The clinical spectrum of HbSC sickle cell disease-not a benign condition.

Sickle cell disease (SCD) includes a group of heterogenous disorders that result in significant morbidities. HbSS is the most common type of SCD and HbSC is the second most common type of SCD. The prevalence of HbSC disease in the United States and United Kingdom is ~1 in 7174 births and 1 in 6174 births respectively. Despite its frequency, however, HbSC disease has been insufficiently studied and was historically categorized as a more 'mild' form of SCD. We conducted this study of HbSC disease as part of the NHLBI funded Sickle Cell Disease Implementation Consortium (SCDIC). The SCDIC registry included 2282 individuals with SCD, ages 15-45 years of whom 502 (22%) had HbSC disease. Compared with people with sickle cell anaemia (SCA), the study found that people with HbSC disease had a higher frequency of splenomegaly (n (%) = 169 (33.7) vs. 392 (22.1)) and retinopathy (n (%) = 116 (23.1) vs. 189 (10.6)). A Many people with HbSC also had avascular necrosis (n (%) = 112 (22.3)), pulmonary embolism (n (%) = 43 (8.6)) and acute chest syndrome (n (%) = 228 (45.4)) demonstrating significant disease severity. HbSC disease is more clinically severe than was previously recognized and deserves additional evaluation and targeted treatments.

Hormonal stimulation reduces numbers and impairs function of human uterine natural killer cells during implantation.

STUDY QUESTION: How does an altered maternal hormonal environment, such as that seen during superovulation with gonadotropins in ART, impact human uterine immune cell distribution and function during the window of implantation? SUMMARY ANSWER: Hormonal stimulation with gonadotropins alters abundance of maternal immune cells including uterine natural killer (uNK) cells and reduces uNK cell ability to promote extravillous trophoblast (EVT) invasion. WHAT IS KNOWN ALREADY: An altered maternal hormonal environment, seen following ART, can lead to increased risk for adverse perinatal outcomes associated with disordered placentation. Maternal immune cells play an essential role in invasion of EVTs, a process required for proper establishment of the placenta, and adverse perinatal outcomes have been associated with altered immune cell populations. How ART impacts maternal immune cells and whether this can in turn affect implantation and placentation in humans remain unknown. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was carried out between 2018 and 2021 on 51 subjects: 20 from natural cycles 8 days after LH surge; and 31 from stimulated IVF cycles 7 days after egg retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial biopsies and peripheral blood samples were collected during the window of implantation in subjects with regular menstrual cycles or undergoing superovulation. Serum estradiol and progesterone levels were measured by chemiluminescent competitive immunoassay. Immune cell populations in blood and endometrium were analyzed using flow cytometry. uNK cells were purified using fluorescence-activated cell sorting and were subjected to RNA sequencing (RNA-seq). Functional changes in uNK cells due to hormonal stimulation were evaluated using the implantation-on-a-chip (IOC) device, a novel bioengineered platform using human primary cells that mimics early processes that occur during pregnancy in a physiologically relevant manner. Unpaired t-tests, one-way ANOVA, and pairwise multiple comparison tests were used to statistically evaluate differences. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were comparable for both groups. As expected, serum estradiol levels on the day of biopsy were significantly higher in stimulated (superovulated) patients (P = 0.0005). In the setting of superovulation, we found an endometrium-specific reduction in the density of bulk CD56+ uNK cells (P < 0.05), as well as in the uNK3 subpopulation (P = 0.025) specifically (CD103+ NK cells). In stimulated samples, we also found that the proportion of endometrial B cells was increased (P < 0.0001). Our findings were specific to the endometrium and not seen in peripheral blood. On the IOC device, uNK cells from naturally cycling secretory endometrium promote EVT invasion (P = 0.03). However, uNK cells from hormonally stimulated endometrium were unable to significantly promote EVT invasion, as measured by area of invasion, depth of invasion, and number of invaded EVTs by area. Bulk RNA-seq of sorted uNK cells from stimulated and unstimulated endometrium revealed changes in signaling pathways associated with immune cell trafficking/movement and inflammation. LIMITATIONS, REASONS FOR CAUTION: Patient numbers utilized for the study were low but were enough to identify significant overall population differences in select immune cell types. With additional power and deeper immune phenotyping, we may detect additional differences in immune cell composition of blood and endometrium in the setting of hormonal stimulation. Flow cytometry was performed on targeted immune cell populations that have shown involvement in early pregnancy. A more unbiased approach might identify changes in novel maternal immune cells not investigated in this study. We performed RNA-seq only on uNK cells, which demonstrated differences in gene expression. Ovarian stimulation may also impact gene expression and function of other subsets of immune cells, as well as other cell types within the endometrium. Finally, the IOC device, while a major improvement over existing in vitro methods to study early pregnancy, does not include all possible maternal cells present during early pregnancy, which could impact functional effects seen. Immune cells other than uNK cells may impact invasion of EVTs in vitro and in vivo, though these remain to be tested. WIDER IMPLICATIONS OF THE FINDINGS: These findings demonstrate that hormonal stimulation affects the distribution of uNK cells during the implantation window and reduces the proinvasive effects of uNK cells during early pregnancy. Our results provide a potential mechanism by which fresh IVF cycles may increase risk of disorders of placentation, previously linked to adverse perinatal outcomes. STUDY FUNDING/COMPETING INTEREST(S): Research reported in this publication was supported by the University of Pennsylvania University Research Funding (to M.M.), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD068157 to M.M., S.S., and S.M.), National Center for Advancing Translational Sciences of the National Institutes of Health (TL1TR001880 to J.K.), the Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania, the Children's Hospital of Philadelphia Research Institute (to S.M.G.), and the National Institute of Allergy and Infectious Diseases (K08AI151265 to S.M.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Prevalence of Sickle Cell Disease among Newborns in St Vincent and the Grenadines: A Retrospective Study.

Objective: In the United States of America (USA), sickle cell disease (SCD) occurs in 1:375 African-American births. However, published data from the Caribbean have revealed higher numbers for some Caribbean islands. St Vincent and the Grenadines (SVG) is a multi-island nation in the Caribbean, and there are currently no data on the incidence or prevalence of the disease in this population. The objective of this study was to obtain birth prevalence estimates for SCD in SVG. Methods: A retrospective review of haemoglobin electrophoresis test results at the laboratory of the main hospital in SVG for the period of October 1, 2005 to December 31, 2013 was done. Test results and demographic data were extracted to determine the estimated birth prevalence of SCD. Results: The estimated birth prevalence of SCD was found to be 1:172 live births, and 86% of the patients were diagnosed after one year of age. Conclusion: The birth prevalence of SCD in SVG was higher than those in the USA, but was similar to the numbers in other Caribbean populations.

Objetivo: En los Estados Unidos de América (EE.UU.), la enfermedad de células falciformes (ECF) ocurre en 1:375 de los nacimientos de afroamericanos. Sin embargo, los datos publicados en el Caribe revelan un número mayor para algunas islas del Caribe. San Vicente y las Granadinas (SVG) es una nación formada por varias islas en el Caribe, y actualmente no existen datos sobre la incidencia o prevalencia de la enfermedad en esta población. El objetivo de este estudio fue obtener estimados de la prevalencia de nacimientos con ECF en SVG. Métodos: Se realizó una revisión retrospectiva de los resultados de pruebas de electroforesis de hemoglobina en el laboratorio del hospital principal de SVG, correspondientes al período de 1 de octubre de 2005 a 31 de diciembre de 2013. Los resultados de la prueba y los datos demográfcos se obtuvieron para hacer un estimado de la prevalencia de nacimientos con ECF. Resultados: Se halló que la prevalencia estimada de nacimientos con ECF fue de 1:172 por nacidos vivos, y que el 86% de los pacientes fueron diagnosticados después de un año de edad. Conclusión: La prevalencia de nacimientos con EFC en SVG fue más alta que la de los EE.UU., pero similar a las estadísticas en otras poblaciones del Caribe.

Changes in the composition and mechanical properties of dentin in mouse models of diabetes.

OBJECTIVES: This study employed mouse models of type 1 (T1D) and type 2 (T2D) diabetes to characterize the changes in tooth dentin composition and its mechanical properties. METHODS: Thirty-two mice were used in this study and divided into T1D, T2D and corresponding control groups. Mandibles were extracted 12 weeks after the onset of diabetes, and dentin from the first molars was evaluated in varying regions of the root. The composition was assessed using Raman Spectroscopy. Nanoindentation and Vickers indentation were employed to study the mechanical properties of the tissue. Statistical significance was evaluated by two-way analysis of variance with respect to the diabetic group and region of the tooth (p ≤ 0.05). RESULTS: In the T2D model, the mineral-to-collagen ratio, hardness, and storage modulus of the intertubular dentin were significantly reduced compared to tissue from the controls, especially in the cervical regions of the tooth. The reduction in the mineral-to-collagen ratio was also observed in the T1D model, but changes in nanomechanical properties were not evident. However, the bulk hardness of the teeth in the T1D model was lower than in the littermate controls. Optical microscopy revealed significant wear of the tooth crowns in both models of diabetes, which appear to result from parafunctional activities. CONCLUSION: This study suggests that both type 1 and type 2 models of diabetes are associated with detrimental changes in dentin. CLINICAL SIGNIFICANCE: Better understanding of how diabetes affects dentin and the contributing mechanisms will be key to improving treatments for people with diabetes.

Prevalence of small osteophytes on knee MRI in several large clinical and population-based studies of various age groups and OA risk factors.

Objective: Osteophytes, also small ones, are an important imaging feature of OA. However, due to their high prevalence on MR, the question has arisen whether these are truly pathophysiologic features of early OA, a result of physiologic aging, or rather a merely transient phenomenon. The aim of this study was to explore the prevalence of osteophytes on MR in various locations of the knee, with special emphasis on small osteophytes, across multiple large studies conducted in our institution comprising a wide range of subjects at different ages. Method: Retrospective explorative study of the prevalence of osteophytes, particularly grade 1 according to MOAKS, among four studies with a wide variety in age and OA risk factors. Results: A large number of grade 1 osteophytes were found in all four studies. The largest number of osteophytes were present in the youngest age group of <30 years (69.6%) compared to 36.8% in the age group of ≥30 â€‹< â€‹50 years and 54,3% when aged ≥50 years, of which most were grade 1 osteophytes. Conclusion: Small osteophytes are highly prevalent among populations with varying age and OA risk factors, in particular among young subjects without other OA features. This might suggest that these "osteophytes" do not necessarily represent early OA, but rather indicate a transient physiologic phenomenon.

Carbon monoxide re-breathing during low-flow anaesthesia in infants and children.

BACKGROUND: Carbon monoxide (CO) has been detected within anaesthesia breathing systems. One potential source in this setting is exhaled endogenous CO. We hypothesized that CO is re-breathed during low-flow anaesthesia (LFA) in infants and children. METHODS: Twenty children (age 2 months-7 yr) undergoing general anaesthesia were evaluated in a prospective observation study. LFA was established for 60 min followed by high-flow anaesthesia (HFA) for the next 60 min. Exhaled and inspired CO were measured every 5 min within the breathing circuit. Carboxyhaemoglobin (COHb%) was measured at baseline, at 60 min, after LFA, and at 120 min, after HFA. RESULTS: CO concentrations increased during LFA. Inspired CO peaked at 14 ppm. During HFA, exhaled CO levels remained constant whereas inspired CO decreased markedly. Exhaled and inspired CO during HFA differed significantly from LFA. The trajectory of change in exhaled and inspired CO was most closely associated with the fresh-gas flow (FGF):minute ventilation ratio. COHb% significantly increased in children <2 yr of age at 60 min after LFA and remained increased. CONCLUSIONS: LFA increased exhaled and inspired CO and increased COHb% in children <2 yr of age. Thus, LFA resulted in re-breathing of exhaled CO and exposure, especially in the youngest children. Re-breathing exhaled gas during LFA could pose a risk for an acute CO exposure in patients who have elevated COHb and high baseline levels of exhaled CO. If practitioners match or exceed minute ventilation with FGF to avoid LFA, CO re-breathing can be limited.

[Diagnosing neoplasia in a kidney transplant unit]. / Diagnóstico de neoplasias en una consulta de trasplante renal.

BACKGROUND AND AIM: Cancer is one of the major causes of death with functioning allograft among renal transplant patients. The increasing age of patients in the waiting list has derived in a higher risk of cancer in this population. The aim of this study was to analyze the incidence of cancer in the waiting list and kidney transplant patients. METHODS: Between November/1996 and November/2007 we assisted 825 patients in the outpatient renal transplant clinic, 467 were transplanted, 120 remained in the waiting list and 238 have been removed from the waiting list or died. RESULTS: During this period, 97 malignancies were diagnosed, 33 of 32 kidney transplant candidates and 64 of 62 renal transplant patients. The comparative analysis between this two groups showed that candidates had higher frequency of solid organ tumours compared with a higher incidence of skin cancer in transplanted patients. Mean time between transplant and cancer diagnosis was 42.6 +/- 32.7 months, 48% of malignancies were diagnosed within the first three years postransplant. When comparing kidney transplant patients with and without cancer diagnosis, the formers were older and had worse patient survival at five years. Allograft survival was similar for both groups. CONCLUSIONS: we want to emphasize the extreme importance of a detailed screening in the renal transplant candidates and transplanted patients due to a higher incidence of malignancies in this population.

Treatment of renal transplant failure.

INTRODUCTION: Among graft failures beyond months, we performed progressive reduction and complete withdrawal of immunosuppressive drugs and steroids over a period of 6 months. PATIENTS AND METHODS: We analyzed the treatment and complications associated with all late allograft failures in 34 patients (8.19%) out of 415 patients transplanted from November 1996 to November 2006. RESULTS: In 21 patients (61.8%), the progressive reduction of immunosuppressive treatment was effective and well tolerated; however, in 13 patients (38.2%) there was rejection of the allograft at 10.74 +/- 8.95 months (0.77-34.80) after the failure. With the reintroduction of these drugs, the rejection was controlled in seven patients, but in the other six we had to embolize the allograft, which had to be repeated in one case. Embolization was well tolerated, but in one case there was migration of one coil to the femoral artery. One patient treated with drug withdrawal experienced emphysematous pyelonephritis after repeated urinary infections, requiring a nephrectomy. Thirteen (38.2%) of the patients with late failures have been admitted for a second transplant; five of them showed HLA sensitization. CONCLUSIONS: Conservative treatment with progressive withdrawal of immunosuppression was effective and well tolerated in two-thirds of the patients with late renal allograft failure, but one-third of the patients rejected the graft and needed allograft embolization. Infection of the graft and HLA sensitization can complicate the course of these patients.

[On-line sequential hemodiafiltration (HDF-OL-S): a new therapeutic option]. / Hemodiafiltración en línea secuencial (HDF-OL-S): una nueva opción terapéutica.

BACKGROUND: on line haemodiafiltration provides the greatest clearance for low and high-molecular weight uremic toxins, which is associated with a lower risk of mortality in our patients. Nowadays, there's increasing evidence about the need of achieving at least 20 litters ultrafiltration in postdilution mode and 70% reduction of beta-2-Microglobulin (B2M), however it requires a vascular access's high blood flow. Unfortunately, we do not succeed in these objectives because of our patients being older, diabetic and with poor vascular access; in this situation high blood flows are more difficult to get at the expense of lower post-dilution exchange volumes. The aim of this study was to assess the efficiency of OL-S-HDF to obtain an equivalent ultrafiltration volume as 20 L in OL-postdilution-HDF (OL-P-HDF). OL-S-HDF initially begins in postdilution mode changing to predilution once the transmembrane pressure (TMP) reached 250 mmHg. METHODS: we performed one high-flux HD session (HF-HD), one OL-P-HDF session and one OL-S-HDF session in each of the 16 adult patients who participated during 3 consecutive weeks. We compared the clearance rates of low and middle molecules such as urea, creatinine, B2M, myoglobulin and levels of albumin and haematocrit between the 3 different techniques. We measured the pre-filter pressure (PFP) by a manometer set before the dialyzer. RESULTS: The main characteristics of the sessions are described in table N1. There wasn't significant difference in Kt/V, urea and creatinine removal between the three techniques. B2M and myoglobulin's clearance rates were significantly higher in both hemodiafiltration modes than in HF-HD (p=0.000), however we didn't find differences between OL-P-HDF and OL-S-HDF. There was a direct correlation between PFP and TMP along the sessions in every technique (p<0.05). We found that PFP was better than TMP to correlate with pre-dialysis levels of albumin and haematocrit and also with the haemoconcentration percentage at the end of the sessions. CONCLUSIONS: This study confirms that OL-S-HDF is as good as OL-P-HDF and it could be a useful technique to treat patients with suboptimal access's blood flow to get to achieve ultrafiltration volumes within the objectives. PFP could offer extra information than TMP.

Benefits derivated from late steroid withdrawal in renal transplant recipients.

Because corticosteroids have adverse metabolic effects, inducing bone-mineral imbalance and contributing to infections among renal transplant recipients, many withdrawal trials have been attempted to reduce adverse events and improve quality of life. We retrospectively analyzed the safety and efficacy of late steroid withdrawal, after the first posttransplant year, among a selected group of kidney allograft recipients. In 42 low immunological risk allograft recipients, among 382 patients transplanted during a decade, corticosteroids were progressively reduced and completely withdrawn. The evolution of clinical and biochemical parameters after the withdrawal were analyzed. Corticosteroid withdrawal was performed as a mean of 52.16 +/- 28.41 months posttransplant, with subsequent follow-up without steroid treatment of 18.13 +/- 16.11 months. Comparing the most recent evaluation with the data previous to steroid withdrawal, patients showed a significant decreases in diastolic pressure (P = .039), total cholesterol (P = .000), and low-density lipoprotein cholesterol levels (P = .039), but not in triglyceride levels (P = .33). Body weight did not change (P = .77), but increased fasting glucose levels were noted (P = .03), in absence of new diagnosed diabetes mellitus. A significant reduction in cyclosporine Neoral (P = .01) or tacrolimus doses were detected (P = .01). At the last visit, serum creatinine in the whole group remained stable (P = .06). Only five patients showed an increase in serum creatinine more than 20% (from 1.44 +/- 0.41 to 1.94 +/- 0.45 mg/dL P = .04) and proteinuria did not increase (P = .94). No patient was diagnosed with a rejection episodes or required corticosteroid resumption. Graft and patient survivals were 100% at the end of follow-up. In conclusion, our data showed that late corticosteroid withdrawal in renal transplant recipients of low immunological risk is safe and is followed by an improvement in their metabolic profile and in blood pressure.

Kidney transplantation with grafts from non-heart-beating donors.

We analyzed the function and outcome of 16 kidney transplants performed in our hospital from non-heart-beating donors who were harvested at other hospitals. The cold ischemia times were longer and the delayed graft function rates higher. However, graft function was no different from that of kidneys from heart-beating donors. This experience has encouraged us to use this type of donor to reduce the transplant waiting list.

Molecular design and biological activity of potent and selective protein kinase inhibitors related to balanol.

BACKGROUND: The protein kinase C (PKC) family of serine/threonine-specific protein kinases is involved in many cellular processes, and the unregulated activation of PKC has been implicated in carcinogenesis. PKC inhibitors thus have significant potential as chemotherapeutic agents. Recently, the fungal metabolite balanol was shown to be an exceptionally potent inhibitor of PKC. We previously developed a practical and efficient total synthesis of balanol. We set out to use this synthetic molecule, and several synthetic analogs, to probe the mechanism of PKC inhibition and to determine the effect of balanol on the activity of other protein kinases. RESULTS: As well as inhibiting PKC, balanol is a potent inhibitor of cyclic AMP-dependent protein kinase (PKA), another protein serine/threonine kinase. Balanol does not, however, inhibit the Src or epidermal growth factor receptor protein tyrosine kinases. The inhibition of both PKC and PKA by balanol can be overcome by high concentrations of ATP, and molecular modeling studies suggest that balanol may function as an ATP structural analog. Although balanol discriminates rather poorly between PKC and PKA, only minor modifications to its molecular structure are required to furnish compounds that are highly specific inhibitors of PKA. CONCLUSIONS: A number of balanol analogs have been designed and synthesized that, unlike balanol itself, exhibit dramatic selectivity between PKA and PKC. Thus, despite the substantial homology between the catalytic domains of PKA and PKC, there is enough difference to allow for the development of potent and selective inhibitors acting in this region. These inhibitors should be useful tools for analyzing signal transduction pathways and may also aid in the development of drugs with significant therapeutic potential.

Soluble monomeric acetylcholinesterase from mouse: expression, purification, and crystallization in complex with fasciculin.

A soluble, monomeric form of acetylcholinesterase from mouse (mAChE), truncated at its carboxyl-terminal end, was generated from a cDNA encoding the glycophospholipid-linked form of the mouse enzyme by insertion of an early stop codon at position 549. Insertion of the cDNA behind a cytomegalovirus promoter and selection by aminoglycoside resistance in transfected HEK cells yielded clones secreting large quantities of mAChE into the medium. The enzyme sediments as a soluble monomer at 4.8 S. High levels of expression coupled with a one-step purification by affinity chromatography have allowed us to undertake a crystallographic study of the fasciculin-mAChE complex. Complexes of two distinct fasciculins, Fas1-mAChE and Fas2-mAChE, were formed prior to the crystallization and were characterized thoroughly. Single hexagonal crystals, up to 0.6 mm x 0.5 mm x 0.5 mm, grew spontaneously from ammonium sulfate solutions buffered in the pH 7.0 range. They were found by electrophoretic migration to consist entirely of the complex and diffracted to 2.8 A resolution. Analysis of initial X-ray data collected on Fas2-mAChE crystals identified the space group as P6(1)22 or P6(5)22 with unit cell dimensions a = b = 75.5 A, c = 556 A, giving a Vm value of 3.1 A3/Da (or 60% of solvent), consistent with a single molecule of Fas2-AChE complex (72 kDa) per asymmetric unit. The complex Fas1-mAChE crystallizes in the same space group with identical cell dimensions.

Inhibition of cyclic AMP efflux by insect pheromones and fatty acids.

Avian erythrocytes export cyclic AMP by a means that prostaglandins A1 and A2, but not other eicosanoids, inhibit (EC50 approximately 45 nM). Several insect pheromones and the fatty acyl components of common membrane phospholipids also inhibit cyclic AMP efflux (EC50 approximately 30 microM). The presence of at least one double bond in the acyl chain enhances the effect. Unlike PGA, fatty acids probably do not act via formation of a glutathione adduct but very likely by altering membrane fluidity. Inhibition of cyclic AMP export provides a mechanism by which products of phospholipid metabolism can influence the cyclic AMP signaling pathway.

Involvement of calcium in interactions between gingival epithelial cells and Porphyromonas gingivalis.

Porphyromonas gingivalis, a periodontal pathogen can invade primary cultures of gingival epithelial cells. This invasion was significantly inhibited (74-81%) by thapsigargin and 1,2-bis(2-aminophenoxy)ethane-N,N,N1,N1-tetraacetic acid, acetoxymethyl ester (BAPTA/AM), but not by EDTA or amiloride. Release of Ca2+ from an intracellular store and the subsequent increase in cytosolic [Ca2+] may, therefore, be involved in the invasion process, while Ca2+ influx is not. Moreover, cytosolic [Ca2+] was found to increase transiently in about 30% of gingival epithelial cells acutely exposed to P. gingivalis, but not in unexposed cells, or in cells exposed to noninvasive Escherichia coli. These findings indicate that P. gingivalis invasion of epithelial cells is correlated with activation of [Ca2+]-dependent host cell signaling systems.

Facilitating a therapeutic milieu in the families of schizophrenia.

For many years, mental health professionals and the families of schizophrenics have coexisted in an atmosphere of mutual distrust and hostility. In this paper, we would like to present some of our experiences in creating a more productive relationship with the families of long-term schizophrenic clients in an aftercare setting. We have found that it is possible to engage these families as allies in the long and difficult process of psychodynamically oriented psychotherapy and resocialization. In many instances, these families actually provide several of the major functions of a vital therapeutic milieu, including containment, support, and structure (Gunderson, 1978).

Munchausen's syndrome: a medico-legal dilemma.

In his or her life-long career, the physician will eventually encounter a patient with factitious disorder, or Munchausen's syndrome. We discuss two patients complaining of renal colic that were identified as having Munchausen's syndrome. We review the literature to identify certain aspects of the disease and to discuss the medical and legal implications for the treating physician and hospital.

Urinary neutrophil gelatinase-associated lipocalin after kidney transplantation: is it a good biomarker to assess delayed graft function?

Delayed graft function (DGF) is a common complication after transplantation. Its incidence is increased among patients receiving a graft from an expanded-criteria donor. Urinary neutrophil gelatinase-associated lipocalin (uNGAL), an acute kidney injury marker, could in the first days after transplantation be an early marker of DGF. We collected urine samples from 38 renal transplant recipients on days 1, 3, 6, and 10 post-transplantation, and months 1 and 6 creatinine to determine uNGAL, serum creatinine, Cystatin C, and albumin/creatinine ratio. We divided the patients into 2 groups, based on whether they developed DGF. We observed that mean uNGAL concentrations, Cystatin C, serum creatinine, and albumin/creatinine ratio were significantly lower in the non-DGF cohort on all measured days. uNGAL at day 3 showed a positive correlation with serum creatinine at day 10 (R = 0.58; P < .00) and day 30 (R = 0.57; P = .016) as well as with the length of hospital stay (r = 0.47; P < .00). Receiver operating characteristic analyses performed to assess the potential of uNGAL to predict DGF showed an area under the curve for day 3 of uNGAL of 0.917 (confidence interval [CI], 0.79-1.00; P = .00), with an optimal cutoff level of 124 ng/mL, sensitivity of 80% (CI, 62%-97%), and specificity of 83% (62%-104%; P = .001). In the first days after transplantation, uNGAL could be an early marker of DGF, providing additional information to standard biomarkers and potentially helping clinicians to take early measures to mitigate DGF.