SH Patients Research Articles

Aplikasi Citicoline dalam Pengobatan Stroke Hemoragik

Background: Choline-containing phospholipids, citicoline, and choline alphoscerate have been proposed as adjuvants in acute stroke treatment. An evidence-based case report (EBCR) was conducted to examine the benefits of citicoline in hemorrhagic stroke (SH) patients. Method: Search for articles published from October 2019-2023 from PubMed, Cochrane, Google Scholar, and ProQuest sources using the keywords “Citicoline”, “Hemorrhagic Stroke”, “Choline”, and “Intracerebral Hemorrhage”. The search results were evaluated using inclusion and exclusion criteria. Selected full-text studies were evaluated. The final selection results were critically reviewed based on validity, importance, and applicability by the three authors. Results: One study was considered valid, important, and applicable. The quality of this study is very high based on the literature review. Conclusion: The study shows that citicoline has the potential as an adjuvant therapy to improve clinical outcomes in SH patients, although it does not sufficiently improve neurological or functional outcomes.

DA-EPOCH-R for High Grade B-Cell Lymphoma Patients with MYC and BCL2 and/or BCL6 Rearrangements: Clinical Results of the Induction Phase of the HOVON-152 Trial

Introduction Patients (pts) with high grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 gene rearrangements (double hit and triple hit (DH/TH)) have poor outcomes to standard R-CHOP. Retrospective studies reported improved disease-free survival (DFS) through intensification with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). This regimen was studied in a small prospective trial including 24 DH/TH and 19 single MYC rearranged (SH) lymphomas (Dunleavy, Lancet Haematol 2019). No prospective studies evaluating DA-EPOCH-R exclusively for pts with DH/TH HGBL have been reported. The HOVON-152 trial aimed to improve outcomes in untreated DH/TH HGBL pts by investigating the efficacy of the immune checkpoint inhibitor nivolumab as consolidation treatment in pts achieving complete metabolic response (CMR) after DA-EPOCH-R induction. Here, we present the efficacy and safety profile of the induction phase with DA-EPOCH-R. Methods HOVON-152 is a prospective, multi-center, single arm phase II trial. Inclusion criteria were pts with newly diagnosed HGBL-DH/TH (according to the WHO 2016 classification), age ≥ 18 years, WHO performance status (PS) 0-3 and Ann Arbor stage II-IV. During the screening period for rearrangement status, pts could receive 1 cycle of R-CHOP or DA-EPOCH-R, followed by 5 cycles of DA-EPOCH-R. All pts received intrathecal CNS prophylaxis. All diagnostic lymphoma samples were centrally reviewed. PET-CT scans were performed at diagnosis, after 3 cycles and at end-of-induction (local review, central review will be reported at the conference). Pts in CMR after induction treatment (Deauville 1-3 or a negative lymphoma biopsy in case of Deauville 4) proceeded to nivolumab consolidation (480 mg every 4 weeks for one year). The HOVON-152 aimed to improve 12 months DFS of pts in CMR after induction from an expected 70% to 85% with nivolumab consolidation. Secondary objectives included evaluation of response rates, overall survival (OS) and safety. With a power of 0.90 a sample size of 97 pts was calculated. Here, we report efficacy (CMR rate) and safety of DA-EPOCH-R induction treatment. Logistic univariate analysis is used to analyze baseline characteristics associated with response. Adverse events (AEs) were defined according to the common terminology criteria for adverse events (CTC AE 5.0), counted by the highest grade per system organ class per patient. Results From August 2018 - March 2022, 97 pts have been enrolled (study inclusion completed). One patient was excluded due to CNS localization. The median age was 62 years (range 35-79); 90 (83%) pts had stage III-IV disease and 52 (54%) had (intermediate-)high international prognostic index (IPI) (Table 1). Central pathology review confirmed DH/TH in all pts. 65 pts (67%) had a BCL2 DH, 11 (12%) a BCL6 DH and 16 (17%) a TH. Dose adjustments were performed conform protocol. The maximum dose-level (DL) achieved was DL1 in 41 (43%), DL2 in 22 (23%), DL3 in 25 (25%), DL4 in 7 (7%) and DL5 in 1 (1%) of the pts. Vincristine dose was reduced in 28/81 (35%) pts. After DA-EPOCH-R induction, 63/96 (66%, 95% CI 55-75%) pts achieved CMR. WHO PS 2-3 (odds ratio (OR) 0.15, 95% CI 0.03-0.85, p=0.03), elevated LDH (OR 0.24, 95%CI 0.10-0.59, p=0.002) and bulky disease defined as ≥10 cm mass (OR 0.23, 95%CI 0.09-0.56, p=0.001), were significantly associated with a lower chance of achieving CMR. During treatment, 7 (7%) pts experienced a grade 5 AE (ileus, intestinal perforation, multi-organ failure/sepsis). Thereof, 4 patients died during DA-EPOCH-R and 3 patients died after DA-EPOCH-R. 31 (32%) experienced a grade 4 AE (e.g. sepsis, perforation, hemorrhage, thrombocytopenia and neutropenia), 21 (22%) a grade 3 AE (e.g. anemia, mucositis, infections and electrolyte disturbances) and 16 (17%) pts a grade 2 AE. Conclusion We report the largest prospective series of DH/TH HGBL patients treated with DA-EPOCH-R. DA-EPOCH-R induction was feasible, with toxicity and dose adjustments as previously described. The observed CMR rate of 66% was lower than previously reported in a prospective cohort of mixed DH/TH and SH patients (74%). For patients achieving CMR, the nivolumab consolidation phase is ongoing. Translational side studies investigating predictive factors to identify patients not achieving CMR are ongoing. For these patients, novel strategies to improve first-line treatment are warranted.

OR30-02 Salivary Cortisol Response To The High Dose ACTH Stimulation Test Provides A Reliable Alternative To Serum Cortisol Measurement In The Evaluation of Suspected Hypoadrenalism, And Is Unaffected By Cortisol-Binding Concentration

Abstract Disclosure: N. El-Farhan: None. S. Rees: None. S. Tennant: None. C. Evans: None. A. Rees: None. Context The serum total cortisol response to the ACTH stimulation test is widely used to assess adrenocortical function but is affected in conditions of altered cortisol-binding globulin (CBG) concentration. Salivary cortisol reflects free cortisol concentrations and may offer a reliable alternative. Objectives: 1. To establish the salivary cortisol response to the high dose ACTH stimulation test in healthy volunteers and in patients with altered CBG concentrations. 2. To evaluate the performance of a lower reference limit (LRL) determined in healthy volunteers in patients with suspected hypoadrenalism. Design: A high dose (250 µg) intravenous ACTH stimulation test was undertaken in 139 (60 male, 79 female) healthy volunteers, 24 women taking an oestradiol-containing oral contraceptive pill (OCP females), 10 patients with low serum protein concentration secondary to the nephrotic syndrome or liver cirrhosis (LP patients) and 29 patients with suspected hypoadrenalism (SH patients). Salivary cortisol was measured by liquid chromatography-tandem mass spectrometry. The mean and estimated LRL of the 30-minute salivary cortisol response to ACTH stimulation (mean - 1.96 SD) were derived from log-transformed concentrations. The LRL was subsequently applied as a diagnostic cut-off in SH patients. Results: CBG concentrations were 58 [42-81] mg/L), 64 mg/L [43-95], 41 [28-60] mg/L and116 [84-159] mg/L in male volunteers, female volunteers, LP patients and OCP females, respectively. The mean 30-minute salivary cortisol concentration was 19.3 [2.5th-97.5th percentile 10.3-36.2] nmol/l in healthy volunteers, with no difference between genders. Corresponding values were not different in OCP females (19.7 [9.5-41.2] nmol/l; p=0.59) and LP patients (19.0 [7.7-46.9] nmol/l; p=0.97), in contrast to 30-minute mean serum cortisol responses which differed between healthy female volunteers (555 [421-731] nmol/l) and OCP females (869 [649-1162] nmol/l; p<0.001). Overall diagnostic agreement between 30-minute salivary and serum responses in patients undergoing evaluation for SH was high (79%). Conclusions: Salivary cortisol response to intravenous ACTH stimulation offers a reliable alternative to serum cortisol measurement in the assessment of patients with suspected hypoadrenalism and may be especially useful in conditions of altered CBG concentration. Presentation: Sunday, June 18, 2023

Disparities in statin prescription among patients with severe hypercholesterolemia in an integrated healthcare system

BackgroundSevere hypercholesterolemia (SH), defined as a low-density lipoprotein cholesterol (LDL-C) level ≥ 190 mg/dl, is associated with an increased risk for premature atherosclerotic cardiovascular disease. Despite guideline recommendations, many patients with severe hypercholesterolemia remain untreated. We conducted an observational analysis of a large pool of SH patients, exploring demographic and social factors contributing to disparities in the prescription of statin and other lipid-lowering therapies. MethodsWe included all adults (age 18 or older) in the University Hospitals Health Care System, with an LDL-C ≥ 190 mg/dl on a lipid profile drawn between January 2, 2014, and March 15, 2022. Variables were compared across relevant categories of age, gender, race and ethnicity, medical history, prescription medication status, insurance type, and provider referral type. We used the Fischer exact test and Pearson Chi-square (χ 2) for variable comparisons. ResultsA total of 7,942 patients were included in the study. The median age was 57 [IQR 48–66] years with 64% female, and 17% Black patients. Only 58% of the total cohort was prescribed statin therapy. Higher age was independently associated with a higher likelihood of receiving a statin, with an odds ratio of 1.25 (95% CI [1.21 – 1.30] per 10 years, p<0.001). Additional factors that were associated with higher rates of statin prescription in patients with SH were Black race (OR 1.90, 95% CI [1.65 – 2.17], p<0.001), smoking (OR 2.42, 95% CI [2.17 -2.70], p<0.001), and presence of diabetes (OR 3.88, 95% CI [3.27 – 4.60], p<0.001). Similar trends were also seen with other lipid-lowering therapies such as ezetimibe and fibrates. ConclusionsIn our Northeast Ohio healthcare system, less than two-thirds of patients with severe hypercholesterolemia are prescribed a statin. Statin prescription rates were highly dependent on age and the presence of additional ASCVD risk factors.

Effect of Smoking History on 30-Day Morbidity Following Bariatric Surgery.

Smoking and postoperative complications are well documented across surgical specialties. Preoperative smoking cessation is frequently recommended by surgeons. In this study, we assessed to what degree documented smoking history increased a patient's risk of postoperative complications. The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database for the years 2015-2018 was used. Patients were included if they underwent primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (LRYGB). Patients with a documented smoking history were assigned to the "SH" cohort and patients without smoking history were assigned to the "NSH" cohort. Patients without documentation regarding smoking history, missing variables, younger than 18, with prior surgery, or lost to follow-up were excluded. 30-day morbidity and mortality data were assessed. Multiple logistic regression analysis was made based on all available patient characteristics and perioperative factors, continuous variables were analyzed using Student's t-test and categorical variables were compared using the chi-square test. After evaluation of 760,076 patients on the MBSAQIP database, 650,930 patients underwent non-revisional bariatric surgery, including 466,270 SG and 184,660 LRYGB. Of the total patients included in the study, 44,606 patients were assigned to the SH cohort and 479,601 were assigned to the NSH cohort. 4628 of patients did not have documented smoking status. Within 30 days SH patients had higher rates of readmission (4.2% vs 3.7%, P < .0001), reoperation (1.3% vs 1.1%, P < .0001), unplanned intubation (.2% vs .1%, P = .0212), and unplanned ICU admission (.7% vs .0.6%, P = .0022). SH patients undergoing bariatric surgery were at significantly increased risk of readmission and reoperation within 30days of procedure. In addition, SH patients were more likely to have unplanned intubation and unplanned ICU admission. Given the higher rates of complications in smoking patients, this study would suggest that preoperative smoking cessation in patients prior to primary bariatric surgery might be beneficial. Further study is warranted to compare short-term cessation vs long-term cessation preoperatively, which was not assessed in our study.

A Propensity Score-Adjusted Comparison of Lenalidomide + R-CHOP Versus R-CHOP for MYC-Rearranged DLBCL Patients

Introduction Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) generally have a poor prognosis following standard treatment with R-CHOP. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission (CMR) rates and survival as more intensive chemotherapy regimens such as DA-EPOCH-R [Chamuleau, Haematologica 2020]. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed DLBCL patients treated with R-CHOP in the Netherlands, including MYC-R patients who were not included in the interventional trial due to logistic reasons. These two cohorts enable to evaluate the added value of lenalidomide to R-CHOP in first-line treatment of newly diagnosed MYC-R DLBCL patients. Methods In the single-arm, phase-II HOVON-130 trial, MYC-R DLBCL patients ≥ 18 years were treated with R-CHOP21 plus lenalidomide 15 mg day 1-15 for 6 cycles [Chamuleau, Haematologica 2020]. Additional inclusion criteria were Ann-Arbor stage II-IV, WHO performance status 0-3, ≥ one lesion of ≥ 1.5 cm on contrast-enhanced CT scan and ≥ one FDG-positive lesion on PET-CT scan. In the observational screening study HOVON-900, MYC, BCL2 and BCL6 fluorescent in situ hybridization (FISH) diagnostics were advocated as part of routine procedures and reviewed by the HOVON Pathology Facility. As a control group, we selected MYC-R patients from this observational cohort who met the inclusion criteria for the interventional trial but were not included, and who were treated with standard R-CHOP. Clinical information at presentation and treatment and outcome data were retrieved from the Netherlands Cancer Registry. We explored three statistical methods that account for baseline imbalances. First, we used multivariable regression, with baseline variables as covariates in the model. Second, we performed one-to-one matching on the IPI risk (low, intermediate, or high). Third, we performed inverse probability of treatment weighting (IPTW) using a propensity score. We calculated a propensity score for being included in the HOVON-130 trial based on the separate components of the IPI score (i.e., age, Ann Arbor stage, WHO performance score, extra-nodal localizations, serum LDH level), sex and rearrangement status. To allow for some degree of misspecification of the model for the propensity score, we used a doubly-robust estimator. Subgroup analyses were performed in single hit (SH: only MYC rearrangement), versus double hit and triple hit (DH/TH: MYC rearrangement with BCL2 and/or BCL6 rearrangement). Results Patients from the interventional trial treated with R2CHOP (n=77) were younger than patients in the control cohort (n=56) treated with R-CHOP (median age 63 versus 70 years, p=0.018) and they were more likely to have a lower WHO performance score (p=0.013). Ann Arbor stage, LDH level, number of extranodal localizations and median days before treatment (15 and 19 in the R-CHOP and R2CHOP group, respectively) did not significantly differ between the groups. Complete remission rates were 69.8% and 80.5% in the R-CHOP and R2CHOP group, respectively (p=0.209). Multivariable analysis, 1:1 matching and weighting using the propensity score consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.53, and 0.59 (Figure 1A), respectively, for OS, and 0.59, 0.53, and 0.60 for PFS (Figure 1B). In the subgroups determined by rearrangement status, we performed unadjusted OS and PFS analysis only, because we were not able to adjust for baseline imbalances because of the low number of events within the subgroups. Both SH patients and DH/TH patients tended to have a longer OS when treated with R2CHOP with HRs of 0.34 and 0.57, respectively. Similarly, for PFS the HRs were 0.66 in the SH subgroup and 0.48 in the DH/TH subgroup. Conclusion In conclusion, this propensity score-adjusted comparison study supports the addition of lenalidomide to R-CHOP as a valuable treatment option for MYC-R DLBCL patients. R2CHOP can be administered on a full outpatient basis, with minimal hospitalization visits. Future studies will explore whether adding next-generation cereblon targeting antigens to R-CHOP can improve the observed effects. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluation of Variations of Qt Interval in Hypothyroidism Through Autonomic and Vascular Profiling of Cardiac Function

Background Hypothyroidism increases the risk of cardiac disease as well as autonomic dysfunction (abnormalities of the autonomic nervous system). A prospective case-control study was conducted. The purpose of this study was to compare the QT variability and vascular stiffness of SH patients. Materials and Methods:Using ABI, we compared female SH patients to age- and sex-matched normal controls in order to better understand their condition. HF (0.15–0.4 Hz) and LF (0.003–0.04 Hz) frequencies were investigated spectroscopically. The HF represents vagal regulation, whereas the LF reflects both vagal and limbic regulation. Result In this case research 32 women participated who were 28.02+7.8 years old and 28 women in control group who were age-matched (30.2+ 7.1). Patients had greater QT variability indices (P = 0.01) than healthy controls. Cases showed a higher LF/HF ratio than controls (P = 0.03), which was statistically significant. It was shown that there was a 0.02 point difference in left-right ABI between patients and controls. Conclusion In these circumstances, sympathetic activity predominated over parasympathetic activity, with less of the latter. QTvi may be beneficial in determining the risk of cardiovascular mortality in this particular patient population.

The Bergen 4-Day Treatment (B4DT) for Obsessive-Compulsive Disorder: Outcomes for Patients Treated After Initial Waiting List or Self-Help Intervention.

The Bergen 4-day treatment (B4DT) for obsessive-compulsive disorder (OCD) was recently tested in a randomized controlled trial, where the results showed that the B4DT was more effective than a self-help intervention (SH) and a waiting list condition (WL). Patients in the SH and WL condition still in need of treatment after the first intervention (N = 26; 13 from each condition) were offered the B4DT. None of the patients declined participation, and there were no dropouts. At post-treatment 59.5% were in remission, 31.0% had treatment response, and 9.5% showed no change. At 3-month follow-up 71.4% were in remission, 19.0% had treatment response, and 9.5% showed no change. There were also significant improvement in self-reported symptoms of OCD, generalized anxiety symptoms, and depressive symptoms. The results are in line with what we previously have found for the B4DT in a number of effectiveness studies. In addition, the results indicate that the patients who previously had received an unsuccessful SH intervention and patients who had first been in a WL condition, profited as much as patients who had received the B4DT as the initial intervention. Implications for clinical guidelines and for dissemination of the B4DT are discussed.

Cardiovascular and metabolic risk factors in patients with subclinical Cushing.

Adrenal incidentalomas (AI) are discovered after work-up unrelated to adrenal gland diseases; up to 30% of AI show subclinical endogenous cortisol excess (SH), frequently associated to hypertension, obesity, metabolic disorders and increased incidence of cardiovascular events (CVEs). We analysed 628 AI patients divided into two groups: 471 non-functional adrenal adenoma (NFA) and 157 SH. All patients underwent complete examinations, 24-h ambulatory blood pressure monitoring, biohumoral parameters and vascular damage markers, such as c-IMT and ankle brachial index. After long-term follow-up, we registered newly onset of CVEs such as myocardial infarction (MI), percutaneous stenting and surgical bypass (PTA/CABG), stroke, overall/cardiovascular mortality. Moreover, SH patients underwent to surgical (SSH) or pharmacological treatment (MSH). SH patients showed higher prevalence of metabolic syndrome, diabetes mellitus, and previous CVEs respect NFA at baseline. After follow-up MSH group showed higher recurrence of major CV events compared with NFA and SSH (RR 2.27 MSH vs NFA for MI; RR 2.30 MSH vs NFA for PTA/CABG; RR 2.41 MSH vs NFA for stroke). In SSH there was a significant reduction of the number of antihypertensive medications needed to reach target blood pressure levels (2.3 ± 1.0 to 1.5 ± 0.4 drugs). None differences were found in SH patients, distinguished in relation to cortisol plasma levels after dexamethasone suppression test (1.8-5 µg/dL, above 5 µg/dL). SH is linked to relevant cardiovascular and metabolic alterations, leading to worsen clinical outcomes. In eligible patients, adrenalectomy is valid and safe option to treat SH, reducing cardiometabolic abnormalities.

Comparative analysis of two different Turkish hospital reports on polytrauma patients with thoracic trauma.

The present study aims to assess whether there are any differences in the management and outcome of polytrauma patients with thoracic trauma in trauma units of two different hospitals in the same country; one hospital is near the Syrian border. A retrospective analysis (January 2012 to January 2014) of 348 polytrauma casualties with thoracic trauma from Manisa Celal Bayar University Hospital (MH) were compared according to age, gender, mechanism of injury, associated injuries, abbreviated injury scale (AIS), injury severity score (ISS), treatment modalities, and mortality with 917 patients of Şanlıurfa Training and Research Hospital (SH) registry (near the Syrian border). Of the 348 patients in the MH, 230 (66%) and of the 917 patients in the SH, 697 (76%) were males (p<0.001). Mean age was 45.6±18.3 yrs in the MH group and 26.4±22.4 yrs in the SH group (p<0.001). The SH patients had a larger proportion of stab wounds (MH; 9% vs. SH; 17%, p<0.05), gunshot injuries (MH; 5% vs. SH; 18%, p<0.05), higher mean ISS (MH; 30.2±8.4 vs. SH; 42.8±10.2, p<0.001), and increased mortality (MH; 2.6% vs. SH; 11.1%, p<0.001). AISabdomen was the highest component in the SH registry (AISabdomen = 4.8±0.7), whereas AIS extremities were the highest component in the MH registry (AISextremities = 3.6±0.2). Significantly different demographic features, mechanisms of injury, worse outcomes and higher mortality rates in SH demonstrate and reflect the surgical challenges depending on the combat environment. Two hospitals in Turkey, one seemingly adjacent to a war zone and another with the more standard civilian experience highlight the impact of the Syrian conflict on the Turkish healthcare system.

Prostatic Artery Embolization in Nonindex Benign Prostatic Hyperplasia Patients: Single-center Outcomes for Urinary Retention and Gross Prostatic Hematuria

To present outcomes for prostatic artery embolization (PAE) to treat urinary retention and gross prostatic hematuria in nonindex benign prostatic hyperplasia patients. Seventy-five patients undergoing PAE from December 2013 to August 2018 (age=77.5 ± 8.6, age-adjusted Charlson comorbidity index=4.6 ± 2.0, prostate volume=224 mL ± 135 mL) for retention (n=46) and/or gross prostatic hematuria (n=55) were retrospectively reviewed. Twenty-six patients had both problems. Urinary retention patients (UR, n=46, catheterization=162.4 ± 148.1 days) underwent voiding trials 1-2 months post-PAE, with International Prostate Symptom Score (IPSS), Quality of Life (QoL), and postvoid residual (PVR) recorded at 3, 6, 12, 24, and 36 months. Pre- and post-PAE hematuria-related visits were compared for gross hematuria patients (GH, n=39), as were transfusion rates for severe hematuria patients requiring bladder irrigation (SH, n=16). Ninety-day adverse event tabulation used Clavien-Dindo classification. Three months post-PAE, 33/38(87%) UR patients were catheter-free (IPSS=8.9 ± 5.3, QoL=1.6 ± 1.7, PVR=158 mL ± 207 mL). Results were similar at 6 months (catheter-free=26/28(93%), IPSS=6.5 ± 4.4, QoL=1.1 ± 0.9, PVR=149 mL ± 139 mL), 12 months (catheter-free=19/20(95%), IPSS=4.7 ± 4.8, QoL=0.6 ± 0.9, PVR=125 mL ± 176 mL), 24 months (catheter-free=11/12(92%), IPSS=4.4 ± 3.0, QoL=0.9 ± 0.8, PVR=66 mL ± 68 mL), and 36 months (catheter-free=5/6(83%), IPSS=5.8 ± 3.8, QoL=0.8 ± 1.0, PVR=99 mL ± 71 mL). Out of 37, 34(92%) GH patients remained hematuria-free at 483 ± 137 days, with 22 hematuria-related visits pre-PAE vs none post-PAE. Hematuria resolved <48 hours post-PAE in 14/16(87.5%) SH patients, with 36 blood units transfused pre-PAE, 4 units transfused <48 hours post-PAE, and none thereafter. Subsequently, 13/16(81%) remained hematuria-free at 500 ± 501 days; 2/16(13%) required fulguration; 1/16(6%) developed bladder tumor. There were 2 deaths <30 days post-PAE, and 8(11%) Grade-II urinary infections. PAE provided safe, effective, and durable treatment for retention and gross hematuria in nonindex benign prostatic hyperplasia patients.

Serum NOX-2 concentrations and paraoxanase-1 activity in subclinical hypothyroidism: a pilot study

Abstract Objective Subclinical hypothyroidism (SH) is one of the most prevalent endocrine disorders. Although recent data suggest an imbalanced oxidative status in SH, the mechanisms of increased oxidative stress are poorly figured out. The primary goal of this research was to analyze potential sources of ROS and the relationship between serum NOX-2 levels and paraoxonase-1 (PON-1) activity in SH. Serum lipid changes in SH patients which had been determined were compared to healthy control group. Materials and methods Thirty-one patients diagnosed with SH and 30 healthy controls were included in the study. The quantitative sandwich ELISA was used for the detection of serum NOX-2 levels. Spectrophotometric method was used to determine serum PON-1 activity. Results Higher median serum NOX-2 levels were determined in patients than in the control group (p = 0.004). Lower median serum PON-1 activity was determined in patients as to aforementioned control group (p &lt; 0.0001). As a consequence, no statistically remarkable correlation was identified between PON-1 activity and NOX-2 levels. Triglyceride (TG) concentrations were determined as superior in patients to control group (p &lt; 0.0001). Conclusion Over-production of NOX-2 and decreased PON-1 activity contribute to the increased oxidative stress in SH patients. Larger prospective studies required to confirm these findings.

Metabolic effects caused by sodium levothyroxine in subclinical hypothyroidism patients with low HDL

IntroductionSubclinical hypothyroidism (SH) is an autoimmune thyroid disorder characterized by elevated TSH with values of T3, T4, free T3 and free T4 within the reference range. High TSH levels are associated with lipid alteration. MethodA total of 21 patients aged between 18 and 80 years were recruited. The sample was composed of 17 females and 4 males, all of whom had TSH values ranging from 5.0 to 9.9 (mlU/L) and normal free T4 levels. They were followed up for 26 months while undergoing sodium levothyroxine replacement therapy (12.5–25 mcg/day). Throughout this period, TSH, free T4 HDL, LDL, triglyceride, total cholesterol and glucose levels were evaluated. ResultsA significant improvement in HDL cholesterol levels was observed. There was also a decrease in fasting glucose. No significant changes were seen in triglyceride levels. ConclusionAs observed throughout this study, SH patients with low HDL under therapy showed a significant increase in HDL levels after TSH levels were normalized. Therefore, it is quite clear that thyroid hormones affect lipid metabolism, and, as a result, metabolic syndrome components.

Cognitive, neurophysiologic and metabolic sequelae of previous hypoglycemic coma revealed by hyperinsulinemic-hypoglycemic clamp in type 1 diabetic patients.

To examine the relationship between electroencephalographic (EEG) activity and hypoglycemia unawareness, we investigated early parameters of vigilance and awareness of various symptom categories in response to hypoglycemia in intensively treated type 1 diabetic (T1DM) patients with different degrees of hypoglycemia unawareness. Hypoglycemia was induced with a hyperinsulinemic-hypoglycemic clamp in six T1DM patients with a history of hypoglycemia unawareness previous severe hypoglycemic coma (SH) and in six T1DM patients without (C) history of hypoglycemia unawareness previous severe hypoglycemic coma. Cognitive function tests (four choice reaction time), counterregulatory responses (adrenaline), and symptomatic responses were evaluated at euglycemia (90mg/dl) and during step-wise plasma glucose reduction (68, 58 and 49mg/dl). EEG activity was recorded continuously throughout the study and analyzed by spectral analysis. Cognitive function deteriorated significantly at a glucose threshold of 55±1mg/dl in both groups (p=ns) during hypoglycemia, while the glucose threshold for autonomic symptoms was significantly lower in SH patients than in C patients (49±1 vs. 54±1mg/dl, p<0.05, respectively). In SH patients, eye-closed resting EEG showed a correlation between the mean dominance frequency and plasma glucose (r=0.62, p<0.001). Theta relative power increased during controlled hypoglycemia compared to euglycemia (21.6±6 vs. 15.5±3% Hz p<0.05) and was higher than in the C group (21.6±6 vs. 13.8±3%, p<0.03). The cognitive task beta activity was lower in the SH group than in the C group (14.8±3Hz, vs. 22.6±4 vs. p<0.03). Controlled hypoglycemia elicits cognitive dysfunction in both C and SH patients; however, significant EEG alterations during hypoglycemia were detected mainly in patients with a history of hypoglycemia unawareness and previous severe hypoglycemic coma. These data suggest that prior episodes of hypoglycemic coma modulate brain electric activity.

Under-recording of diabetes on medical record may be associated with adverse in-hospital outcomes

Materials and methods This is a retrospective analysis including 62136 adults (> 18 yrs.) admissions in groups NL (69%), DM (17%), DMNR (5%), and SH (9%), hospitalized between 2010 and 2013. Patients were classified according to five coded discharge diagnoses registered in electronic medical record. The inclusion criteria for DMNR were registration of DM in previous admissions and omission of diagnosis in consecutive readmission. Inclusion criteria were length of stay between 2 and 120 days, availability of capillary glucose (at least one measurement for NL patients and two measurements for DM, DMNR and SH patients). Exclusion criteria were pregnancy. In hospital outcomes included in the retrospective analysis were nosocomial infection, sepsis, intensive care unit admission and death. To compare the proportion of adverse outcomes we perform chi-square test. Results Average age was 54,8 yrs., the proportion of females was 52%. The proportion of hospitalizations with surgical interventions was 44%. The average length of stay among NL, DM, DMNR and SH, were 4,7; 7,3; 13,9 and 17,1 days respectively. The incidence of nosocomial infection were 0,4%; 0,9%; 2,3% and 3,9% and the incidence of sepsis were 1,5%; 4.0%; 13,7% and 16% in NL, DM, DMNR and SH, respectively. The mortality rate were 0,8%, 1,4%, 10,2% and 12,7%, respectively. P values were < 0.05 for every outcome described.

Pharmacological interventions for self-harm in adults.

Self-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and strongly associated with suicide. This is an update of a broader Cochrane review on psychosocial and pharmacological treatments for deliberate SH, first published in 1998 and previously updated in 1999. We have now divided the review into three separate reviews. This review is focused on pharmacological interventions in adults who self harm. To identify all randomised controlled trials of pharmacological agents or natural products for SH in adults, and to conduct meta-analyses (where possible) to compare the effects of specific treatments with comparison types of treatment (e.g., placebo/alternative pharmacological treatment) for SH patients. For this update the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) Trials Search Co-ordinator searched the CCDAN Specialised Register (September 2014). Additional searches of MEDLINE, EMBASE, PsycINFO, and CENTRAL were conducted to October 2013. We included randomised controlled trials comparing pharmacological treatments or natural products with placebo/alternative pharmacological treatment in individuals with a recent (within six months) episode of SH resulting in presentation to clinical services. We independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and 95% CI. Meta-analysis was only possible for one intervention (i.e. newer generation antidepressants) on repetition of SH at last follow-up. For this analysis, we pooled data using a random-effects model. The overall quality of evidence for the primary outcome was appraised for each intervention using the GRADE approach. We included seven trials with a total of 546 patients. The largest trial included 167 participants. We found no significant treatment effect on repetition of SH for newer generation antidepressants (n = 243; k = 3; OR 0.76, 95% CI 0.42 to 1.36; GRADE: low quality of evidence), low-dose fluphenazine (n = 53; k = 1; OR 1.51, 95% CI 0.50 to 4.58; GRADE: very low quality of evidence), mood stabilisers (n = 167; k = 1; OR 0.99, 95% CI 0.33 to 2.95; GRADE: low quality of evidence), or natural products (n = 49; k = 1; OR 1.33, 95% CI 0.38 to 4.62; GRADE: low quality of evidence). A significant reduction in SH repetition was found in a single trial of the antipsychotic flupenthixol (n = 30; k = 1; OR 0.09, 95% CI 0.02 to 0.50), although the quality of evidence for this trial, according to the GRADE criteria, was very low. No data on adverse effects, other than the planned outcomes relating to suicidal behaviour, were reported. Given the low or very low quality of the available evidence, and the small number of trials identified, it is not possible to make firm conclusions regarding pharmacological interventions in SH patients. More and larger trials of pharmacotherapy are required. In view of an indication of positive benefit for flupenthixol in an early small trial of low quality, these might include evaluation of newer atypical antipsychotics. Further work should include evaluation of adverse effects of pharmacological agents. Other research could include evaluation of combined pharmacotherapy and psychological treatment.

Peculiarity of prooxidant-antioxidant balance indicators in patients with nonalcoholic fatty liver disease who have been exposed to ionizing radiation due to the Chornobyl NPP accident

To define the features of prooxidant antioxidant balance in patients with nonalcoholic fatty liver disease who have been exposed to radiation as a result of the Chornobyl accident. using Indicators characterizing the processes of oxidative modification of macromolecules by blood lev els of compounds with isolated double bonds (CIDB), diene conjugates (DC) oxodiene conjugates (ODC), secondary products of lipid peroxiodation reacting with thiobarbituric acid, products of oxidative modification of proteins in blood serum by levels of neutral and basic 2,4 dynitrofenilhidrazones, superoxide dismutase and catalase content in erythrocytes and ceruloplasmin in plasma were determined for the diagnosis of oxidative stress. The factor of antiox idant state was calculated. In the absence of differences between the ratios between the primary and intermediate products of lipids peroxidation increasing relative content of DC and ODC in patients with nonalcoholic steatohepatitis (NASH), which suffered radiation exposure, was found compared with patients without nonalcoholic fatty liver disease (NAFLD) and NASH patients, who had no history of radiation exposure. This may be a manifestation of insignificant activation of lipid peroxidation and disturbance of LPO products transformation at different stages. In irradiated steatohepato sis (SH) patients, unlike SH patients who have not undergone radiation exposure,, the proportionalityof lipid perox idation products between the content of izopropanol phase lipid extracts of blood was violated, and Spearman cor relation coefficients between CIDB and DC and DC and ODC did not exceed the limits average values. In the group of patients with SH who suffered from radiation exposure level CIDB was slightly higher compared with patients with NASH. Regardless of whether there was a history of radiation exposure, the level of oxidative protein modification (OMB) products in NASH patients was higher compared with patients with SH, but the difference reached significant values only in the subgroup of non irradiated patients with NASH by 2.4 dinitrophenilhydrazones of neutral charac ter. Mean values ??of catalase activity in patients with NASH also exceeded the corresponding values of SH patient. The average values of the factor of antioxidant status in patients with both SH and NASH subjected to radiation exposure, were lower than in the corresponding subgroups of non irradiated patients by 29 and 21%, respectively. Existing dismetabolic disorders may contribute to the development of endogenous intoxication and deepening of pathological changes in the liver of NAFLD patients from SH to NASH.

Natural History and Comorbidities of Subjects with Subclinical Hyperthyroidism: Analysis at a Tertiary Hospital Setting

Subclinical hyperthyroidism (SH, grade 1, thyrotropin (TSH) ≥0.1 mU/L and grade 2, TSH <0.1 mU/L) is a common disorder with increased prevalence in older subjects. There is evidence for increased morbidities in SH, such as atrial fibrillation and osteoporosis. We aim to study the natural history and comorbidities of SH from patients referred to a tertiary endocrine clinic in Singapore as they are currently unknown. Retrospective evaluation of SH subjects for natural progression and comorbidities. One hundred and thirteen SH subjects (male/female: 24/89, mean age: 67.2 years, grade 1/grade 2: 60/53) were identified from the endocrine clinic. The aetiology of SH include 52 multinodular goitre, 15 Graves' disease, 7 toxic adenoma and 39 unclassified. A minority of SH patients (5.3 %) progressed to overt hyperthyroidism while 13% remitted to euthyroid state (1 to 3 years with a mean follow-up of 18 months) in the total cohort. Most of the patients remained in SH state during follow-up (50/60 in grade 1 SH and 42/53 in grade SH). However, no single predictive factor could be identified for progression or remission of SH. The prevalence of morbidities in SH subjects include ischaemic heart disease (16.8%), heart failure (8.9%), tachyarrhythmias (13.3%), any cardiovascular disease (28%), cerebrovascular disease (28%), osteoporosis (28%), and any fracture (15.9%). Most of SH cases in our cohort remain in subclinical state with very few progressing to overt hyperthyroidism. Significant proportion of SH subjects have vascular disease, but this association needs to be confirmed in prospective controlled studies.

SAT0333 Efficacy of sodium hyaluronate versus hylan G-F 20 in the treatment of tibiofemoral osteoarthritis

BackgroundCrosslinked hylan is perceived to have longer efficacy than native hyaluronic acid in the treatment of osteoarthritis (OA).ObjectivesTo compare the efficacy of intra-articular injections of native sodium hyaluronate 1% (SH)...

Complete Blood Cell Count Biomarkers Provide No Additional Benefit Over Traditional Lipid Biomarkers for Assessing Cardiovascular Disease Risk in Non-alcoholic Steatohepatitis

Purpose: Non-alcoholic steatohepatitis (NASH) has been associated with increased cardiovascular disease (CVD) risk compared with individuals without NASH. Recently, the neutrophil/lymphocyte (N/L) ratio and the mean platelet volume (MPV) have been proposed as independent predictors and risk factors of CVD. In this study, we evaluated whether the N/L ratio and MPV provided any additional benefit to the more traditional lipid biomarkers of CVD in a well characterized cohort of NASH patients. Methods: We compared biopsy proven NASH patients with a control group of subjects with no evidence of fatty liver on imaging or who had a normal liver biopsy. Subjects with gastric bypass surgery were excluded. The groups were matched 1:1 based on age, body mass index, gender, diabetes and hypertension. The groups were compared on different indirect markers of cardiovascular risk. Results: There were 93 subjects in each group. Both groups had 50 (53.8%) females. The mean age was 50.4 (+10.5) years in the control group and 50 (+10.9) years in the NASH group. The mean body mass index was 33 for both groups with 73 obese subjects in the control group and 72 in the NASH group. The groups had diabetes present in 32% and hypertension in 48%. The NASH group had significantly lower high density lipoprotein (HDL) levels (45+12.6 mg/dL vs. 52.6+12.9 mg/dL; p <0.002) and higher triglyceride (TG) levels (152 [108, 195] mg/dL vs. 109 [68, 177] mg/dL; p=0.015). The NASH group had a lower N/L ratio (NASH 2.2+1.3 vs. controls 2.8+1.8; p=0.021). There was no significant difference in MPV between the two groups (NASH 10.8+0.92 vs. controls 10.5+0.91; p=0.097). SH patients have increased CVD risk factors but the newly proposed complete blood cell count biomarkers of CVD, N/L ratio and MPV, provide no additional benefit over the more traditional lipid biomarkers.Table: Cardiovascular risk measures