Self-reported hypoglycaemia in insulin-treated patients with diabetes mellitus: results from the Singapore cohort of the International Operations Hypoglycaemia Assessment Tool study

INTRODUCTIONHypoglycaemia constitutes a significant barrier to achieving glycaemic control with insulin in both Type 1 (T1DM) and Type 2 diabetes mellitus (T2DM). The International Operations Hypoglycaemia Assessment Tool (IO HAT) study was designed to determine the incidence of hypoglycaemia in insulin-treated patients with T1DM and T2DM.METHODSThe IO HAT study retrospectively and prospectively assessed the incidence of hypoglycaemia in patients with insulin-treated diabetes mellitus in nine countries. This sub-analysis included patients from Singapore with T1DM or T2DM who were aged ≥ 21 years and had completed two self-assessment questionnaires (SAQ1 and SAQ2).RESULTSOf the 50 T1DM and 320 T2DM patients who completed the SAQ1, 39 T1DM and 265 T2DM patients completed SAQ2; 100% and 90.9%, respectively, experienced at least one hypoglycaemic event prospectively. The incidence rates of any hypoglycaemia were 49.5 events per patient-year (EPPY) and 16.1 EPPY for T1DM and T2DM patients, respectively, in the four-week prospective period. Hypoglycaemia rate did not differ in terms of glycated haemoglobin level. The vast majority of T1DM or T2DM patients (92.0% and 90.7%, respectively) knew the overall definition of hypoglycaemia before study participation, although over half of the patients (T1DM 54.0%, T2DM 51.9%) defined hypoglycaemia based only on symptoms.CONCLUSIONHigh proportions of insulin-treated patients with diabetes mellitus in Singapore reported hypoglycaemic events prospectively, showing that they had underreported hypoglycaemic episodes retrospectively. Patient education can help in improving hypoglycaemia awareness and its management in the region.     

Outcomes following selective fetoscopic laser ablation for twin-to-twin transfusion syndrome: a single-centre experience

INTRODUCTIONFetoscopic laser photocoagulation (FLP), a treatment option for twin-to-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies, is currently the treatment of choice at our centre. We previously reported on our experience of FLP from June 2011 to March 2014. This paper audits our fetal surgery performance since then.METHODS15 consecutive patients who underwent FLP for Stage II–III TTTS before 26 weeks of gestation from June 2011 to January 2017 were retrospectively reviewed, consisting of five cases from our initial experience and ten subsequent cases. Perioperative, perinatal and neonatal outcomes were analysed.RESULTSOf 15 pregnancies, 10 (66.7%) and 5 (33.3%) were for Stage II and III TTTS respectively, with FLP performed at an earlier Quintero stage in the later cohort. Overall mean gestational ages at presentation, laser and delivery were comparable between the cohorts at 19.7 (15.4–24.3) weeks, 20.3 (16.3–25.0) weeks and 31.2 (27.6–37.0) weeks, respectively. 2 (13.3%) cases had intra-amniotic bleeding and 1 (6.7%) had iatrogenic septostomy. 1 (6.7%) case had persistent TTTS requiring repeat FLP, and another (6.7%) had preterm premature rupture of membranes at seven weeks post procedure. The overall perinatal survival rate was 21 (75.0%) out of 28 infants. One mother underwent termination of pregnancy for social reasons at 1.4 weeks post procedure. Double survival occurred in 8 (57.1%) out of 14 pregnancies, while 13 (92.9%) had at least one survivor.CONCLUSIONFLP requires a highly specialised team and tertiary neonatal facility. Continual training improves maternal and perinatal outcomes, ensuring comparable standards with international centres.     

Preoperative level of serum amyloid A is superior to C‐reactive protein in the prognosis of esophageal squamous cell carcinoma

Preoperative elevations in the levels of serum amyloid A (SAA) or C‐reactive protein (CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma (ESCC). In total, 252 patients with ESCC who had undergone surgery with curative‐intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic (ROC) curve (AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Cox's proportional hazards model. The 1‐, 3‐, and 5‐year overall survival (OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant (r² = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels (AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III (P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor (P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis.     

ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity

A very rare syndrome of rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) has been recently described as causing morbidity due to hypothalamic dysfunction and respiratory arrest. Its prognosis is poor and often cardiac arrest occurs due to alveolar hypoventilation. This disorder can mimic genetic obesity syndromes and several endocrine disorders. We present a 13-year-old female patient who was reported to be healthy until the age of 3 years. She was admitted to our emergency department, presenting with respiratory distress. Features matching ROHHAD syndrome such as rapid-onset obesity, alveolar hypoventilation, central hypothyroidism, hyperprolactinemia, Raynaud phenomenon and hypothalamic hypernatremia were detected in the patient. In addition to these features, the patient was found to have hypergonadotropic hypogonadism and megaloblastic anemia. Because of its high mortality and morbidity, the possibility of ROHHAD syndrome needs to be considered in all pediatric cases of early- and rapid-onset obesity associated with hypothalamic-pituitary endocrine dysfunction.     

The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion?

BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft‐versus‐host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin‐G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV‐specific cytotoxic T cells in healthy adults as well as in post‐HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors.     

Effect of zinc treatment on clinical outcomes in patients with liver cirrhosis:A systematic review and meta-analysis

BACKGROUND Zinc is an essential trace element integral to many cellular and immune functions. Zinc deficiency is highly prevalent in patients with cirrhosis and related to disease severity.AIM To evaluate whether zinc supplementation improves clinical outcomes(disease severity and mortality) in patients with cirrhosis.METHODS This prospectively registered systematic review(PROSPERO reference: CRD42018118219) included all studies in Medline, Embase or Cochrane database with inclusion criteria of adult human studies, comparing zinc supplementation of at least 28 d with standard care or placebo in patients with cirrhosis. Mortality and clinical severity score data were extracted. Random effects meta-analyses compared mortality at 6 mo and 2 years. Risk of bias was assessed using the National Institutes of Health quality assessment tool.RESULTS Seven hundred and twelve articles were identified of which four were eligible. Zinc formulations and doses varied(elemental zinc 3.4-214 mg daily) for different intervention periods in patients with differing etiology and severity of cirrhosis. Two studies were considered to be at high risk of bias. There was no significant difference in 6-mo mortality between patients treated with zinc versus controls [risk ratio 0.98(0.90-1.05)]. Changes in severity scores were not reported in any study.CONCLUSION Zinc supplementation is not associated with reduced mortality in patients with cirrhosis. Findings are limited by the small number of eligible studies and significant heterogeneity in intervention and patient population.     

Oxidative stress in alcohol-related liver disease

Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs. Heavy alcohol misuse leads to alcohol-related liver disease, which is responsible for a significant proportion of alcohol-attributable deaths globally. Other than reducing alcohol consumption, there are currently no effective treatments for alcohol-related liver disease. Oxidative stress refers to an imbalance in the production and elimination of reactive oxygen species and antioxidants. It plays important roles in several aspects of alcohol-related liver disease pathogenesis. Here, we review how chronic alcohol use results in oxidative stress through increased metabolism via the cytochrome P4502E1 system producing reactive oxygen species, acetaldehyde and protein and DNA adducts. These trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and necrosis. Reactive oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic signaling. There is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic regulation. Increased global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory genes. This review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic regulation. Improved understanding of these processes may identify novel targets for therapy.     

Transcervical minimally invasive esophagectomy: hemodynamic study on an animal model

BackgroundTranscervical esophagectomy is a less invasive procedure performed within mediastinum. However, the mediastinum offers limited surgical space and the surgery via this route differs from conventional minimally invasive esophagectomy. Therefore, the physiological study of this surgical approach on an animal model would be necessary before the procedure gained more popularity.MethodsWe conducted transcervical minimally invasive esophagectomy on animal model (swine) under CO₂ pneumomediastinum. The hemodynamic parameters were monitored using float catheter cannulated via right jugular vein. At different anatomical level (the upper, middle, and lower thoracic part of the animal esophagus), increased artificial pneumomediastinal pressures (0, 4, 8, 12, and 16 mmHg) were consecutively allocated to record the intra-operative changes of blood pressure, cardiac output (CO), central venous pressure (CVP), pulmonary artery pressure (PAP) and extravascular lung water (EVLW). Meanwhile, the surgical field under different pneumomediastinum pressure was recorded and balanced with animals’ hemodynamic changes to determine the optimal pressure for transcervical minimally invasive esophagectomy.ResultsThe animal procedures were accomplished without conversions. During the upper thoracic stage, increased CO₂ pressures did not lead to significant changes in hemodynamic parameters including the blood pressure, CO, CVP, PAP or the level of EVLW. During the middle thoracic stage, pneumomediastinum under 4–12 mmHg did not lead to significant changes in hemodynamic parameters. However, pneumomediastinum at 16 mmHg resulted in lower CO (P=0.038) when compared to 0–12 mmHg. During lower thoracic stage, as the pneumomediastinum pressures increased from 0 to 16 mmHg, significant decrease in CO (P=0.022), and increase in CVP (P=0.036) was recorded. In compared to 4 mmHg pneumomediastinum, the surgical field under 8–16 mmHg artificial CO₂ pneumomediastinum was suitable for mediastinal manipulation.ConclusionsDuring transcervical minimally invasive esophagectomy on animal model, the mobilization of swine thoracic esophagus with optimal pneumomediastinum pressure 8–12 mmHg is safe and effective based on hemodynamic analysis.