DNR Group Research Articles

연명의료결정법 대상 환자의 연명의료결정과 사망 전 의료이용에의 영향요인

This study embarks on a detailed cohort analysis to identify the factors influencing life-sustaining treatment (LST) decisions and healthcare usage before death. Utilizing multinomial logistic regression, it examines a diverse sample of 1,072 patients, categorized into three groups: self-determination, family determination, and DNR. The majority of the cohort, 49.4%, falls under the self-determination group, with a significant proportion of patients (92.8%) suffering from cancer. We find that the most common medical intervention in the week preceding death was blood transfusions, accounting for 49.2% of cases. The study reveals that the self-determination group experienced lower daily healthcare costs, higher hospice utilization rates, and longer intervals between physician orders for life-sustaining treatment(POLST) or DNR completion and death, compared to the other groups. Moreover, patients with stupor on admission were significantly more likely to be in the family determination group (36.225 times) or the DNR group (19.422 times) than in the self-determination group. Furthermore, the likelihood of ICU use was higher in the family determination (3.627 times) and DNR groups (4.137 times), with the application of mechanical ventilation being 2.372 times more common in the family determination group and 4.209 times in the DNR group. Lastly, cardiopulmonary resuscitation was 9.122 times more prevalent in the DNR group compared to the self-determination group. The study concludes that self-determination in LST can significantly reduce unnecessary healthcare utilization before death and promote hospice care utilization, underscoring the necessity of supporting patients in planning their end-of-life care, including decisions about LST.

Idarubicin Versus Daunorubicin Versus Mitoxantrone for Induction Chemotherapy in Acute Myeloid Leukemia: Patient Registration Study of Turkish Society of Hematology-Acute Myeloid Leukemia Working Group

Introduction: Standard induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) includes a combination of standard-dose cytarabine and an anthracycline (idarubicin [IDA], daunorubicin [DNR], or mitoxantrone [MXR]). Anthracycline selection is still not standardized, and the impact of anthracycline selection on survival and response in patients with adverse genetic risk is of interest. The study aimed to retrospectively compare the effectiveness of induction regimens with respect to anthracycline preference. Methods: The study population was recruited from the Turkish AML Registry project database based on documentation of newly diagnosed AML and induction chemotherapy with IDA, DAU, or MXR in combination with cytarabine. Patients diagnosed before 31 August 2022 were received typical “7 + 3” induction chemotherapy containing 3 days of IDA, DAU, or MXR. Results: The study included 317 newly diagnosed AML patients (median age 51; range, 18 - 79; 55.2% male). Of the patients, IDA was administered in 266 (83.9%), DNR in 42 (13.2%), and MXR in 9 (2.8%). The three anthracycline treatment groups were similar between age, gender, type of AML by the World Health Organization (WHO), and risk classification by 2017 European LeukemiaNet (ELN) when evaluated according to the baseline disease characteristics. At the time of diagnosis, although the median white blood cell levels were 19 x 10 9/L (0.4 - 355) in the IDA, 7.8 x 10 9/L (0.7 - 357.2) in the DAU, and 5.5 x 10 9/L (0.6 - 34) in the MXR therapy group (p = 0.019); the hemoglobin and platelet levels and bone marrow blast percentage were similar between the treatment groups. FMS-like tyrosine kinase-3 internal tandem duplication ( FLT3-ITD) (p = 0.561) and Nucleophosmin 1 gene ( NPM1) (p = 0.430) mutation frequencies were also similar between treatment groups. Morphological complete remission (CR) was documented in 65% of all evaluable patients. Among the patient groups, CR was 67.7% for IDA, 50% for DNR, and 55.6% for MXR (p = 0.081). In univariate analysis (Table 1), significant predictors of overall survival (OS) were age ≥60 years (p <0.001), acute leukemias of ambiguous lineage (p <0.001), presence of disseminated intravascular coagulation (DIC) (p = 0.012), and FLT3-ITD mutation (p = 0.018); no significant interaction was noted between NPM1 mutation and OS (p = 0.059). Additionally, when idarubicin was taken as a reference, there was no meaningful relationship between anthracycline type and OS (p values for daunorubicin and mitoxantrone were 0.145 and 0.356, respectively). In multivariate analysis (Table 1), age ≥60 years (p = 0.001), acute leukemias of ambiguous lineage (p = 0.007), and the presence of DIC (p = 0.040) remained significant. After a median follow-up of 29.8 months, 32.5% relapse cases were documented and similarly distributed among IDA (33.1%), DNR (31%), and MXR (22.2%) therapy groups (p = 0.771). During the same period, allogeneic hematopoietic stem cell transplantation (AHSCT) was documented in 10.9% and 26.2% of patients treated for IDA and DNR, respectively. No patient progressed to AHSCT in the MXR arm (p <0.001). In the study, 142 (44.8%) deaths were reported, and there was a 48.5%, 26.2%, and 22.2% mortality rate between the IDA, DNR, and MXR treatment groups, respectively. There was no significant difference in OS by anthracycline type in both the study cohort and age group <60 years (Figures 1A and 1B). There was also no significant difference in OS in patients with the adverse genetic risk group and <60 years age group with adverse genetic risk, according to 2017ELN (Figures 1C and 1D). The results may have been influenced by the number of patients in the treatment groups of the retrospective study and by differences in fitness levels that needed to be measured systematically. Conclusions: We are encouraged that our findings mostly agree with previously published studies and that IDA, DNR, and MXR offer comparable survival values in the research and the younger patient groups. In the future, the ever-changing treatment environment in patient groups with targetable mutations makes choosing the optimal anthracycline for induction chemotherapy in AML much more difficult.

Does cognitive frailty predict delayed neurocognitive recovery after noncardiac surgery in frail elderly individuals? Probably not.

Delayed neurocognitive recovery (DNR) is a common post-surgical complication among the elderly. Cognitive frailty (CF) is also an age-related medical syndrome. However, little is known about the association between CF and DNR. Therefore, this study aimed to study whether CF is associated with DNR in elderly patients undergoing elective noncardiac surgery, as well as to explore the potential risk factors for DNR in frail elderly individuals and construct a prediction model. This prospective cohort study administered a battery of cognitive and frailty screening instruments for 146 individuals (≥65 years old) scheduled for elective noncardiac surgery. Screening for CF was performed at least one day before surgery, and tests for the presence of DNR were performed seven days after surgery. The association between CF and DNR was investigated. Moreover, the study subjects were randomly divided into a modeling group (70%) and a validation group (30%). Univariate and multivariate logistic regression was performed to analyze the modeling group data and identify the independent risk factors for DNR. The R software was used to construct DNR's nomogram model, verifying the model. In total, 138 individuals were eligible. Thirty-three cases were diagnosed with DNR (23.9%). No significant difference in the number of patients with CF was observed between the DNR and non-DNR groups (P > 0.05). Multivariate analysis after adjusting relevant risk factors showed that only the judgment of line orientation (JLOT) test score significantly affected the incidence of DNR. After internal validation of the constructed DNR prediction model, the area under the curve (AUC) of the forecast probability for the modeling population (n = 97) for DNR was 0.801, and the AUC for the validation set (n = 41) was 0.797. The calibration curves of both the modeling and validation groups indicate that the prediction model has good stability. Cognitive frailty is not an independent risk factor in predicting DNR after noncardiac surgery in frail elderly individuals. The preoperative JLOT score is an independent risk factor for DNR in frail elderly individuals. The prediction model has a good degree of discrimination and calibration, which means that it can individually predict the risk probability of DNR in frail elderly individuals.

Abstract 14519: End Stage Heart Failure Patients With Do-Not-Resuscitate Code Status Have Dramatically Reduced Hospitalization Cost and Length of Stay

Introduction: End-stage CHF (ES-CHF) poses a significant burden on healthcare system, DNR orders are often associated with comfort care measures, decreased pain and suffering, as well as healthcare resource utilization (cost and LOS). Objective: To quantify the discrepancy in cost and LOS between ES-CHF patients with DNR orders versus without DNR code status. Methodology: Nationwide Inpatient Sample (NIS) database years 2017-2018 was invoked for hospitalizations with primary or secondary diagnosis of ES-CHF, DNR status, comorbidities, and hospitalization outcome using ICD-10 codes. Characteristics of ES-CHF hospitalization with DNR versus no DNR code status were compared. Because of the nature of NIS database, timing of diagnoses and DNR code status could not be established, thus regression analysis for predictors of hospital charges, cost, and LOS was not feasible. Regression analyses were performed to explore predictors of mortality. Stata/MP 16.0 software was used. Results: 40,655 adult hospitalization had the diagnosis of ES-CHF in years 2017-2018 in the United States, among them, 12,300 (30%) had DNR code status, 35% were females, 83% of patients had >=3 comorbid conditions (Charlson comorbidity index>=3). Overall inpatient mortality rate was 12% (25% vs 7% in DNR vs no DNR group, respectively, p<0.001), mean LOS was 10+-15 days (8 vs 11 days in DNR vs no DNR group, respectively, p<0.001), mean total hospital charges was $159,122+-358,186 ($79,434 vs $193,873 in DNR vs no DNR group, respectively, p<0.001). Significantly higher rates of CABG history, atrial fibrillation, COPD, peripheral vascular disease, hypothyroidism, CKD, liver disease, electrolyte disturbances, AKI, and sepsis were found among DNR group. In all patients with ES-CHF, independent predictors of inpatient mortality included older age, DNR status, history of CABG, peripheral vascular disease, liver disease, electrolyte disturbances, smoking, AKI, and sepsis. Conclusion: The presence of DNR code status in ES-CHF patients admitted to the hospital for any was associated with had dramatically reduced hospital charges and cost by more than the half, and with significantly shorter LOS.

Polymorphisms in HIF-1a gene are not associated with diabetic retinopathy in China.

BACKGROUNDIt has been reported that vascular endothelial growth factor (VEGF) is a susceptibility gene for both type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR). In response to hypoxia, VEGF mRNA levels are increased, which is mainly mediated by the binding of hypoxia-inducible factor-1 (HIF-1) and hypoxia response element upstream of the transcriptional start site of VEGF. Therefore, HIF-1a is supposed to be involved in pathology of DR.AIMTo investigate whether the polymorphisms in HIF-1a gene are associated with DR.METHODSTwo hundred and ninety-nine type 2 diabetic patients (128 males and 171 females) and 144 healthy volunteers were recruited. Mean age was 56.04 ± 21.05 years. According to the results of fundus fluorescein angiography and examination of ophthalmoscopy, patients were divided into two groups, DNR group (diabetes without retinopathy) and DR group (diabetes with retinopathy). There are 150 cases in DNR group and 149 cases in DR group. Two single nucleotide polymorphisms (SNP) of the HIF-1a gene were tested using matrix-assisted laser desorption/Ionization time of flight mass spectrometry. The frequency of genotypes and alleles, and odds ratio were measured.RESULTSThe mean age of the cases with diabetes was 55.84 ± 3.66 years, the mean age of the cases with DR was 55.97 ± 4.66 years and that of controls was 56.32 ± 4.70 years. Two variations were found in 76 patients. Rs11549465 is the change of C-T base, rs11549467 is the change of G-A base. The rs11549467 G/A genotype was 5.33% in diabetes and 6.04% in DR patients, respectively. The rs11549465 C/T genotype was 10% and 12.75% in patients with diabetes and DR. The rs11549467 A allele frequencies and rs11549465 T frequencies was similar to that of controls. Paired SNP linkage disequilibrium analysis indicated that rs11549467 was in linkage disequilibrium with rs11549465. Haplotype association analysis denoted that the haplotype association exhibited similar distribution in the patients compared to the normal controls.CONCLUSIONThis study suggests that there is no relationship between the genetic variations of HIF1a and diabetes or DR.

Association analysis of 374T/A (rs1800624) receptor for advanced glycation end-products (RAGE) gene polymorphism with diabetic retinopathy in Pakistani patients.

Objectives:to determine the relationship of 374T/A (rs1800624) polymorphism in the gene encoding RAGE with Type-2 diabetes mellitus (T2DM), diabetic retinopathy (DR) and serum soluble RAGE (sRAGE) level in Pakistani patients.Methods:A case-control study, conducted from January 2017 to December 2018, involving 150 healthy controls (HC), 150 T2DM patients with no retinopathy (DNR) and 150 DR patients diagnosed by coloured fundus photography. Tetra-primer amplification refractory mutation system – polymerase chain reaction (T-ARMS-PCR) was used for genotyping. Serum sRAGE levels were measured by enzyme-linked immunosorbent assays (ELIZA).Results:The frequency of TT, TA and AA genotypes of rs1800624 polymorphism were: 92.7%, 6%, 1.3% in HC, 80%, 17.3%, 2.7% in DNR and 76.7%, 19.3%, 4.3% in DR groups. Heterozygous TA genotype and mutant A allele showed significant association with diabetes and DR vs HC. In dominant model, mutant allele showed significant association with DNR and DR vs HC. No significant association of rs1800624 was detected with DR and its sub-groups, non-proliferative DR (NPDR) and proliferative DR (PDR) vs DNR. Dividing NPDR into mild, moderate and severe, heterozygous TA genotype showed significant association with moderate and severe NPDR vs DNR. In DNR and DR groups, TA genotype was significantly associated with raised sRAGE.Conclusion:rs1800624 RAGE gene polymorphism might be a risk factor for T2DM and NPDR in Pakistani patients. Raised sRAGE levels have a positive correlation with PDR and are associated with heterozygosity of rs1800624 polymorphism in DNR and DR groups

Comparative Analysis of Dorsal Nerve Relocation versus Dorsal Neurectomy in the Surgical Management of Morton's Neuroma

This clinical study compares the use of dorsal nerve relocation (DNR; also known as dorsal nerve transfer) and dorsal neurectomy (DN) in the surgical management of Morton's neuroma within the surgical directorate of an NHS Hospital Trust (Princess Royal University Hospital) in the South East of England between 2002 and 2009. Approaches to the surgical management of Morton's neuroma are dependent on the views of individual surgeons, rather than empirical evidence and varied considerably, so this study was essentially all about checking whether best practice is being followed and making improvements. Data were collected using an in-depth review of patients' case notes and patient questionnaires. In total, there were 47 cases (51 web spaces), 25 (28 web spaces) in the DNR group, and 22 (23 web spaces) in the DN group. The key indication for surgery in all cases reviewed was failure of the condition to improve using conservative methods. The mean follow-up duration was 36 months (12-89) in the DNR group and 41 months (12 69) in the DN group. Coughlin's criterion was used to analyze individual records. The results suggest that DNR is more effective (92%) than DN in the surgical management of Morton's neuroma (82%). Key advantages of DNR include earlier return to wearing routine footwear, earlier return to normal routine/work, and better resolution of sensory symptoms in the toes. Although DNR is a slightly longer procedure than DN, minor difficulties were encountered relating to nerve mobilization because of overlying prominent veins or multiple nerve branches rather than a single nerve. DNR avoids the risk of a stump neuroma formation. Our results, although supporting the literature, are not statistically significant. There are no direct comparative studies between DNR and DN in the literature, and therefore potential for more studies in the form of prospective randomized trials to establish a robust evidential basis for the surgical management of Morton's neuroma are needed.

Cardiopulmonary Resuscitation Preferences of People Receiving Dialysis

Whether the cardiopulmonary resuscitation (CPR) preferences of patients receiving dialysis align with their values and other aspects of end-of-life care is not known. To describe the CPR preferences of patients receiving dialysis and how these preferences are associated with their responses to questions about other aspects of end-of-life care. Cross-sectional survey study of a consecutive sample of patients receiving dialysis at 31 nonprofit dialysis facilities in 2 US metropolitan areas (Seattle, Washington, and Nashville, Tennessee) between April 22, 2015, and October 2, 2018. Analyses for this article were conducted between December 2018 and April 2020. Participants were asked to respond to the question "If you had to decide right now, would you want CPR if your heart were to stop beating?" Those who indicated they would probably or definitely want CPR were categorized as preferring CPR. This study examined the association between preference for CPR and other treatment preferences, engagement in advance care planning, values, desired place of death, expectations about prognosis, symptoms, and palliative care needs. Of the 1434 individuals invited to complete the survey, 1009 agreed to participate, and 876 were included in the analytic cohort (61.1%). The final cohort had a mean (SD) age of 62.6 (14.0) years; 492 (56.2%) were men, and 528 (60.3%) were White individuals. Among 738 of 876 participants (84.2%) who indicated that they would definitely or probably want CPR (CPR group), 555 (75.2%) wanted mechanical ventilation vs 13 of 138 (9.4%) of those who did not want CPR (do not resuscitate [DNR] group) (P < .001). A total of 249 of 738 participants (33.7%) in the CPR group vs 84 of 138 (60.9%) in the DNR group had documented treatment preferences (P < .001). In terms of values about future care, 171 participants (23.2%) in the CPR group vs 5 of 138 (3.6%) in the DNR group valued life prolongation (P < .001); 320 in the CPR group (43.4%) vs 109 of 138 in the DNR group (79.0%) valued comfort (P < .001); and 247 participants (33.5%) in the CPR group vs 24 of 138 (17.4%) in the DNR group were unsure about their wishes for future care (P < .001). In the CPR group, 207 (28.0%) had thought about stopping dialysis vs 62 of 138 (44.9%) in the DNR group (P < .001), and 181 (24.5%) vs 58 of 138 (42.0%) had discussed stopping dialysis (P = .001). No statistically significant associations were observed between CPR preference and documentation of a surrogate decision maker, thoughts or discussion of hospice, preferred place of death, expectations about prognosis, reported symptoms, or palliative care needs. The CPR preferences of patients receiving dialysis were associated with some, but not all, other aspects of end-of-life care. How participants responded to questions about these other aspects of end-of-life care were not always aligned with their CPR preference. More work is needed to integrate discussions about code status with bigger picture conversations about patients' values, goals, and preferences for end-of-life care.

Effects of Garcinia Acid Combined with Daunorubicin on Expression of Pregnane X Receptor in Leukemia Cell Line K562/A02

To explore the expression of PXR (Pregnane X receptor) in several malignant hematological cell lines, and to investigate the reversal effect of Gambogic acid (GA) on multi-drug resistance (MDR) of K562/A02 cell line and its reversal mechanism. Transcription of PXR was detected by real-time PCR in several malignant hematological cell lines. The growth inhibition rate of K562/A02 in different experimental groups was assayed by MTT method, and the expression of PXR protein was measured by Western blot. PXR gene transcription could be detected in several hematological malignancy cell lines, and it was significantly higher in K562/A02 cell line, compared with the other cell lines used in this experiment. Low-dose GA could enhance cell growth inhibition rate, increasing the effect of chemotherapy, which may be associated with down-regulation of PXR expression. PXR gene transcription and protein expression in GA and DNR+GA groups decreased as compared with control group and the DNR group, suggesting that low-dose GA can down-regulate PXR gene transcription and protein expression. PXR gene transcription can be detected in several hematological malignancy cell line, which is significantly higher in K562/A02 cell line, as compared with the other cell lines used in this experiment. Low-dose GA can enhance cell growth inhibition rate, increasing the effect of chemotherapy, which may be associated with down-regulation of PXR expression.

Role of NF-κB activation and VEGF gene polymorphisms in VEGF up regulation in non-proliferative and proliferative diabetic retinopathy.

The present study was aimed to investigate the relation between nuclear factor kappa beta (NFκB) activation and downstream up-regulation of vascular endothelial growth factor (VEGF) in diabetic retinopathy (DR). Moreover the study was intended to evaluate the role of VEGF gene single nucleotide polymorphisms (SNPs) in DR occurrence and to investigate the functional relevance of VEGF gene SNPs in terms of VEGF expression in DR. Serum level of VEGF, VEGF R1 (receptor 1), VEGF R 2 (receptor 2) and NFκB (p50/65) activity was measured by enzyme linked immune sorbent assay. Genotyping and allelic composition of different SNPs i.e., rs2010963, rs3025039, rs1570360 and rs 2071559 were investigated by Taqman SNP genotyping assay. VEGF, NFκB p50/p65, and VEGF R1 & R2 gene expressions were quantified by real time quantitative polymerase chain reaction. Increased NFκB p50/p65 activity and expressions were observed in non proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) subjects compared to type 2 diabetes mellitus without retinopathy (DNR) group. Significantly elevated levels of serum VEGF and highest VEGF expression were found among PDR subjects compared to DNR or NPDR subjects. CC genotype and C allele of rs2010963 and TT genotype and T allele of rs3025039 were significantly over represented among PDR subjects compared to DNR group. Increased activation of NFκβ in NPDR and PDR subjects might involve increased up regulation of VEGF. VEGF SNPs i.e., rs2010963 C allele and rs3025039 T allele might be associated with PDR occurrence and in turn regulates VEGF expression among PDR subjects.

The intestinal fatty acid binding protein-2 Ala54Thr polymorphism is associated with diabetic retinopathy in Chinese population.

ObjectiveEndothelial dysfunction which is induced by serum saturated fatty acids increasing is one of pathogenesis of diabetic retinopathy (DR). The intestinal fatty acid binding protein-2 (FABP2) Ala54Thr polymorphism results in serum saturated fatty acids elevating. In the present study, we assessed the association of FABP2 gene polymorphism (Ala54Thr) with DR in Chinese population.Materials/MethodsIn this case–control association study, 810 T2DM patients were recruited. 420 patients with retinal neovascularization, microneurysms and hemorrhages were considered as cases (DR) and 390 patients with T2DM and no clinical signs of retinopathy (DNR), were recruited as controls. Genotypes for FABP2(Ala54Thr) polymorphisms were assessed with the PCR-RFLP method.ResultsA significant difference in genotype distribution and allele frequency was observed between cases and controls. Patients with DR had significantly higher frequency of the Ala/Thr + Thr/Thr genotypes compared to DNR group [62.6% vs. 46.2%; OR (95% CI), 1.95 (1.48-2.59); p < 0.001]. The DR group showed a significantly higher frequency of the the Thr allele compared to the DNR group [39.5% vs. 29.4%; OR (95% CI), 1.56 (1.16-2.09); p = 0.003]. Binary logistic analyses showed FFA levels (p = 0.014) and Ala54Thr (p = 0.011) were independent correlates of the presence of DR.ConclusionsWe examined that FABP2 polymophism on the Ala54Thr is significant and independent associated with DR.

Plasma vitamin D status in patients with type 2 diabetes with and without retinopathy

ObjectiveDiabetic retinopathy (DR) is a common cause of blindness. Although an association between hypovitaminosis D and type 1 diabetes is known, the association between vitamin D (VD) and type 2 diabetes (T2D) and its complications such as DR has been unclear. The aim of this study was to investigate the status of VD in T2D patients with and without DR. MethodsA cross-sectional case–control study was conducted with 99 normal control (CN) participants and 164 patients with T2D, of which 82 had retinopathy (DR) and 82 did not (DNR). After a complete ophthalmic examination, inclusive of fundus fluorescein angiography, the clinical profile and the plasma levels of VD and calcium were analyzed. ResultsAlthough the mean plasma VD levels were significantly lower in the DNR and DR groups compared with the CN group, no significant differences were observed between the groups with diabetes. Although the mean levels of VD in all three groups were below the normal range, the prevalence of VD deficiency (VDD) was higher in the DNR and DR groups (66% and 63%) than in the CN group (45%), suggesting that the prevalence of VDD was higher in individuals with diabetes, regardless of the presence or absence of retinopathy. However, there were no group differences in the plasma levels of calcium. Additionally, VDD did not seem to be related to patient's age or body mass index, but was related to the duration of diabetes. ConclusionResults from this study suggest a possible association between VDD and T2D, but not specifically with DR. Further investigations are warranted.

Association of polymorphisms of angiotensin I converting enzyme 2 with retinopathy in type 2 diabetes mellitus among Chinese individuals.

To examine the association of Angiotensin I converting enzyme 2 (ACE2) gene polymorphisms and retinopathy in a Chinese type 2 diabetes mellitus (T2DM) cohort. A total of 743 T2DM participants were involved in this study including 408 female and 335 male cases. Female cases were divided into two groups: diabetes without retinopathy (DNR group, n=171) and with retinopathy (DR group, n=237), the latter was further subclassified into nonproliferative DR (NPDR group, n=121) and proliferative DR (PDR group, n=116). Male cases were assigned to DNR group (n=153) and DR group (n=182) which was further grouped into NPDR group (n=86) and PDR group (n=96). Two single nucleotide polymorphisms (SNPs; rs2074192 and rs714205) in ACE2 gene were genotyped. In female cases, the frequency of genotypes TT in rs2074192 and CC in rs714205 were higher in DR and PDR group than in DNR group (P<0.05). The frequency of alleles T in SNP rs2074192 and C in SNP rs714205 was higher in DR group (P<0.05) and PDR group (P<0.05) than in DNR group. The frequency of allele T in SNP rs2074192 was higher in PDR group (P=0.04) than in NPDR group. The frequency of haplotype TC and CG was higher in DR and PDR groups, respectively (P<0.05). No positive results were found in male cases. Our results revealed that SNPs rs2074192 and rs714205 in ACE2 gene were associated with the susceptibility of DR and PDR.

The gene polymorphisms of UCP1 but not PPAR γ and TCF7L2 are associated with diabetic retinopathy in Chinese type 2 diabetes mellitus cases.

This study was designed to investigate the association between the polymorphisms in three insulin resistance-related genes, uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor γ (PPARγ) and transcription factor 7-like 2 (TCF7L2) and the susceptibility to diabetic retinopathy (DR) in a Chinese type 2 diabetes mellitus (T2DM) cohort. A total of 792 patients with T2DM were enrolled and categorized into two groups: (1) the DR group consisted of 448 patients, which was further subclassified into a proliferative DR (PDR) group with 220 patients and a non-proliferative DR (NPDR) group with 228 patients; (2) the diabetes without retinopathy (DNR) group, comprised 344 patients who had no signs of DR. Single-nucleotide polymorphisms (SNPs), rs1800592 in the UCP1 gene, rs1801282, rs3856806 and rs1249719 in the PPARγ gene and rs11196205 in the TCF7L2 gene were genotyped in this study. For SNP rs1800592 of the UCP1 gene, the frequency of allele G and genotype GG was significantly higher in the PDR group than in the DNR group (allele OR: 1.32, 95% CI: 1.03-1.68, p = 0.03; genotype OR: 1.72, 95%CI: 1.06-2.79, p = 0.03). No evident association was found between the allele frequencies and genotype distributions of any individual SNP in the PPARγ or TCF7L2 genes and DR, PDR or NPDR. Haplotype analyses of the PPARγ gene did not provide any evidence for an association with DR, PDR or NPDR in this Chinese T2DM cohort. This study suggests that the SNP rs1800592 in the UCP1 gene is associated with increased risk of PDR in the Chinese T2DM population.

Oxidative Stress-Associated Neuroretinal Dysfunction and Nitrosative Stress in Diabetic Retinopathy

The present study was intended to investigate whether oxidative stress is the key regulator to alter neuroretinal biochemical homeostasis and in turn aggravate the process of diabetic retinopathy by inducing nitrosative stress in the retinal neurovascular unit. Peripheral blood mononuclear cell reactive oxygen species level was measured by flow cytometry along with spectrophotometric detection of malondialdehyde (MDA) and glutamate from serum or plasma and a vitreous sample of study groups (i.e. subjects with proliferative diabetic retinopathy [PDR], type 2 diabetes without retinopathy [DNR] and healthy controls [HCs]). Further, nitrosative stress assessment was performed by spectrophotometric and enzyme-linked immunosorbent assay-based detection of serum and vitreous nitrite and nitrotyrosine concentrations, respectively. The plasma glutamate level remains insignificant between subjects with PDR and DNR (p=0.505) or in HC (p=0.1344) individuals. However, serum MDA (p=0.0004), nitrite (p=0.0147) and nitrotyrosine (p=0.0129) were found to be strikingly higher among PDR subjects compared with the DNR group. Significantly increased levels of peripheral blood mononuclear cell reactive oxygen species (p<0.0001), vitreous glutamate (p=0.0009, p<0.0001), MDA (p=0.0058, p=0.0003), nitrite (p=0.0014, p<0.0001) and nitrotyrosine (p=0.0008, p<0.0001) were found in PDR subjects compared with DNR and HC subjects, respectively. Our observation suggests that oxidative stress is associated with impairment in neuroretinal biochemical homeostasis among PDR subjects, which further augments retinal nitrosative stress and thus worsens the pathogenic process of retinopathy among PDR subjects.

More DNR Patients Die After Emergency Surgery

San Francisco – Elderly patients with preexisting Do Not Resuscitate directives appear to be less likely to pursue rescue (aggressive treatment) of complications following emergency surgery than similar patients without such orders, according to an analysis of data from the National Surgical Quality Improvement Program. When patients with preoperative DNRs were propensity-matched with non-DNR patients, major complication rates were similar – 42% for the DNR group and 41% for the non-DNR group. However, 37% of DNR patients died, compared with 22% of non-DNR patients, Dr. John E. Scarborough reported at the annual meeting of the American Surgical Association. The investigators adjusted for baseline differences in level of illness to create a propensity-matched cohort of 1,053 patients in each group. “While we called this outcome failureto-rescue, we believe that term to be misleading. The term implies that rescue from complications is attempted but is unsuccessful. ... We had no reason to believe that the DNR patients in this well-matched cohort were any less capable of being rescued than nonDNR patients,” Dr. Scarborough said. “Instead, we believe that the DNR patients in the matched cohort were less likely than non-DNR patients to pursue rescue from complications.” This conclusion is supported by the finding that DNR patients were significantly less likely to undergo reoperation within 30 days of the index procedure (odds ratio, 0.67). The authors used participant files from the National Surgical Quality Improvement Program (NSQIP) for 2005–2010, involving medical records for 25,558 patients. These patients were at least 65 years old and underwent an emergency operation for one of 10 common surgical diagnoses. The primary predictor variable was preoperative DNR status, which was defined as “an order signed or cosigned by an attending physician in the 30 days prior to surgery ... regardless of whether the DNR order was subsequently rescinded immediately before the index operation.” Other predictor variables included patient demographics, chronic comorbid disease burden, acute physical condition at presentation, and complexity of the emergency operation. Outcome variables included the 30-day postoperative mortality rate and the 30-day major complication rate – organ/space surgical site infection, wound dehiscence, deep vein thrombosis, pulmonary embolism, pneumonia, reintubation, ventilator use longer than 48 hours, cardiac arrest, myocardial infarction, sepsis, shock, coma longer than 24 hours, prosthetic/graft failure, and bleeding. The failure-to-rescue rate was defined as the mortality rate among patients who had one or more major complications.

Association analysis of −429T/C and −374T/A polymorphisms of receptor of advanced glycation end products (RAGE) gene in Malaysian with type 2 diabetic retinopathy

Conflicting results have been reported in different populations on the association between two particular RAGE gene polymorphisms (−429T/C and −374T/A) and retinopathy in diabetic patients. Therefore this study was designed to assess the association between both gene polymorphisms with retinopathy in Malaysian diabetic patients. A total of 342 type 2 diabetic patients [171 without retinopathy (DNR) and 171 with retinopathy (DR)] and 235 healthy controls were included in this study. Genomic DNA was obtained from blood samples and the screening for the gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism approach. Overall, the genotype distribution for both polymorphisms was not statistically different (p>0.05) among the control, DNR and DR groups. The −429C minor allele frequency of DR group (12.0%) was not significantly different (p>0.05) when compared to DNR group (16.1%) and healthy controls (11.3%). The −374A allele frequency also did not differ significantly between the control and DNR (p>0.05), control and DR (p>0.05) as well as DNR and DR groups (p>0.05). This is the first study report on RAGE gene polymorphism in Malaysian DR patients. In conclusion, −429T/C and −374T/A polymorphisms in the promoter region of RAGE gene were not associated with Malaysian type 2 DR patients.

2245G/A polymorphism of the receptor for advanced glycation end-products (RAGE) gene is associated with diabetic retinopathy in the Malaysian population

Background/aimsThe receptor for advanced glycation end-products (RAGE) has been implicated in the pathogenesis of diabetic microvascular complications. The aim of this study was to investigate the association between 2245G/A gene...

Status of B-Vitamins and Homocysteine in Diabetic Retinopathy: Association with Vitamin-B12 Deficiency and Hyperhomocysteinemia

Diabetic retinopathy (DR) is a common cause of blindness. Although many studies have indicated an association between homocysteine and DR, the results so far have been equivocal. Amongst the many determinants of homocysteine, B-vitamin status was shown to be a major confounding factor, yet very little is known about its relationship to DR. In the present study, we, therefore, investigated the status of B-vitamins and homocysteine in DR. A cross-sectional case–control study was conducted with 100 normal control (CN) subjects and 300 subjects with type-2 diabetes (T2D). Of the 300 subjects with T2D, 200 had retinopathy (DR) and 100 did not (DNR). After a complete ophthalmic examination including fundus fluorescein angiography, the clinical profile and the blood levels of all B-vitamins and homocysteine were analyzed. While mean plasma homocysteine levels were found to be higher in T2D patients compared with CN subjects, homocysteine levels were particularly high in the DR group. There were no group differences in the blood levels of vitamins B1 and B2. Although the plasma vitamin-B6 and folic acid levels were significantly lower in the DNR and DR groups compared with the CN group, there were no significant differences between the diabetes groups. Interestingly, plasma vitamin-B12 levels were found to be significantly lower in the diabetes groups compared with the CN group; further, the levels were significantly lower in the DR group compared with the DNR group. Higher homocysteine levels were significantly associated with lower vitamin-B12 and folic acid but not with other B-vitamins. Additionally, hyperhomocysteinemia and vitamin-B12 deficiency did not seem to be related to subjects' age, body mass index, or duration of diabetes. These results thus suggest a possible association between vitamin-B12 deficiency and hyperhomocysteinemia in DR. Further, the data indicate that vitamin-B12 deficiency could be an independent risk factor for DR.

Pre-existing do-not-resuscitate orders are not associated with increased postoperative morbidity at 30 days in surgical patients*

To assess the relationship between pre-existing do-not-resuscitate orders and the incidence of postoperative 30-day minor morbidity in surgical patients. Retrospective analysis of prospectively collected data from the American College of Surgeons National Surgical Quality Improvement Program database in patients undergoing general surgical procedures between 2005 and 2008. All U.S. hospitals that participated in the American College of Surgeons National Surgical Quality Improvement Program, which is the nationally validated, risk-adjusted, outcomes-based program that uses a prospective, peer-controlled, validated database to quantify 30-day risk-adjusted surgical outcomes, allowing valid comparison of outcomes among all hospitals in the program. American College of Surgeons National Surgical Quality Improvement Program data included preoperative risk factors, intraoperative variables, and 30-day postoperative mortality and morbidity outcomes for patients undergoing major surgical procedures in both the inpatient and outpatient setting. The data were collected, validated, and submitted by a trained Surgical Clinical Reviewer at each site. Association between do-not-resuscitate status and minor and major morbidities was assessed using proportional hazards models adjusting for death as a competing risk. Of 635,265 patients in the database, 576,745 patients were analyzed. Propensity-matched analysis successfully matched 2,199 (of 2,687 [81.8%]) patients having pre-existing do-not-resuscitate orders (DNR group) with 6,002 non-do-not-resuscitate control subjects (nonDNR group). At any time point within 30 days of surgery, DNR patients were 16% (95% confidence interval, 3-28%; p = .02) less likely to have a minor complication as compared with nonDNR patients after accounting for the competing risk of death. DNR patients were more likely to experience 30-day mortality compared with nonDNR patients (hazard ratio, 2.3; 95% confidence interval, 1.9-2.7; p < .001). However, there was no association between pre-existing do-not-resuscitate orders and occurrence of any major complication (p = .65) treating death as a competing risk event. When associations between do-not-resuscitate orders and individual minor complications were analyzed, a pre-existing do-not-resuscitate order remained independently associated only with decreased odds of superficial surgical site infection (p = .001). Undergoing surgery with a pre-existing do-not-resuscitate order did not increase the risk of having a postoperative minor or major morbidity at any time within the 30-day postoperative period. Results of health care in U.S. hospitals do not differ based on presence of do-not-resuscitate orders.