Calcium, Vitamin D, and Bone Derangement in Nephrotic Syndrome.

INTRODUCTION: Derangement in calcium homeostasis is common in nephrotic syndrome (NS). It is postulated that low serum total calcium and vitamin D levels are due to loss of protein-bound calcium and vitamin D. It is unclear if free calcium and free vitamin D levels are truly low. The guideline is lacking with regards to calcium and vitamin D supplementation in NS. This study aims to examine calcium and vitamin D homeostasis and bone turnover in NS to guide practice in calcium and vitamin D levels supplementation. METHODOLOGY: This is a prospective pilot study of ten patients diagnosed with NS, and eight healthy controls. Calcium, vitamin D, and bone turnover-related analytes were assessed at baseline, partial and complete remission in NS patients and in healthy controls. RESULTS: NS patients had low free and total serum calcium, low total 25(OH)D, normal total 1,25(OH)D levels and lack of parathyroid hormone response. With remission of disease, serum calcium and vitamin D metabolites improved. However, nephrotic patients who do not attain complete disease remission continue to have low 25(OH)D level. CONCLUSION: In this study, the vitamin D and calcium derangement observed at nephrotic syndrome presentation trended towards normalisation in remission. This suggested calcium and vitamin D replacement may not be indicated in early-phase nephrotic syndrome but may be considered in prolonged nephrotic syndrome.

Impact of Pump Speed on Hemodynamics With Exercise in Continuous Flow Ventricular Assist Device Patients.

At fixed speed, the spontaneous increase in pump flow accompanying exercise in patients with continuous flow left ventricular assist devices (cfLVADs) is slight in comparison to normal physiologic response, limiting exercise capacity. We systematically exercised 14 patients implanted with an isolated HeartWare HVAD undergoing routine right heart catheterization at baseline and at maximal safe pump speed. In addition to hemodynamics, mixed venous oxygen saturation (SvO2), echocardiography and noninvasive mean arterial pressure, and heart rate were measured. Significantly greater pump flows were achieved with maximum pump speed compared with baseline speed at rest (mean ± standard deviation [SD]: 5.0 ± 0.7 vs. 4.6 ± 0.8 L/min) and peak exercise (6.7 ± 1.0 vs. 5.9 ± 0.9 L/min, p = 0.001). Pulmonary capillary wedge pressure was significantly reduced with maximum pump speed compared to baseline pump speed at rest (10 ± 4 vs. 15 ± 5 mmHg, p < 0.001) and peak exercise (27 ± 8 vs. 30 ± 8 mmHg, p = 0.002). Mixed venous oxygen saturation decreased with exercise (p < 0.001) but was unaffected by changes in pump speed. In summary, although higher pump speeds synergistically augment the increase in pump flow associated with exercise and blunt the exercise-induced rise in left heart filling pressures, elevated filling pressures and markedly diminished SvO2 persist at maximal safe pump speed, suggesting that physiologic flow increases are not met by isolated cfLVADs in the supported failing heart.

Assessment of the Type 2 Diabetes Patient at Risk of Cardio-renal Complications

@#Diabetes patients are at high risk of developing cardiovascular and renal complications. These conditions increase cardiovascular mortality as well as the development of end-stage renal disease. In this article, we will discuss the mechanisms behind the development of heart and renal disease in diabetic patients and how to evaluate these patients to aid in the early detection of these conditions and identify high-risk patients who may benefit from treatment with new glucose-lowering therapies.

Ultrafiltration in patients with decompensated heart failure and diuretic resistance: an Asian centre's experience

<p><b>INTRODUCTION</b>Diuretics are the mainstay of therapy for restoring the euvolaemic state in patients with decompensated heart failure. However, diuretic resistance remains a challenge.</p><p><b>METHODS</b>We conducted a retrospective cohort study to examine the efficacy and safety of ultrafiltration (UF) in 44 hospitalised patients who had decompensated heart failure and diuretic resistance between October 2011 and July 2013.</p><p><b>RESULTS</b>Among the 44 patients, 18 received UF (i.e. UF group), while 26 received diuretics (i.e. standard care group). After 48 hours, the UF group achieved lower urine output (1,355 mL vs. 3,815 mL, p = 0.0003), greater fluid loss (5,058 mL vs. 1,915 mL, p < 0.0001) and greater weight loss (5.0 kg vs. 1.0 kg, p < 0.0001) than the standard care group. The UF group also had a shorter duration of hospitalisation (5.0 days vs. 9.5 days, p = 0.0010). There were no differences in the incidence of 30-day emergency department visits and rehospitalisations for heart failure between the two groups. At 90 days, the UF group had fewer emergency department visits (0.2 vs. 0.8, p = 0.0500) and fewer rehospitalisations for heart failure (0.3 vs. 1.0, p = 0.0442). Reduction in EQ-5D™ scores was greater in the UF group, both at discharge (2.7 vs. 1.4, p = 0.0283) and 30 days (2.5 vs. 0.3, p = 0.0033). No adverse events were reported with UF.</p><p><b>CONCLUSION</b>UF is an effective and safe treatment that can improve the health outcomes of Asian patients with decompensated heart failure and diuretic resistance.</p>

Patient barriers to implantable cardioverter defibrillator implantation for the primary prevention of sudden cardiac death in patients with heart failure and reduced ejection fraction

<p><b>INTRODUCTION</b>Device therapy is efficacious in preventing sudden cardiac death (SCD) in patients with reduced ejection fraction. However, few who need the device eventually opt to undergo implantation and even fewer reconsider their decisions after deliberation. This is due to many factors, including unresolved patient barriers. This study identified the factors that influenced patients' decision to decline implantable cardioverter defibrillator (ICD) implantation, and those that influenced patients who initially declined an implant to reconsider having one.</p><p><b>METHODS</b>A single-centre survey was conducted among 240 patients who had heart failure with reduced ejection fraction and met the ICD implantation criteria, but had declined ICD implantation.</p><p><b>RESULTS</b>Participants who refused ICD implantation were mostly male (84%), Chinese (71%), married (72%), currently employed (54%), and had up to primary or secondary education (78%) and monthly income of < SGD 3,000 (51%). Those who were more likely to reconsider their decision were aware that SCD was a consequence of heart failure with reduced ejection fraction, knowledgeable of the preventive role of ICDs, currently employed and aware that their doctor strongly recommended the implant. Based on multivariate analysis, knowledge of the role of ICDs for primary prophylaxis was the most important factor influencing patient decision.</p><p><b>CONCLUSION</b>This study identified the demographic and social factors of patients who refused ICD therapy. Knowledge of the role of ICDs in preventing SCD was found to be the strongest marker for reconsidering ICD implantation. Measures to address this information gap may lead to higher rates of ICD implantation.</p>

Microwave-assisted synthesis of sec/tert-butyl 2-arylbenzimidazoles and their unexpected antiproliferative activity towards ER negative breast cancer cells.

A new series of N-sec/tert-butyl 2-arylbenzimidazole derivatives was synthesised in 85-96% yields within 2-3.5 min by condensing ethyl 3-amino-4-butylamino benzoate with various substituted metabisulfite adducts of benzaldehyde under focused microwave irradiation. The benzimidazole analogues were characterised using (1)H NMR, (13)C NMR, high resolution MS and melting points. Evaluation of antiproliferative activity of the benzimidazole analogues against MCF-7 and MDA-MB-231 revealed several compounds with unexpected selective inhibitions of MDA-MB-231 in micromolar range. All analogues were found inactive towards MCF-7. The most potent inhibition against MDA-MB-231 human breast cancer cell line came from the unsubstituted 2-phenylbenzimidazole 10a.

Peripartum cardiomyopathy: experience in an Asian tertiary centre

<p><b>INTRODUCTION</b>Peripartum cardiomyopathy (PPCM) is a rare but life-threatening condition. We report 11 patients admitted to the National Heart Centre Singapore with a diagnosis of PPCM over a period of 14 months.</p><p><b>METHODS</b>Baseline demographics, pregnancy history, haematology, serum biochemistry and echocardiographic findings of women admitted with a diagnosis of PPCM were analysed.</p><p><b>RESULTS</b>The incidence of PPCM was 0.89 per 1,000 live births in our cohort. 63.6% of the patients were Malay and 27.3% were Chinese. 45.5% of the patients were smokers and 45.5% had a history of pregnancy-induced hypertension or preeclampsia. There was no maternal mortality. Mean left ventricular ejection fractions at diagnosis and at six months were 26.9% ± 9.1% and 51.9% ± 10.6%, respectively. Mean left ventricular internal diameters in end-diastole at diagnosis and at six months were 5.5 ± 0.5 cm and 5.1 ± 0.6 cm, respectively. All patients were treated successfully for the acute episode and all but one patient had returned to New York Heart Association functional class I status at six months.</p><p><b>CONCLUSION</b>PPCM remains a rare condition and appears to occur more commonly in Malay patients. Smoking and pregnancy-induced hypertension appear to be significant risk factors. While short-term outcome remains excellent, collaborative studies with other tertiary centres will help enhance our understanding of the long-term management of and clinical outcomes in these patients.</p>

Cathepsin S mediates gastric cancer cell migration and invasion via a putative network of metastasis-associated proteins.

Cancer progression is governed by multifaceted interactions of cancer cells with their microenvironment and one of these ways is through secreted compounds. Substances released by gastric cancer cells have not being profiled in a proteome-wide manner. ITRAQ-based tandem mass spectrometry was employed to quantify proteins secreted by HFE145 normal, MKN7 well-differentiated, and MKN45 poorly differentiated gastric cancer cell lines. The expression levels of 237 proteins were found to be significantly different between normal and cancer cells. Further examination of 16 gastric cell lines and 115 clinical samples validated the up-regulation of CTSS expression in gastric cancer. Silencing CTSS expression suppressed the migration and invasion of gastric cancer cells in vitro. Subsequent secretomics revealed that CTSS silencing resulted in changes in expression levels of 197 proteins, one-third of which are implicated in cellular movement. Proteome-wide comparative secretomes of normal and gastric cancer cells were produced that constitute a useful resource for gastric cancer research. CTSS was demonstrated to play novel roles in gastric cancer cell migration and invasion, putatively via a network of proteins associated with cell migration, invasion, or metastasis. Cathepsin S is member of a large group of extracellular proteases, which are attractive drug targets. The implicated role of CTSS in gastric cancer metastasis provides an opportunity to test existing compounds against CTSS for adjuvant therapy and/or treatment of metastatic gastric cancers.

Type 2 diabetic patients with resistant hypertension should be screened for primary aldosteronism.

BP control in diabetic patients is often poor. The contribution of secondary hypertension due to undiagnosed PA in hypertensive type 2 diabetic patients is not well studied. We prospectively screened 100 consecutive Asian type 2 diabetic patients with difficult-to-control or resistant hypertension for PA. PAC (pmol/L) to PRA (ng/mL/h) ratio was measured; those with PAC-to-PRA ratio >550 (corresponding PAC >415) underwent intravenous 0.9% SLT. Patients with PAC >/=140 following SLT had CT adrenals and bilateral AVS. Thirteen patients (13%) were confirmed to have PA, and all had resistant hypertension. Eight had a surgically correctable form of PA. Patients with PA had higher mean (SD) systolic [159.0 (10.6) vs. 146.0 (10.7) mmHg, p=0.001] and diastolic BP [94.6 (6.0) vs. 87.6 (5.9) mmHg, p=0.001], lower serum potassium [3.5 (0.6) vs. 4.3 (0.5) mmol/L, p=0.001], and higher PAC [679.3 (291.0) vs. 239.5 (169.4) pmol/L, p=0.001]. Identification and institution of definitive treatment for PA resulted in better BP control and in a reduction in the use of antihypertensive medications. Our findings demonstrate a high prevalence of PA in type 2 diabetic patients with resistant hypertension. Systematic screening for PA in this select group is recommended, as targeted treatment improves BP control.

Demands and challenges of modern medicine

Modern medicine, characterised by the enormous impact of rapid advances in science and technology, has vastly enhanced the doctor's professional capabilities and has made the practice of medicine more intellectually challenging as well as professionally satisfying. It has also made medicine more complex and demanding. In addition to having to keep pace with rapid medical advances, the doctor has to deal with 1) the issue of sorting the wheat from the chaff out of the deluge of new drugs and equipment presented to him, 2) the issue of rationing and determining priorities within the limits of finite resources, 3) the issue of appropriate response to new ethical challenges presented by the application of new technologies and 4) the issue of maintaining the human face of medicine in the context of growing presence and impact of technology. As doctors, we have the responsibility to ensure that through steadfast commitment to professionalism, through wisdom and insight we can harvest and maximise the vast potential of technology in caring for our patients. This is a challenge we must accept in the cause of our patients' welfare, the paramount concern of our professional creed.