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Women with bipolar disorder have a high recurrence rate in the perinatal period. However, the use of prophylactic medication can be a concern during pregnancy and breastfeeding. There are few studies looking at the impact of prophylactic medication on the risk of recurrence.The aims of this study are to describe the use of medication in women with bipolar disorder in the perinatal period and the impact of that prophylactic medication on the rate of postnatal recurrence.
The BDRN (Bipolar Disorder Research Network Study) is the largest individual network of individuals with bipolar disorder and related mood disorders in the world. The BDRN pregnancy study is a prospective observational study which took place in the UK. We collected sociodemographic, clinical and medication data from pregnant women with a diagnosis of bipolar disorder and who were euthymic entering the postpartum period. The clinical data were collected via interviews during pregnancy and the postpartum and access to clinical records where those were available.
Data were analysed for association using χ2 tests and logistic regression.
Our total sample for this analysis comprised of 103 women who met the criteria.
We found that 71 (70%) were taking medication at delivery: 43 (43%) antipsychotics, 9 (9%) antidepressants, 10 (10%) mood stabilisers, (6 lithium, 4 anticonvulsants and 9 multiple medication classes).
Of the total sample, 44 (43%) experienced a postpartum recurrence: 21 (20%) had an episode of postpartum psychosis, 15 (15%) of non-psychotic depression and 8 (8%) of hypomania. Of the postpartum psychotic episodes 11 were of mania with psychosis, 8 of mania without psychosis and 2 of psychotic depression.
There was no significant association between taking medication at delivery and postpartum recurrence χ2 (1)=0.116, p=0.73.
In a multivariable analysis there continued to be no association when adjusted for age, ethnicity, parity, severity (previous admissions, age at impairment, bipolar subtype) and previous psychotic symptoms aOR 1.35 95%CI [0.45; 4.00], p=0.59.
A high number of bipolar women are taking medication at delivery and in the majority, antipsychotics are prescribed. The postnatal recurrence rate in both medicated and unmedicated women is high.
Our findings align with recent electronic health records and observational studies, but differ from older clinical cohort and higher Lithium-prescribing sample studies. Limitations include the study design and confounding by indication. Further research in larger populations is necessary to inform clinical decision-making for women and their healthcare providers.
OBJECTIVES/GOALS: The purpose of this study is to develop a clinically relevant mouse model of Radiation-Induced Heart Disease (RIHD) and characterize the resulting phenotype to find biomarkers and therapeutic targets as well as to understand the changes in cellular and molecular mechanisms of bioenergetics. METHODS/STUDY POPULATION: We used a two-beam method in the axillary region targeting the heart to irradiate male BALB/c mice at an isodose of 22, 16 and 8 Gray (Gy). We examined cardiac damage (i.e., vacuolization), inflammation, and DNA damage at 10 days post irradiation using histology and immunohistochemistry of heart tissue and cardiac function at day 35 by echocardiography. Additionally, cardiac tissue of mice irradiated at 22 Gy was collected at day 10 and day 35 post irradiation and sent for RNA sequencing. Data from RNA sequencing was analyzed using gProfiler, GSEA, and Cytoscape to enrich and visualize differentially expressed genes. RT-qPCR was performed to validate findings of significantly differentially expressed genes. RESULTS/ANTICIPATED RESULTS: Significantly increased phosphorylation of H2A.X indicated that irradiated mice were undergoing DNA double strand break repair indicating cardiac damage. Additionally, we found that regulators of mitochondrial function were decreased in the heart at day 10 for all doses. We found that mice that received 22 Gy developed cardiomyopathy at day 35 based on increased global longitudinal strain (GLS). Radiation decreased T cells, macrophages, and mast cells in the heart of irradiated mice by RT-qPCR at day 10 indicating damage to immune cells by radiation at all doses. Thus, we successfully created a clinically relevant model of RIHD in male BALB/c mice. DISCUSSION/SIGNIFICANCE: Patients undergoing radiation therapy for thoracic malignancies can develop cardiomyopathy (DCM) due to radiation damage. Previously published animal models utilized mouse strains resistant to developing DCM (female mice, C57BL/6 strain) and used high doses of radiation. Establishing a translational model is crucial for prevention of RIHD.
Sleep disturbances are important symptoms to monitor in people with bipolar disorder (BD) but the precise longitudinal relationships between sleep and mood remain unclear. We aimed to examine associations between stable and dynamic aspects of sleep and mood in people with BD, and assess individual differences in the strength of these associations.
Participants (N = 649) with BD-I (N = 400) and BD-II (N = 249) provided weekly self-reports of insomnia, depression and (hypo)mania symptoms using the True Colours online monitoring tool for 21 months. Dynamic structural equation models were used to examine the interplay between weekly reports of insomnia and mood. The effects of clinical and demographic characteristics on associations were also assessed.
Increased variability in insomnia symptoms was associated with increased mood variability. In the sample as a whole, we found strong evidence of bidirectional relationships between insomnia and depressive symptoms but only weak support for bidirectional relationships between insomnia and (hypo)manic symptoms. We found substantial variability between participants in the strength of prospective associations between insomnia and mood, which depended on age, gender, bipolar subtype, and a history of rapid cycling.
Our results highlight the importance of monitoring sleep in people with BD. However, researchers and clinicians investigating the association between sleep and mood should consider subgroup differences in this relationship. Advances in digital technology mean that intensive longitudinal data on sleep and mood are becoming increasingly available. Novel methods to analyse these data present an exciting opportunity for furthering our understanding of BD.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
To assess the comorbidity rates of alcohol use disorders (AUDs) in bipolar disorder (BD) and to explore possible sources of heterogeneity.
Studies were identified through database searches. Meta-analytic techniques were employed to aggregate data on lifetime comorbidity and to explore possible sources of heterogeneity. Funnel plots were used to detect publication bias.
In clinical studies, AUDs affected more than one in three subjects with BD. Significant heterogeneity was found, which was largely explained by the geographical location of study populations and gender ratio of participants. AUDs affected more than one in five women and two in five men.
AUDs are highly prevalent in BD. Our study revealed a substantial heterogeneity across studies. Further research including control groups is needed. Patients with BD should be assessed for current and previous AUDs.
The perinatal period is a high-risk period for the development of illness episodes in women with bipolar disorder. Relapse rates vary between 9 and 75% depending on the study. The overall risk of a severe episode is approximately 20%. The impact on women, the relationships with their babies and their families can be devastating. In the UK costs to society are £8.1 billion per year-cohort of births. The advice currently given to women is based of general risk rates. Women's needs of information for decision-making in the perinatal period are not being met.
To review the risk prediction approaches used for women with bipolar disorder in the perinatal period.
To understand the existing risk prediction models and approaches used for prognosis of the risk of recurrence of bipolar disorder for women in the perinatal period.
Systematic literature search of public medical electronic databases and grey literature on risk prediction for bipolar episodes in the perinatal period.
We will present the existing models and approaches used for risk prediction of illness episodes in the perinatal period.
Awareness of existing risk prediction models for recurrence of bipolar disorder in the perinatal period will allow better informed risk-benefit analysis of treatment and management options.
This person-centred approach will help women and clinicians in their decision-making at this crucial high-risk period.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
For women with bipolar disorder, childbirth is a high-risk period with 40–50% experiencing a recurrence and 20% developing a severe episode of postpartum psychosis. Bipolar episodes in the perinatal period affect women and their families.
Managing bipolar disorder in pregnancy and postpartum is a challenge. There is lack of literature to inform that and an urgent need for more data.
To develop and validate a risk prediction model for individual prognosis of the risk of recurrence of bipolar disorder for women in the perinatal period.
To provide evidence-based information to help women and the clinicians that look after them make decisions about their care, taking into account the most recent scientific knowledge and their individual characteristics.
The development of the model will be done in retrospective data from a large clinical cohort from the Bipolar Disorder Research Network (BDRN.org). The validation will be done in a prospectively recruited sample.
Participants will be 2181 parous women with a lifetime diagnosis of bipolar disorder from BDRN and 300 prospectively recruited pregnant women with a history of postpartum psychosis or bipolar disorder.
Predictors will be chosen based on clinical experience and literature, from data collected via semi-structured interview (in pregnancy and 3 months postpartum, medical and psychiatric notes) e.g. medication, smoking, parity, obstetric complications and sleep.
We will present the full prediction model (regression coefficients and model intercept) and report performance measures (with CIs).
We will discuss its potential clinical use and implications for future research.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
OBJECTIVES/SPECIFIC AIMS: More men than women develop urinary stones and their prevalence alters in women with menopause suggesting a steroidal influence. In men the incidence of stones is highest during July and August suggesting that environmental factors such as Vitamin D (VitD), a steroid, may affect stone formation. Previous studies have found differences in the development of stones between men and women; however, the reasons for sex differences in stone formation and type remain unclear. METHODS/STUDY POPULATION: We examined VitD levels in men and women (n = 18,753) that had no diseases based on a lack of an ICD-9 or ICD-10 code in their electronic medical record. We found that normal, healthy women had significantly higher levels of sera VitD compared to men (p = 6x10-6). We then examined whether sex differences existed for key endpoints/data from the Mayo Clinic Urinary Stone Disease (USD) Registry, which has around 1,600 urinary stone patients that are well-phenotyped according to sex, age and stone type. RESULTS/ANTICIPATED RESULTS: Control women were found to have higher sera VitD levels than men, but the sex difference no longer exists in kidney stone disease patients. When we further separated by race, we found that differences in VitD levels reappeared; this suggests that race also plays a role in sera VitD variances. DISCUSSION/SIGNIFICANCE OF IMPACT: We are developing a disease severity score, which we will use to correlate to sera VitD levels in patients according to sex, age and race. Future analyses will take into account whether subjects had VitD and calcium supplementation. This project begins to explore the mechanism behind the sex differences known to exist in urinary stone disease, which is critically needed to provide improved diagnosis and therapy for this debilitating disease.
Most people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).
To reach consensus regarding threshold definitions criteria for TRBD and MTRBD.
Based on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method.
TRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy.
The proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.
Declaration of interest
In the past 3 years, M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer and Servier. A.J.C. has in the past 3 years received honoraria for speaking from Astra Zeneca and Lundbeck, honoraria for consulting from Allergan, Janssen, Lundbeck and LivaNova and research grant support from Lundbeck. G.M.G. holds shares in P1Vital and has served as consultant, advisor or CME speaker for Allergan, Angelini, Compass pathways, MSD, Lundbeck, Otsuka, Takeda, Medscape, Minervra, P1Vital, Pfizer, Servier, Shire and Sun Pharma. J.G. has received research funding from National Institute for Health Research, Medical Research Council, Stanley Medical Research Institute and Wellcome. H.G. received grants/research support, consulting fees or honoraria from Gedeon Richter, Genericon, Janssen Cilag, Lundbeck, Otsuka, Pfizer and Servier. R.H.M.-W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. R.M. has received research support from Big White Wall, Electromedical Products, Johnson and Johnson, Magstim and P1Vital. S.N. received honoraria from Lundbeck, Jensen and Otsuka. J.C.S. has received funds for research from Alkermes, Pfizer, Allergan, J&J, BMS and been a speaker or consultant for Astellas, Abbott, Sunovion, Sanofi. S.W has, within the past 3 years, attended advisory boards for Sunovion and LivaNova and has undertaken paid lectures for Lundbeck. D.J.S. has received honoraria from Lundbeck. T.S. has reported grants from Pathway Genomics, Stanley Medical Research Institute and Palo Alto Health Sciences; consulting fees from Sunovion Pharamaceuticals Inc.; honoraria from Medscape Education, Global Medical Education and CMEology; and royalties from Jones and Bartlett, UpToDate and Hogrefe Publishing. S.P. has served as a consultant or speaker for Janssen, and Sunovion. P.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. E.V. received grants/ research support, consulting fees or honoraria from Abbott, AB-Biotics, Allergan, Angelini, Dainippon Sumitomo, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka and Sunovion. L.N.Y. has received grants/research support, consulting fees or honoraria from Allergan, Alkermes, Dainippon Sumitomo, Janssen, Lundbeck, Otsuka, Sanofi, Servier, Sunovion, Teva and Valeant. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has also previously received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth. P.R.A.S. has received research funding support from Corcept Therapeutics Inc. Corcept Therapeutics Inc fully funded attendance at their internal conference in California USA and all related expenses. He has received grant funding from the Medical Research Council UK for a collaborative study with Janssen Research and Development LLC. Janssen Research and Development LLC are providing non-financial contributions to support this study. P.R.A.S. has received a presentation fee from Indivior and an advisory board fee from LivaNova.
Major, trace element composition and Sr isotopic data were collected for gabbroic rocks, plagiogranites and albitites in the ophiolite assemblage from Swat Valley (NW Frontier Province, Pakistan). Petrographic study revealed that these rocks were subjected to important structural and mineralogical modifications due to greenschist-epidote-amphibolite facies sub-sea-floor metamorphism and to brecciation. On the other hand, the examination of whole rock chemical composition and of chemical trends showed that these rocks were affected by some chemical modifications, concerning especially Na2O, K2O and Rb. The very low contents of HFS (high field strength) and RE elements found in gabbroic rocks and plagiogranites were considered to be a primary magmatic feature pointing in part to their cumulitic nature and in part to an origin from a refractory parental magma. The Sr isotopic data indicate that gabbroic rocks and plagiogranites were subjected to exchange with sea water. The particular chemical features shared by gabbroic rocks and plagiogranites suggested that fractional crystallization was a possible evolution process. In contrast, albitites are characterized by anomalously high contents in HFSE and LREE and by values of the 87Sr/86Sr ratio very close to sea water. These features suggest a more complex origin with respect to gabbroic rocks and plagiogranites.
Pregnancy and childbirth are a period of high risk for women with bipolar disorder and involve difficult decisions particularly about continuing or stopping medications.
To explore what clinical predictors may help to individualise the risk of perinatal recurrence in women with bipolar disorder.
Information was gathered retrospectively by semi-structured interview, questionnaires and case-note review from 887 women with bipolar disorder who have had children. Clinical predictors were selected using backwards stepwise logistic regression, conditional permutation random forests and reinforcement learning trees.
Previous perinatal history of affective psychosis or depression was the most significant predictor of a perinatal recurrence (odds ratio (OR) = 8.5, 95% CI 5.04–14.82 and OR = 3.6, 95% CI 2.55–5.07 respectively) but even parous women with bipolar disorder without a previous perinatal mood episode were at risk following a subsequent pregnancy, with 7% developing postpartum psychosis.
Previous perinatal history of affective psychosis or depression is the most important predictor of perinatal recurrence in women with bipolar disorder and can be used to individualise risk assessments.
Sleep loss may trigger mood episodes in people with bipolar disorder but individual differences could influence vulnerability to this trigger.
To determine whether bipolar subtype (bipolar disorder type I (BP-I) or II (BD-II)) and gender were associated with vulnerability to the sleep loss trigger.
During a semi-structured interview, 3140 individuals (68% women) with bipolar disorder (66% BD-I) reported whether sleep loss had triggered episodes of high or low mood. DSM-IV diagnosis of bipolar subtype was derived from case notes and interview data.
Sleep loss triggering episodes of high mood was associated with female gender (odds ratio (OR) = 143, 95% CI 1.17–1.75, P<0.001) and BD-I subtype (OR=2.81, 95% CI 2.26–3.50, P<0.001). Analyses on sleep loss triggering low mood were not significant following adjustment for confounders.
Gender and bipolar subtype may increase vulnerability to high mood following sleep deprivation. This should be considered in situations where patients encounter sleep disruption, such as shift work and international travel.
Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.
Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.
Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).
Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.
Background and objective: We reviewed retrospectively the anaesthetic management and perioperative course of eight right hepatectomies for living liver donation.
Methods: After preoperative psychiatric evaluation, eight ASA I–II individuals donated the right lobe of their liver to a family member. A graft-recipient body weight ratio of 0.8–1.0% was required for patient selection. Indications for liver transplantation were: hepatitis C viral-related cirrhosis in six patients; combined hepatitis C and B viral cirrhosis in one patient; multifocal hepatocellular carcinoma – four lesions, involving both liver lobes – of hepatitis C viral-related cirrhosis in another patient. Indication for adult-to-adult living-donor liver transplantation was retained in the latter because of rapid deterioration of liver disease, rare recipient's blood group and extended, unresectable hepatocellular carcinoma. Hepatitis C viral-related cirrhosis was casually the primary indication for adult-to-adult living-donor liver transplantation in this group. The condition of the donated hepatic lobe was optimized by appropriate drug and perfusion management. Preoperative investigations included: blood tests (full cell count and film, thyroid function tests, pregnancy tests, full virological tests and bacteriological cultures, and immunological typing), chest radiograph, electrocardiogram plus Doppler cardiac ultrasound, spirometry, aminopyrine breath test, liver Doppler examination, magnetic resonance imaging, angiography and cholangiography and a volumetric study of the whole liver and the right lobe. Haemoglobin and lactate concentrations, liver function tests and international normalized ratio were measured before and after operation. The volume and weight of the resected right lobe was calculated. Anaesthesia was induced with propofol 300 mL h−1 and sufentanil 0.3 μg kg−1 intravenously; cisatracurium, 0.15 mg kg−1, was given to facilitate tracheal intubation. Anaesthesia was maintained during normocapnic ventilation of the lungs with oxygen 40% in air, isoflurane 1–1.5 MAC and sufentanil. Routine anaesthetic monitoring included electrocardiography, pulse oximetry, invasive blood pressure, central venous pressure, urine output, state of neuromuscular blockade and core temperature. Periods of hypotension (< 80% of the preoperative blood pressure) or haemodynamic instability (requiring inotropic or vasoactive support) were registered. Total blood loss and transfusion (homologous, autologous or cell-saver blood) requirements were measured; volume replacements were derived.
Results: Data are presented as mean (range). There was no morbidity or mortality and no periods of intraoperative hypotension or haemodynamic instability. The operation time averaged 619 (525–780) min. Four donors were extubated in the operating room immediately after surgery; the others were extubated in the intensive care unit, where the mean extubation time was 16.3 (5–25) h after arrival. The estimated blood loss was 967 (550–1600) mL. No homologous blood was administered; five donors received autologous blood,intraoperatively; three donors received a cell-saver blood transfusion. Intraoperative fluid replacement was with crystalloids, colloids and 4% albumin. Total urine output was 1472 (700–3100)mL. Although intraoperative hypothermia occurred all subjects were normothermic at the end of operation. The pre- and immediately postoperative haemoglobin concentration averaged 13.6 (9.8–15.6) and 10.5 (6.9–13.0) g dL−1 respectively. On the first postoperative day, the haemoglobin was 11.7 (8.4–15.1) g dL−1. The donors' liver function tests were transiently elevated in the initial postoperative period. The intensive care unit discharge time was 2 (1–3) days. The hospital stay was 13 (7–17) days. There was no morbidity or mortality.
Conclusions: The study demonstrates that right-lobe living-donor surgery was well tolerated, without intraoperative hypotension or haemodynamic instability, without perioperative anaesthetic or surgical complications, and with an excellent general outcome.
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