Saira Nawaz

Background: Obesity poses significant challenges to healthcare globally, particularly through its bi-directional relationship with co-morbid metabolic conditions such as type 2 diabetes and hypertension. There is also emerging evidence of an association between obesity and chronic kidney disease (CKD) which is less well characterized. Methods: A literature search of electronic libraries was conducted to identify and present a narrative review of the interplay between obesity and CKD. Findings: Obesity may predispose to CKD directly as it is linked to the histopathological finding of obesity-related glomerulopathy and indirectly through its widely recognized complications such as atherosclerosis, hypertension, and type 2 diabetes. The biochemical and endocrine products of adipose tissue contribute to pathophysiological processes such as inflammation, oxidative stress, endothelial dysfunction, and proteinuria. The prevention and management of obesity may prove critical in counteracting both the development and advancement of CKD. Moreover, measures of abdominal adiposity such as waist circumference, are generally associated with worse morbidity and mortality in individuals receiving maintenance hemodialysis. Conclusion: Obesity is a risk factor for the onset and progression of CKD and should be recognized as a potential target for a preventative public health approach to reduce CKD rates within the general population. Future research should focus on the use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors in patients with CKD and obesity due to their multi-faceted actions on major outcomes.

The aims of this study were to 1) examine pharyngoesophageal and cardiorespiratory responses to provoking pharyngeal stimuli, and 2) to determine potential contributory factors impacting heart rate (HR) changes to provide insight into cardiorespiratory events occurring in preterm infants. Forty-eight neonates (19 females and 29 males, born at 27.7 ± 0.5 wk; mean ± SE) pending discharge on full oral feeds were studied at 38.7 ± 0.2 wk postmenstrual age using concurrent pharyngoesophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor. Pharyngoesophageal and cardiorespiratory responses (prevalence, latency, and duration) were quantified upon abrupt pharyngeal water stimuli (0.1, 0.3, and 0.5 ml in triplicate). Mixed linear models and generalized estimating equations were used for comparisons between HR changes. Contributory factors included stimulus characteristics and subject characteristics. Of 338 pharyngeal stimuli administered, HR increased in 23 (7%), decreased in 108 (32%), and remained stable in 207 (61%) neonates. HR decrease resulted in repetitive swallowing, increased respiratory-rhythm disturbance, and decreased esophageal propagation rates (all, P < 0.05). HR responses were related to stimulus volume, stimulus flow rate, and extreme prematurity (all, P < 0.05). In preterm infants, HR remains stable in a majority of pharyngeal provocations. HR decrease, due to pharyngeal stimulation, is related to aberrant pharyngoesophageal motility and respiratory dysregulation and is magnified by prematurity. We infer that the observed aberrant responses across digestive, respiratory, and cardiovascular systems are related to maladaptive maturation of the parasympathetic nervous system. These aberrant responses may provide diagnostic clues for risk stratification of infants with troublesome cardiorespiratory events and swallowing difficulty. NEW & NOTEWORTHY Cardiorespiratory rhythms concurrent with pharyngeal, upper esophageal sphincter, and esophageal body responses were examined upon pharyngeal provocation in preterm-born infants who were studied at full-term maturation. Decreased heart rate (HR) was associated with extreme preterm birth and stimulus flow/volume. With HR decrease responses, aerodigestive reflex abnormalities were present, characterized by prolonged respiratory rhythm disturbance, repetitive multiple swallowing, and poor esophageal propagation. Promoting esophageal peristalsis may be a potential therapeutic target.

BACKGROUND: A common osmolality threshold for feedings is to stay <450 mOsm/kg for normal infants. Preterm formulas are frequently modified to improve growth, modify nutrition, and manage gastroesophageal reflux (GER) or dysphagia. Relationships between osmolality and additives to ready-to-feed preterm formulas are unclear. Our aims were to evaluate and compare the effects of caloric density, thickening agent recipes, and supplements to ready-to-feed preterm formula on osmolality. METHODS: A freezing point osmometer was used to measure the osmolality of 47 preterm infant formula combinations with varying caloric densities (ready-to-feed 22 and 30 cal/oz), thickening agents (rice vs oatmeal cereal), thickener amounts (0.0, 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 tsp/oz), and combinations of supplements (saline, iron, vitamin D, or multivitamin). Ten samples per combination were tested using a 10-μL pipette. Comparisons were made using analysis of variance and t-tests for group and pair-wise comparisons, respectively. RESULTS: A total of 470 osmolality samples were analyzed: (1) raters had high agreement (r = 0.98; P < .001); (2) for every 0.5 tsp/oz of thickener, the osmolality increases by 30 mOsm/kg (P < .001); (3) osmolality was higher with the oatmeal (vs rice) thickening agent (P < .001); and (4) vitamin and electrolyte supplement combinations increase osmolality. CONCLUSIONS: Alteration of ready-to-feed preterm formulas may significantly increase osmolality and have unintended consequences. Caution and monitoring should be exercised with modifying ready-to-feed preterm formulas for regurgitation, rumination, GER, dysphagia, feeding intolerance, or emesis. This study supports the concept of achieving volume tolerance before further manipulation of additives.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible lung disease. Licensed treatment options for IPF are pirfenidone and nintedanib. The aim of this study was to assess the impact of antifibrotic therapy in patients with IPF with preserved lung function based upon a forced vital capacity (FVC) above 80%. METHOD: This is a retrospective single-centre cohort study, performed as part of a service evaluation, between January 2007 and September 2018. Patient demographic, treatment and lung function profiles were collected using electronic patient records. A linear mixed model and Kaplan-Meier estimator were utilised to assess changes in FVC and survival over 36 months. RESULTS: A total of 161 patients were included in this study. Mean age was 72 ± 4. Twenty-four (14.9%) received pirfenidone, 86 (53.4%) received nintedanib and 18 (11.2%) received both antifibrotics provided by a compassionate use program (CUP), as the National Institute of Heath and Clinical excellence (NICE) criteria for antifibrotics in the UK is restricted to an FVC 50-80%. Thirty-three (20.5%) patients did not receive treatment. Patients without antifibrotic therapy had a statistically higher baseline FVC compared to other groups: 3.55 l (100%) vs 2.85 l (89.7%) pirfenidone (p = 0.012), vs 2.99 l (93.5%) nintedanib (p = 0.04) and 3.10 l (92.7%) (p = 0.07) for both antifibrotics. FVC decline over 1 year was similar in groups receiving pirfenidone, nintedanib or no treatment [3.72% (158.1 ml) untreated vs 2.77% (139 ml) pirfenidone vs 2.96% (131 ml) nintedanib]; however, it was significantly greater in patients who received both antifibrotics [6.36% (233 ml), p = 0.01]. Use of antifibrotics was associated with a higher median survival post diagnosis; 3.5, 3 and 3.75 years respectively in pirfenidone, nintedanib and both antifibrotic cohorts, compared to the untreated cohort (2.5 years). CONCLUSION: One in five untreated patients with an average FVC of 100% die within a median of 2.5 years. Antifibrotic therapy was associated with a higher median survival of 3-3.75 years despite treatment groups having lower baseline lung function.