Effects of photobiomodulation and caffeine treatment on acute kidney injury in a hypoxic ischemic neonatal rat model.

Hypoxic ischemic encephalopathy (HIE) occurs in 2-5/1000 births, with acute kidney injury (AKI) occurring in 40%. AKI increases morbidity and mortality. Caffeine, an adenosine receptor antagonist, and photobiomodulation (PBM), working on cytochrome c oxidase, are potential treatments for AKI. To examine effects of caffeine and PBM on AKI in rats, Day 7 pups underwent a HIE intervention (Modified Rice-Vannucci model) replicating pathology observed in humans. Caffeine was administered for 3 days and/or PBM for 5 days following HIE. Weights and urine for biomarkers (NGAL, albumin, KIM-1, osteopontin) were collected prior to HIE, daily post intervention and at sacrifice. Both treatments reduced kidney injury seen on electron microscopy, but not when combined. HIE elevated urinary NGAL and albumin on Days 1-3 post-HIE, before returning to control levels. This elevation was significantly reduced by PBM or caffeine. KIM-1 was significantly elevated for 7 days post-HIE and was reduced by both treatments. Osteopontin was not altered by HIE or the treatments. Treatments, individually but not in combination, improved HIE-induced reductions in the enzymatic activity of mitochondrial complexes II-III. PBM and caffeine also improved weight gain. PBM and caffeine reduces AKI diagnosed by urinary biomarkers and confirmed by EM findings.

The Menstrual Disorder of Teenagers (MDOT) Study No. 2: Period ImPact and Pain Assessment (PIPPA) Tool Validation in a Large Population-Based Cross-Sectional Study of Australian Teenagers.

STUDY OBJECTIVE: To validate the Period ImPact and Pain Assessment (PIPPA) self-screening tool for menstrual disturbance in teenagers. DESIGN: Cross-sectional study. SETTING: Three senior high schools in the Australian Capital Territory (ACT), Australia. PARTICIPANTS: A total of 1066 girls between 15 and 19 years of age. INTERVENTIONS AND MAIN OUTCOME MEASURES: A quantitative paper survey collected self-reports of menstrual bleeding patterns, typical and atypical symptoms, morbidities, and interference with daily activities. Multiple correspondence analysis was used to examine associations between PIPPA questions. Generalized linear models compared total score and subscores by validation criteria: pain, school absence, and body mass index (BMI). Receiver operating characteristic curves were used to evaluate the predictiveness of menstrual disturbance indicators by total PIPPA score. RESULTS: Reports of pain, interference, and concern within the PIPPA items and between both the MDOT and PIPPA questionnaires were significantly correlated (P < .0001). The indicator "missing school" was highly associated (P < .0001) with pain and interference. Obesity (BMI ≥30) was associated with higher PIPPA scores, as was underweight (BMI≤18.4). Where 0 = no disturbance, 5 = high disturbance, aggregated PIPPA scores found 75% scoring 0-2 (out of 5) and 25% scoring 3-5 (257/1037). High scores of 4 or 5 (out of 5) were 7% (72/1037) and 3.7% (38/1037), respectively. CONCLUSION: PIPPA is a valid screening tool for pain-related menstrual disturbance that affects functioning in young women. PIPPA subdomains of pain/interference have good validity relative to indicators of pain and interference and are responsive to age, BMI, and school absence differences.

Do Maternal Vitamin D Levels Influence Vitamin D Levels in Preterm Neonates?

OBJECTIVE: To determine the prevalence of Vitamin D (VitD) deficiency/insufficiency in mothers of preterm neonates less than or equal to 32 weeks of gestation and determine if the current level of VitD supplementation used for preterm neonates is appropriate. DESIGN: Prospective study from 10th May 2015 to 1st November 2016. SETTING: Neonatal Intensive Care Unit at the Canberra Hospital. PATIENTS: Mothers and their preterm neonates born less than or equal to 32 weeks gestation. INTERVENTIONS: Maternal VitD levels were obtained within 3-4 days following delivery. Neonatal VitD levels were obtained in the first 3-4 days of life, at 3-4 weeks of age, and at 6-8 weeks of age. Demographic data and data on VitD intake from parenteral nutrition, enteral feeds, and vitamin supplementation agents were collected. RESULTS: 70 neonates were enrolled into the study. Median gestation was 29 (27-30) weeks and median birth weight 1197 (971.2-1512.5) grams. Median maternal VitD level was 54.5 (36-70.7) nmol/L, median neonatal Vit D level at birth was 57 (42-70) nmol/L. Median Vit D level at 3 weeks and 6 weeks were 63.5 nmol/L (53-80.2) nmol/L and 103 (71.5-144) nmol/L respectively. 22/55 (40%) mothers were VitD deficient/insufficient. 25/70 (36%) neonates were VitD deficient/insufficient at birth. Of those neonates who were VitD deficient/insufficient at birth 5/25(10%) were deficient/insufficient at 6 weeks. The median intake of VitD at 6 weeks was 826.5 (577.5-939.5) IU/day. CONCLUSIONS: VitD deficiency/insufficiency in mothers of preterm neonates and in preterm neonates at birth is common. Routine screening of maternal VitD and their preterm neonates along with individualized supplementation regimens in mothers and preterm infants may optimize VitD status and reduce risk of ongoing VitD deficiency/insufficiency.

Neonatal Acute Kidney Injury: A Survey of Neonatologists' and Nephrologists' Perceptions and Practice Management.

BACKGROUND: Neonatal acute kidney injury (AKI) occurs in 40 to 70% of critically ill neonatal intensive care admissions. This study explored the differences in perceptions and practice variations among neonatologists and pediatric nephrologists in diagnostic criteria, management, and follow-up of neonatal AKI. METHODS: A survey weblink was emailed to nephrologists and neonatologists in Australia, Canada, New Zealand, India, and the United States. Questions consisted of demographic and unit practices, three clinical scenarios assessing awareness of definitions of neonatal AKI, knowledge, management, and follow-up practices. RESULTS: Many knowledge gaps among neonatologists, and to a lesser extent, pediatric nephrologists were identified. Neonatologists were less likely to use categorical definitions of neonatal AKI (p < 0.00001) or diagnose stage 1 AKI (p < 0.00001) than pediatric nephrologists. Guidelines for creatinine monitoring for nephrotoxic medications were reported by 34% (aminoglycosides) and 62% (indomethacin) of respondents. Nephrologists were more likely to consider follow-up after AKI than neonatologists (p < 0.00001). Also, 92 and 86% of neonatologists and nephrologists, respectively, reported no standardization or infrastructure for long-term renal follow-up. CONCLUSION: Neonatal AKI is underappreciated, particularly among neonatologists. A lack of evidence on neonatal AKI contributes to this variation in response. Therefore, dissemination of current knowledge and areas for research should be the priority.

A safety and feasibility study of the use of 670 nm red light in premature neonates.

OBJECTIVE: Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina affecting extremely preterm or low birth weight infants The aim of this study was to assess the feasibility and safety of 670 nm red light use in a neonatal intensive care unit. STUDY DESIGN: Neonates <30 weeks gestation and <1150 g were enrolled within 48 h of birth. Data collected included cause of preterm delivery, Apgar scores and birthweight. 670 nm red light was administered for 15 min per day from a distance of 25 cm, delivering 9 J cm(-)(2), from the time of inclusion in the study until 34 weeks postmenstrual age. Infants were assessed daily for the presence of any skin burns or other adverse signs. RESULT: Twenty-eight neonates were enrolled, seven 24 to 26 weeks and twenty-one 27 to 29 weeks gestation. The most common cause for preterm delivery was preterm labor (14/28) with five of these having evidence of chorioamnionitis. There were no skin burns or other documented adverse events. Entry into the study was readily achieved and treatment was well accepted by parents and nursing staff. CONCLUSION: 670 nm red light appears to be a safe and feasible treatment for further research in respect to ROP.

Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat.

Indomethacin and ibuprofen are administered to close a patent ductus arteriosus (PDA) during active glomerulogenesis. Light and electron microscopic glomerular changes with no change in glomerular number were seen following indomethacin and ibuprofen treatment during glomerulogenesis at 14 days after birth in a neonatal rat model. This present study aimed to determine whether longstanding renal structural changes are present at 30 days and 6 mo (equivalent to human adulthood). Rat pups were administered indomethacin or ibuprofen antenatally on days 18-20 (0.5 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen) or postnatally intraperitoneally from day 1 to 3 or day 1 to 5 (0.2 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen). Control groups received no treatment or normal saline intraperitoneally. Pups were killed at 30 days of age and 6 mo of age. Tissue blocks from right kidneys were prepared for light and electron microscopic examination, while total glomerular number was determined in left kidneys using unbiased stereology. Eight pups were included in each group from 14 maternal rats. At 30 days and 6 mo, there were persistent electron microscopy abnormalities of the glomerular basement membrane in those receiving postnatal indomethacin and ibuprofen. There were no significant light microscopy findings at 30 days or 6 mo. At 6 mo, there were significantly fewer glomeruli in those receiving postnatal indomethacin but not ibuprofen (P = 0.003). In conclusion, indomethacin administered during glomerulogenesis appears to reduce the number of glomeruli in adulthood. Alternative options for closing a PDA should be considered including ibuprofen as well as emerging therapies such as paracetamol.

Length of time from extubation to cardiorespiratory death in neonatal intensive care patients and assessment of suitability for organ donation.

OBJECTIVE: A common concern for parents when end of life decisions are made is the length of time their baby may take to die. Postcardiac death organ donation is now becoming more common, along with neonatal organ donation. The aim was to determine the length of time from extubation until cardiorespiratory death (CRD) in neonatal intensive care patients and consideration of potential organ donation. DESIGN: Retrospective review of medical records of neonates who died in a neonatal intensive care unit between 2000 and 2009. PATIENTS: Data collected included gestation at birth, age at death, birth weight, reason for cessation of intensive care, inotrope and ventilation requirements, sedation and muscle relaxation prior to death, time from extubation to documented CRD. An assessment was made for potential suitability for consideration of organ donation with a gestation at birth ≥ 34 weeks and birth weight >2.0 kg. RESULTS: 117 neonates were included, median gestation 29 weeks and median birth weight 1220 grams. The median age at death was 4 days of age. The median time from discussing prognosis to death was 137 min. The median time from extubation to CRD was 30 min. Seven (6%) neonates were considered suitable for organ donation, and for these infants the median time from extubation to CRD was 120 min. Two neonates donated heart valves. CONCLUSIONS: This provides a guide for grieving parents on time frames for the interval between extubation and CRD. More accurate postextubation CRD times are required to determine likely potential for postcardiac death organ donation.

Comparison of metabolomic profiles obtained using chemical ionization and electron ionization MS in exhaled breath.

The exhaled breath is rich in a wide range of volatile organic compounds with the potential to provide readily accessible biomarkers for metabolic activity in the body as a result of normal or abnormal/disease processes. Exhaled breath samples from five healthy volunteers have been analyzed by thermal desorption GC-MS using electron impact and chemical ionization. A total of eight compounds: 2-propenoic acid; 2-methyl, methyl ester; toluene; hexanal; 1,4-cyclohexadiene, 1-methyl-4-(1methlethyl); phenol; nonanal; dodecane and indole, have been evaluated to establish differences in selectivity and sensitivity using these two mechanisms of ionization. The combination of both electron impact and chemical ionization profiles could prove valuable when prospecting for breath-derived biomarkers as they result in complementary information that aids the identification of unknown components.

Locally advanced breast cancer: is surgery warranted following chemotherapy?

Various methods of management of locally advanced breast cancer have been proposed, including combinations of chemotherapy, surgery, radiotherapy, immunotherapy and hormone manipulation. This retrospective study evaluated the effectiveness of chemotherapy in the management of locally advanced breast cancer in pre- and perimenopausal women by examining the pathology of the mastectomy specimens. Sixteen women who on initial clinical examination had breast cancers measuring 5 cm or greater underwent chemotherapy prior to surgery. Four women were also treated with radiotherapy prior to surgery. All 16 women underwent mastectomy and axillary clearance. All specimens showed residual tumour in the mastectomy specimen or the regional lymph nodes. Chemotherapy is useful in reducing tumour burden to allow surgical resection, but does not produce centripetal shrinkage of tumour, nor sterilize the breast of cancer. In this small series, the addition of radiotherapy also failed to clear the patient of tumour. Wide surgical excision including the original tumour margins is thus required to achieve locoregional control. Until chemotherapy and radiotherapy regimens can be proved to sterilize the breast of tumour, we caution against the use of any surgery less than total mastectomy if optimal local control is to be achieved for locally advanced breast cancer in pre- and perimenopausal women.

Endoscopic retrograde cholangiopancreatography following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is the preferred method of treatment for symptomatic choledocholithiasis. Since its introduction there has been an increase in postoperative diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to assess the indications and results of ERCP following laparoscopic cholecystectomy. Sixty-one patients had an ERCP following laparoscopic cholecystectomy. Two broad groups were identified: Group 1 (35 patients) had filling defects (consistent with stones) noted on operative cholangiography, which were not successfully flushed or extracted at the time of laparoscopic cholecystectomy; Group 2 consisted of patients who developed problems following laparoscopic cholecystectomy. Nine patients had post-laparoscopic cholecystectomy pain with abnormal liver function tests (LFT), four of whom had common bile duct (CBD) injuries and three had CBD stones. Eleven patients had post-laparoscopic cholecystectomy pain with a normal diameter common bile duct on ultrasound and normal LFT; only one had a CBD stone. Five patients with a persisting bile leak following laparoscopic cholecystectomy had an ERCP and endoscopic sphincterotomy. In three the leak ceased, while two required subsequent open surgery to drain bile collections and ligate the cystic duct. One patient presented with an episode of transient jaundice but had a normal ERCP. There were six post-ERCP complications; three patients had mild pancreatitis, two had a minor haemorrhage and one an asymptomatic duodenal perforation. Endoscopic retrograde cholangiopancreatography post-laparoscopic cholecystectomy was most valuable for the management of retained stones and the diagnosis and management of post-laparoscopic cholecystectomy pain in association with abnormal LFT. The diagnostic yield was low (9%) when the LFT were normal.

Ten year review of thoracic and abdominal penetrating trauma management.

A ten year review of penetrating thoracic and abdominal trauma examined pattern of injury, patient management and outcome. Ninety-six patients were included in the study, 55 with injury to the abdomen, 31 the thorax and 10 with injury to both areas. Fifty-eight cases were managed non-operatively; 5 combined abdominal and thoracic injuries, 26 thoracic and 27 abdominal. Two cases went on to require operative management for intra-abdominal injury. Thirty-eight cases were managed operatively; 5 combined cavity injuries, 5 thoracic and 28 abdominal. Injuries were found in all of the combined cavity and thoracic cavity cases. Of the 28 abdominal cases, nine were found on laparotomy to have no significant visceral or vessel injury, one, however, was performed for omentum protruding through the wound. While a negative laparotomy was a relatively safe procedure, non-operative management had the advantages of a shorter hospital stay without wound-related morbidity. Selective non-operative management was found to be a relatively safe approach in this series.

Malignant rhabdoid tumor of the extremity.

Two cases of malignant rhabdoid tumor (MRT) involving the sciatic nerve are described. Despite the close affiliation of the tumor with neural tissue, staining characteristics in these patients do not suggest a neural origin of MRT. Survival in patients with renal and extrarenal MRT has been poor. Our patients were treated with an aggressive chemotherapy program using cisplatin, Adriamycin (doxorubicin), vincristine, cyclophosphamide, actinomycin D, and DTIC. One child died of progressive disease; the other is well 35 months after diagnosis.