Evaluation of the management of intestinal perforation in very low birth infants, a 10-year review.

AIM: The aim of this study was to assess outcomes of peritoneal drainage and laparotomy in the management of intestinal perforation secondary to necrotizing enterocolitis (NEC) and spontaneous intestinal perforation. METHODS: A retrospective review of all preterm infants (birthweight ≤1500 g) who underwent surgical intervention (peritoneal drainage and/or laparotomy) for intestinal perforation between March 2010 and March 2020. RESULTS: A total of 43 infants who underwent surgical intervention for intestinal perforation were included [19 (44%) with NEC and 24 (56%) with spontaneous intestinal perforation]. Peritoneal drainage was more commonly placed as the initial surgical procedure for management of spontaneous intestinal perforation compared with surgical NEC [23 (96%) vs. 11 (58%), p = 0.003]. Mortality was greater for infants who were initially managed with peritoneal drainage [11 (32%)] compared with those who underwent primary laparotomy [2 (22%), p = 0.5]. CONCLUSION: Initial surgical management of intestinal perforation is more often according to underlying pathology. Our data support primary laparotomy for infants with perforated NEC.

Structural Determinants of Indole-2-carboxamides: Identification of Lead Acetamides with Pan Antimycobacterial Activity.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is one of the leading causes of death in developing countries. Non-tuberculous mycobacteria (NTM) infections are rising and prey upon patients with structural lung diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis. All mycobacterial infections require lengthy treatment regimens with undesirable side effects. Therefore, new antimycobacterial compounds with novel mechanisms of action are urgently needed. Published indole-2-carboxamides (IC) with suggested inhibition of the essential transporter MmpL3 showed good potency against whole-cell M.tb, yet had poor aqueous solubility. This project focused on retaining the required MmpL3 inhibitory pharmacophore and increasing the molecular heteroatom percentage by reducing lipophilic atoms. We evaluated pyrrole, mandelic acid, imidazole, and acetamide functional groups coupled to lipophilic head groups, where lead acetamide-based compounds maintained high potency against mycobacterial pathogens, had improved in vitro ADME profiles over their indole-2-carboxamide analogs, were non-cytotoxic, and were determined to be MmpL3 inhibitors.

Yeast ß-Glucan Improves Insulin Sensitivity and Hepatic Lipid Metabolism in Mice Humanized with Obese Type 2 Diabetic Gut Microbiota.

SCOPE: Gut microbiota alterations are associated with obesity and type 2 diabetes. Yeast ß-glucans are potential modulators of the innate immune-metabolic response, by impacting glucose, lipid, and cholesterol homeostasis. The study examines whether yeast ß-glucan interacts differentially with either an obese healthy or obese diabetic gut microbiome, to impact metabolic health through hepatic effects under high-fat dietary challenge. METHODS AND RESULTS: Male C57BL/6J mice are pre-inoculated with gut microbiota from obese healthy (OBH) or obese type 2 diabetic (OBD) subjects, in conjunction with a high-fat diet (HFD) with/without yeast ß-glucan. OBD microbiome colonization adversely impacts metabolic health compared to OBH microbiome engraftment. OBD mice are more insulin resistant and display hepatic lipotoxicity compared to weight matched OBH mice. Yeast ß-glucan supplementation resolves this adverse metabolic phenotype, coincident with increasing the abundance of health-related bacterial taxa. Hepatic proteomics demonstrates that OBD microbiome transplantation increases HFD-induced hepatic mitochondrial dysfunction, disrupts oxidative phosphorylation, and reduces protein synthesis, which are partly reverted by yeast ß-glucan supplementation. CONCLUSIONS: Hepatic metabolism is adversely affected by OBD microbiome colonization with high-fat feeding, but partially resolved by yeast ß-glucan. More targeted dietary interventions that encompass the interactions between diet, gut microbiota, and host metabolism may have greater treatment efficacy.

Neonatal emergency transport teams and general emergency departments: Who will intubate the neonate?

OBJECTIVE: Confidence treating critically ill infants presenting to general ED may be limited by inexperience, with procedures deferred until specialised transport teams arrive. METHODS: This retrospective cohort study analysed critical procedures performed by referring ED physicians, compared with a neonatal emergency transport service, on infants transferred over a 12-month period. RESULTS: All 150 eligible infants were included, with median (interquartile range) age 28 (16-43) days. Forty critical procedures were performed in this cohort. Of 26 intubations, 17 (65%) were performed by local ED physicians. CONCLUSION: Referring ED physicians perform the majority of critical procedures where infants require inter-hospital transfer by neonatal emergency transport service.

Use of tissue samples in diagnosing diploid triploid mosaicism.

Diploid triploid mosaicism (DTM) is a rare genetic condition where there is an extra haploid set of chromosomes in mosaic form. We describe an infant for whom DTM was detected antenatally through amniocentesis. Prenatal counselling suggested a guarded prognosis. The infant's phenotypic presentation and postnatal course reflect the varied presentation and prognosis associated with DTM. We highlight potential challenges in diagnosing DTM postnatally, with many having normal blood karyotype with 46 chromosomes.

Bench-top comparison of thermometers used in newborn infants.

We wished to determine the accuracy of thermometers used to measure temperature in newborn infants. We measured the temperature of a water bath with three types of thermometer set at 0.5°C increments between 32.5°C and 38.5°C and compared the values to a control. We recorded the time to display steady-state temperature. The Microlife thermometer most closely approximated control temperature (mean difference <0.1°C (SD<0.1°C)) and displayed a reading in a mean time of 29 s (SD 2 s). Used in 'predictive' (default) mode, the Welch Allyn SureTemp Plus 692 thermometer differed from the control by a mean of 0.6°C (SD 0.3°C), displaying a temperature at 15 s (SD 3 s). This device consistently overestimated temperature. In 'continuous' mode, the mean difference was <0.1°C (SD<0.1°C) at 5 min. The Phillips probe differed from the control by a mean of 0.4°C (SD 0.2°C). Thermometers used to measure temperature in newborn infants may underestimate hypothermia. A prospective study in newborn infants is needed.

Utilising a milk-based meal replacement programme in a bariatric patient with poorly controlled type 2 diabetes mellitus.

A 45-year-old man with poorly controlled type 2 diabetes (T2DM) (HbA1c 87 mmol/mol) despite 100 units of insulin per day and severe obesity (BMI 40.2 kg/m2) was referred for bariatric intervention. He declined bariatric surgery or GLP1 agonist therapy. Initially, his glycaemic control improved with dietary modification and better adherence to insulin therapy, but he gained weight. We started a low-energy liquid diet, with 2.2 L of semi-skimmed milk (equivalent to 1012 kcal) per day for 8 weeks (along with micronutrient, salt and fibre supplementation) followed by 16 weeks of phased reintroduction of a normal diet. His insulin was stopped within a week of starting this programme, and over 6 months, he lost 20.6 kg and his HbA1c normalised. However, 1 year later, despite further weight loss, his HbA1c deteriorated dramatically, requiring introduction of linagliptin and canagliflozin, with good response. Five years after initial presentation, his BMI remains elevated but improved at 35.5 kg/m2 and his glycaemic control is excellent with a HbA1c of 50 mmol/mol and he is off insulin therapy. Whether semi-skimmed milk is a safe, effective substrate for carefully selected patients with severe obesity complicated by T2DM remains to be determined. Such patients would need frequent monitoring by an experienced multidisciplinary team. Learning points: Meal replacement programmes are an emerging therapeutic strategy to allow severely obese type 2 diabetes patients to achieve clinically impactful weight loss. Using semi-skimmed milk as a meal replacement substrate might be less costly than commercially available programmes, but is likely to require intensive multidisciplinary bariatric clinical follow-up. For severely obese adults with poor diabetes control who decline bariatric surgery or GLP1 agonist therapy, a milk-based meal replacement programme may be an option. Milk-based meal replacement in patients with insulin requiring type 2 diabetes causes rapid and profound reductions in insulin requirements, so rigorous monitoring of glucose levels by patients and their clinicians is necessary. In carefully selected and adequately monitored patients, the response to oral antidiabetic medications may help to differentiate between absolute and relative insulin deficiency.

Effects of an icon-based menu labelling initiative on consumer food choice.

AIMS: The purpose of this study was to examine the impact of an icon-based menu labelling initiative on consumer buying behaviour. METHODS: This quasi-experimental study recruited a convenience sample of eight food service establishments, all with at least one menu item meeting the heart healthy criteria. Data from sales of all menu items sold over an 8-week period were collated 4 weeks prior to and 4 weeks during the display of information icons related to healthy food choices on menus. RESULTS: The absolute change in menu item sales showed a non-significant trend towards an increase in healthier menu item selections. Furthermore, there was no association between the type of food service establishment and the percentage change in labelled menu item sales. CONCLUSION: The study did not find a statistically significant influence of the icon-based menu labels on consumer food choice. Given the limited amount of research that examines alternative menu labelling formats in real-world settings, more studies are necessary to confirm these results. Further research is needed to identify the optimal format, content and impact of menu labels on consumer behaviour.

Phenotypic extremes in liveborn monozygotic twins with mosaic Edwards syndrome.

Mosaic trisomy 18 (Edwards syndrome) in monozygotic diamniotic liveborn twins is rare. We describe such a case involving preterm male infants. Although both infants had a low percentage of trisomy 18 cells in peripheral blood leucocytes, their varied phenotypic presentation of mosaic trisomy 18 resulted in one twin surviving, with the other twin's demise at 1 month of age. Despite the presence of trisomy 18 in peripheral leucocytes, further analysis of a buccal smear and skin biopsy of the surviving twin did not show evidence of trisomy 18. Establishing such diagnoses in a timely manner is imperative for the child, parents and clinicians. The clinical course of these twins reflects the unpredictable prognosis associated with the diagnosis of mosaic trisomy 18, and emphasises the challenges that can be encountered when counselling parents.

Effects of an eight-week supervised, structured lifestyle modification programme on anthropometric, metabolic and cardiovascular risk factors in severely obese adults.

BACKGROUND: Lifestyle modification is fundamental to obesity treatment, but few studies have described the effects of structured lifestyle programmes specifically in bariatric patients. We sought to describe changes in anthropometric and metabolic characteristics in a cohort of bariatric patients after participation in a nurse-led, structured lifestyle programme. METHODS: We conducted a retrospective, observational cohort study of adults with a body mass index (BMI) ≥ 40 kgm(-2) (or ≥ 35 kgm(-2) with significant co-morbidity) who were attending a regional bariatric service and who completed a single centre, 8-week, nurse-led multidisciplinary lifestyle modification programme. Weight, height, waist circumference, blood pressure, HbA1c, fasting glucose and lipid profiles as well as functional capacity (Incremental Shuttle Walk Test) and questionnaire-based anxiety and depression scores before and after the programme were compared in per-protocol analyses. RESULTS: Of 183 bariatric patients enrolled, 150 (81.9%) completed the programme. Mean age of completers was 47.9 ± 1.2 years. 34.7% were male. There were statistically significant reductions in weight (129.6 ± 25.9 v 126.9 ± 26.1 kg, p < 0.001), BMI (46.3 ± 8.3 v 44.9 ± 9.0 kgm(-2), p < 0.001), waist circumference (133.0 ± 17.1 v 129.3 ± 17.5 cm in women and 143.8 ± 19.0 v 135.1 ± 17.9 cm in men, both p < 0.001) as well as anxiety and depression scores, total- and LDL-cholesterol and triglyceride levels, with an increase in functional capacity (5.9 ± 1.7 v 6.8 ± 2.1 metabolic equivalents of thermogenesis (METS), p < 0.001) in completers at the end of the programme compared to the start. Blood pressure improved, with reductions in systolic and diastolic blood pressure from 135 ± 16.2 to 131.6 ± 17.1 (p = 0.009) and 84.7 ± 10.2 to 81.4 ± 10.9 mmHg (p < 0.001), respectively. The proportion of patients achieving target blood pressure increased from 50.3 to 59.3% (p = 0.04). The proportion of patients with diabetes achieving HbA1c <53 mmol/mol increased from 28.6 to 42.9%, p = 0.02. CONCLUSIONS: Bariatric patients completing an 8 week, nurse-led structured lifestyle programme had improved adiposity, fitness, lipid profiles, psychosocial health, blood pressure and glycaemia. Further assessment of this programme in a pragmatic randomised controlled trial seems warranted.

Construct validity of the misrepresentation scales of the psychological screening inventory.

This study provides construct validity evidence and reliabilities (consistency and stability) for 5 misrepresentation (response distortion) scales of the Psychological Screening Inventory (PSI; Lanyon, 1970, 1973, 1978) in assessing 3 constructs: exaggeration of psychopathology, exaggeration of personal virtue, and exaggeration of health problems. Using data from forensic cases, the existence and independence of these 3 constructs were confirmed in data from the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) and the Balanced Inventory of Desirable Responding (Paulhus, 1986, 1991). The PSI scales were then shown to load highly on these constructs. The PSI scales also showed the expected patterns when their mean scores were examined for 15 sets of responses from participant groups with varied motivations to misrepresent. We present receiver operating characteristic data to show the success of the scales in distinguishing between simulators and appropriate comparison groups. Using the same data, we also present classification accuracy in terms of positive predictive power and negative predictive power based on a sensitivity level of 90% and misrepresentation base rates of .20 and .10.