision team comprised highly motivated and trained staff and external monitoring was carried out regularly to ensure that supportive supervision was provided on time. The results of the study cannot be directly generalized to situations in which a lack of equipment, drugs, supplies or human resources is a major problem or to places where a different form of supportive supervision is being used .,–In line with other studies on quality improvement interventions, our outcomes were process outcomes  rather than health outcomes.A limitation of the study is that the data collectors were not blinded to the allocation group. However, information about the 10 indicators of inappropriate case management was collected from medical records, which are legal documents and, as such, should be considered reliable, and the assessment was based on predefined case definitions, criteria and reference standards,–,–We did not include cost, patient satisfaction or the satisfaction of health-care providers as study outcomes. However, the administrative data collected suggested that the cost of drugs, especially parenteral drugs, in most intervention hospitals had decreased and interviews with staff and patients indicated anecdotally that satisfaction had increased. Future studies should include a cost–effectiveness analysis and evaluate staff and patient satisfaction. In addition, future research should investigate which approach to supportive supervision results in the greatest improvements in different settings. The existing literature suggests that supportive supervision must be tailored to the local context to some extent. For example, low- or moderate-intensity supportive supervision can be effective in some settings, whereas high-intensity supervision may be needed in others to bring about real changes in behaviour, knowledge and practices.The ideal providers of supportive supervision may vary according to the setting. In our study and a study in Kenya,The intervention hospitals in our study should be further assessed after a longer period of time to determine whether the improvements observed are maintained. Future studies in these hospitals and in different contexts elsewhere should identify the most cost-effective way of providing effective supportive supervision over the long term. Furthermore, projects should also aim to improve case management in primary care and to strengthen referral systems, thereby ensuring better coordination between different levels of care. Our results indicate that policy-makers should consider using supportive supervision to increase adherence to evidence-based guidelines for paediatric hospital care.


P < 0.05).Patients with RDW that maintained more than 15.5% upon completion of therapy showed a shorter OS (P < 0.05) and PFS (P < 0.05) compared with patients with an RDW that decreased to a lower level.The multivariate analysis showed that RDW ≥ 15.5% after the completion of first-line therapy were an independent prognostic marker of poorer OS (P = 0.044) and PFS (P = 0.034). Therefore,we demonstrated that RDW at diagnosis, as well as at completion of first-line therapy is an independent predictor for mutiple myeloma patients.RDW maintained at high level, irrespective of whether RDW decreased to the cutoff value predicted an unfavorable prognosis in patients with MM.To investigate the prognostic value of the red blood cell distribution width(RDW) recovery from low levels at diagnosis after completion of first line therapy in mutiple myeloma (MM)patients,we enrolled 78 consecutive patients with MM and followed up from 2005 to 2016 in our hospital. The RDW was measured following completion of first-line therapy.The log-rank test, univariate analysis, and Cox regression analysis were used to evaluate the relationship between RDW and survival. We found that patients with an RDW ≥ 15.5% at diagnosis, as well as at completion of first-line therapy, had significantly lower progression-free survival (PFS) and overall survival(OS) rates than those with an RDW < 15.5%( Multiple myeloma (MM) is an incurable blood cancer of plasma cells characterized by the clonal proliferation of plasma cells in the bone marrow and production of monoclonal proteins in the blood or urine. Patients with MM have highly variable prognoses . The IntSeveral molecular markers of MM have been identified, but cost and technical limitations make their routine application impractical –4.Hence Recent studies have shown that the RDW obtained at diagnosis using the complete blood count (CBC) may predict clinical outcomes in MM,the overall response rates (ORR) and complete response (CR) rate of initial therapy were markedly higher in the low-RDW group compared to the high-RDW group. RDW was significant lower in CR in comparison to Non-CR groups in patients treated with bortezomib-based regimens as induction therapy –19. The There were 78 patients enrolled in this retrospective study .The male to female ratio was 1.51:1. The majority of MM subtype was IgG (47.4%).IgA account for 25.6% MM patients and 23.1% of 78 MM patients had light chain disease.According to the ISS,5 patients were stage I (6.4%), 46 patients stage II (59.0%) and 27 patients stage III (34.6%).Regarding the DS,5 patients were stage I (6.4%), 19 patients stage II (24.4%) and 54 patients stage III (69.2%).The distribution of additional baseline characteristics of these patients are shown in Table P = 0.042).As shown in Figure P = 0.000] and PFS Figure P = 0.000] than those with an RDW ≥ 15.5% at diagnosis. The median RDW upon completion of therapy was 14.9% (range:12.1–18.8%). 33(42.3%) patients decreased to a lower RDW at the completion of therapy, but 12(15.4%) patients failed to do so. A total of 43 (55.1%) had RDW ≥ 15.5% and 35 patients (44.9%) had RDW < 15.5% upon completion of therapy.The patients’ baseline of RDW ≥ 15.5% and RDW < 15.5% upon completion of therapy was similar. However,as shown in Figure P = 0.046] and PFS [Figure P = 0.011] than those with an RDW ≥ 15.5% upon completion of therapy.We found that patients whose RDW ≥ 15.5% upon completion of therapy experienced poorer prognosis. Therefore,we investigated whether patients who started with a high RDW ≥ 15.5% at diagnosis but then obtained a low RDW < 15.5% showed longer survival compared to patients maintained at high RDW ≥ 15.5% at the completion of therapy.In addition,we explored whether patients who started with a low RDW < 15.5% at diagnosis but then obtained a high RDW ≥ 15.5% upon completion of therapy showed shorter survival compared with patients who maintained a low RDW < 15.5% upon completion of therapy.The median RDW at diagnosis was 15.46% (range:12.0%–18.4%). A total of 46 (59.0%) patients had RDW ≥ 15.5% and 32 (41.0%) had RDW < 15.5% at diagnosis. RDW ≥ 15.5% at diagnosis was significantly correlated with 1q21 amplification  and PFS (P = 0.517), group ii obtained longer OS and PFS compared to group iii, implying that RDW approaching to 15.5% upon completion of therapy even if the MM patients started with a high RDW ≥ 15.5% at diagnosis led to a superior clinical outcome.Based on the cluster analysis showing that patients with a high RDW, who did not decrease a lower RDW value upon completion of therapy, obtained the most poor clinical outcomes, group iv obtained longer OS and PFS compared to group iii. The distribution of additional baseline characteristics of group iii and group iv patients are shown in Table P = 0.018] and PFS Figure P = 0.022 compared with patients with a low RDW upon completion of therapy.Patients with RDW ≥ 15.5% at diagnosis but RDW< 15.5% upon completion of therapy showed longer OS and PFS. We then observed that compared with the patients with a high RDW ≥ 15.5% upon completion of therapy,patients who started with a high RDW ≥ 15.5% at diagnosis and then decreased to a lower value, but the value did not lower than 15.5% upon completion of therapy, presented longer survival.To elucidate the problems, patients who started with a high RDW ≥ 15.5% at diagnosis were classified into four subgroups. Group i consisted of patients with an RDW < 15.5% upon completion of therapy.Group ii obtained patients with an RDW decreased to a lower value, but the RDW value maintained more than 15.5% upon completion of therapy. Group iii obtained patients who then failed to decrease to a lower value and maintain a high level RDW ≥ 15.2%upon completion of therapy.Group i plus group ii makes group iv. As desired from the cluster analysis, patients in group i showed longer OS and PFS compared to the group iii Figures P = 0.034), RDW ≥ 15.5% after treatment (P = 0.012) ,RDW maintain at high level after treatment (P = 0.034)and β2-microglobulin > 5.5 mg/L (P = 0.012). Multivariate analysis that included all the parameters having a P value of less than 0.05 in the univariate analysis revealed that ISS stage (P = 0.034), RDW ≥ 15.5% after treatment (P = 0.044) and β2-microglobulin > 5.5 mg/L (P = 0.018) are independent prognostic factors for OS.Univariate Cox-regression analysis indicated that prognostic factors for PFS were with ISS stage (P = 0.005),and RDW ≥ 15.5% after treatment (P = 0.037).Multivariate analysis revealed that ISS stage (P = 0.005) and RDW ≥ 15.5% after treatment (P = 0.034) are independent prognostic factors for PFS.Results of the univariate and multivariate analysis for factors influencing OS and PFS in patients with MM are reported in Table RDW is a measure of size variability and heteOur results are in accord with the study by Wang et al –18, who Therefore,decreased RDW after therapy is representative of metabolic status recovery. Which also means the patients benefit from chemotherpy and they had a better prognosis.In a similar way,RDW remain at high level at diagnosis, after the completion of therapy, is associated with poor clinical outcomes.One of the limitations of the present study was the retrospective nature, recruitment was performed in a single institution. further multicenter prospective studies are required.Another potentially limiting factor of our study is that the translocation of IgH was detected by an IgH break-apart rearrangement probe but not by tand t probes due to the high fee. Furthermore,we had no complete and detailed information on the influence factors for RDW in MM, such as Interleukin 6 and serum ferritin levels for the total cohort, thus we could not adjust the association of RDW with risk of death for these influence factors –26.In conclusion, the results in this study indicated that RDW at diagnosis, as well as at completion of first-line therapy is an independent predictor for mutiple myeloma patients.RDW maintained at high level, irrespective of whether RDW decreased to the cutoff value predicted an unfavorable prognosis in patients with MM.RDW which is a part of complete blood count and is a routinely measured and automatically generated blood paramete,may represent one of the easiest measurements to be used as a prognostic marker in patients with MM. Further investigations are required to illustrate the exact mechanisms underlying the influence of distribution width on red blood cells in patients with MM.The inclusion criteria were a diagnosis of de novo MM according to the criteria of NCCN guideline,and all patients were treated at the First Affiliated Hospital of Wenzhou Medical University between February 2005 and December 2016.Patients who had the complete information and details concerning laboratory parameters were included.Patients who were diagnosed with monoclonal gammopathy of undetermined significance, asymptomatic MM, amyloidosis, and plasma cell leukemia were excluded.Written informed consent was obtained from each patient before entering the study according to the Declaration of Helsinki, and the study was approved by the Institutional ethics committee.Bortezomib-based regimen were used as first-line therapy in all 78 patients,which included PAD , VD(bortezomib and dexamethasone) and PCD .Thalidomide-based regimen which included TD , TCD  and MPT  was used in 17 patients (21.8%).Two patients (2.6%) received VAD as first-line chemotherapy.In addition, 9 patients (11.5%) underwent auto-SCT and 3 (3.8%) received related allogeneic SCT.RDW were obtained from standard complete blood cell count (CBC) data; The RDW upon completion of first-line therapy was calculated when the CBC reached a plateau after the bone marrow had recovered from first-line therapy. It is the standard practice of our clinicians to obtain a CBC 3 months after completion of chemotherapy. Therefore, we used RDW data from the 3-month follow-up visits.The threshold of 15.5% was established as the maximum (sensitivity+specificity) point according to the area under curve (AUC) of the receiver operating characteristics curve .Correlations of the RWD with clinical parameters were evaluated using the chi-square or Fisher’s exact test. OS and PFS were analyzed using Kaplan-Meier curves, which were compared using the log-rank test. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal RWD cutoffs yielding the maximal combined sensitivities and specificities. A


Fiberoptic tracheo-bronchoscopy is the most commonly used procedure for percutaneous dilational tracheotomy (PDT). However, PDT can be associated with major complications, including death. Furthermore it is unclear, whether the tracheal ring fractures may contribute to the development of tracheal stenosis after PDT nor whether tracheal ring fractures can be prevented by using a rigid endoscope for this procedure. The purpose of this study was to evaluate the feasibility of and the incidence of complications for PDT using the rigid tracheotomy endoscope (TED).P values ≤ 0.05 were considered significant.In a prospective multicenter observational study from 2006 to 2010, 180 adult patients in intensive care and those scheduled for ear, nose and throat surgery underwent PDT using TED. Data collection was performed using a structured protocol. The patients were observed according to PDT phase . The descriptive data are given as the number (percent) of cases and the mean ± standard deviation (SD) where appropriate. The relationships between dichotomous and categorical parameters were analyzed using the chi-square test. PDT was performed in 179 patients. The procedure time was 14.8 ± 6.2 (mean ± SD) minutes. Pneumothorax or procedure-related lethal complications did not occur. Other adverse events included tracheal ring fractures (17.1%), desaturations (6.8%), special incidents (6.2%), bleeding (5.5%), anesthesia complications (4.5%) and posterior tracheal wall injuries (1.1%).The use of TED in PDT is feasible, and the incidence of complications and adverse events was comparable with that of PDT using the flexible endoscope. Tracheal ring fractures in PDT cannot be avoided by the use of a rigid endoscope. With TED, the airway always remains open thus the use of jet ventilation via the TED during PDT is possible. PDT, performed in the ICU, should be considered the procedure of choice for performing elective tracheostomies in critically ill adult patients . As an aBecause the feasibility and safety of this PDT technique with TED and SHFJV were shown in a case series with 24 patients, the aim of the present study was to assess the feasibility, adverse events and complications of this new technique in a larger prospective multicenter investigation .All consecutive patients who were scheduled for elective PDT with TED at one of four German hospitals: Hospital Dresden-Friedrichstadt (city of Dresden), Cardiovascular Center (city of Cottbus), Hospital Ernst von Bergmann (city of Potsdam) and Hospital Chemnitz (city of Chemnitz) from 2006 to 2010 were included in this prospective multicenter observational investigation. The exclusion criteria were as follows: age <18 years, emergency cases, primary critical oxygenation parameters, severe gastroesophageal reflux disease, anatomical peculiarities , difficult airway, coagulopathy with an international normalized ratio (INR) <1.5 and platelet count ≤50 Gpt/l, phlegmonous inflammation of the neck, and conditions after neck dissection or radiation therapy. The protocol was approved by the local independent ethics committee . All patients  gave their written informed consent to participate.All patients underwent PDT with rigid endoscopic guidance with TED Figs.  and 2, wData collection was performed using a structured protocol. Based on previous observational PDT research , the comP values ≤ 0.05 were considered significant.Statistical analysis was performed using SPSS 21.0 software . The descriptive data are given as number (percent) of cases and as the mean ± standard deviation (SD) where appropriate. The relationships between dichotomous and categorical parameters were analyzed using the chi-square test. 2 (Table P ≥ 0.05).One hundred eighty patients (66 women) were scheduled to undergo elective PDT with TED, 56 patients 31.1%) in Hospital Dresden-Friedrichstadt, 40 patients 22.2%) in Cardiovascular Center (city of Cottbus), 20 patients (11.1%) in Hospital Ernst von Bergmann (city of Potsdam) and 64 (35.6%) in Hospital Chemnitz (city of Chemnitz). The mean age of the patients was 64.0 ± 14.7 (range 19–86) years and the mean body mass index (BMI) was 26.7 ± 5.0  kg/m2.2% in C1.1% in Hp = 0.424) and among the study centers . In addition, the differences between the various phases of PDT  were not significant.In seven patients, the bleeding exceeded 10 ml of blood loss and required additional treatment during PDT. In 2 cases, the bleeding stopped after suction, in 1 case, bronchoscopy was necessary with the change from HFJV to IPPV. In 1 case of bleeding at the lower edge of the tracheostomy, electrical coagulation was required. Another patient developed outward bleeding from a superficial vein, which stopped after suction and compression. The procedure-associated administration of blood products, nor any other additional procedures were required. The conversion of PDT to ST was necessary in two patients because of bleeding Fig. . Death op = 0.000)Tracheal ring fractures occurred in 30 out of 173 patients (17.1%); 23 of these fractures occurred during phase 2 of PDT (Table Two patients (1.1%) suffered mild lesions of the posterior tracheal wall. One posterior tracheal wall injury occurred in phase 1 as a result of difficulty locating the puncture site; the tracheal posterior wall was punctured below the TED by a needle Table . A seconn = 178 valid cases). Five anesthesia complications during phase 1 were related to ventilation and oxygenation, and four of these complications required the change of ventilation mode from HFJV to IPPV. The sixth complication resulted from an insufficient depth of anesthesia: as a result adrenergic stimulation occurred and the trachea moved synchronously with vascular pulsation because of transitory hypertension, making it difficult to perform PDT. In phase 2, one patient was switched from HFJV to IPPV because of desaturation and hypercapnia; another patient developed hypotension that required correction with volume administration. No anesthesia complications occurred during phase 3. There were no differences in anesthesia complications between genders  and among study centers . However, there was a difference in the incidence of anesthesia complications between the phases of PDT .In eight patients (4.5%), anesthesia complications occurred. Six anesthesia complications were documented in phase 1 , among study centers  and among the phases of PDT .In 12 patients (6.8%), short transitory desaturations with Son Table . The notIn one out of the 118 patients (0.85%) with remaining teeth, the tooth, which was loose prior to PDT, was removed during rigid endoscopy with TED. The patient’s teeth were described as extremely carious before the PDT procedure. An experienced otolaryngologist performed the endoscopy with TED.P = 0.001).Easy placement of the TED was confirmed in 90.6% of patients. In 17 patients (9.4%), the introduction of the TED was difficult Table . CormackPDT with TED was feasible in four study centers, and the time required for the PDT procedure (14.8 ± 6.2 [mean ± SD]) minutes was comparable with that the time required when using a flexible endoscope 13.6 ± 4.0) . The ove.6 ± 4.0 Bleeding during PDT is a frequent event occurring in 1.3–5.7% of patients ; in our PDT-related injuries to the posterior tracheal wall occur in 0.7 to 2.6% of cases , 13. OnePostmortem evidence of tracheal ring fracture caused by PDT and a reported incidence of up to 28.4% suggest that this complication is often under-diagnosed . The incThe incidence of pneumothorax after PDT (0.6%) is rather low but can be life threatening if undetected . PneumotAnesthesia complications were closely linked to desaturation, insufficient ventilation and a need for vasopressor support in intensive care patients. When patients ventilated with HFJV had been excluded from the analysis, the incidence of desaturation was 3.3%, similar to previous reports , except We assume that the probability of tooth damage might be higher with TED than during fiberoptic tracheoscopy. Per oral rigid endoscopic procedures are commonly used in ENT surgery. For rigid endoscopy in ENT surgery, tooth damage is reported for 0.15% patients . BecauseLoss of the airway during PDT may have fatal consequences. During PDT with or without fiberoptic control, intraoperative airway loss occurs in 1.9% to 7.4% of cases , 20. TheThe use of TED for PDT is feasible in clinical setting. The procedure time and the incidences of complications and adverse events are comparable with those of flexible bronchoscopy. Tracheal ring fractures in PDT cannot be avoided by the use of a rigid endoscope. With TED, the airway always remains open thus the use of jet ventilation via the TED during PDT is possible. The question whether the use of TED during PDT may reduce the rate of complications should be addressed in a randomized clinical trial.