Pregnancy after deceased donor vs living donor kidney transplant: associated obstetric and graft outcomes.

BACKGROUND: Outside of pregnancy, recipients of a deceased donor kidney transplant experience worse graft and overall survival compared with recipients of a living donor kidney transplant. In pregnancy, it is unknown whether the type of donor graft modifies either graft health in the peripartum period or pregnancy outcomes. OBJECTIVE: This study aimed to define characteristics and outcomes in pregnancy based on donor type in kidney transplant recipients. STUDY DESIGN: This was a retrospective cohort study of adult kidney transplant recipients who received their graft between 2000 and 2019 with a subsequent pregnancy enrolled in the Transplant Pregnancy Registry International. The primary outcome was graft loss within 2 years of delivery. The secondary outcomes included severe maternal morbidity and neonatal composite morbidity. Univariate, multivariable logistic regression, and Cox proportional-hazards models were constructed for statistical analysis, with recipients of a living unrelated donor as the referent. RESULTS: Overall, 638 pregnant patients after kidney transplant had pregnancy outcomes that met our inclusion criteria. Of these patients, 168 (26.3%) received a graft from a deceased donor, 310 (48.6%) received a graft from a living related donor, and 160 (25.1%) received a graft from a living unrelated donor. Recipients of a deceased donor were more likely to be nulliparous, have an unplanned pregnancy, and self-identify as non-White. Moreover, recipients of a deceased donor were more likely to experience urinary tract infections (deceased donor: 21.8%; living related donor: 10.1%; living unrelated donor: 20.6%; P=.018). Severe maternal morbidity (deceased donor: 3.4%; living related donor: 2.8%; living unrelated donor: 7.2%) and neonatal composite morbidity (deceased donor: 8.4%; living related donor: 17.1%; living unrelated donor: 14.4%) did not differ by donor type. Deceased donor transplant was associated with graft loss within 2 years of delivery (deceased donor: 6.7%; living related donor: 3.7%; living unrelated donor: 1.3%; adjusted odds ratio, 7.52; 95% confidence interval, 1.53-60.8) and long-term graft loss from transplant (adjusted hazard ratio, 2.08; 95% confidence interval, 1.10-3.95). CONCLUSION: Although our study demonstrated an association between deceased donor transplant and graft loss after pregnancy, it did not provide evidence that pregnancy itself causes graft loss. Recipients of a deceased donor kidney transplant should not be discouraged from pursuing pregnancy based on their donor type, but these patients should undergo preconception counseling with a discussion of their individualized obstetrical and graft risks, close intrapartum monitoring for infection and hypertensive disease, and continued surveillance for at least 2 years after delivery with a multidisciplinary obstetrics and transplant team.

Pregnancy after transplant in the older adolescent: Anticipatory guidance for the pediatric provider.

BACKGROUND: Healthcare providers who care for adolescent and young adult transplant recipients should be aware of contraception counseling and potential for pregnancy in this at-risk cohort. METHODS: This paper will review contraceptive options in general for transplant recipients. There will also be a review of common immunosuppressive medications and their risk profile regarding pregnancy after transplantation. Data from the Transplant Pregnancy Registry International were analyzed looking at recipients conceiving under the age of 21 and were compared to overall pregnancy outcomes. RESULTS: Overall pregnancy outcomes in recipients under the age of 21 are like the adult cohort. CONCLUSION: It is imperative to provide contraception counseling to the adolescent and young adult and inform their caregiver that pregnancy can happen if the recipient is sexually active. Pregnant adolescent and young adult transplant recipients should be followed by a multidisciplinary team to assure a positive outcome for the recipient, transplant, and neonate.

Kidney transplant in pediatric gut transplant recipients - Technical challenges and outcomes.

BACKGROUND: There is limited data in the literature about pediatric kidney transplant (KT) following gut transplant (GT). The purpose of this study is to highlight the technical challenges and outcomes of KT in pediatric gut recipients who developed kidney failure (KF). METHODS: A retrospective single-center study of pediatric GT recipients from January 2000 to December 2019 was performed. In total, 14 (7%) out of 206 pediatric GT recipients developed KF and were listed for KT. Ten patients underwent kidney after gut transplant (KAGT), three patients underwent simultaneous kidney and re-do gut transplant (SKAGT), and one patient died on the KT waitlist. RESULTS: 1-, 5-, and 10-year kidney graft survival was 100%, 91%, and 78%, respectively. 1-, 5-, and 10-year GT graft survival was 100%, 77%, and 77%, respectively. 1-, 5-, and 10-year patient survival was 100%, 91%, and 91%, respectively. CONCLUSION: Despite the technical complexity, KAGT and SKAGT for pediatric GT recipients that develop KF can be performed with favorable outcomes.

Donor-derived Ehrlichiosis: 2 Clusters Following Solid Organ Transplantation.

Ehrlichiosis has been infrequently described as transmissible through organ transplantation. Two donor-derived clusters of ehrlichiosis are described here. During the summer of 2020, 2 cases of ehrlichiosis were reported to the Organ Procurement and Transplantation Network (OPTN) and the Centers for Disease Control and Prevention (CDC) for investigation. Additional transplant centers were contacted to investigate similar illness in other recipients and samples were sent to the CDC. Two kidney recipients from a common donor developed fatal ehrlichiosis-induced hemophagocytic lymphocytic histiocytosis. Two kidney recipients and a liver recipient from another common donor developed ehrlichiosis. All 3 were successfully treated. Clinicians should consider donor-derived ehrlichiosis when evaluating recipients with fever early after transplantation after more common causes are ruled out, especially if the donor has epidemiological risk factors for infection. Suspected cases should be reported to the organ procurement organization and the OPTN for further investigation by public health authorities.

The epidemiology of airplane headache: A cross-sectional study on point prevalence and characteristics in 50,000 travelers.

BACKGROUND: The current knowledge on the epidemiology and clinical manifestation of airplane headache is mostly derived from case series and small cohort studies without evidence from large populations. METHODS: This cross-sectional study was conducted over a five-month period in the arrival area of two international airports in Germany. 50,000 disembarking passengers were addressed about headaches during their flight to determine headache prevalence, and those confirming and willing to participate underwent a structured interview. RESULTS: Headache during travel was reported by 374 passengers (0.75%), and 301 underwent a structured interview. One hundred and one (0.2%) met the diagnostic criteria of airplane headache. Six passengers suffered from migraines and 134 from tension-type headaches. The differences in the age and gender distribution between the airplane headache and non-airplane headache groups were not statistically significant. The onset (79.2%), duration (82.2%), and location (73.3%) of airplane headache mostly complied with current diagnostic criteria but pain intensity (42.6%) and quality (42.6%) did less so. CONCLUSION: Our data suggest a substantially lower prevalence of airplane headaches than previously reported. The pain intensity and quality seem less characteristic than assumed, suggesting a need to refine the current diagnostic criteria.

Association of early hyponatremia and the development of acute kidney injury in critically ill children.

BACKGROUND: Hyponatremia is an independent prognostic factor for mortality; however, the reason for this remains unclear. An observed relationship between hyponatremia and the development of acute kidney injury (AKI) has been reported in certain disease states, but hyponatremia has not been evaluated as a predictor of AKI in critically ill patients or children. METHODS: This is a single-center retrospective cohort study of critically ill children admitted to a tertiary care center. We performed regression analysis to assess the association between hyponatremia at ICU admission and the development of new or worsening stage 2 or 3 (severe) AKI on days 2-3 following ICU admission. RESULTS: Among the 5057 children included in the study, early hyponatremia was present in 13.3% of children. Severe AKI occurred in 9.2% of children with hyponatremia compared to 4.5% of children with normonatremia. Following covariate adjustment, hyponatremia at ICU admission was associated with a 75% increase in the odds of developing severe AKI when compared to critically ill children with normonatremia (aOR 1.75, 95% CI 1.28-2.39). Evaluating sodium levels continuously, for every 1 mEq/L decrease in serum sodium level, there was a 0.05% increase in the odds of developing severe AKI (aOR 1.05, 95% CI 1.02-1.08). Hyponatremic children who developed severe AKI had a higher frequency of kidney replacement therapy, AKI or acute kidney disease at hospital discharge, and hospital mortality when compared to those without. CONCLUSIONS: Hyponatremia at ICU admission is associated with the development of new or worsening AKI in critically ill children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation.

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT-angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic ß2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.

Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue.

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell's score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell's score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.

Molecular Stacking on Graphene.

The sequential vertical polyfunctionalization of 2D addend-patterned graphene is still elusive. Here, we report a practical realization of this goal via a "molecular building blocks" approach, which is based on a combination of a lithography-assisted reductive functionalization approach and a post-functionalization step to sequentially and controllably link the molecular building blocks ethylpyridine, cis-dichlorobis(2,2'-bipyridyl)ruthenium, and triphenylphosphine (4-methylbenzenethiol, respectively) on selected lattice regions of a graphene matrix. The assembled 2D hetero-architectures are unambiguously characterized by various spectroscopic and microscopic measurements, revealing the stepwise stacking of the molecular building blocks on the graphene surface. Our method overcomes the current limitation of a one-layer-only binding to the graphene surface and opens the door for a vertical growth in the z-direction.

Surface oxidation-induced restructuring of liquid Pd-Ga SCALMS model catalysts.

We have examined model systems for the recently reported Pd-Ga Supported Catalytically Active Liquid Metal Solutions (SCALMS) catalysts using near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) under oxidizing conditions. Gallium is known to be highly prone to oxidation and in practical applications, handling of the catalyst material in air or the presence of traces of oxygen in the reactor are unavoidable. Therefore, we expect our results to be of high relevance for the application of Ga-based SCALMS catalysts. Pd-Ga alloy samples of 1.3 and 1.8 at% Pd content were exposed to molecular oxygen at different pressures between 3 × 10-7 and 1 mbar and a temperature of 550 K. We observe the formation of wetting Ga2O3 films upon exposure to molecular oxygen. The absolute thicknesses of the oxide films depend on oxygen pressure, with values ranging from ∼12 Å at 10-7 to 10-5 mbar to ∼50 Å at 1 mbar. The formed metal-oxide interface leads to a redistribution of Pd, which accumulates at the boundary between the wetting oxide film and the metal substrate as a response to the oxide film growth. A maximum Pd 3d intensity is observed at an oxide thickness of 5 Å. For thicker films, the Pd 3d signal and the Ga 3d signal ascribed to the metallic substrate decrease in parallel, which is attributed to the oxide layer growing on top of the liquid metal alloy. From this observation, we conclude that no significant amount of Pd is bound in the newly formed oxide film. Density-functional theory (DFT) calculations support the experimental observations.

Association of HLA Typing and Alloimmunity With Posttransplantation Membranous Nephropathy: A Multicenter Case Series.

RATIONALE & OBJECTIVES: Posttransplantation membranous nephropathy (MN) represents a rare complication of kidney transplantation that can be classified as recurrent or de novo. The clinical, pathologic, and immunogenetic characteristics of posttransplantation MN and the differences between de novo and recurrent MN are not well understood. STUDY DESIGN: Multicenter case series. SETTING & PARTICIPANTS: We included 77 patients from 5 North American and European medical centers with post-kidney transplantation MN (27 de novo and 50 recurrent). Patients with MN in the native kidney who received kidney allografts but did not develop recurrent MN were used as nonrecurrent controls (n = 43). To improve understanding of posttransplantation MN, we compared de novo MN with recurrent MN and then contrasted recurrent MN with nonrecurrent controls. FINDINGS: Compared with recurrent MN, de novo MN was less likely to be classified as primary MN (OR, 0.04; P < 0.001) and had more concurrent antibody-mediated rejection (OR, 12.0; P < 0.001) and inferior allograft survival (HR for allograft failure, 3.2; P = 0.007). HLA-DQ2 and HLA-DR17 antigens were more common in recipients with recurrent MN compared with those with de novo MN; however, the frequency of these recipient antigens in recurrent MN was similar to that in nonrecurrent MN controls. Among the 93 kidney transplant recipients with native kidney failure attributed to MN, older recipient age (HR per each year older, 1.03; P = 0.02), recipient HLA-A3 antigen (HR, 2.5; P = 0.003), steroid-free immunosuppressive regimens (HR, 2.84; P < 0.001), and living related allograft (HR, 1.94; P = 0.03) were predictors of MN recurrence. LIMITATIONS: Retrospective case series, limited sample size due to rarity of the disease, nonstandardized nature of data collection and biopsies. CONCLUSIONS: De novo and recurrent MN likely represent separate diseases. De novo MN is associated with humoral alloimmunity and guarded outcome. Potential predisposing factors for recurrent MN include recipients who are older, recipient HLA-A3 antigen, steroid-free immunosuppressive regimen, and living related donor kidney.

Use of C-Reactive Protein and Ferritin Biomarkers in Daily Pediatric Practice.

Recent pediatric clinical research has begun to focus on risk stratification tools using multibiomarker models. C-reactive protein (CRP) and ferriti biomarkers are widely available and used to varying degrees in daily practice, but there is no single source examining the evidence behind their use.We set out to summarize the evidence behind the use of CRP and ferritin biomarkers in pediatric practice and to begin development of a consensus for their future use for pediatricians.All the literature involving CRP and ferritin in pediatrics available on PubMed was surveyed. Research applicable to daily pediatric practice was summarized in the body of the article. Pediatric clinicians of various subspecialties contributed to the summary of the use of CRP and ferritin biomarkers in clinical practice in various disease processes. A clinical decision pathway is described, and evidence is summarized.CRP and ferritin biomarkers have diverse uses with various cutoff values in the literature, making their use in daily practice difficult. Elevation of these markers coincides with their significant elevation in uncontrolled inflammation.CRP and ferritin biomarkers are widely used in pediatrics. This review provides a resource summarizing evidence into a single source. There is sufficient evidence to indicate that these biomarkers of inflammation can be useful in guiding clinical decision making in specific clinical scenarios; however, further work is needed to improve their use in clinical practice.

Reproductive health in women following abdominal organ transplant.

Fertility is commonly impaired in women with end-stage kidney and liver disease, although most women will have restoration of fertility within 1 year of transplant. Family planning is therefore critical to discuss with reproductive-aged transplant recipients in the early posttransplant period, in order to ensure timely initiation of contraception, and optimal timing for conception. For women seeking pregnancy, the risks to the mother, graft, and baby should be discussed, including evaluation of immunosuppression safety and potential for adjusting medications prior to conception. With an increasing number of transplant patients now breastfeeding, immunosuppression safety in lactation continues to carry great importance.

Belatacept during pregnancy in renal transplant recipients: Two case reports.

Impaired fertility is common among patients with chronic organ failure, including end-stage renal disease (ESRD). Women of childbearing age undergoing transplantation may experience rapid return of fertility. Pregnancy posttransplant presents numerous risks for the patient, fetus, and allograft. Maternal risks include hypertension and preeclampsia. Allograft risks include acute rejection and failure of the organ, and fetal risks include miscarriage, birth defects from immunosuppressants, premature delivery, and low birth weight. Belatacept, a selective T cell costimulation blocker, was approved for use in kidney transplant recipients in the United States in 2011. Little is known about the safety of belatacept during pregnancy in humans. We describe 2 cases of successful pregnancy and delivery with the use of belatacept-based immunosuppression. The Transplant Pregnancy Registry International (TPR) is a voluntary registry for transplant recipients who have had pregnancies or fathered a pregnancy posttransplant. To date, these 2 cases are the only known exposures to belatacept that have been reported to the TPR.

Mild prolonged chronic hyponatremia and risk of hip fracture in the elderly.

BACKGROUND: Hip fractures are among the most serious bone fractures in the elderly, producing significant morbidity and mortality. Several observational studies have found that mild hyponatremia can adversely affect bone, with fractures occurring as a potential complication. We examined if there is an independent association between prolonged chronic hyponatremia (>90 days duration) and risk of hip fracture in the elderly. METHODS: We performed a retrospective cohort study in adults >60 years of age from a prepaid health maintenance organization who had two or more measurements of plasma sodium between 2005 and 2012. The incidence of hip fractures was assessed in a very restrictive population: subjects with prolonged chronic hyponatremia, defined as plasma sodium values <135 mmol/L, lasting >90 days. Multivariable Cox regression was performed to determine the hazard ratio (HR) for hip fracture risk associated with prolonged chronic hyponatremia after adjustment for the propensity to have hyponatremia, fracture risk factors and relevant baseline characteristics. RESULTS: Among 31 527 eligible patients, only 228 (0.9%) had prolonged chronic hyponatremia. Mean plasma sodium was 132 ± 5 mmol/L in hyponatremic patients and 139 ± 3 mmol/L in normonatremic patients (P < 0.001). The absolute risk for hip fracture was 7/282 in patients with prolonged chronic hyponatremia and 411/313 299 in normonatremic patients. Hyponatremic patients had a substantially elevated rate of hip fracture [adjusted HR 4.52 (95% CI 2.14-9.6)], which was even higher in those with moderate hyponatremia (<130 mmol/L) [adjusted HR 7.61 (95% CI 2.8-20.5)]. CONCLUSION: Mild prolonged chronic hyponatremia is independently associated with hip fracture risk in the elderly population, although the absolute risk is low. However, proof that correcting hyponatremia will result in a reduction of hip fractures is lacking.

Fatal Hyponatremic Encephalopathy as a Result of Child Abuse From Forced Exercise.

We report a case of fatal hyponatremic encephalopathy in a child who was forced to exercise as a form of punishment. A 9-year-old girl with attention-deficit/hyperactivity disorder was forced to run repeated 50-ft sprints to the point of exhaustion by her grandmother as punishment for taking candy from a classmate. After more than 3 hours of forced running, the child collapsed, began to vomit, and had repeated clonic seizures. Upon presentation to the emergency department, she was nonresponsive with a Glasgow Coma Scale score of 11 and had noncardiogenic pulmonary edema with serum sodium of 117 mEq/L. She was treated with antiepilectic medications and transferred to a university children's hospital where she later died. On postmortem examination, she was found to have massive cerebral edema with transtentorial herniation and pulmonary edema. Her clinical presentation closely resembled exercise-associated hyponatremic encephalopathy seen in adult endurance athletes. This appears to be the first report of fatal exercise-associated hyponatremia in a child.

Treatment of hyponatremic encephalopathy with a 3% sodium chloride protocol: a case series.

BACKGROUND: 3% sodium chloride solution is the accepted treatment for hyponatremic encephalopathy, but evidence-based guidelines for its use are lacking. STUDY DESIGN: A case series. SETTING & PARTICIPANTS: Adult patients presenting to the emergency department of a university hospital with hyponatremic encephalopathy, defined as serum sodium level < 130 mEq/L with neurologic symptoms of increased intracranial pressure without other apparent cause, and treated with a continuous infusion of 500mL of 3% sodium chloride solution over 6 hours through a peripheral vein. PREDICTORS: Hyponatremic encephalopathy defined as serum sodium level < 130 mEq/L with neurologic symptoms of increased intracranial pressure without other apparent cause. OUTCOMES: Change in serum sodium level within 48 hours, improvement in neurologic symptoms, and clinical evidence of cerebral demyelination, permanent neurologic injury, or death within 6 months' posttreatment follow-up. RESULTS: There were 71 episodes of hyponatremic encephalopathy in 64 individuals. Comorbid conditions were present in 86% of individuals. Baseline mean serum sodium level was 114.1±0.8 (SEM) mEq/L and increased to 117.9±1.3, 121.2±1.2, 123.9±1.0, and 128.3±0.8 mEq/L at 3, 12, 24, and 48 hours following the initiation of 3% sodium chloride solution treatment, respectively. There was a marked improvement in central nervous system symptoms within hours of therapy in 69 of 71 (97%) episodes. There were 12 deaths, all of which occurred following the resolution of hyponatremic encephalopathy and were related to comorbid conditions, with 75% of deaths related to sepsis. No patient developed neurologic symptoms consistent with cerebral demyelination at any point during the 6-month follow-up period. LIMITATIONS: Lack of a comparison group and follow-up neuroimaging studies. Number of cases is too small to provide definitive assessment of the safety of this protocol. CONCLUSIONS: 3% sodium chloride solution was effective in reversing the symptoms of hyponatremic encephalopathy in the emergency department without producing neurologic injury related to cerebral demyelination on long-term follow-up in this case series.