The therapeutic potential of typical plant-derived compounds for the management of metabolic disorders.

Obesity and Type 2 diabetes are prevalent metabolic dysfunctions that present significant health challenges worldwide. Available cures for these ailments have constraints with accompanying unwanted effects that persistently exist. Compounds originated from plants have recently been introduced as hopeful remedies to treat metabolic disorders because of their diverse pharmacological activities. This detailed observation gives an introduction into the treatment capacity of plant-derived compounds regarding metabolic syndromes while analyzing various groups alongside their performance in this field despite unique mechanisms designed by nature itself. Interestingly, this study provides some examples including curcumin, resveratrol, quercetin, berberine, epigallocatechin gallate (EGCG), and capsaicin, which highlights potential therapeutic impacts for future testing. However, current clinical trials inspecting human studies investigating efficacies concerning metabolism challenge present limitations. Finally, the review weighs up bad reactions possibly inflicted after administering plant-originated materials though suggestive insights will be provided later. Above all, it outlines the chance to identify novel therapies encapsulated within natural substances based upon recent developments could hold significant promise toward managing misplaced metabolisms globally.

Proton-pump inhibitor use amongst patients with severe hypomagnesemia.

Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors. Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia. Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (<0.4 mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17-2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05-7.00), low BMI (OR, 0.90; 95% CI: 0.86-0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29-2.98), renal impairment (OR, 3.85; 95% CI: 2.58-5.75), and diuretic use (OR, 1.68; 95% CI: 1.09-2.61). Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose.

Recalcitrant hypercalcemia in a dialysis patient: Case report, literature review, and proposed management algorithm.

A 62-year-old male on maintenance hemodialysis, who was bedbound after a cerebrovascular accident, developed progressive hypercalcemia during a prolonged hospital stay. The etiology of hypercalcemia was attributed to immobility after extensive workup including imaging for malignancy or granulomatous disease, parathyroid hormone levels, parathyroid hormone related peptide, and vitamin D levels were unyielding. Low calcium dialysate would transiently reduce serum calcium levels, but levels would rebound in the interdialytic period. In view of recalcitrant hypercalcemia presenting with crisis, denosumab was successfully used to lower serum calcium. We review the literature and propose a management algorithm for severe hypercalcemia in a patient on dialysis.

25-OH vitamin D threshold for optimal bone mineral density in elderly patients with chronic kidney disease.

Introduction: Vitamin D deficiency is common in chronic kidney disease (CKD) and is associated with lower bone mineral density (BMD), decreased muscle strength, and increased hip fracture risk. Guidelines have suggested targeting 25-OH vitamin D (25(OH)D) levels between 20 and 30 ng/ml. However, vitamin D metabolism is altered in CKD, and threshold levels for optimal BMD are unknown. Methods: We included 1097 patients with hip fractures. CKD was defined as estimated glomerular filtration rate <60 ml/min/1.73 m (Mucsi et al., Clin. Nephrol., 2005, 64(4), 288-294) and low BMD defined as T score ≤ -2.5 at femoral neck. We assessed the association of 25(OH)D with low BMD in patients with and without CKD: using the conventional threshold 25(OH)D < 30 ng/dl, as well as a new threshold. Results: CKD was present in 479 (44%) patients. Using a threshold of 25(OH)D < 30 ng/ml, there were no significant differences in patients with CKD and low BMD when compared to the other groups. We identified 27 ng/ml as a better threshold with the Youden index. Using 25(OH)D < 27 ng/ml as a threshold, 360 of 482 patients (74.7%) with low 25(OH)D had low BMD, compared to only 185/276 (67%) of patients with adequate vitamin D, p = 0.02, which was irrespective of the presence or absence of CKD. Furthermore, patients with CKD and 25(OH)D < 27 ng/ml had a higher odds ratio of mortality upon follow-up, 1.61, 95% CI: 1.08-2.39, compared to those with CKD and 25(OH)D ≥ 27 ng/ml. Conclusion: We find that 25(OH)D < 27 ng/ml is associated with low BMD in patients with and without CKD. Further prospective studies targeting vitamin D repletion to at least 27 ng/ml and the outcome of hip fractures will be useful to validate these findings.

Acute kidney injury without need for dialysis, incidence, its impact on long-term stroke survival and progression to chronic kidney disease.

INTRODUCTION: Patients who had a stroke are at increased risk of sepsis, dehydration and fluctuations in blood pressure, which may result in acute kidney injury (AKI). The impact of AKI on long-term stroke survival has not been studied well. OBJECTIVE: We aimed to identify incidence of AKI during acute stroke, follow-up period and its impact on long-term survival and development of chronic kidney disease (CKD). DESIGN, SETTING AND PARTICIPANTS: Retrospective analysis of patients who had a stroke admitted at the rehabilitation facility in Changi General Hospital, Singapore, between June 2008 and May 2017, with median follow-up of 141 (95% CI 120 to 163) months. OUTCOME MEASURES AND RESULTS OF UNIVARIATE ANALYSIS: Total 681 patients, median age (63.6) years, 173 (28%) died during follow-up. Elevated blood urea (3.02, 95% CI 2.17 to 4.22; p≤0.001) and creatinine (1.96, 95% CI 1.50 to 2.57; p≤0.001) during stroke affected survival adversely.Excluding patients with CKD, we analysed the remaining 617 patients. AKI was noted in 75 (12.15%) patients during the index admission, and it affected survival adversely (2.16, 95% CI 1.49 to 3.13; p<0.001). Of the patients with AKI, 21 of 75 (28%) progressed to CKD over a median follow-up of 40.7 months. CONCLUSIONS: We found AKI during stroke admission was associated with increased mortality as compared with those without AKI on univariate analysis. AKI without need of renal replacement therapy was also associated with progression to CKD in this cohort. This suggests that patients with AKI need to have their renal function monitored longitudinally for development of CKD.

Serum anion gap revisited: a verified reference interval for contemporary use.

BACKGROUND: The anion gap (AG) is often used to evaluate acid-base disorders. The reference interval for normal AG is used to differentiate between raised (gap) or normal AG (non-gap) acidosis. Historically accepted AG values may not be valid with the evolution of modern analytical techniques and the reference interval requires revalidation. AIMS: To determine the reference interval for AG based on current laboratory techniques. METHODS: During a health-screening exercise, 284 participants with no major illnesses volunteered surplus blood for analysis. The samples were tested in an internationally accredited clinical laboratory. AG was calculated by [Na+ ] - [Cl- ] - [HCO3 - ] and AGK by [Na+ ] + [K+ ] - [Cl- ] - [HCO3 - ]. The reference interval was determined at 2.5th-97.5th percentiles. Analysis was further undertaken for a subcohort of 156 individuals with no suboptimal health indicators. RESULTS: Median age was 35 years, body mass index 23.4 kg/m2 and the glomerular filtration rate was 106 mL/min/1.73 m2 . Median AG was 13 mmol/L and the reference interval for normal AG is 10-18 mmol/L with a 99% level of confidence. Statistically significant differences in AG were detected for sex, race, obesity and serum albumin, but the difference was 1 mmol/L between subgroups. The reference interval was the same for the sub-cohort of 156 individuals. Median AGK was 17.7 mmol/L and reference interval was 14.6-22.5 mmol/L. CONCLUSIONS: The AG reference interval of 10-18 mmol/L is valid for laboratories with similar reference intervals for electrolytes. Lower values expected with current laboratory techniques were not observed. The median AG of 13 mmol/L may be used to differentiate gap acidosis, non-gap acidosis or mixed acid-base disorders.

An Uncommon Cause of Recurrent Dialysis Catheter-Related Bacteremia.

A 54-year-old man on maintenance hemodialysis with recurrent catheter-related bloodstream infections due to Staphylococcus aureus was admitted. Multiple prior transthoracic echocardiograms failed to reveal any vegetation. Subsequently on transesophageal echocardiography a mass consistent with fibrin sheath vegetations was identified and a follow-up diagnostic computed tomography (CT) venogram confirmed the presence of a fibrin sheath with vegetations.

Hip fractures in elderly patients with non-dialysis dependent chronic kidney disease: Outcomes in a Southeast Asian population.

ABSTRACT: Chronic kidney disease (CKD) causes bone and mineral disorders and alterations in vitamin D metabolism that contribute to greater skeletal fragility. Hip fracture in elderly is associated with significant morbidity and mortality. The aim of this study was to investigate the outcome of elderly patients with non-dialysis dependent CKD and hip fracture undergoing surgery.Retrospective study with IRB approval of patients above 65 years of age, with hip fractures admitted between June 2014 to June 2016 in a Southeast Asian cohort. Data collected included demographic variables and the haematological and biochemical parameters HBA1c, estimated glomerular filtration rate (eGFR), serum calcium, phosphorous, and 25(OH) Vitamin D. Co-morbidities investigated were ischemic heart disease, congestive heart failure, peripheral vascular disease, malignancy, chronic obstructive pulmonary disease, cerebro vascular accident, hypertension and hyperlipidaemia. All patients were followed up from index date to either death or June 1, 2018.Of the 883 patients, 725 underwent surgery and 334 had CKD. Death rates for CKD patients with hip fractures and those with normal renal function did not differ significantly [8.08% vs 6.54%, (HR= 1.33, 95% CI: 0.95, 1.86; P = .102)], whilst median hospital length of stay was significantly higher in CKD patients [10.5 vs 9.03 days (P = .003)]. Significant risk factors associated with higher risk of mortality in the elderly with hip fracture were male gender, age ≥80 years and serum albumin < 30 g/L (all, P < .0001).In summary, in elderly, non-dialysis dependent CKD patient with hip fracture we found that male gender, age ≥80 years, low serum albumin and eGFR < 30 mL/min/1.73 m2 were associated with higher risk of death. The hospital stay in the CKD group was also longer. Additional studies are needed to validate our findings.

Regional citrate anti-coagulation dose titration: impact on dose of continuous renal replacement therapy.

BACKGROUND: Regional citrate anti-coagulation (RCA) is the recommended anti-coagulation for continuous renal replacement therapy (CRRT). Citrated replacement fluids provide convenience but may compromise effluent delivery when adjusted to maintain circuit ionised calcium levels (circuit-iCa). This study aims to evaluate the effect of RCA titration on the delivered CRRT effluent dose. METHODS: This prospective observational study evaluated patients on RCA-CRRT in continuous veno-venous hemodiafiltration mode. Citrated replacement fluid was titrated to target circuit-iCa 0.26-0.40 mmol/L. Patients were then stratified into 'reduced-dose' who required citrate down-titration and 'stable-dose' who did not. RESULTS: Data from 200 RCA-CRRT sessions were collected. The reduced-dose RCA group (n = 114) had higher median initial citrate dose (3.00 vs 2.50; P < 0.001) but lower time-averaged dose (2.49 vs 2.60; P < 0.001). In addition, median prescribed effluent dose was 33.3 mL/kg/h (28.6-39.2) but median delivered effluent dose was significantly lower at 29.9 mL/kg/h (25.4-36.9; P < 0.001). Mortality was higher in the reduced-dose RCA group (39.5% vs 25.6%; P = 0.022) and in patients with delivered-to-prescribed effluent dose ratio of < 0.9 vs ≥ 0.9 (51.3% vs 29.2%; P = 0.014). CONCLUSION: RCA titration can significantly impact delivered CRRT effluent dose. Measures should be taken to address the CRRT dose deficit and prevent poor outcomes due to inadequate dialysis.

A calcified central venous fibrin sheath mimicking a fractured catheter.

A 75-year-old female with end stage kidney failure had her tunneled central venous dialysis catheter (CVC) removed. A subsequent computed tomopgraphy (CT) scan of the chest reported a filling defect in the central vein that appeared to represent a fractured remnant of the CVC. The catheter had been retained for culture and was available for direct visualization, which showed it to be entirely intact. A subsequent venogram confirmed that the CT findings represented a retained calcified central venous fibrin sheath. As retained CVC fragments may require intervention, this diagnosis should be established carefully. A calcified fibrin sheath associated with a chronic CVC is a known, although rare, complication and should be considered in the differential diagnosis of an apparent CVC fracture prior to further interventions.

Ipsilateral vocal fold paralysis: An unusual complication of internal jugular tunnelled dialysis catheter insertion.

BACKGROUND: Central venous catheters are extensively used in critical care units and in dialysis centres to gain access to the blood stream for the purpose of invasive monitoring, drug administration, parenteral nutrition and to perform renal replacement therapy. One of the common areas of central venous catheter insertion is right internal jugular vein due to its anatomical continuity with the superior vena cava. The complication rates of central venous catheter insertion can be more than 15%, including early and late complications. CASE REPORT: We present an unusual complication of recurrent laryngeal nerve palsy, leading to right vocal fold paralysis, following insertion of a right internal jugular tunnelled dialysis catheter. The vocal fold paralysis improved over next 8 months with conservative management alone. CONCLUSION: This case illustrates an unusual complication of central venous catheter insertion and the importance of recognizing the possibility of such complications, to prevent them from happening and also to manage them appropriately.

Effect of multidisciplinary intensive targeted care in improving diabetes mellitus outcomes: a randomized controlled pilot study - the Integrated Diabetes Education, Awareness and Lifestyle modification in Singapore (IDEALS) Program.

BACKGROUND: There is a global pandemic of type 2 diabetes mellitus (T2DM), especially in Asia. Singapore has a prevalence of T2DM at 10.5%, which is higher than the world average of 8.8%. Multiple studies have shown that multidisciplinary, team-based, coordinated care has been associated with improved measures of quality care and reduced healthcare utilization. Patients with poor glycemic control and nephropathy are at the highest risk of developing cardiovascular complications and renal failure. In this study, we aimed to investigate the impact of intensive multidisciplinary diabetes mellitus care with patient empowerment versus routine clinical care on the rate of progression of micro and macrovascular complications and peripheral atherosclerotic burden, as measured by changes in femoral intima-media thickness (IMT) in patients with persistently elevated HbA1c and nephropathy. METHODS: The study is a single-center randomized controlled trial (RCT) with two study arms - intensive diabetes mellitus care versus routine clinical care. Patients in the intensive arm will receive care from a multidisciplinary team consisting of an endocrinologist, diabetes nurse educator, dietitian, renal pharmacist and medical social worker for counselling. In addition, patients will be provided with tools for self-care empowerment such as glucometers, blood pressure monitors and android tablets to facilitate care, monitoring and education. Patients in the routine clinical care arm will receive standard clinical care. Follow up (FU) will be for 3 years. Primary outcomes include cardiovascular events, rate of progression of nephropathy and development of end-stage renal disease. Secondary endpoints include the proportions of patients with documented improved control of cardiovascular risk factors (HbA1c, blood pressure, low density lipoprotein-C (LDL-C), reduction in body weight), frequency of hypoglycemia, hospitalization days and changes in femoral IMT. We will also examine the prevalence of peripheral atherosclerosis and the predictive value and usability of lower extremity arterial ultrasound to predict cardio-cerebrovascular events, amputation and peripheral intervention. DISCUSSION: Diabetes mellitus carries significant healthcare costs. Patients with poor glycemic control and nephropathy are at highest risk of developing cardiovascular complications and renal failure. Intensive diabetes mellitus care with patient empowerment may lead to sustained glycemic control, reduction of clinical complications and progression of nephropathy, and incidence of cardiovascular complications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03413215 . Registered on 29 January 2019.

Role of Parathyroid Hormone Assay and Bedside Ultrasound in the Emergency Department in Differentiating Acute Kidney Injury from Chronic Kidney Disease: A Systematic Review.

INTRODUCTION: It is not uncommon for patients without preceding history of kidney disease to present to the Emergency department with renal failure. The absence of prior medical records or renal imaging presents a diagnostic challenge. Elevated parathyroid hormone levels or echogenic contracted kidneys on ultrasound are known to point to a diagnosis of chronic kidney disease. The literature in this regard is surprisingly limited. The objective of this study is to assess the role of intact parathyroid (iPTH) blood level and bedside ultrasound in differentiating acute kidney injury from chronic kidney disease. METHODS: A systematic review which included a literature search of 3 databases, PubMed, Embase, and Cinahl (R) as also secondary sources, was done. The inclusion criteria evaluated studies which evaluated iPTH or bedside ultrasound in differentiating acute kidney injury from chronic kidney disease. We excluded studies which used other laboratory biomarkers like neutrophil gelatin associated lipocalin (NGAL) or carbamylated haemoglobin. A total of 2256 articles were identified. After screening, the relevant articles were reviewed, and an assessment of their methodological quality was made based on the CASP: Critical Appraisals Skill Programme. RESULTS: Of the 2256 articles identified, after screening, only 5 were identified as relevant. CONCLUSIONS: An elevated parathyroid hormone level and echogenic contracted kidneys on bedside ultrasound in the Emergency department can help differentiate acute kidney injury from chronic kidney disease. This differentiation helps decide need for admission as well as further management. Although iPTH level may also rise in acute kidney injury, the value (2.5 times normal) can discriminate it from chronic kidney disease.

Evaluation of unplanned dialysis as a predictor of mortality in elderly dialysis patients: a retrospective data analysis.

BACKGROUND: Increasing numbers of elderly patients are undergoing long-term dialysis. However, the role of dialysis in survival and quality of life is unclear, and poor outcomes may be associated with comorbidities rather than with age only. The initiation of unplanned dialysis in elderly patients with chronic kidney disease (CKD) has been reported to be associated with poor survival. We evaluated patient and practice factors associated with poor survival. METHODS: We performed a retrospective analysis of 90 consecutive elderly patients (≥75 years) with CKD initiated on long-term dialysis at our renal unit between October 2010 and February 2014. Six patients were excluded; data from 84 remaining patients (≥75 years) with end-stage renal disease undergoing planned or unplanned dialysis were analyzed. Patients were followed up until death or January 2015. Patient factors such as age at initiation of dialysis and comorbidities (i.e., diabetes mellitus, ischemic heart disease [IHD], peripheral vascular disease, cancer, chronic obstructive pulmonary disease, and cognitive dysfunction) were analyzed. Practice factors such as planned or unplanned initiation of dialysis were compared in relation to survival outcomes. "Unplanned dialysis" was defined as a patient with known CKD stage 4 or 5 who had not been evaluated by a nephrologist in the 3 months before dialysis initiation. RESULTS: The average age at dialysis initiation was 81.5 ± 4.5 years), serum albumin level was 24.8 ± 6 g/L, body mass index was 22.5 ± 4.8 kg/m2, and glycated hemoglobin A1c level was 6.3 ± 1.3. Overall, 51 (61%) and 33 (39%) patients underwent unplanned and planned dialysis, respectively. On univariate analysis, the presence of IHD, peripheral vascular disease, ≥3 comorbidities, and unplanned initiation of dialysis were significantly related to death. On multivariate analysis, unplanned start of dialysis, ischemic heart diseases and peripheral vascular disease remained significant. Survival rates at 3 and 12 months were 38.6% vs. 90.9% and 14.4% vs. 73.6% for unplanned vs. planned dialysis, respectively (p < 0.001). Unplanned dialysis was significantly associated with greater mortality. CONCLUSIONS: In elderly dialysis patients, unplanned start of dialysis was associated with poor survival. Patient characteristics such as associated peripheral vascular disease and IHD were associated with poor survival.

Detection and Significance of Human Epidermal Growth Factor Receptor 2 Expression in Gastric Adenocarcinoma.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is involved in the pathogenesis of several types of cancer, including gastric cancer. Overexpression of HER2 is noted in 10%-22.8% of gastric adenocarcinoma and its identification is of immense importance for management by targeted drugs. Detection of HER2 expression in gastric malignancies has not been undertaken previously in the local population. OBJECTIVE: To ascertain HER2 immunohistochemical expression in gastric adenocarcinoma and its relationship with the anatomic location and histomorphology. MATERIALS AND METHODS: A total of 47 cases of gastric adenocarcinoma diagnosed over 2 years constituted the study group. Clinical history, type of operation, gross morphology, and hematoxylin and eosin (H and E) stained sections were reviewed. Two paraffin blocks were selected, immunostain was performed using rabbit monoclonal HER2 antibody and Hoffmann scoring system was applied. RESULTS: Most of gastric carcinomas occurred in male (42 cases), having a mean age of 53.6 years. A total of eight cases (17.1%) had expressed a score of 3+ HER2 positivity. All positivity was noted in intestinal type according to Lauren classification (25%) and none in diffuse type. All HER2 score of 3+ was noted in histological grade of well and moderately differentiated adenocarcinoma. Score 2+ was noted in seven cases, among them, only two were poorly differentiated gastric adenocarcinoma. CONCLUSION: HER2 overexpression was noticeably associated with an intestinal subtype, and well and moderately differentiated adenocarcinomas. Such cases of gastric adenocarcinoma are considered for targeted therapy with trastuzumab in the local population.

Secondary hypertension in adults

Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately.