Perinatal outcomes of fetoscopic laser surgery for twin-twin transfusion syndrome in triplet pregnancy: cohort study, systematic review and meta-analysis.

OBJECTIVES: The aims of this study were to investigate the perinatal outcome of dichorionic triamniotic (DCTA) and monochorionic triamniotic (MCTA) triplet pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) in two academic fetal centers, and to conduct a systematic review of previously published data to investigate perinatal survival in this targeted population. METHODS: The first part of the study was a retrospective cohort study of prospectively collected data of consecutive triplet pregnancies with TTTS that underwent FLP at two fetal treatment centers between 2012 and 2020. Demographic, preoperative and operative variables and postoperative outcome were collected. Perinatal outcomes were investigated. The second part of the study was a systematic review and meta-analysis of studies evaluating the outcome of DCTA and/or MCTA triplet pregnancies, including our cohort study. PubMed, Web of Science and Scopus were searched from inception to September 2020. Primary outcomes were fetal survival (survival to birth), neonatal survival (survival to 28 days of age) and gestational age (GA) at birth. RESULTS: A total of 31 sets of triplets with TTTS managed with FLP were included in the cohort study. Of these, 24 were DCTA and seven were MCTA. There were no significant differences in preoperative and operative variables between the two groups. There were also no significant differences between groups in GA at delivery or perinatal survival rate, including fetal and neonatal survival of at least one triplet, at least two triplets and all three triplets. Nine studies, including our cohort study, were included in the systematic review (156 DCTA and 37 MCTA triplet pregnancies treated with FLP). The overall fetal and neonatal survival was 79% (95% CI, 75-83%) and 75% (95% CI, 71-79%), respectively, in DCTA cases and 74% (95% CI, 52-92%) and 71% (95% CI, 49-89%), respectively, in MCTA cases. The rate of preterm birth before 28 weeks and before 32 weeks' gestation was 14% (95% CI, 4-29%) and 61% (95% CI, 50-72%), respectively, in DCTA triplets and 21% (95% CI, 3-45%) and 82% (95% CI, 62-96%), respectively, in MCTA triplets. CONCLUSIONS: Triplet pregnancies with TTTS are at high risk of adverse perinatal outcome and preterm birth, regardless of chorionicity. The rate of survival after FLP in MCTA triplets was higher in our study than that reported in previous studies and is currently comparable with survival in DCTA triplets, which could be due to improved surgical skills. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

B-flow/spatiotemporal image correlation M-mode: novel ultrasound method that detects decrease in spiral artery luminal diameter in first trimester in primate model of impaired spiral artery remodeling.

OBJECTIVE: To determine if B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography detects a decrease in spiral artery luminal diameter and volume flow during the first trimester in a non-human primate model of impaired spiral artery remodeling (SAR). METHODS: Pregnant baboons were treated daily with estradiol benzoate on days 25-59 of the first trimester (term, 184 days), or remained untreated. On day 60 of gestation, spiral artery luminal diameter (in seven untreated and 12 estradiol-treated baboons) and volume flow (in four untreated and eight estradiol-treated baboons) were quantified by B-flow/STIC M-mode ultrasonography. In addition, in 15 untreated and 18 estradiol-treated baboons, the percent of spiral arteries remodeled by extravillous trophoblasts was quantified ex vivo by immunohistochemical image analysis on placental basal plate tissue collected via Cesarean section on day 60. Findings were compared between treated and untreated animals. The correlation between spiral artery luminal diameter and percent of SAR was assessed in three untreated and six estradiol-treated baboons which underwent both B-flow/STIC M-mode ultrasound and quantification of SAR. RESULTS: The proportion of spiral arteries greater than 50 µm in diameter remodeled by extravillous trophoblasts was 70% lower in estradiol-treated baboons than in untreated animals (P = 0.000001). Spiral artery luminal diameter in systole and diastole, as quantified by B-flow/STIC M-mode in the first trimester of pregnancy, was 31% (P = 0.014) and 50% (P = 0.005) lower, respectively, and volume flow was 85% lower (P = 0.014), in SAR-suppressed baboons compared with untreated animals. There was a significant correlation between spiral artery luminal diameter as quantified by B-flow/STIC M-mode ultrasonography and the percent of SAR (P < 0.05). CONCLUSION: B-flow/STIC M-mode ultrasonography provides a novel real-time non-invasive method to detect a decrease in uterine spiral artery luminal diameter and volume flow during the cardiac cycle, reflecting decreased distensibility of the vessel wall, in the first trimester in a non-human primate model of defective SAR. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Iatrogenic chorioamniotic separation and septostomy following fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

OBJECTIVE: To compare the perinatal outcomes of pregnancies complicated by chorioamniotic separation (CAS) vs septostomy following fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS). METHODS: This was a retrospective cohort analysis of monochorionic diamniotic twin pregnancies with TTTS that underwent FLP at one of two university-affiliated tertiary medical centers between January 2012 and December 2020. CAS and septostomy were diagnosed either during the procedure or by ultrasonography within 24-48 h after FLP. Data on procedure and postprocedure parameters, pregnancy outcomes and survival were collected from the patients' electronic medical records. Pregnancies were stratified according to the presence of CAS, septostomy or neither. Patients diagnosed with both CAS and septostomy were analyzed separately. RESULTS: Of the 522 women included in the cohort, 38 (7.3%) were diagnosed with CAS, 68 (13.0%) with septostomy and 23 (4.4%) with both CAS and septostomy. The remaining 393 (75.3%) women comprised the control group. Groups did not differ in demographic characteristics. The septostomy group had a lower rate of selective fetal growth restriction than did the CAS and control groups (24.2% vs 36.8% vs 42.7%, respectively; P = 0.017). Moreover, intertwin size discordance was lower in the septostomy group (15.1% vs 23.4% in the CAS group and 25.5% in the control group; P = 0.001). Median gestational age at FLP was significantly lower in the CAS group (19.3 weeks vs 20.4 weeks in controls and 20.9 weeks in the septostomy group; P = 0.049). The rate of delivery prior to 34 weeks was significantly higher in the CAS group (89.2%), followed by the septostomy group (80.9%), compared with the control group (69.0%) (P = 0.006). A secondary analysis demonstrated that patients with both CAS and septostomy presented the highest rates of delivery prior to 34 weeks (100%) and 32 weeks (68.2%). CONCLUSIONS: CAS and septostomy following laser surgery for TTTS are independently associated with higher rates of preterm delivery. The presence of these two findings in the same patient enhances the risk of prematurity. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Efficacy of long-term indomethacin therapy in prolonging pregnancy after fetoscopic laser surgery for twin-to-twin transfusion syndrome: a collaborative cohort study.

OBJECTIVE: To evaluate the efficacy of long-term indomethacin therapy (LIT) in prolonging pregnancy and reducing spontaneous preterm birth (PTB) in patients undergoing fetoscopic laser surgery (FLS) for the management of twin-to-twin transfusion syndrome (TTTS). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Collaborative multicentre study. POPULATION: Five hundred and fifty-seven consecutive TTTS cases that underwent FLS. METHODS: Long-term indomethacin therapy was defined as indomethacin use for at least 48 hours. Log-binomial regression was used to estimate the relative risk of PTB in the LIT group compared with a non-LIT group. Cox regression was used to evaluate the association between LIT use and FLS-to-delivery survival. MAIN OUTCOME MEASURES: Gestational age (GA) at delivery. RESULTS: Among the 411 pregnancies included, a total of 180 patients (43.8%) received LIT after FLS and 231 patients (56.2%) did not. Median GA at fetal intervention did not differ between groups (20.4 weeks). Median GA at delivery was significantly higher in the LIT group (33.6 weeks) compared with the non-LIT group (31.1 weeks; P < 0.001). FLS-to-delivery interval was significantly longer in the LIT group (P < 0.001). The risks of PTB before 34, 32, 28 and 26 weeks of gestation were all significantly lower in the LIT group compared with the non-LIT group (relative risks 0.69, 0.51, 0.37 and 0.18, respectively). The number needed to treat with LIT to prevent one PTB before 32 weeks of gestation was four, and to prevent one PTB before 34 weeks was five. CONCLUSION: Long-term indomethacin after FLS for TTTS was found to be associated with prolongation of pregnancy and reduced risk for PTB. TWEETABLE ABSTRACT: Long-term indomethacin used after fetoscopic laser surgery for twin-to-twin transfusion syndrome is effective in prolonging pregnancy and reducing the risk for preterm birth; especially extreme preterm birth.

Early laser surgery is not associated with very preterm delivery or reduced neonatal survival in TTTS.

OBJECTIVE: To evaluate the association of laser photocoagulation of placental anastomoses (LPA) prior to 18 weeks' gestation (early LPA) with very preterm delivery and neonatal survival in pregnancies with twin-twin transfusion syndrome (TTTS). METHODS: This was a retrospective cohort study of monochorionic diamniotic twin pregnancies with TTTS undergoing LPA between 2002 and 2018 at two institutions. The rates of delivery < 28, < 30 and < 32 weeks' gestation, preterm prelabor rupture of membranes (PPROM) and 30-day survival of one or both infants were compared between pregnancies undergoing early LPA and those undergoing LPA ≥ 18 weeks' gestation. Regression analysis was performed to determine the association of early LPA with very preterm delivery and 30-day survival, adjusted for Quintero stage, study phase, selective fetal growth restriction, gestational age at delivery, maternal age ≥ 35 years, body mass index > 35 kg/m2 , placental location, use of Seldinger method to place the operative trocar, size of the trocar, participating center, use of Solomon technique, cerclage and PPROM. Survival analysis using the Cox proportional hazard model was applied to examine the LPA-to-delivery interval according to the timing of surgery, adjusted for confounding variables. RESULTS: A total of 414 TTTS pregnancies were included in the study, of which 68 (16.4%) underwent early LPA. In the total cohort, the incidence of delivery at < 28, < 30 and < 32 weeks' gestation was 22.7%, 39.6% and 53.4%, respectively. Survival of both twins and survival of at least one twin at 30 days were 67.5% and 90.8%, respectively. No significant difference was noted between pregnancies that underwent early LPA and those that had LPA ≥ 18 weeks in the rate of delivery < 28 weeks (19.1% vs 23.4%; P = 0.4), < 30 weeks (38.2% vs 39.9%; P = 0.8) and < 32 weeks (44.1% vs 55.2%; P = 0.1) and PPROM (29.0% vs 24.1%; P = 0.4), or in the incidence of double-twin survival (63.9% vs 68.1%; P = 0.5) and survival of at least one infant (91.8% vs 90.6%; P = 0.7) at 30 days. Early LPA was not associated with very preterm delivery or neonatal survival in the regression analyses. Early LPA was associated with a longer LPA-to-delivery interval compared with LPA performed ≥ 18 weeks (median, 106.9 days (range, 2-164 days) vs median, 69.3 days (range, 0-146 days); P < 0.001) when adjusted for confounding variables (hazard ratio, 2.56 (95% CI, 1.76-3.73); P < 0.001). CONCLUSION: Laser surgery before 18 weeks is not associated with an increased rate of very preterm delivery and PPROM or with reduced neonatal survival when compared with LPA after 18 weeks. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

Impact of structural and metabolic variations on the toxicity and carcinogenicity of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes.

The metabolic fate of a compound is determined by numerous factors including its chemical structure. Although the metabolic options for a variety of functional groups are well understood and can often provide a rationale for the comparison of toxicity based on structural analogy, at times quite minor structural variations may have major consequences for metabolic outcomes and toxicity. In this perspective, the effects of structural variations on metabolic outcomes is detailed for a group of related hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. These classes of compounds are naturally occurring constituents of a variety of botanical-based food items. The classes vary from one another by the presence or absence of alkylation of their para-hydroxyl substituents and/or the position of the double bond in the alkyl side chain. We provide an overview of how these subtle structural variations alter the metabolism of these important food-borne compounds, ultimately influencing their toxicity, particularly their DNA reactivity and carcinogenic potential. The data reveal that detailed knowledge of the consequences of subtle structural variations for metabolism is essential for adequate comparison of structurally related chemicals. Taken together, it is concluded that predictions in toxicological risk assessment should not be performed on the basis of structural analogy only but should include an analogy of metabolic pathways across compounds and species.

Risk factors associated with preterm delivery after fetoscopic laser ablation for twin-twin transfusion syndrome.

OBJECTIVE: Despite improved perinatal survival following fetoscopic laser ablation (FLA) for twin-twin transfusion syndrome (TTTS), prematurity remains an important contributor to perinatal mortality and morbidity. The objective of the study was to identify risk factors for complicated preterm delivery after FLA. METHODS: Retrospective cohort study of prospectively collected data on maternal/fetal demographics and pre-operative, operative and postoperative variables of 459 patients treated with FLA in three USA fetal centers. Multivariate linear regression was performed to identify significant risk factors associated with preterm delivery, which were cross-validated using the k-fold method. Multivariate logistic regression was performed to identify risk factors for early compared with late preterm delivery based on median gestational age at delivery of 32 weeks. RESULTS: There were significant differences in case selection and outcomes between the centers. After controlling for the center of surgery, multivariate analysis indicated that a lower maternal age at procedure, a history of previous prematurity, shortened cervical length, use of amnioinfusion, a cannula diameter of 12 French (Fr), lack of a collagen plug placement and iatrogenic preterm premature rupture of membranes (iPPROM) were significantly associated with a lower gestational age at delivery. CONCLUSIONS: Specific fetal/maternal and operative variables are associated with preterm delivery after FLA for the treatment of TTTS. Further studies to modify some of these variables may decrease the perinatal morbidity after laser therapy.

When are amniotic fluid viral PCR studies indicated in prenatal diagnosis?

OBJECTIVE: To determine which prenatal ultrasound findings indicate the need to also obtain PCR studies for viral genome in women undergoing midtrimester amniocentesis. METHODS: This was a retrospective observational study on women that underwent amniotic fluid karyotyping and viral PCR testing for history or ultrasound based indication. Amniotic fluid was tested for adenovirus, cytomegalovirus, respiratory syncytial virus, enterovirus, Epstein-Barr virus, and parvovirus B19 using multiplex PCR study with multiple appropriate controls. Ultrasound findings were coded as normal or abnormal with 34 categories of ultrasound abnormality stratified into 18 subgroups. Relationships between these subgroups and karyotype/PCR results were tested by Pearson chi-square method or Fisher's exact test and overall logistic regression analysis. RESULTS: Amniotic fluid samples from 1191 patients were obtained for the study. Abnormal karyotype was detected in 5.4% of cases (64/1191), and PCR was positive in 6.5% of cases (77/1191). Abnormal fetal ultrasonographic findings were observed in 28.4% of cases (338/1191). There was an association between intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies or neural tube defects (NTDs), and PCR positivity. NTDs were associated with PCR positivity in fetuses with normal karyotype and nuchal thickening, cardiac or ventral wall defects were specifically associated with aneuploidy. CONCLUSION: Amniotic fluid viral PCR testing should be considered for fetuses with intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies, or NTDs. After aneuploidy is excluded, NTDs are associated with PCR positivity.

Duration of persistent abnormal ductus venosus flow and its impact on perinatal outcome in fetal growth restriction.

OBJECTIVE: To study if the duration of individual Doppler abnormalities is an independent predictor of adverse outcome in fetal growth restriction (FGR) caused by placental dysfunction. METHODS: This was a secondary analysis of patients with FGR (abdominal circumference < 5(th) percentile and umbilical artery (UA) pulsatility index (PI) elevation) who had at least three examinations before delivery. Days of duration of absent/reversed UA end-diastolic velocity (UA-AREDV), low middle cerebral artery PI (brain sparing), ductus venosus (DV) and umbilical vein Doppler abnormalities were related to stillbirth, major neonatal morbidity and intact survival. RESULTS: One hundred and seventy-seven study participants underwent a total of 1069 examinations. The duration of an absent/reversed a-wave in the DV (DV-RAV) was significantly higher in stillbirths (median, 6 days) compared with intact survivors and those with major morbidity (median, 0 days for both; P = 0.006 and P = 0.001, respectively). Duration of brain sparing was also longer in stillbirth cases compared with intact survivors (median, 19 days vs. 9 days, P = 0.02). Stepwise multinomial logistic regression showed that gestational age at delivery was a significant codeterminant of outcome for all arterial Doppler abnormalities when the DV a-wave was antegrade. However, when present, the duration of DV-RAV was the only contributor to stillbirth (probability of stillbirth = 1/(1 + exp - (interval to delivery × 1.03 - 2.28)), r2 = 0.73). Receiver-operating characteristics curve statistics showed that a DV-RAV for > 7 days predicted stillbirth (100% sensitivity, 80% specificity, likelihood ratio = 5.0, P < 0.0001). In contrast, neither neonatal death nor neonatal morbidity was predicted by the days of persistent DV-RAV. CONCLUSIONS: The duration of absent or reversed flow during atrial systole in the DV is a strong predictor of stillbirth that is independent of gestational age. While prematurity remains the strongest predictor of neonatal risks it is unlikely that pregnancy can be prolonged by more than 1 week in this setting.

Produced water extracts from North Sea oil production platforms result in cellular oxidative stress in a rainbow trout in vitro bioassay.

Produced water (PW) discharged from offshore oil industry contains chemicals known to contribute to different mechanisms of toxicity. The present study aimed to investigate oxidative stress and cytotoxicity in rainbow trout primary hepatocytes exposed to the water soluble and particulate organic fraction of PW from 10 different North Sea oil production platforms. The PW fractions caused a concentration-dependent increase in reactive oxygen species (ROS) after 1h exposure, as well as changes in levels of total glutathione (tGSH) and cytotoxicity after 96 h. Interestingly, the water soluble organic compounds of PW were major contributors to oxidative stress and cytotoxicity, and effects was not correlated to the content of total oil in PW. Bioassay effects were only observed at high PW concentrations (3-fold concentrated), indicating that bioaccumulation needs to occur to cause similar short term toxic effects in wild fish.

Placental growth factor in the first trimester: relationship with maternal factors and placental Doppler studies.

OBJECTIVE: Placental growth factor (PlGF) is a potent angiogenic factor that impacts on early placental vascular development. It was our aim to clarify relationships between PlGF and first-trimester maternal/placental factors that are related to placental development. METHODS: Prospectively enrolled patients at 11-14 weeks' gestation had serum PlGF measurement by enzyme-linked immunosorbent assay. Results were related to maternal age, parity, race, body mass index, mean arterial blood pressure (MAP), smoking/caffeine use and parameters of placental blood flow resistance. RESULTS: In 110 consecutive patients PlGF levels ranged between 1.0 and 176.1 pg/mL, showing a linear relationship with gestational age (GA) (PlGF = (1.4251 x GA) -74.951, r(2) = 0.0765, F = 8.941, P = 0.03). PlGF did not relate to maternal demographics but negatively correlated with MAP (Spearman rho = -0.191, P < 0.05). Bilateral uterine artery notching was associated with lower PlGF (40.7 (range, 1.01-131.6) vs. 51.1 (range, 6.4-176.1) pg/mL; Mann-Whitney P = 0.034.). A trend to lower levels was also observed when umbilical artery end-diastolic flow was absent (37.1 (range, 6.8-95) vs. 49.3 (range, 1.01-176.1) pg/mL; P = 0.05). CONCLUSION: PlGF in the first trimester is related to maternal cardiovascular factors and placental Doppler findings that are associated with subsequent placental dysfunction. The utility of this parameter as a first-trimester screening tool on a population basis requires further investigation.

Infant neurodevelopment following fetal growth restriction: relationship with antepartum surveillance parameters.

OBJECTIVES: To evaluate the relationship between fetal Doppler parameters, biophysical profile score (BPP) and neurodevelopmental delay at 2 years of corrected age in infants who had been growth-restricted in utero. METHODS: This was a prospective observational study including 113 pregnancies complicated by intrauterine growth restriction (IUGR) (abdominal circumference<5th percentile and elevated umbilical artery (UA) pulsatility index). The relationships of UA, middle cerebral artery and ductus venosus (DV) Doppler features, BPP, birth acidemia (artery pH<7.0+/or base deficit>12), gestational age at delivery, birth weight and neonatal morbidity (i.e. bronchopulmonary dysplasia, >Grade 2 intraventricular hemorrhage, or necrotizing enterocolitis) with a 2-year neurodevelopmental delay were evaluated. Best Beginnings Developmental Screen, Bayley Scale of Infant Development II (BSID) and Clinical Adaptive/Clinical Linguistic Auditory Milestone Stage were used. BSID<70, cerebral palsy, abnormal tone, hearing loss and/or blindness defined neurodevelopmental delay. RESULTS: Seventy-two of the 113 pregnancies completed assessment; there were 10 stillbirths, 19 neonatal deaths, three infant deaths and nine pregnancies with no follow-up. Twenty fetuses (27.8%) had UA reversed end-diastolic velocity (REDV), 34 (47.2%) abnormal DV Doppler features and 31 (43.1%) an abnormal BPP. Median gestational age at delivery and birth weight were 30.4 weeks and 933 g, respectively. Twelve infants had acidemia and 28 neonatal morbidity. There were 38 (52.8%) infants with neurodevelopmental delay, including 37 (51.4%) with abnormal tone, 20 (27.8%) with speech delay, 23 (31.9%) with an abnormal neurological examination, eight (11.1%) with a hearing deficit and six (8.3%) with cerebral palsy. Gestational age at delivery was associated with cerebral palsy (r2=0.52, P<0.0001; 92% sensitivity and 83% specificity for delivery at <27 weeks). UA-REDV was associated with global delay (r2=0.31, P=0.006) and birth weight with neurodevelopmental delay (r2=0.54, P<0.0001; 82% sensitivity and 64% specificity for BW<922 g). CONCLUSIONS: Although UA-REDV is an independent contributor to poor neurodevelopment in IUGR no such effect could be demonstrated for abnormal venous Doppler findings or BPP. Gestational age and birth weight remain the predominant factors for poor neurodevelopment in growth-restricted infants.

Intraoperative parathormone measurement from the internal jugular vein predicts post-thyroidectomy hypocalcaemia.

BACKGROUND: The most common significant complication of total thyroidectomy is hypoparathyroidism. Intraoperative prediction of which patients are likely to be affected would allow both intraoperative and postoperative interventions to be utilised in these patients. Selection of these patients is essential if we are to be successful at discharging total thyroidectomy patients on the first postoperative day. We investigated the utility of intraoperative parathormone measurement from the internal jugular vein at predicting postoperative hypocalcaemia. MATERIALS AND METHODS: Prospective collection of data was done on 45 consecutive total thyroidectomy patients. Preoperative calcium, intraoperative parathormone and postoperative calcium and parathormone were collected. The accuracy of intraoperative parathormone in predicting those with postoperative hypocalcaemia was assessed. RESULTS: Intraoperative parathormone of less than 2 pmol l(-1) had a sensitivity of 100% and a specificity of 95% in predicting those with postoperative hypocalcaemia. An intraoperative sample less than 2 pmol l(-1) was a highly significant predictor (p < 0.0001) of postoperative hypocalcaemia. CONCLUSION: Intraoperative assessment of parathormone is an accurate predictor of those patients who will become hypoparathyroid in the postoperative period. Intraoperative prediction allows for targeted autotransplantation of glands in those at risk and selected early institution of postoperative supplementation in these patients. Patients not identified as at risk can be safely discharged.

Role of intraoperative frozen section in the management of thyroid nodules.

BACKGROUND: The role of intraoperative frozen section in the management of thyroid nodules is controversial. Its potential benefit is to facilitate one-stage total thyroidectomy. Most literature on this topic originates from overseas tertiary referral centres with a high percentage of cancer cases and a fully resourced frozen section service. The aim of the present study was to review all patients undergoing frozen section at a typical general surgical department in New Zealand (North Shore Hospital, Auckland) to see how often frozen section altered surgical strategy. METHODS: A retrospective review of all frozen sections between November 1999 and June 2003 was performed. Patient records, operation notes and pathology reports were reviewed. RESULTS: Forty-seven sequential frozen sections were included in the study. Thirteen patients had thyroid carcinoma (five follicular, three Hurthle cell, and five papillary). In only one patient did the result of an intraoperative frozen section result in a total thyroidectomy being performed instead of a thyroid lobectomy. The reason for this was the rare condition of Riedel's thyroiditis. In no patients did frozen section detect a cancer that was not diagnosed on preoperative fine-needle aspirate biopsy. CONCLUSION: The present review found little benefit in performing intraoperative frozen section in this setting. As a diagnostic test the cost of frozen section (NZ $200 for each frozen section) needs to be weighed against its low clinical benefit.

A retrospective survey on the safety of Replenine, a high-purity factor IX concentrate.

PURPOSE: To assess the safety of a plasma-derived highly purified factor IX concentrate (Replenine) in routine clinical use. METHODS: Following guidelines entitled Safety Assessment of Marketed Medicines (SAMM), safety data were collected in the UK by retrospective review of the hospital notes of 114 patients who received an estimated 14.8 million IU of Replenine. Included were 40 patients undergoing 44 surgical procedures or dental extractions [corrected]. RESULTS: The study detected a total of nine adverse events (AEs), four of which were possibly product-related, four that were unrelated to the product and one whose causality was unknown. None of these cases had been notified to the manufacturer through conventional spontaneous reporting procedures. One patient was switched from Replenine because of infusion site irritation, but no unexpected adverse reactions were noted. There were no reports of virus transmission or new factor IX inhibitor development. The mean factor IX recovery value was 1.44 IU/dl per IU/kg (95%CI: 1.31-1.57 IU/dl per IU/kg). CONCLUSIONS: The study was a practical application of the SAMM guidelines to the collection of pharmacovigilance data on patients with Haemophilia B. Replenine is well tolerated in routine clinical practice.

Sentinel node biopsy in breast cancer: validation study and comparison of blue dye alone with triple modality localization.

BACKGROUND: Sentinel node biopsy (SNB) for breast cancer patients is a new technique with the potential to provide an accurate staging of the axillary nodal status while avoiding the morbidity of an axillary dissection. The objective of the present study is to validate the use of sentinel node biopsy in a New Zealand hospital and to compare the ability of patent blue dye (PB) alone with triple modality (TM) (preoperative lymphoscintigraphy, intraoperative gamma probe and intraoperative blue dye) to identify the sentinel node. METHODS: A total of 104 patients who had a palpable breast lump that was confirmed to be malignant by radiology and cytology and a clinical diagnosis of stage I or stage II breast cancer, were enrolled for SNB and randomly assigned to triple modality or blue dye alone for the localization of the sentinel node. Axillary dissection was performed after the sentinel node(s) had been removed. RESULTS: There were 63 patients in the PB group and 41 patients in the TM group. Both groups are comparable, with a similar mean age and primary tumour size. A sentinel node was identified in 57 (90%) of the PB group patients and 40 (98%) of the TM group patients. Of these 23 (37%) of the PB group and 23 (56%) in the TM group had axillary nodes positive for malignancy. There was one false negative SNB in the PB group and two false negative results in the TM group. Therefore, the PB group had an accuracy of 98% and a sensitivity of 96% compared to an accuracy of 95% and a sensitivity of 91% for the TM group. CONCLUSION: The results of the present study validate the use of SNB in suitable breast cancer patients. Identification and the accuracy of the sentinel node localization were similar between the two groups. Therefore, in hospital centres without adequate access to a nuclear medical facility, it would be feasible to conduct SNB using blue dye alone.