Using transcutaneous carbon dioxide monitor (TOSCA 500) to detect respiratory failure in patients with amyotrophic lateral sclerosis: A validation study

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, respiratory failure being the commonest cause of death. Quality of life and survival can be improved by supporting respiratory function with non-invasive ventilation. Transcutaneous carbon dioxide monitoring is a non-invasive method of measuring arterial carbon dioxide levels enabling simple and efficient screening for respiratory failure. The aim of this study was to validate the accuracy of carbon dioxide level recorded transcutaneously with a TOSCA 500 monitor. It is a prospective, observational study of 40 consecutive patients with ALS, recruited from a specialist ALS clinic. The partial pressure of carbon dioxide (PCO(2)) in each patient was determined by both transcutaneous monitoring and by an arterialized ear lobe capillary blood sample. The carbon dioxide (CO(2)) levels obtained with these two methods were compared by Bland-Altman analysis. The results showed that the mean difference between arterialized and transcutaneous readings was - 0.083 kPa (SD 0.318). The Bland-Altman limits of agreement ranged from 0.553 to - 0.719 kPa. The difference was ?0.5 kPa, with a maximum recorded difference of 0.95 kPa. In conclusion, non-invasive carbon dioxide monitoring using a TOSCA monitor is a useful clinical tool in neurology practice. Users should be aware of the possibility of occasional inaccurate readings. A clinically unexpected or incompatible reading should be verified with a blood gas analysis, especially when a decision to provide ventilatory support is required.     

Sigmoid volvulus in pregnancy and puerperium: a surgical and obstetric catastrophe. Report of a case and review of the world literature

ABSTRACT: Sigmoid volvulus is a rare surgical complication occurring in pregnancy and puerperium. Only 84 cases of sigmoid volvulus in pregnancy have been reported in the English literature so far. We have reviewed the available literature on this subject and present another case recently managed at our institution. The available literature suggests that over the years, there has been an improvement in the maternal and fetal outcome for this critical condition, but delay in presentation and a further delay in diagnosis remain a challenge for the treating physicians. Our patient was a 30-week pregnant lady, who presented late with 6?days history of abdominal pain, distension and absolute constipation. She had evidence of multi-organ dysfunction at presentation due to complicated sigmoid volvulus. She was resuscitated and surgical exploration revealed gangrenous large bowel. Bowel resection with diverting ileostomy was performed, but she succumbed to the septic shock due to late presentation. Acute surgical pathology may be overlooked in pregnant patients due to reluctance in radiological workup and a high index of suspicion is essential for enhanced outcome. There is a need to increase the awareness amongst the obstetricians and general practitioners. Early diagnosis and referral and timely surgical intervention could significantly improve the outcome of this surgical and obstetric catastrophe.     

Characterization of multidrug-resistant Klebsiella pneumoniae from Australia carrying blaNDM-1

bla_NDM genes, encoding metallo-β-lactamases providing resistance to carbapenems, have been reported in many locations since the initial report in 2008, including in several Enterobacteriaceae isolates in Australia/New Zealand. Here, we compare 4 additional carbapenem-resistant Klebsiella pneumoniae carrying bla_NDM-1 isolated in Australia. Two are sequence type ST147, previously associated with bla_NDM in Australia and elsewhere. They carry bla_NDM-1 and different 16S rRNA methylase genes (armA or rmtC) on different conjugative plasmids, in 1 case with an IncFII_Y replicon. One isolate belongs to the globally important ST11 but did not transfer a plasmid to Escherichia coli. The fourth isolate belongs to the novel ST1068 and transferred bla_NDM-1, armA, and an IncA/C plasmid. Amplification and sequencing of ompK porin genes suggest that, unlike the case for other carbapenemase genes, ompK36 defects may not be required for NDM to cause clinically relevant levels of carbapenem resistance.     

Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production

Chronic hyperglycemia impairs insulin action, resulting in glucotoxicity, which can be ameliorated in animal models by inducing glucosuria with renal glucose transport inhibitors. Here, we examined whether reduction of plasma glucose with a sodium-glucose cotransporter 2 (SGLT2) inhibitor could improve insulin-mediated tissue glucose disposal in patients with type 2 diabetes. Eighteen diabetic men were randomized to receive either dapagliflozin (n = 12) or placebo (n = 6) for 2 weeks. We measured insulin-mediated whole body glucose uptake and endogenous glucose production (EGP) at baseline and 2 weeks after treatment using the euglycemic hyperinsulinemic clamp technique. Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose. Insulin-mediated tissue glucose disposal increased by approximately 18% after 2 weeks of dapagliflozin treatment, while placebo-treated subjects had no change in insulin sensitivity. Surprisingly, following dapagliflozin treatment, EGP increased substantially and was accompanied by an increase in fasting plasma glucagon concentration. Together, our data indicate that reduction of plasma glucose with an agent that works specifically on the kidney to induce glucosuria improves muscle insulin sensitivity. However, glucosuria induction following SGLT2 inhibition is associated with a paradoxical increase in EGP. These results provide support for the glucotoxicity hypothesis, which suggests that chronic hyperglycemia impairs insulin action in individuals with type 2 diabetes.     

Cancer stem cells in lung cancer: Evidence and controversies

The cancer stem cell (CSC) model is based on a myriad of experimental and clinical observations suggesting that the malignant phenotype is sustained by a subset of cells characterized by the capacity for self‐renewal, differentiation and innate resistance to chemotherapy and radiation. CSC may be responsible for disease recurrence after definitive therapy and may therefore be functionally synonymous with minimal residual disease. Similar to other solid tumours, several putative surface markers for lung CSC have been identified, including CD133 and CD44. In addition, expression and/or activity of the cytoplasmic enzyme aldehyde dehydrogenase ALDH and capacity of cells to exclude membrane permeable dyes (known as the ‘side population’) correlate with stem‐like function in vitro and in vivo. Embryonic stem cell pathways such as Hedgehog, Notch and WNT may also be active in lung cancers stem cells and therefore may be therapeutically targetable for maintenance therapy in patients achieving a complete response to surgery, radiotherapy or chemotherapy. This paper will review the evidence regarding the existence and function of lung CSC in the context of the experimental and clinical evidence and discuss some ongoing controversies regarding this model.     

Obesity cardiomyopathy and systolic function: Obesity is not independently associated with dilated cardiomyopathy

Obesity is a growing worldwide problem and the prevalence of heart failure is also on the rise. Obesity itself is an independent risk factor for the development of heart failure and the case of obesity-related heart failure is thought to be multifactorial. Obesity leads to increased central and total blood volumes along with decreased systemic arterial resistance resulting in high cardiac output state related adaptations in the cardiac structure. Persistence of these hemodynamic changes ultimately results in diastolic dysfunction, however, whether these changes progress to significant systolic dysfunction or not is doubtful. Some MUGA (Multi Gated Acquisition) scan-based studies had shown mild degree of left ventricular systolic dysfunction in the obese, however, these findings could not be confirmed with recent echocardiogram-based studies. Using extensive literature review, we found no evidence of obesity-related cardiomyopathy leading to significant systolic dysfunction fulfilling criterion for the diagnosis of dilated cardiomyopathy (LVEF <35 %). Therefore, any obese patient presenting with severe LV dysfunction should prompt further investigations to evaluate for the underlying etiology.     

Tackling metabolic syndrome by functional foods

The metabolic syndrome is one of the most vibrant and widely prevailing health concerns worldwide. It is characterized by several metabolic abnormalities, which involve obesity, insulin resistance, dyslipidemia, enhanced oxidative stress; hypertension and increased pro-inflammatory state that ultimate contribute towards poor health. The prevalence of metabolic syndrome in Pakistan according to different definitions is reported to be from 18 % to 46 %. Fifty percent of Pakistani population is at high risk of metabolic syndrome as being hypertensive. In studying dyslipidemia in Pakistan, hypertriglyceridemia is found in 27–54 % of the population, whereas 68–81 % has low levels of high-density lipoprotein (HDL). Population likes to eat healthier diet without changing their fundamental dietary pattern. Nutrition science has moved on from the classical concepts of avoiding nutrient deficiencies and basic nutritional adequacy to the concept of positive or optimal nutrition. Many traditional food products including fruits, vegetables, flaxseed, oat, barley, whole grains, soy and milk have been found to contain component with potential health benefits. Nowadays, functional foods are used in the prevention and amelioration of several chronic diseases, such as the metabolic syndrome. The relation of the consumption of certain functional foods and the improvement in health status is regulated through health claims. This review focuses on the different features of the metabolic syndrome and the influence of functional foods on these aspects, involving dyslipidemia, improvement of insulin sensitivity, serum lipid profile, antioxidant status, anti-inflammatory status and weight management of humans.