Influence of gastric residual assessment in preterm neonates on time to achieve enteral feeding (the GRASS trial)-Multi-centre, assessor-blinded randomised clinical trial.

PURPOSE: Gastric residual measurement is routinely performed in premature infants prior to feeding despite a lack of evidence of benefit. We aimed to evaluate if the exclusion of routine gastric residual measurement and evaluation has an impact on the time taken to achieve full enteral feeding in preterm neonates. METHODS: International multi-centre randomised controlled trial. Clinically stable, appropriate for gestational age infants between 26+0 and 30+6 weeks of gestation and less than 1.5 kg birth weight were eligible. Infants were randomised to the intervention arm (no monitoring of gastric aspirates) or control arm (routine care). Primary outcome was the achievement of enteral feeds of 100 ml/kg/day by day 5 of life. RESULTS: Ninety-five infants were recruited with 88 included in an intention-to-treat analysis, 45 in the intervention arm and 43 in the control arm. There was no imbalance in baseline characteristics. Thirty-three (73.3%) infants in the intervention group and 32 infants (74.4%) in the control group reached full feeds by day 5 of life (p = 0.91) with no difference in median time to full feeds. There were no statistically significant differences in survival or the major morbidities of prematurity. CONCLUSION:  There was no difference in time to attainment of enteral feeds of 100 ml/kg/day in premature infants when gastric residuals were not monitored. In the absence of a clinical benefit to routine monitoring, it may be appropriate to discontinue this practice and only monitor residuals when clinical concern of feeding intolerance or gastrointestinal pathology arises in this group of patients. TRIAL REGISTRATION:  NCT03111329- https://clinicaltrials.gov/ . Registered 06/04/2017. WHAT IS KNOWN: • Previous randomized trials have shown little benefit to the performance of routine assessment of gastric residuals in preterm infants. Despite this, they continue to be performed due to concerns from observational data regarding development of NEC. Meta-analysis to date has failed to answer the question regarding NEC. WHAT IS NEW: • In very low birth weight infants who are fed using modern feeding practice of faster feed advancement, to minimize use of central access and parenteral nutrition, exclusion of routine checks of gastric residuals did not increase the proportion of infants reaching full enteral feeds by day 5. No harm was seen when residual checks were not performed. • In the absence of a clinical benefit to the routine performance of gastric residuals in very low birth weight infants, it may be appropriate to discontinue their use and instead check residuals when clinical concern of pathology arises.

Altered inflammasome activation in neonatal encephalopathy persists in childhood.

Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)-1ß, IL-1ra and IL-18 are activated by the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat domain (LRR)- and NOD-like receptor protein 3 (NLRP3) inflammasome; furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in proinflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex enzyme-linked immunosorbent assay (ELISA) in neonates and children with NE in the absence or presence of lipopolysaccharide (LPS) endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL-1ß and ASC by polymerase chain reaction (PCR). Serum samples from 40 NE patients at days 1 and 3 of the first week of life and in 37 patients at age 4-7 years were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on days 1 and 3 was observed compared to neonatal controls. IL-1ra in NE was decreased to normal levels at school age, whereas serum IL-18 in NE was even higher at school age compared to school age controls and NE in the first week of life. Percentage of LPS response was higher in newborns compared to school-age NE. NLRP3 and IL-1ß gene expression were up-regulated in the presence of LPS in NE neonates and NLRP3 gene expression remained up-regulated at school age in NE patients compared to controls. Increased inflammasome activation in the first day of life in NE persists in childhood, and may increase the window for therapeutic intervention.

Central catheter removal timing and growth patterns in preterm infants.

BACKGROUND: Early discontinuation of total parenteral nutrition (TPN) at 100 ml/kg/day of enteral feeds, compared with 140 ml/kg/day, led to significant delay in time to regain the birth weight in very low birth weight infants (birth weight < 1500 g, VLBW). Our aim was to compare the growth of infants in relation with timing of TPN discontinuation up to 2 years corrected gestational age (CGA). METHODS: Posttrial follow-up study using review of paper medical records. Participants of the randomized controlled trial studying effect of early parenteral nutrition discontinuation on time to regain birth weight in VLBW infants were included. Growth parameters inclusive of weight, length, and occipital-frontal circumference (OFC) were collected. Z-scores were calculated at five predefined time points-birth, 0-11 weeks CGA, 12-35 weeks CGA, 36-60 weeks CGA, and 61-96 weeks CGA and compared for control and intervention groups. RESULTS: Regarding weight, we found lower mean Z-score in the intervention group between 0 and 11 weeks CGA, with larger difference in extremely low birth weight infants (birth weight < 1000 g, ELBW), but this did not reach the statistical significance. Regarding length, the same difference, slightly delayed to 35 weeks CGA was observed and reached statistical significance for ELBW infants between 12 and 35 weeks CGA. There was no difference in OFC mean Z-scores at any timepoint. CONCLUSIONS: The discontinuation of TPN at 100 ml/kg/day showed significantly lower Z-score for length in ELBW infants between 12 and 35 weeks CGA. There were no differences in Z-scores by 2 years CGA.

CURRENT TREATMENT OPTIONS OF DUPUYTREN´S DISEASE.

Dupuytren's disease (fibromatosis of the palmar fascia, benign neoplastic fibromatosis, Dupuytren's contracture) is a disease characterized by growth and successive contracture of single parts of the palmar aponeurosis. This condition is known and has been treated for several centuries. In the advanced stages of the disease, it leads to significant limitation of hand function, resulting in reduced quality of life of the patient. Dupuytren's disease (DD) is a life-long disease with a variable course and a heterogeneous clinical presentation. Therapy focuses on the clinical manifestations of the disease as well as on reduction of the functional limitation of the hand caused by the disease. In addition to conservative and surgical procedures, there are also some mini-invasive methods available. Treatment should be reserved for centres and experienced surgeons specialized in hand surgery.

SURGICAL TREATMENT OF MELANOMA.

Malignant melanoma is a serious disease, the incidence of which rises. Since the most important treatment method is sufficient wide skin and subcutaneous tissue excision, plastic surgeon is often the only specialist who is able to close the resulting defect. This paper deals with recommendations and treatment options for malignant melanoma from the point of a plastic surgeon. The primary width of excised safety rim of healthy tissue with regards to the depth of melanoma invasion differs. Safety margin is 0.5 cm for melanoma in situ, 1 cm in Breslow up to 2 mm and 2 cm in Breslow over 2 mm. Furthermore, there is indication for sentinel lymph node biopsy, which should be performed in melanoma with Breslow over 1 mm, and in risky melanoma in Breslow above 0.75 mm. Every patient with stage IIB malignant melanoma and above according to TNM classification should undergo adjuvant therapy in a specialized centre. Ideal condition for the patient is a permanent and close cooperation between a dermatologist, oncologist and plastic surgeon, who supplement each other in diagnostics, therapy and follow up of the patients.

Arterial supply of the thumb: Systemic review.

We offer a complete systemic review of the anatomy of arteries of the thumb, including their sources in the first web space. Eleven studies were selected from the PubMed, Medline, Embase, Scopus and Ovid databases. Data about each artery of the thumb were obtained; in particular, the incidence and dominance of each of these arteries were calculated. The ulnopalmar digital artery of the thumb (UPDAT) was found in 99.63%, the radiopalmar digital artery of the thumb (RPDAT) in 99.26%, the ulnodorsal digital artery of the thumb (UDDAT) in 83.39%, and the radiodorsal digital artery of the thumb (RDDAT) in 70.38%. The sources for the thumb arteries are the first palmar metacarpal artery (for UPDAT in 63.15%, for RPDAT in 78.88%, for UDDAT in 56.95% and for RDDAT in 41.48%), the first dorsal metacarpal artery (for UPDAT in 20.54%, for RPDAT 2.53%, for UDDAT in 20.62%, and for RDDAT in 4.81%) and the superficial palmar arch, either complete or incomplete (for UPDAT in 25.57%, for RPDAT in 23.04%, for UDDAT in 0%, and for RDDAT in 5.19%). The dominant source could be identified in 88.2% of cases: the first palmar metacarpal artery (66.2%), the first dorsal metacarpal artery (15.5%) and the superficial palmar arch, complete or incomplete (8.2%). Four arteries usually supply the thumb. Any artery in the first web space can be a source for the thumb arteries. We propose a new classification of the arteries of the hand, dividing them into three systems (superficial palmar, deep palmar and dorsal system), and suggest that the term "princeps pollicis artery" be reconsidered and systemic anatomical terms of the thumb arteries preferred. Clin. Anat. 30:963-973, 2017. ©2017 Wiley-Liss, Inc.

A conservative treatment of patent ductus arteriosus in very low birth weight infants.

BACKGROUND: Treatment of the patent ductus arteriosus (PDA) in the preterm infant remains contentious. There are numerous options of the PDA management from early targeted treatment, late (symptomatic) treatment to no treatment at all. AIMS: To evaluate a three different PDA management approaches in very low birth weight (VLBW) infants. STUDY DESIGN: A retrospective observational time series study of three cohorts of VLBW infants born between 2004 and 2011. SUBJECTS: Infants in Symptomatic Treatment Group (STG) were echocardiographically evaluated when clinical signs suggestive of a PDA were present and treated if a haemodynamically significant PDA was confirmed. Early Targeted Group (ETG) underwent echocardiography within the first 48h and infants received ibuprofen if a large PDA was present. Conservative Treatment Group (CTG) was screened by echocardiography on day seven of life; patients with PDA were managed with increased positive end expiratory pressure and fluid restriction as a first line intervention. OUTCOMES: The primary outcome was medical and surgical treatment in the three time periods. Secondary outcomes included mortality, severe periventricular and intraventricular haemorrhage, respiratory distress syndrome and chronic lung disease. RESULTS: There were 138 infants diagnosed with PDA; 52 infants in STG, 52 infants in ETG and 34 infants in CTG. Ibuprofen therapy and ligation were less frequent in CTG. There was significantly decreased incidence of chronic lung disease in CTG compared to STG (18% vs. 51%; p=0.003) and to ETG (18% vs. 46%; p=0.02). There was no difference in the other short term outcomes. CONCLUSION: Conservative treatment of persistent ductus arteriosus in VLBW infants is a feasible option and future randomized trials of conservative management are warranted.

Reporting on data monitoring committees in neonatal randomised controlled trials is inconsistent.

AIM: To evaluate the reported use of data monitoring committees (DMCs), the frequency of interim analysis, prespecified stopping rules and early trial termination in neonatal randomised controlled trials (RCTs). METHODS: We reviewed neonatal RCTs published in four high-impact general medical journals, specifically looking at safety issues including documented involvement of a DMC, stated interim analysis, stopping rules and early trial termination. We searched all journal issues over an 11-year period (2003-2013) and recorded predefined parameters on each item for RCTs meeting inclusion criteria. RESULTS: Seventy neonatal trials were identified in four general medical journals: Lancet, New England Journal of Medicine (NEJM), British Medical Journal and Journal of American Medical Association. A total of 43 (61.4%) studies reported the presence of a DMC, 36 (51.4%) explicitly mentioned interim analysis, stopping rules were reported in 15 (21.4%) RCTs and seven (10%) trials were terminated early. The NEJM most frequently reported these parameters compared to the other three journals reviewed. CONCLUSION: While the majority of neonatal RCTs report on DMC involvement and interim analysis, there is still scope for improvement. Clear documentation of safety-related issues should be a central component of reporting in neonatal trials involving newborn infants.

CURRENT CONCEPTS IN PERIPHERAL NERVE INJURY REPAIR.

Even though reconstructive surgery of the nerves underwent significant progress due to experimental and clinical research over the past 40 years, injuries to the peripheral nerves still remain a great challenge for microsurgery. Literature results of these procedures are often evaluated as very good but the final result is often characterized by an achievement of only a useful and not full function, which is rather rare. It is not only a simple suture; the success is also based on functional regeneration and interconnection of the nerve fibres. This is limited by correct surgical technique, the age of the patient, delay from the time of injury and the mechanism or localization of the injury. Some injuries even now remain untreatable (such as the most severe brachial plexus injuries or long traction injuries of the peroneal nerve). Apart from standard neurolysis and epi- or perineural suture with or without nerve grafts, distal nerve transfers (in case of proximal injuries) and end-to-side neurorrhaphy (mainly in trauma of sensitive nerves) have recently been frequently used. The future is however based on influence of nerve regeneration at the cellular level using substances with growth potential. The main prerequisite of successful surgery is however early indication of surgical revision in a specialized centre.