Early Demise Research Articles

Early Aptian development and OAE 1a-linked demise of a carbonate platform in the western Tethys: Lower Cretaceous of Sierra Mariola (South Iberian Paleomargin, SE Spain)

A carbonate platform succession of early Aptian age is described from the Sierra Mariola, which is located within the Prebetic Zone of the Betic External Zones (BEZ) of the Southern Iberian Palaeomargin, in SE Spain. The facies and stratigraphic architecture of the studied succession are described and analysed from multiple logged sections to characterize different depositional environments.The cyclic stacking of facies observed suggests a possible orbital forcing of climate transmitted to sedimentation. Superbundles are recognized describing two sequences of Regressive-Transgressive (R-T) evolution. Analysis of carbon-isotope data identifies both the interval before the hyperthermal event of the early Aptian Oceanic Anoxic Event (OAE 1a) and the onset of the latter event, with an abrupt change in sedimentation marking the demise of the carbonate platform. The field outcrop thus preserves a record of the transition from a greenhouse world to a hothouse event.

MHC Class II Deficiency: Clinical, Immunological, and Genetic Insights in a Large Multicenter Cohort

BackgroundMajor Histocompatibility Complex Class II (MHC-II) deficiency, a combined immunodeficiency, results from loss of Human Leukocyte Antigen class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation (HSCT) stands as the sole curative approach, though factors influencing patient outcomes remain insufficiently explored. ObjectiveOur aim was to elucidate the clinical, immunological, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates. MethodsIn this multicenter retrospective analysis, we gathered data from 35 patients diagnosed with MHC-II deficiency across 12 centers in Turkey. We recorded infection histories, gene mutations, immune cell subsets, and surface MHC-II expression on blood cells. We conducted survival analyses to evaluate the impact of various factors on patient outcomes. ResultsPredominant symptoms observed were pneumonia (n=29, 82.9%), persistent diarrhea (n=26, 74.3%), and severe infections (n=26, 74.3%). The RFXANK gene mutation (n=9) was the most frequent, followed by mutations in RFX5 (n=8), CIITA (n=4), and RFXAP (n=2) genes. Patients with RFXANK mutations presented with later onset and diagnosis compared to those with RFX5 mutations (p=0.0008 and p=0.0006, respectively), alongside a more significant diagnostic delay (p=0.020). A notable founder effect was observed in 5 patients with a specific RFX5 mutation (c.616G>C). The overall survival rate for patients was 28.6% (n=10), showing a significantly higher proportion in individuals with HSCT (n=8, 80%). Early demise (p=0.006) and higher CD8+ T-cell counts were observed in patients with the RFX5 mutations compared to RFXANK-mutant patients (p=0.006 and p=0.009, respectively). ConclusionThe study delineates the genetic and clinical panorama of MHC-II deficiency, emphasizing the prevalence of specific gene mutations such as RFXANK and RFX5. These insights facilitate early diagnosis and prognosis refinement, significantly contributing to the management of MHC-II deficiency.

Agronomic monsoon onset definitions to support planting decisions for rainfed rice in Bangladesh

The usability gaps between climate information producers and users have always been an issue in climate services. This study aims to tackle the gap for rice farmers in Bangladesh by exploring the potential value of tailored agronomic monsoon onset definitions. Summer aman rice is primarily cultivated under rainfed conditions, and farmers rely largely on monsoon rainfall and its onset for crop establishment. However, farmers’ perception of the arrival of sufficient rains does not necessarily coincide with meteorological definitions of monsoon onset. Therefore, localized agronomic definitions of monsoon onset need to be developed and evaluated to advance in the targeted actionable climate forecast. We analyzed historical daily rainfall from four locations across a north-south gradient in Bangladesh and defined dynamic definitions of monsoon onset based on a set of local parameters. The agronomic onset definition was evaluated in terms of attainable yields simulated by a rice simulation model compared to results obtained using conventional meteorological onset parameters defined by the amount of rainfall received and static onset dates. Our results show that average simulated yields increase up to 7 – 9% and probabilities of getting lower yields are reduced when the year-to-year varying dynamic onset is used over the two drier locations under fully rainfed conditions. It is mainly due to earlier transplanting dates, avoiding the impact of drought experienced with early monsoon demise. However, no yield increases are observed over the two wetter locations. This study shows the potential benefits of generating “localized and translated” climate predictions.

The role of the nutrition in malnourished cancer patients: Revisiting an old dilemma

Background & aimsGLIM definition of malnutrition is recognised all over the world and, when is referring to cancer, it specifies that weight or muscle loss are associated with an inflammatory status. However, the real-world practice shows that GLIM definition cannot encompass all the wide and heterogenous clinical presentations of cancer patients with malnutrition, which involves many other drivers beyond inflammation. Moreover, placing an excessive emphasis on the inflammation can overshadow, in the clinical practice, the role of the nutritional support in malnourished cancer patients. The aim of this paper is not to criticize the rationale of the GLIM definition of cancer cachexia, but to show the complexity and heterogeneity of malnutrition of cancer patients and reasons why nutritional support should deserve such a better consideration among the oncologists. MethodsLiterature pertinent to pathophysiology of malnutrition of cancer patients is scrutinised and reasons for the frequent underuse of nutritional support are critically analysed. ResultsThe appraisal of the literature shows that there are various pathophysiological patterns of malnutrition among cancer patients and inflammatory markers are not universally present in weight-losing cancer patients. Inflammation alone does not account for weight loss in all cancer patients and factors other than inflammation can drive hypophagia and weight loss, and hypophagia appears to be a primary catalyst for weight loss. Furthermore, malnutrition may be the consequence of the presence of several Nutrition Impact Symptoms or of the oncologic therapy.The nutritional support may fail to show benefits in malnourished cancer patients because the golden standard to validate a therapy relies on RCT, but it is ethically impossible to have an unfed control group of malnourished patients. Furthermore, nutritional interventions often fell short of the optimal standards, adherence to treatment plans was often poor, nutritional support was mainly reserved for very advanced patients and the primary endpoints of the studies on nutritional support were sometimes unrealistic. ConclusionThere is a gap between the suggestion of the guidelines which advocate the use of nutritional support to improve the compliance of patients facing intensive oncologic treatments or to prevent an early demise when patients enter a chronic phase of slow nutritional deterioration, and the poor use of nutrition in the real-world practice. This requires a higher level of awareness of the oncologists concerning the reasons for the lacking evidence of efficacy of the nutritional support and an understanding of its potential contribute to improve the outcome of the patients. Finally, this paper calls for a change of the oncologist’s approach to the cancer patient, from only focusing on the cure of the tumour to taking care of the patient as a whole.

Congenital Insensitivity to Pain: A Fatal Entity

Abstract Congenital insensitivity to pain (CIP), also known as congenital analgesia, is an autosomal recessive, extraordinarily rare condition, in which a patient cannot feel pain in any part of his or her body. These patients may experience hyperthermia due to anhidrosis and sustain multiple fatal injuries because they are unable to feel pain at all. All these contribute to the early demise of the patient at a young age. Herein, we attempt to highlight the potentially catastrophic effects of CIP in a 4-year-old girl and reevaluate the representative features that a prudent physician should be aware of.

Abstract IA016: Metabolic reprogramming and cancer progression in patients

Abstract IA016: Metabolic reprogramming and cancer progression in patients

The growth and demise of a Middle Miocene carbonate platform in Central Luconia, offshore Malaysia

The evolution and facies distribution of relatively small carbonate platforms, ∼30 km2, are not well documented, even though they are common in ancient and modern carbonate systems. This study investigates depositional facies and evolution of a Miocene carbonate platform in Central Luconia, offshore Malaysia. An integrated approach, including core-described lithofacies, well-log correlation, and seismic analysis, allowed for the mapping of facies through time. The platform was divided into five stratigraphic zones (1 [top], 2 Upper, 2 Lower, 3 Upper, 3 Lower [bottom]) separated by low porosity intervals. Five depositional facies groups were recognized in core samples: (1) bioclastic wacke-packstone facies deposited in a platform interior, (2) bioclastic packstone facies deposited in backreef environments, (3) coral boundstone facies deposited at the reef margin, (4) interbedded shale and carbonate facies deposited on the slope, and (5) argillaceous carbonate facies deposited across the platform as flooding layers. Well D penetrated almost the entire platform, and facies in that well changed upward from mainly bioclastic wacke-packstone at the bottom to mainly bioclastic packstone in the middle to coral boundstone near the top before being covered by interbedded shale and carbonate. Six seismic facies were identified and combined with well data to map the five facies groups through time. The platform shows repeated backstepping of facies at flooding layers followed by aggradation of facies belts up to exposure surfaces, resulting in a long-term backstepping of depositional environments until the platform drowned. Sr-isotopes dating near the top of the platform yielded an age of approximately 12 Ma. This suggests that the platform drowned earlier than other carbonate platforms in Central Luconia (8–10 Ma). More tectonic subsidence in this area during the Middle Miocene is proposed as the main cause of the early demise of this carbonate platform compared to other Luconia platforms.

Undifferentiated sarcomatoid carcinoma of the pancreas-a single-institution experience with 23 cases

BackgroundThe clinical course and surgical outcomes of undifferentiated sarcomatoid carcinoma of the pancreas (USCP) remain poorly characterized owing to its rarity. This study aimed to describe the histology, clinicopathologic features, perioperative outcomes, and overall survival (OS) of 23 resected USCP patients.MethodsWe retrospectively described the histology, clinicopathologic features, perioperative outcomes and OS of patients who underwent pancreatectomy with a final diagnosis of USCP in a single institution.ResultsA total of 23 patients were included in this study. Twelve patients were male, the median age at diagnosis was 61.5 ± 13.0 years (range: 35–89). Patients with USCP had no specific symptoms and characteristic imaging findings. The R0 resection was achieved in 21 cases. The En bloc resection and reconstruction of mesenteric–portal axis was undertaken in 9 patients. There were no deaths attributed to perioperative complications in this study. The intraoperative tumor-draining lymph nodes (TDLNs) dissection was undergone in 14 patients. The 1-, 3- and 5-year survival rates were 43.5%, 4.8% and 4.8% in the whole study, the median survival was 9.0 months. Only 1 patient had survived more than 5 years and was still alive at last follow-up. The presence of distant metastasis (p = 0.004) and the presence of pathologically confirmed mesenteric–portal axis invasion (p = 0.007) was independently associated with poor OS.ConclusionsUSCP was a rare subgroup of pancreatic malignancies with a bleak prognosis. To make a diagnose of USCP by imaging was quite difficult because of the absence of specific manifestations. Accurate diagnosis depended on pathological biopsy, and the IHC profile of USCP was mainly characterized by co-expression of epithelial and mesenchymal markers. A large proportion of patients have an early demise, especially for patients with distant metastasis and pathologically confirmed mesenteric–portal axis invasion. Long-term survival after radical resection of USCPs remains rare.

Frequent expression of PD-L1 in BLS-type diffuse large B-cell lymphoma: implications for aggressiveness and immunotherapy

BLS-type diffuse large B-cell lymphoma (DLBCL) denotes an uncommon, aggressive variant of DLBCL presenting initially in bone marrow, liver and spleen without lymphadenopathy or mass lesion. Patients with BLS-type DLBCL present frequently with haemophagocytic syndrome which often leads to early patient demise. Programmed death ligand 1 (PD-L1) plays a negative regulatory role on effector T cells and is an important target of immunotherapy. Assessment of PD-L1 expression in BLS-type DLBCL may carry therapeutic implications and provide mechanistic insights. Standard immunohistochemical analysis for PD-L1 was performed in seven cohorts for this study: (1) DLBCL-not otherwise specified (NOS) (n=201); (2) Epstein-Barr virus (EBV)-positive DLBCL (n=26); (3) thymic (primary mediastinal) DLBCL (n=12); (4) intravascular LBCL (n=3); (5) high-grade B-cell lymphoma, NOS (n=12); (6) BLS-type DLBCL (n=37); and (7) systemic DLBCL involving bone marrow (n=28). We found that PD-L1 was positive in 12.9% of DLBCL-NOS cases, 46.2% of EBV-positive DLBCL, 91.7% of thymic LBCL, none of intravascular LBCL, 8.3% of high-grade B-cell lymphoma-NOS, and 56.8% of BLS-type DLBCL. By comparison, only 14.3% of bone marrow cases involved by systemic DLBCL were positive for PD-L1 (p<0.001). Interestingly, BLS-type DLBCL more frequently showed activated B-cell phenotype (86.5% vs 65.2%, p=0.010), a high Ki-67 proliferative index (97.1% vs 63.3%, p<0.001), MYC overexpression (90.9% vs 56.2%, p=0.023), presence of haemophagocytic syndrome (86.5% vs 4.0%, p<0.001), and poorer overall survival (p<0.001) than DLBCL-NOS. These data suggest that the poor prognosis of BLS-type DLBCL may be explained by both extrinsic tumour microenvironment factors and intrinsic genetic factors of tumour cells, such as PD-L1-associated inactivation of anti-tumour immunity for the former, and MYC pathway activation-related aggressiveness for the latter.

Future Projections of Low‐Level Atmospheric Circulation Patterns Over South Tropical South America: Impacts on Precipitation and Amazon Dry Season Length

AbstractThe last few decades have shown evidence of a lengthening dry season in southern Amazonia, which is associated with a delay in the onset of the South American Monsoon System (SAMS). Using a pattern recognition framework of atmospheric circulation patterns (CPs), previous studies have identified specific atmospheric situations related to the onset of the SAMS. Here, we analyze the future changes in the CPs that largely define the main hydro‐climatological states of Tropical South America. We evaluated the CP changes that occurred between two periods: historical (1970–2000) and future (2040–2070), using six General Circulation Models (GCMs) from the Coupled Model Intercomparison Project Phase 6. Future GCM projections show significant spatio‐temporal changes in the CPs associated with the dry season in southern Amazonia during the mid‐21st century. These changes are related to both a late onset of the SAMS and an early demise of the SAMS. Particularly, the CP methodology allowed for a better understanding of the behavior of the southern Amazon dry season under future conditions, showing an increase in the frequency of the CPs typically observed during the dry season. The occurrence of dry days in the Amazon basin during the austral winter of the mid‐21st century increases by 19.4% on average, with respect to the historical period. This methodology also identified a future increase in the frequency of dry CPs, both at the beginning of the dry‐to‐wet transition period (8%) and at the end of the wet‐to‐dry transition season (11%).

The effect of a vanishing twin on first- and second-trimester maternal serum markers and ultrasound screening for aneuploidy.

A vanishing twin (VT) is the early demise of a twin fetus. It is estimated to occur in 20-30% of pregnancies associated with assisted reproductive technology. VT becomes increasingly prominent when assisted fertilization is used, because one or more embryos are transferred to the uterus. Maternal serum screening tests during pregnancy can screen for trisomy chromosomes 21, 18, and 13 and are divided into first- and second-trimester tests. In singleton pregnancies, the first trimester screening test is performed at 11-13 weeks and 6 days of gestation. It consists of two serum markers, pregnancy-associated plasma protein A and β-human chorionic gonadotropin (β-hCG), and measures nuchal translucency thickness. The second-trimester screening test was performed at 15-20 weeks and 6 days of gestation. It consists of four serum markers: alpha-fetoprotein, β-hCG, unconjugated estriol, and inhibin A. More effective screening for trisomy 21 in singleton pregnancies is achieved by analyzing cell-free DNA in the maternal blood. A VT includes a demise of the fetus. Although it affects maternal serum markers, it has not been corrected. Five studies examined the effect of VT on maternal serum markers, but the results were controversial. This study aimed to review the patterns of changes in maternal serum markers in VTs, interpret prenatal tests for pregnant women with VTs in clinical practice, and consider what information should be provided.

Was the post-war international trade order bound to succeed while the Bretton Woods monetary order established in 1944 was doomed to fail?

This paper explores the reasons embedded in the original architecture of both the international trade and monetary regimes that determined different outcomes for both. It proposes that the original version of the Bretton Woods monetary regime showed faster its essential failures and basically had to be replaced as early as 1971, while the trade regime embodied in the GATT and later in the WTO managed to at least survive until present day. It posits that correspondence (or the lack of it) of the basic characteristics of the said regimes with the underlying political reality where the regimes would apply (in line with Ruggie´s depiction of «embedded liberalism») accounts for the differentiated outcomes. It explains that the international trade regime showed more flexible traits that allowed it to adjust to the underlying political and led to its survival. The lack of that adaptability element would likewise explain the early demise of the original Bretton woods scheme.

Pregnancy outcomes of fetal reduction in patients with intrauterine haematoma following double embryo transfer

Research questionIs there an association between intrauterine hematoma(IUH) and pregnancy outcomes in patients receiving fetal reduction(FR) after double embryo transfer? What is the relationship between IUH-related characteristics and pregnancy outcomes? DesignClinical information and pregnancy outcomes of women receiving FR after double embryo transfer were analyzed. Patients with other systematic diseases, ectopic pregnancy or heterotopic pregnancy, monochorionic twin pregnancies and incomplete data were excluded. Stratification of IUH pregnancies was done according to IUH-related characteristics. The main outcome measures included incidence of fetal demise(<24 weeks) while other adverse pregnancy outcomes were considered as secondary outcomes. Result(s)34 IUH patients and 136 non-IUH patients receiving FR after double embryo transfer(DET) were included based on 1:4 match for age, cycle type and fertilization method. IUH patients had higher incidence of early fetal demise(20.6% vs. 7.4%, p=0.048), threatened abortion(48.1% vs. 10.3%, p<0.001) and postpartum hemorrhage(14.8% vs. 4.0%, p=0.030)after FR compared with non-IUH patients, whereas IUH was an independent risk factor for early fetal demise(OR 3.34 95%CI 1.14-9.77) and threatened abortion(OR 8.61, 95%CI: 3.28-22.61) after adjusting for potential confounders. IUH pregnancies undergoing FR resulted in miscarriage had larger IUH volumes and earlier diagnosis. However, IUH characteristics(i.e. volume, changing pattern, presence or absence of cardiac activities) were not correlated with fetal demise and threatened abortion. Conclusion(s)Fetal reduction should be performed with caution in IUH pregnancies after double embryo transfer since the risks of fetal demise is relatively high. Special attention should be given to IUH patients after FR noticing the early signs of threatened abortion and inevitable fetal demise.

Changes in the Southern Hemisphere westerlies during last interglacial marine isotope stage 5e and its linkage to the Asian summer monsoon

Considerable ambiguity remains over the triggers for the abrupt climate deterioration that terminated the Last Interglacial Marine Isotope Stage 5e (MIS5e) period. A prevailing explanation is a sudden reduction in Atlantic Meridional Overturning Circulation (AMOC) in response to the reduced boreal summer insolation. Nonetheless, this opinion is challenged by the early weakening of the Asian summer monsoon (ASM) documented in the Chinese speleothem oxygen isotope (δ18O) ratio records. Here we propose a new mechanism involving a northerly shift of the Southern Hemisphere mid-latitude westerlies (SHW), based on saturation magnetization (Ms) and stable carbon (δ13C) and oxygen isotopes from a speleothem in northern Tasmania. The Ms record shows high-frequent peaks at 122.8–119.7 ka B.P., while δ18O and δ13C ratios first increase significantly (122.8–122.2 ka B.P.) and then decrease (122.2–119.7 ka B.P.). These Ms peaks suggest a northward shift of SHW at 122.8–119.7 ka B.P., which precedes the earliest ASM weakening for MIS5e demise and coincides with the reduced Agulhas leakage. This indicates that when SHW reaches a northerly position, the reduced Agulhas leakage leads to an anomalous warming in the southern Indian Ocean, further weakening the cross-equatorial flow. Such a process would aggravate the ASM weakening caused by the decline in boreal summer insolation and initiate an early MIS5e demise.

Outcome of primary posterior tracheopexy in thoracoscopically repaired esophageal atresia neonates with tracheomalacia; single center's experience

BackgroundTracheomalacia frequently develops in esophageal atresia patients (EA) especially in those with tracheoesophageal fistula (TEF). Conservative management has been the standard treatment; however, it was reported that delay in management could result in chronic lung conditions. Thus, early surgical interventions have been recently recommended. Patients and MethodsWe enrolled patients presented with type-C esophageal atresia, with concomitant moderate to severe tracheomalacia, who had their thoracoscopic intervention done during the study period 2019–2022. Early and intermediate- term outcomes were studied and compared to another cohort with mild or no tracheomalacia. ResultsDuring the allocated study period, 24 patients met the inclusion criteria for tracheopexy, but only 17 were followed up due to early demise of the other seven. During the follow-up period, 7/17 patients developed respiratory symptoms, which were attributed to esophageal stricture in 5 patients, recurrent TEF in 2 patients and one of them had residual tracheomalacia in addition to the developed recurrent TEF. The outcomes of the enrolled patients for tracheopexy were similar to those with no or mild tracheomalacia. ConclusionsPrimary posterior tracheopexy during the primary repair might be considered a safe and feasible option not only to alleviate respiratory symptoms secondary to tracheomalacia in EA patients, but also to decline the need of further surgical interventions. However, more comprehensive studies with long-term follow-ups are mandatory.

Variants in FGF10 cause early onset of severe childhood interstitial lung disease: A detailed description of four affected children.

Fibroblast growth factor 10 (FGF10) is a signaling molecule with a well-established role for lung branching morphogenesis. Rare heterozygous, deleterious variants in the FGF10 gene are known causes of the lacrimo-auriculo-dento-digital (LADD) syndrome and aplasia of lacrimal and salivary glands.Previous studies indicate that pathogenic variants in FGF10 can cause childhood Interstitial Lung Disease (chILD) due to severe diffuse developmental disorders of the lung, but detailed reports on clinical presentation and follow-up of affected children are lacking. We describe four children with postnatal onset of chILD and heterozygous variants in FGF10, each detected by exome or whole genome sequencing. All children presented with postnatal respiratory failure. Two children died within the first 2 days of life, one patient died at age of 12 years due to right heart failure related to severe pulmonary hypertension (PH) and one patient is alive at age of 6years, but still symptomatic. Histopathological analysis of lung biopsies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia and interstitial fibrosis. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis. Our report extends the phenotype of FGF10-related disorders to early onset chILD with progressive interstitial lung fibrosis and PH. Therefore, FGF10-related disorder should be considered even without previously described syndromic stigmata in children with postnatal respiratory distress, not only when leading to death in the neonatal period but also in case of persistent respiratory complaints and PH.

GPI-anchoring disorders and the heart: Is cardiomyopathy an overlooked feature?

Glycosylphosphatidylinositol anchoring disorders (GPI-ADs) are a subgroup of congenital disorders of glycosylation. GPI biosynthesis requires proteins encoded by over 30 genes of which 24 genes are linked to neurodevelopmental disorders. Patients, especially those with PIGA-encephalopathy, have a high risk of premature mortality which sometimes is attributed to cardiomyopathy. We aimed to explore the occurrence of cardiomyopathy among patients with GPI-ADs and to raise awareness about this potentially lethal feature. Unpublished patients with genetically proven GPI-ADs and cardiomyopathy were identified through an international collaboration and recruited through the respective clinicians. We also reviewed the literature for published patients with cardiomyopathy and GPI-AD and contacted the corresponding authors for additional information. We identified four novel and unrelated patients with GPI-AD and cardiomyopathy. Cardiomyopathy was diagnosed before adulthood and was the cause of early demise in two patients. Only one patients underwent cardiac workup after being diagnosed with a GPI-AD. All were diagnosed with PIGA-encephalopathy and three had a disease-causing variant at the same residue. The literature reports five additional children with GPI-AD related cardiomyopathy, three of which died before adulthood. We have shown that patients with GPI-ADs are at risk of developing cardiomyopathy and that regular cardiac workup with echocardiography is necessary.

ARPC5 deficiency leads to severe early-onset systemic inflammation and mortality.

The Arp2/3 complex drives the formation of branched actin networks that are essential for many cellular processes. In humans, the ARPC5 subunit of the Arp2/3 complex is encoded by two paralogous genes (ARPC5 and ARPC5L) with 67% identity. Through whole-exome sequencing, we identified a biallelic ARPC5 frameshift variant in a female child who presented with recurrent infections, multiple congenital anomalies, diarrhea and thrombocytopenia, and suffered early demise from sepsis. Her consanguineous parents also had a previous child who died with similar clinical features. Using CRISPR/Cas9-mediated approaches, we demonstrate that loss of ARPC5 affects actin cytoskeleton organization and function in vitro. Homozygous Arpc5-/- mice do not survive past embryonic day 9 owing to developmental defects, including loss of the second pharyngeal arch, which contributes to craniofacial and heart development. Our results indicate that ARPC5 is important for both prenatal development and postnatal immune signaling, in a non-redundant manner with ARPC5L. Moreover, our observations add ARPC5 to the list of genes that should be considered when patients present with syndromic early-onset immunodeficiency, particularly if recessive inheritance is suspected.

Congenital hyperoxalosis: a rare metabolic disorder in a term neonate with perinatal autopsy findings

Introduction: Primary hyperoxaluria (PH) is a rare autosomal recessive metabolic disorder resulting from an inborn error of metabolism. It causes renal tubular oxalosis which often leads to renal failure and early foetal demise. Only a few cases of PH detected in the neonatal period have been published in the literature.Case report: This baby girl was the second child of a 30-year-old woman of a second-degree consanguineous marriage. Maternal gestational diabetes mellitus was diagnosed during the antenatal period. The baby was delivered at 37 weeks + 2 days of gestation following an emergency lower segment caesarean section due to the absence of liquor. A few hours after birth the baby developed respiratory distress and reduced urine output. Investigations revealed high serum creatinine levels. The ultrasound scan was suggestive of acute kidney injury and the baby died on day 2. There was no known family history of renal diseases. During the pathological autopsy examination, there were no definite dysmorphic features. The internal examination revealed bilateral lung hypoplasia and patent ductus arteriosus. The kidneys were of normal size and shape and the microscopy showed numerous, widespread, polarizable oxalate crystals within the renal tubules, in favour of primary hyperoxaluria.Discussion and conclusion: The extensive renal damage imparted by oxalate deposition may have contributed to the impaired renal function and resulted in obstruction to the urine output, leading to oligohydramnios and pulmonary hypoplasia. Confirmation of the diagnosis of PH requires examination of urine and serum for high oxalate levels and detection of specific genetic mutations. Family screening and genetic counselling are necessary.

Non-invasive prenatal testing (NIPT) in twin pregnancies affected by early single fetal demise: A systematic review of NIPT and vanishing twins.

The screening performance of non-invasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies is relatively unknown. To close this knowledge gap, we conducted a systematic review of the available literature. Studies describing the test performance of NIPT for trisomy 21, 18, 13, sex chromosomes and additional findings in pregnancies with a VT were retrieved from a literature search with a publication date until October 4, 2022. The methodological quality of the studies was assessed with the quality assessment tool for diagnostic accuracy studies-2 (QUADAS-2). The screen positive rate of the pooled data and the pooled positive predictive value (PPV) were calculated using a random effects model. Seven studies, with cohort sizes ranging from 5 to 767, were included. The screen positive rate of the pooled data for trisomy 21 was 35/1592 (2.2%), with a PPV of 20% (confirmation in 7/35 cases [95% CI 9.8%-36%]). For trisomy 18, the screen positive rate was 13/1592 (0.91%) and the pooled PPV 25% [95% CI 1.3%-90%]. The screen positive rate for trisomy 13 was 7/1592 (0.44%) and confirmed in 0/7 cases (pooled PPV 0% [95% CI 0%-100%]). The screen positive rate for additional findings was 23/767 (2.9%), of which none could be confirmed. No discordant negative results were reported. There is insufficient data to fully evaluate NIPT performance in pregnancies with a VT. However, existing studies suggest that NIPT can successfully detect common autosomal aneuploidies in pregnancies affected by a VT but with a higher false positive rate. Further studies are needed to determine the optimal timing of NIPT in VT pregnancies.