Risks of adverse obstetric outcomes among female survivors of adolescent and young adult cancer in England (TYACSS): a population-based, retrospective cohort study.

BACKGROUND: There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer. METHODS: The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population. FINDINGS: Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater. INTERPRETATION: Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer. FUNDING: Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.

Live birth and maternity outcome in childhood and adolescent cancer survivors under 18 years at diagnosis: a 40-year population-based cohort study.

BACKGROUND: Survival from childhood and adolescent cancer has increased, but the chance of a livebirth in female survivors under 18 years at diagnosis may be reduced. METHODS: We performed a national population-based analysis, including all female cancer survivors diagnosed in Scotland before the age of 18 years between 1981 and 2012. Scottish Cancer Registry records were linked to Scottish maternity records. Females from the exposed group with no pregnancies before cancer diagnosis (n = 2118) were compared with three general population controls matched for age and year of diagnosis. FINDINGS: The cumulative incidence of a livebirth for all diagnoses was reduced to 37% (95% CI 33-40%) for cancer survivors at 30 years of age vs 58% (57-60%) for controls. The deficit varying by diagnosis: for lymphoid leukaemia, the cumulative incidence at 30 years was 29% (23-36%) vs 57% (52-61%) for controls with similar deficits in CNS tumours and retinoblastoma. There was a steady improvement in the chance of livebirth in those diagnosed more recently. INTERPRETATION: We have shown a reduced chance of livebirth in female survivors of cancer diagnosed before age 18. The deficit is present for all diagnoses.

Semen analysis and reproductive hormones in boys with classical Hodgkin lymphoma treated according to the EuroNet-PHL-C2 protocol.

STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters? SUMMARY ANSWER: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility. WHAT IS KNOWN ALREADY: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. The present study aims to assess the (gonadotoxic) impact of this treatment protocol on semen parameters and reproductive hormones in boys aged ≤18 years. STUDY DESIGN, SIZE, DURATION: This international, prospective, multi-centre cohort study was an add-on study to the randomized phase-3 EuroNet-PHL-C2 trial, where the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) was compared to intensified OEPA-DECOPDAC-21 chemotherapy (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide). Patients were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligibility criteria included male patients, diagnosed with classical HL before or at the age of 18 years, and treated according to the EuroNet-PHL-C2 protocol in any of the 18 participating sites in the Netherlands, Germany, Belgium, Czech Republic, and Austria. Sperm parameters (sperm concentration, progressive motility, sperm volume, and calculated total motile sperm count) were assessed at diagnosis and 2 years after diagnosis in (post)pubertal boys. Laboratory measurements (serum follicle-stimulating hormone (FSH) and inhibin B) were performed in samples drawn at diagnosis, during treatment (2-3 times), and at 2 years post-diagnosis, and (age-adjusted) analyses were conducted separately for pre-pubertal and (post)pubertal boys. Outcomes were compared between the treatment levels (TL1, TL2, and TL3) and consolidation treatment schemes (COPDAC-28 and DECOPDAC-21). MAIN RESULTS AND THE ROLE OF CHANCE: In total, 101 boys were included in the present analysis: 73 were (post)pubertal (median age 15.4 years, (IQR 14.4; 16.6), 10 TL1, 29 TL2, 34 TL3, 62% of TL2/3 patients received COPDAC-28) and 28 boys were pre-pubertal (median age 9.6 years (IQR 6.6; 11.4), 4 TL1, 7 TL2, 17 TL3, 38% of TL2/3 patients received COPDAC-28). The study included six boys who had received pelvic radiotherapy; none were irradiated in the inguinal or testicular area. At diagnosis, 48 (post)pubertal boys delivered semen for cryopreservation; 19 (40%) semen samples were oligospermic and 4 (8%) were azoospermic. Low sperm concentration (<15 mil/ml) appeared to be related to the HL disease itself, with a higher prevalence in boys who presented with B symptoms (76% vs 26%, aOR 2.3 (95% CI 1.0; 3.8), P = 0.001) compared to those without such symptoms. At 2 -years post-diagnosis, 31 boys provided semen samples for analysis, of whom 12 (39%) boys had oligozoospermia and 4 (13%) had azoospermia, while 22 boys (71%) had low total motile sperm counts (TMSC) (<20 mil). Specifically, the eight boys in the TL3 group treated with DECOPDAC-21 consolidation had low sperm counts and low progressive motility after 2 years (i.e. median sperm count 1.4 mil/ml (IQR <0.1; 5.3), n = 7 (88%), low sperm concentration, low median progressive motility 16.5% (IQR 0.0; 51.2), respectively). Age-adjusted serum FSH levels were significantly raised and inhibin B levels (and inhibin B:FSH ratios) were decreased during chemotherapy in (post)pubertal boys, with subsequent normalization in 80% (for FSH) and 60% (for inhibin B) of boys after 2 years. Only 4 out of the 14 (post)pubertal boys (29%) with low sperm concentrations after 2 years had elevated FSH (>7.6 IU/l), while 7 (50%) had low inhibin B levels (<100 ng/l). In pre-pubertal boys, reproductive hormones were low overall and remained relatively stable during chemotherapy. LIMITATIONS, REASONS FOR CAUTION: The present analyses included sperm and laboratory measurements up to 2 years post-diagnosis. Long-term reproductive outcomes and potential recovery of spermatogenesis remain unknown, while recovery was reported up to 5- or even 10-year post-chemotherapy in previous studies.Boys who were pre-pubertal at diagnosis were still too young and/or physically not able to deliver semen after 2 years and we could not assess a potential difference in gonadotoxicity according to pubertal state at the time of treatment. Overall, the statistical power of the analyses on sperm concentration and quality after 2 years was limited. WIDER IMPLICATIONS OF THE FINDINGS: Results of the semen analyses conducted among the 31 boys who had provided a semen sample at 2 years post-treatment were generally poor. However, additional long-term and adequately powered data are crucial to assess the potential recovery and clinical impact on fertility. The participating boys will be invited to deliver a semen sample after 5 years. Until these data become available, benefits of intensified chemotherapy in cHL treatment to reduce radiotherapy and lower risk for development of secondary tumours should be carefully weighed against potentially increased risk of other late effects, such as diminished fertility due to the increased chemotherapy burden. Boys with newly diagnosed cHL should be encouraged to deliver sperm for cryopreservation whenever possible. However, patients and clinicians should also realize that the overall state of disease and inflammatory milieu of cHL can negatively affect sperm quality and thereby reduce chance of successful fertility preservation. Furthermore, the measurement of FSH and inhibin B appears to be of low value in predicting low sperm quality at two years from cHL treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M.-K., D.K., W.H.W., D.H., MC, A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors declare no potential conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The impact of treatment for childhood classical Hodgkin lymphoma according to the EuroNet-PHL-C2 protocol on serum anti-Müllerian Hormone.

STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)? SUMMARY ANSWER: Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL. WHAT IS KNOWN ALREADY: Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol. STUDY DESIGN, SIZE, DURATION: This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatment-levels (TL1, TL2, and TL3) and treatment-arms (OEPA-COPDAC-28 and OEPA-DECOPDAC-21). Serum samples obtained from patients after receiving pelvic radiotherapy were excluded from the main analyses. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 104 females, with median age at diagnosis of 15.6 years (IQR 13.7; 17.0), were included in the analysis. Ninety-nine were (post)pubertal. Eighteen girls were diagnosed with an early stage of cHL (TL1) and 86 with intermediate or advanced stage disease (50 TL2 and 36 TL3, 66% received COPDAC-28 and 34% DECOPDAC-21). Five patients received pelvic radiotherapy. Median AMH level at diagnosis was 1.7 µg/l (IQR 0.9; 2.7). After two courses of OEPA chemotherapy, AMH levels decreased substantially in all patients (98% <0.5 µg/l), followed by a significant increase during the consolidation treatment and follow-up. After 2 years, 68% of patients reached their baseline AMH value, with overall median recovery of 129% (IQR 75.0; 208.9) compared to baseline measurement. Five patients (7%) had AMH <0.5 µg/l. In patients treated for advanced stage disease, AMH levels remained significantly lower compared to early- or intermediate stage disease, with median serum AMH of 1.3 µg/l (IQR 0.8; 2.1) after 2 years. Patients who received DECOPDAC-21 consolidation had lower AMH levels during treatment than patients receiving COPDAC-28, but the difference was no longer statistically significant at 2 years post-diagnosis. Of the 35 postmenarchal girls who did not receive hormonal co-treatment, 19 (54%) experienced treatment-induced amenorrhea, two girls had persisting amenorrhea after 2 years. LIMITATIONS, REASONS FOR CAUTION: The studied population comprises young girls with diagnosis of cHL often concurring with pubertal transition, during which AMH levels naturally rise. There was no control population, while the interpretation of AMH as a biomarker during childhood is complex. The state of cHL disease may affect AMH levels at diagnosis, potentially complicating assessment of AMH recovery as a comparison with baseline AMH. The current analysis included data up to 2-5 years post-diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: The current PANCARE guideline advises to use the cyclophosphamide-equivalent dose score (CED-score, as an estimation of cumulative alkylating agent exposure) with a cut-off of 6000 mg/m2 to identify females aged <25 years at high risk of infertility. All treatment-arms of the EuroNet-PHL-C2 protocol remain below this cut-off, and based on this guideline, girls treated for cHL should therefore be considered low-risk of infertility. However, although we observed an increase in AMH after chemotherapy, it should be noted that not all girls recovered to pre-treatment AMH levels, particularly those treated for advanced stages of cHL. It remains unclear how our measurements relate to age-specific expected AMH levels and patterns. Additional (long-term) data are needed to explore clinical reproductive outcomes of survivors treated according to the EuroNet-PHL-C2 protocol. STUDY FUNDING/COMPETING INTEREST(S): The fertility add-on study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M-K., D.K., W.H.W., D.H., M.C., A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors indicated no potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Extended Reichardt's Dye-Synthesis and Solvatochromic Properties.

Three new pyridinium-phenolate dyes based on the benchmark solvatochromic dye Betaine 30 were synthesised. The dyes contained phenylene spacers between the donor and acceptor groups. Their UV-Vis absorption spectra were measured, with the dyes showing strong negative solvatochromic behaviour comparable to that of Betaine 30. These results stood in contrast to the behaviour of the π-extended dye Betaine 21, originally reported in 1963. This dye was synthesised and found to be significantly more solvatochromic than previously reported but prone to degrade. All π-extended dyes synthesised were found to be unstable in certain solvents. Although the increased distance between donor and acceptor did not enhance solvatochromism to the extent predicted, it was still determined that the reduced planarity caused by a phenylene spacer is not as detrimental as believed.

Protection of Boronic Acids Using a Tridentate Aminophenol ONO Ligand for Selective Suzuki-Miyaura Coupling.

Boronic acid protecting group chemistry powerfully enhances the versatility of Suzuki-Miyaura cross-coupling. Prominent examples include trifluoroborate salts, N-methyliminodiacetic acid (MIDA) boronates, and 1,8-diaminonaphthalene boronamides. In this work, we present a bis(2-hydroxybenzyl)methylamine (BOMA) ligand that forms tridentate complexes with boronic acids much like the MIDA ligand but the deprotection is facilitated by organic acids. The BOMA boronates showed considerable stability in both aqueous base and acid, and a variety of chemoselective reactions were performed on these boronates, including selective Suzuki-Miyaura coupling, palladium-catalyzed borylation, ester hydrolysis, alkylation, lithiation-borylation, and oxidative hydroxydeboronation.

Prognostic implications of and clinical risk factors for acute lung injury and organizing pneumonia after lung transplantation: Data from a multicenter prospective cohort study.

We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.

Surveillance for subsequent neoplasms of the CNS for childhood, adolescent, and young adult cancer survivors: a systematic review and recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Exposure to cranial radiotherapy is associated with an increased risk of subsequent CNS neoplasms among childhood, adolescent, and young adult (CAYA) cancer survivors. Surveillance for subsequent neoplasms can translate into early diagnoses and interventions that could improve cancer survivors' health and quality of life. The practice guideline presented here by the International Late Effects of Childhood Cancer Guideline Harmonization Group was developed with an evidence-based method that entailed the gathering and appraisal of published evidence associated with subsequent CNS neoplasms among CAYA cancer survivors. The preparation of these guidelines showed a paucity of high-quality evidence and highlighted the need for additional research to inform survivorship care. The recommendations are based on careful consideration of the evidence supporting the benefits, risks, and harms of the surveillance interventions, clinical judgment regarding individual patient circumstances, and the need to maintain flexibility of application across different health-care systems. Currently, there is insufficient evidence to establish whether early detection of subsequent CNS neoplasms reduces morbidity and mortality, and therefore no recommendation can be formulated for or against routine MRI surveillance. The decision to start surveillance should be made by the CAYA cancer survivor and health-care provider after careful consideration of the potential harms and benefits of surveillance for CNS neoplasms, including meningioma.

Fertility preservation for female patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Female patients with childhood, adolescent, and young adult cancer are at increased risk for fertility impairment when treatment adversely affects the function of reproductive organs. Patients and their families desire biological children but substantial variations in clinical practice guidelines reduce consistent and timely implementation of effective interventions for fertility preservation across institutions. As part of the PanCareLIFE Consortium, and in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in female patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. This clinical practice guideline leverages existing evidence and international expertise to develop transparent recommendations that are easy to use to facilitate the care of female patients with childhood, adolescent, and young adult cancer who are at high risk for fertility impairment. A complete review of the existing evidence, including a quality assessment, transparent reporting of the guideline panel's decisions, and achievement of global interdisciplinary consensus, is an important result of this intensive collaboration.

Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Male patients with childhood, adolescent, and young adult cancer are at an increased risk for infertility if their treatment adversely affects reproductive organ function. Future fertility is a primary concern of patients and their families. Variations in clinical practice are barriers to the timely implementation of interventions that preserve fertility. As part of the PanCareLIFE Consortium, in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in male patients who are diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. Recognising the need for global consensus, this clinical practice guideline used existing evidence and international expertise to rigorously develop transparent recommendations that are easy to use to facilitate the care of male patients with childhood, adolescent, and young adult cancer who are at high risk of fertility impairment and to enhance their quality of life.

Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

Unusual Alternating Crystallization-Induced Emission Enhancement Behavior in Nonconjugated ω-Phenylalkyl Tropylium Salts.

The alternating physical properties, especially melting points, of α,ω-disubstituted n-alkanes and their parent n-alkanes had been known since Baeyer's report in 1877. There is, however, no general and comprehensive explanation for such a phenomenon. Herein, we report the synthesis and examination of a series of novel ω-phenyl n-alkyl tropylium tetrafluoroborates, which also display alternation in their physicochemical characters. Despite being organic salts, the compounds with odd numbers of carbons in the alkyl bridge exist as room temperature ionic liquids. In stark contrast to this, the analogues with even numbers of carbons in the linker are crystalline solids. These solid nonconjugated molecules exhibit curious photoluminescent properties, which can be attributed to their ability to form through-space charge-transfer complexes to cause crystallization-induced emission enhancement. Most notably, the compound with the highest photoluminescent quantum yield in this series showed an unusual arrangement of carbocationic dimer in the solid state. A combination of XRD analysis and ab initio calculations revealed interesting insights into these systems.

Counseling and surveillance of obstetrical risks for female childhood, adolescent, and young adult cancer survivors: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Female childhood, adolescent, and young adult cancer survivors have an increased risk of adverse pregnancy outcomes related to their cancer- or treatment-associated sequelae. Optimal care for childhood, adolescent, and young adult cancer survivors can be facilitated by clinical practice guidelines that identify specific adverse pregnancy outcomes and the clinical characteristics of at-risk subgroups. However, national guidelines are scarce and vary in content. Here, the International Late Effects of Childhood Cancer Guideline Harmonization Group offers recommendations for the counseling and surveillance of obstetrical risks of childhood, adolescent, and young adult survivors. A systematic literature search in MEDLINE database (through PubMed) to identify all available evidence published between January 1990 and December 2018. Published articles on pregnancy and perinatal or congenital risks in female cancer survivors were screened for eligibility. Study designs with a sample size larger than 40 pregnancies in childhood, adolescent, and young adult cancer survivors (diagnosed before the age of 25 years, not pregnant at that time) were eligible. This guideline from the International Late Effects of Childhood Cancer Guideline Harmonization Group systematically appraised the quality of available evidence for adverse obstetrical outcomes in childhood, adolescent, and young adult cancer survivors using Grading of Recommendations Assessment, Development, and Evaluation methodology and formulated recommendations to enhance evidence-based obstetrical care and preconception counseling of female childhood, adolescent, and young adult cancer survivors. Healthcare providers should discuss the risk of adverse obstetrical outcomes based on cancer treatment exposures with all female childhood, adolescent, and young adult cancer survivors of reproductive age, before conception. Healthcare providers should be aware that there is no evidence to support an increased risk of giving birth to a child with congenital anomalies (high-quality evidence). Survivors treated with radiotherapy to volumes exposing the uterus and their healthcare providers should be aware of the risk of adverse obstetrical outcomes such as miscarriage (moderate-quality evidence), premature birth (high-quality evidence), and low birthweight (high-quality evidence); therefore, high-risk obstetrical surveillance is recommended. Cardiomyopathy surveillance is reasonable before pregnancy or in the first trimester for all female survivors treated with anthracyclines and chest radiation. Female cancer survivors have increased risks of premature delivery and low birthweight associated with radiotherapy targeting the lower body and thereby exposing the uterus, which warrant high-risk pregnancy surveillance.

Systematic study of precursor effects on structure and oxygen reduction reaction activity of FeNC catalysts.

In this work, the effect of porphyrin loading and template size is varied systematically to study its impact on the oxygen reduction reaction (ORR) activity and selectivity as followed by rotating ring disc electrode experiments in both acidic and alkaline electrolytes. The structural composition and morphology are investigated by 57Fe Mössbauer spectroscopy, transmission electron microscopy, Raman spectroscopy and Brunauer-Emmett-Teller analysis. It is shown that with decreasing template size, specifically the ORR performance towards fuel cell application gets improved, while at constant area loading of the iron precursor (here expressed in number of porphyrin layers), the iron signature does not change much. Moreover, it is well illustrated that too large area loadings result in the formation of undesired side phases that also cause a decrease in the performance, specifically in acidic electrolyte. Thus, if the impact of morphology is the focus of research it is important to consider the area loading rather than its weight loading. At constant weight loading, beside morphology the structural composition can also change and impact the catalytic performance. This article is part of the theme issue 'Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 2)'.

IgG4-related kidney disease with systemic Epstein-Barr virus infection: A case report.

IgG4-related disease (IgG4-RD) is a newly recognized multi-organ fibro-inflammatory condition with characteristic histopathological findings of increased IgG4+ plasma cells in tissue and usually with increased IgG4 serum levels. Kidney involvement in IgG4-RD has been well described since 2006. Epstein-Barr virus (EBV) has reportedly been associated with nodal IgG4-RD, but not in extra-nodal disease. We report a case of renal IgG4-RD in the setting of acute EBV infection in a young healthy man, resulting in severe renal failure. Biopsy of kidney revealed IgG4+ plasma cell-rich tubulointerstitial nephritis, tissue eosinophilia, early-stage membranous nephropathy, and scattered EBV-positive cells. Oral prednisone and acyclovir only partially rescued his renal function.

BOLA (BolA Family Member 3) Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension.

BACKGROUND: Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with poorly defined molecular origins. BOLA3 (BolA Family Member 3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined. METHODS: In vitro assessment of BOLA3 regulation and gain- and loss-of-function assays were performed in human pulmonary artery endothelial cells using siRNA and lentiviral vectors expressing the mitochondrial isoform of BOLA3. Polymeric nanoparticle 7C1 was used for lung endothelium-specific delivery of BOLA3 siRNA oligonucleotides in mice. Overexpression of pulmonary vascular BOLA3 was performed by orotracheal transgene delivery of adeno-associated virus in mouse models of PH. RESULTS: In cultured hypoxic pulmonary artery endothelial cells, lung from human patients with Group 1 and 3 PH, and multiple rodent models of PH, endothelial BOLA3 expression was downregulated, which involved hypoxia inducible factor-2α-dependent transcriptional repression via histone deacetylase 1-mediated histone deacetylation. In vitro gain- and loss-of-function studies demonstrated that BOLA3 regulated Fe-S integrity, thus modulating lipoate-containing 2-oxoacid dehydrogenases with consequent control over glycolysis and mitochondrial respiration. In contexts of siRNA knockdown and naturally occurring human genetic mutation, cellular BOLA3 deficiency downregulated the glycine cleavage system protein H, thus bolstering intracellular glycine content. In the setting of these alterations of oxidative metabolism and glycine levels, BOLA3 deficiency increased endothelial proliferation, survival, and vasoconstriction while decreasing angiogenic potential. In vivo, pharmacological knockdown of endothelial BOLA3 and targeted overexpression of BOLA3 in mice demonstrated that BOLA3 deficiency promotes histological and hemodynamic manifestations of PH. Notably, the therapeutic effects of BOLA3 expression were reversed by exogenous glycine supplementation. CONCLUSIONS: BOLA3 acts as a crucial lynchpin connecting Fe-S-dependent oxidative respiration and glycine homeostasis with endothelial metabolic reprogramming critical to PH pathogenesis. These results provide a molecular explanation for the clinical associations linking PH with hyperglycinemic syndromes and mitochondrial disorders. These findings also identify novel metabolic targets, including those involved in epigenetics, Fe-S biogenesis, and glycine biology, for diagnostic and therapeutic development.

Re-Engage: A Novel Nurse-Led Program for Survivors of Childhood Cancer Who Are Disengaged From Cancer-Related Care.

BACKGROUND: Survivors of childhood cancer often experience treatment-related chronic health conditions. Survivorship care improves survivors' physical and mental health, yet many are disengaged from care. Innovative models of care are necessary to overcome patient-reported barriers to accessing survivorship care and to maximize survivors' health. METHODS: We piloted a novel survivorship program, called "Re-engage," a distance-delivered, nurse-led intervention aiming to engage, educate, and empower survivors not receiving any cancer-related care. Re-engage involves a nurse-led consultation delivered via telephone/online to establish survivors' medical history and needs. Participants completed questionnaires at baseline, 1 month postintervention, and 6-month follow-up. RESULTS: A total of 27 survivors who had not accessed survivorship care in the last 2 years participated (median age, 31 years; interquartile range [IQR], 27-39 years); of which, 82% were at high-risk for treatment-related complications. Participation in Re-engage was high (75%) and there was no attrition once survivors enrolled. At 1 month postintervention, 92% of survivors reported that Re-engage was "beneficial," which all survivors reported at 6-month follow-up. Survivors' overall satisfaction with their care increased from 52% before Re-engage to 84% at 1 month postintervention. Survivors' mean self-efficacy scores remained similar from baseline to 1 month postintervention (b = -0.33, 95% CI, -1.31 to 0.65), but increased significantly from baseline to 6-month follow-up (b = 1.64, 95% CI, 0.28-3.00). At 6-month follow-up, 73% of survivors showed an increase in health-related self-efficacy compared with baseline. CONCLUSIONS: Re-engage is a highly acceptable and feasible intervention and promotes health-related self-efficacy, which is integral to survivors being advocates for their own health. Further empirical work is needed to evaluate the long-term efficacy of Re-engage. TRIAL REGISTRATION: ACTRN12618000194268.

Triplet fusion upconversion using sterically protected 9,10-diphenylanthracene as the emitter.

Improving the efficiency of triplet fusion upconversion (TF-UC) in the solid-state is still challenging due to the aggregation and phase separation of chromophores. In this work, two 9,10-diphenylanthracene (DPA) derivatives based on the modification of the 9,10-phenyl rings with bulky isopropyl groups (bDPA-1 and bDPA-2) were used as emitters. By using platinum octaethylporphyrin (PtOEP) as the sensitizer, TF-UC performance was comprehensively investigated in 3 media: toluene solution, polyurethane thin film and nano/micro-crystals in a polyvinyl alcohol matrix. Only a small difference in upconversion efficiency between the bulky DPAs and the DPA reference was observed in toluene solution and polyurethane thin film. However, a large improvement of TF-UC quantum yield was achieved in bDPA-2/PtOEP crystals (ΦUC = (0.92 ± 0.05)%) with a low excitation intensity threshold (52 mW cm-2) compared to that of DPA/PtOEP crystals (ΦUC = (0.09 ± 0.03)%). This difference was largely attributed to improved dispersibility of the PtOEP sensitizer in the bDPA-2 emitter crystals. The bulky DPAs also show excellent stability under UV irradiation with exposure to oxygen compared to DPA. These results provide a strategy for developing efficient solid-state TF-UC systems based on nano/micro-particles of emitter-sensitizer mixtures.

Bilirubin analogues as model compounds for exciton coupling.

A series of phycobilin analogues have been investigated in terms of coupled excitonic systems. These compounds consist of a monomer, a tetrapyrrole structurally similar to bilirubin (bR), and two conjugated bR analogues. Spectroscopic and computational methods have been used to investigate the degree of interchromophore coupling. We find the synthesised bR analogue shows stronger excitonic coupling than bR, owing to a different molecular geometry. The excitonic coupling in the conjugated molecules can be controlled by modifying the bridge side-group. New computed energy levels for bR using the DFT/MRCI method are also presented, which improve on published values and re-assign the character of excited singlet states.

Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features in Children: An Institutional Experience and Literature Review.

BACKGROUND: Papillary thyroid carcinoma (PTC) in children has a distinctive set of clinicopathologic features and molecular signature compared to their adult counterparts. The recent recommendation to reclassify encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) without invasion as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is based on evidence derived almost exclusively from studies in adults. Clinicopathologic studies restricted to pediatric NIFTP are limited. METHODS: We retrospectively analyzed all pediatric PTC and NIFTP diagnosed and treated in our institution from 1999 to 2016 (n = 31). RESULTS: Using recently published consensus diagnostic criteria, we identified 3 NIFTP and 2 infiltrative follicular variants of papillary thyroid carcinoma (FVPTC) among 31 cases. Two of the NIFTP cases were initially diagnosed as EFVPTC. All 3 patients with NIFTP had unifocal tumors of lower American Joint Committee on Cancer (AJCC) classification (T2 or lower) and were free of lymph node or distant metastasis. Total (n = 1) or completion (n = 2) thyroidectomy was performed in all cases, and only 1 NIFTP patient received subsequent radioablative therapy. No residual or recurrent disease has been observed during follow-up (15-138 months) in patients with NIFTP. CONCLUSIONS: Our experience with NIFTP in children is similar to outcomes reported in adult studies, suggesting that pediatric NIFTP behave indolently as evidenced by the absence of local recurrence in our cohort.