Acetylated DNMT1 Downregulation and Related Regulatory Factors Influence Metastatic Melanoma Patients Survival

The role of post-translational modifications (PTM) of the key epigenetic factor DNMT1 protein has not been well explored in cutaneous metastatic melanoma progression. The acetylated DNMT1 (ac-DNMT1) protein level was assessed using an anti-acetylated lysine antibody in a clinically annotated melanoma patient tumor specimen cohort. In this study, we showed that surgically resected tumors have significantly higher DNMT1 protein expression in metastatic melanoma (stage III metastasis n = 17, p = 0.0009; stage IV metastasis n = 164, p = 0.003) compared to normal organ tissues (n = 19). Additionally, reduced ac-DNMT1 protein levels were associated with melanoma progression. There was a significant inverse correlation between ac-DNMT1 and DNMT1 protein levels in stage IV metastatic melanoma (r = −0.18, p = 0.02, n = 164). Additionally, ac-DNMT1 protein levels were also significantly positively correlated with TIP60 (r = 0.6, p < 0.0001) and USP7 (r = 0.74, p < 0.0001) protein levels in stage IV metastatic melanoma (n = 164). Protein analysis in metastatic melanoma tumor tissues showed that with high ac-DNMT1 (p = 0.006, n = 59), or concurrent high ac-DNMT1 with low DNMT1 (p = 0.05, n = 27), or high TIP60 (p = 0.007, n = 41), or high USP7 (p = 0.01, n = 48) consistently showed better 4-year melanoma-specific survival (MSS). Multivariate Cox proportional hazard analysis showed that ac-DNMT1 level is a significant independent factor associated with MSS (HR, 0.994; 95% confidential interval (CI), 0.990–0.998; p = 0.002). These results demonstrated that low ac-DNMT1 levels may represent an important regulatory factor in controlling metastatic melanoma progression and a promising factor for stratifying aggressive stage IV metastasis.

MRI-based radiomics approach for differentiation of hypovascular non-functional pancreatic neuroendocrine tumors and solid pseudopapillary neoplasms of the pancreas

Background This study aims to investigate the value of radiomics parameters derived from contrast enhanced (CE) MRI in differentiation of hypovascular non-functional pancreatic neuroendocrine tumors (hypo-NF-pNETs) and solid pseudopapillary neoplasms of the pancreas (SPNs). Methods Fifty-seven SPN patients and twenty-two hypo-NF-pNET patients were enrolled. Radiomics features were extracted from T1WI, arterial, portal and delayed phase of MR images. The enrolled patients were divided into training cohort and validation cohort with the 7:3 ratio. We built four radiomics signatures for the four phases respectively and ROC analysis were used to select the best phase to discriminate SPNs from hypo-NF-pNETs. The chosen radiomics signature and clinical independent risk factors were integrated to construct a clinic-radiomics nomogram. Results SPNs occurred in younger age groups than hypo-NF-pNETs (P < 0.0001) and showed a clear preponderance in females (P = 0.0185). Age was a significant independent factor for the differentiation of SPNs and hypo-NF-pNETs revealed by logistic regression analysis. With AUC values above 0.900 in both training and validation cohort (0.978 [95% CI, 0.942–1.000] in the training set, 0.907 [95% CI, 0.765–1.000] in the validation set), the radiomics signature of the arterial phase was picked to build a clinic-radiomics nomogram. The nomogram, composed by age and radiomics signature of the arterial phase, showed sufficient performance for discriminating SPNs and hypo-NF-pNETs with AUC values of 0.965 (95% CI, 0.923–1.000) and 0.920 (95% CI, 0.796–1.000) in the training and validation cohorts, respectively. Delong Test did not demonstrate statistical significance between the AUC of the clinic-radiomics nomogram and radiomics signature of arterial phase. Conclusion CE-MRI-based radiomics approach demonstrated great potential in the differentiation of hypo-NF-pNETs and SPNs.

Predictive Factor to Castrate-Resistant Prostate Cancer (CRPC) after Primary Androgen Deprivation Therapy (ADT): Single Center Experience in Indonesia

ADT is the main therapy in prostate cancer, especially in advanced stages, although ADT does not limit the progression of this disease to become CRPC, where the mortality rate will be much higher when CRPC has occurred. This study aims to examine corellating factors influenced the short duration to CRPC after primary ADT administration. 205 prostate cancer patients with CRPC or mCRPC in Saiful Anwar Malang Hospital from 2013 to 2018 were included in this study. Data recorded were age, initial PSA level, Gleason score, prostate cancer stage, type of ADT, nadir PSA, time between ADT and nadir PSA, and testosterone levels after ADT. To see the independent factors that influence the occurrence of CRPC, the Cox proportional hazards regression model was used. The average age of patients was 67, 53  6.86 years with an average level of initial PSA of 674.87  1405.80 80 / dL. The average time for CRPC to occur was 24.7  9.74 months. In multivariate analysis it was found that the stage of cancer with metastasis (HR 1,616, p 0,048), testosterone level after ADT was > 20ng / dL (HR 4,638, p 0,000), nadir PSA > 4ng / dL (HR 1,716, p 0,023) and time to reach Nadir PSA <6 months (HR 1.596, p 0.004) is a significant independent factor for CRPC occurrence. The conclusion is cancer stage, testosterone levels after ADT, nadir PSA and time needed to reach nadir PSA were independent factors for CRPC in patients with prostate cancer who had primary ADT.

Serum-to-urine renalase ratio and renalase fractional excretion in healthy adults and chronic kidney disease patients.

Background: Renalase is a flavoprotein that plays a protective role in chronic kidney disease (CKD) and cardiovascular diseases. The secretion and way of action of this protein are still discussed. The aim of our study was to estimate the balance between serum and urine renalase in healthy individuals and CKD patients, using two parameters: fractional excretion (FE) and serum-to-urine renalase ratio (StURR). Methods: Our study involved 28 healthy volunteers and 62 patients with CKD in stages I to IV. The concentration of renalase in serum and urine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (EIAab, Wuhan, China). We analyzed associations between renalase levels in urine and serum, and other parameters: sex, age, GFR, presence of hypertension, diabetes, and proteinuria, and determined the serum-to-urine renalase ratio and fractional excretion of renalase. Results: Renalase and serum-to-urine ratio were significantly higher in CKD patients in comparison with the control group. Fractional excretion was lower in CKD patients but this difference did not reach the statistical significance (p=0.092). Multivariate analysis performed in the CKD group showed, that from mentioned parameters, serum renalase was the only significant independent factor strongly positively associated with urinary renalase concentration. Conclusions: The serum-to-urine ratio is significantly and about 6.5-fold higher in CKD patients, and the fractional excretion of renalase is 3-fold, but not significantly lower in CKD patients. Renalase levels in both serum and urine are not related to glomerular filtration rate and not associated with blood pressure.

Professional who attended childbirth and breastfeeding in the first hour of life

ABSTRACT Objectives: To investigate the association between the professionals who attended vaginal delivery and breastfeeding in the first hour of life. Methods: This is a cross-sectional study with data from the Nascer no Brasil (Born in Brazil) survey, conducted in the 2011-2012 period. Data from 8,466 puerperae were analyzed using a logistic regression model with a hierarchical approach. Results: The proportion of mothers who breastfed at birth was higher in deliveries attended by nurses (70%). A nurse-assisted delivery was 64% more likely to breastfeed in the first hour of life. Other factors associated with the outcome: residing in the North; age less than 35 years; multiparity; prenatal guidance on breastfeeding in the first hour of life; birth at Baby-Friendly Hospital; companion at birth; and female newborn. Conclusions: Obstetrician nurse/nurse-assisted delivery was a significant independent factor associated with breastfeeding in the first hour of life, suggesting the importance of strengthening the role of the obstetrician nurse.

Serum-to-urine renalase ratio and renalase fractional excretion in healthy adults and chronic kidney disease patients.

Background: Renalase is a flavoprotein that plays a protective role in chronic kidney disease and cardiovascular diseases. The secretion and way of action of this protein are still discussed. The aim of our study was to estimate the balance between serum and urine renalase in healthy individuals and chronic kidney disease (CKD) patients, using two parameters: fractional excretion (FE) and serum-to-urine renalase ratio (StURR). Methods: Our study involved 28 healthy volunteers and 62 patients with CKD in stages I to IV. The concentration of renalase in serum and urine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (EIAab, Wuhan, China). We analyzed associations between renalase levels in urine and serum, and other parameters: sex, age, GFR, presence of hypertension, diabetes, and proteinuria, and determined the serum-to-urine renalase ratio and fractional excretion of renalase. Results: Renalase and serum-to-urine ratio were significantly higher in CKD patients in comparison with the control group. Fractional excretion was lower in CKD patients but this difference did not reach the statistical significance (p=0.092). Multivariate analysis performed in the CKD group showed, that from mentioned parameters, serum renalase was the only significant independent factor strongly positively associated with urinary renalase concentration. Conclusions: The serum-to-urine ratio is significantly and about 6.5-fold higher in CKD patients, and the fractional excretion of renalase is 3-fold, but not significantly lower in CKD patients. Renalase levels in both serum and urine are not related to glomerular filtration rate and not associated with blood pressure.

Serum-to-urine renalase ratio and its differences between healthy adults and chronic kidney disease patients

Background: Renalase is a flavoprotein that plays a protective role in chronic kidney disease and cardiovascular diseases. The secretion and way of action of this protein are still discussed. The aim of our study was to estimate the balance between serum and urine renalase in healthy individuals and chronic kidney disease (CKD) patients, using two parameters: fractional excretion (FE) and serum-to-urine renalase ratio (StURR). Methods: Our study involved 28 healthy volunteers and 62 patients with CKD in stages I to IV. The concentration of renalase in serum and urine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (EIAab, Wuhan, China). We analyzed associations between renalase levels in urine and serum, and other parameters: sex, age, GFR, presence of hypertension, diabetes, and proteinuria, and determined the serum-to-urine renalase ratio and fractional excretion of renalase. Results: Renalase and serum-to-urine ratio were significantly higher in CKD patients in comparison with the control group. Fractional excretion was lower in CKD patients but this difference did not reach the statistical significance (p=0.092). Multivariate analysis performed in the CKD group showed, that from mentioned parameters, serum renalase was the only significant independent factor strongly positively associated with urinary renalase concentration. Conclusions: The serum-to-urine ratio is significantly and about 6.5-fold higher in CKD patients, and the fractional excretion of renalase is 3-fold, but not significantly lower in CKD patients. Renalase levels in both serum and urine are not related to glomerular filtration rate and not associated with blood pressure.

Anti-Müllerian Hormone Gene Polymorphism is Associated with Clinical Pregnancy of Fresh IVF Cycles

The aim of this study was to examine the effects of single-nucleotide polymorphisms (SNPs) in the anti-Müllerian hormone (AMH) and AMH type II receptor (AMHRII) genes on in vitro fertilization (IVF) outcomes. In this prospective cohort study, we genotyped the AMH 146 T > G, AMHRII −482 A > G and AMHRII IVS1 +149 T > A variants in 635 women undergoing their first cycle of controlled ovarian stimulation for IVF. DNA was extracted from the peripheral blood of all participants, and the SNPs were genotyped by real-time polymerase chain reaction. The distributions, frequencies of genes, and correlation with clinical pregnancy of IVF were analyzed. The AMH 146 T > G G/G genotype in women was associated with a lower clinical pregnancy rate (T/T: 55.0%, T/G: 51.8%, G/G: 40.0%; p < 0.05). Women with the AMH 146 T > G GG genotype were half as likely to have a clinical pregnancy compared with women with TT genotypes (OR = 0.55, 95% CI: 0.34–0.88, p = 0.014). With multivariate analysis, the AMH 146 T > G GG genotype remains as a significant independent factor to predict clinical pregnancy (p = 0.014). No significant difference was found between AMHRII polymorphisms and clinical pregnancy outcomes of IVF. In conclusion, our results show that AMH 146 T > G seems to be a susceptibility biomarker capable of predicting IVF pregnancy outcomes. Further studies should focus on the mechanism of these associations and the inclusion of other ethnic populations to confirm the findings of this study.

Prescription of opioids to post-operative orthopaedic patients at time of discharge from hospital: a prospective observational study

Background and aims: Excessive opioid prescribing can lead to adverse consequences including stockpiling, misuse, dependency, diversion and mortality. Increased prescriptions to post-operative inpatients as part of their discharge planning may be a significant contributor. Primary aims included comparing the amount of opioids prescribed, consumed, left unused and their relationship with pain and functionality. Methods: A total of 132 consecutive patients who underwent elective orthopaedic surgery were prospectively audited. Daily oral morphine equivalent (DME) of opioids prescribed was compared with opioids consumed and amount left unused 7–10 days after discharge. For analysis, patients were split into three groups: total knee replacement (TKR), hand surgery (Hands), and miscellaneous (Misc). Results: The mean dose of opioid prescribed per patient was 108.5 mg DME. TKR consumed 33–35% more opioids than Misc (p=0.0283) and Hands (p=0.0975). Age was a significant independent factor for opioid consumption in the 50th and 75th percentiles of Hands (p≤0.05). An average of 36 mg DME per patient was left unused with Hands having the highest median DME (37 mg) unused. In the total cohort, 26% of patients were discharged with more DME than their last 24 h as an inpatient and had at least 50% of their tablets left unused at follow-up. Conclusions: Over-prescription of opioids occurs at discharge which can increase the risk of harm. New intervention is needed to optimise prescribing practises. Implications: Changes to prescribing habits and workplace culture are required to minimise unnecessary opioid prescribing but will be challenging to implement. A multi-layered approach of electronic prescribing, opioid stewardship and targeted educational awareness programmes is recommended.