Does obesity really affect renal transplantation outcomes?

INTRODUCTION: Kidney transplantation is the treatment of choice for patients with stage 5 chronic kidney disease (CKD). About 60% of CKD patients are overweight or obese at the time of kidney transplantation, and post-transplant obesity occurs in 50% of patients, with a weight gain of 10% in the first year and high risk of cardiovascular mortality. Obesity is associated with an increased risk of delayed graft function (DGF), acute rejection, surgical complications, graft loss and mortality. The aim of this study is to assess the clinical evolution of obese and overweight patients that have received a kidney transplant, based on short- and long-term complications associated with a higher BMI. MATERIAL AND METHODS: A descriptive, observational, cross-sectional study was conducted with 104 kidney or pancreas-kidney transplant patients between March 2017 and December 2020, with a follow-up until April 2021. For comparative analysis, patients were grouped according to BMI. RESULTS: Mean age was of 56.65 years, 60.6% male and 39.4 % female. Overweight patients experienced prolonged surgeries, more surgical wound dehiscence, delayed graft function, hernias, proteinuria and more indications for renal biopsies. Additionally, obese patients displayed more DGF, indications for renal biopsies, proteinuria, development of diabetes mellitus, atrial fibrillation and needed prolonged hospital stays. CONCLUSIONS: Despite a high prevalence of comorbidity in the overweight and/or obese population, we found no reduction in patient and/or graft survival. However, longer follow-up is needed.

The molecular epidemiology of SARS-CoV-2 in the Pityusic Islands shows multiple introductions and fast replacements of variants in a touristic worldwide hot spot.

The public health emergency caused by the Covid-19 outbreak in March 2020 encouraged worldwide initiatives to monitor the genetic diversity and features of the SARS-CoV-2 circulating variants, mainly based on the genomic surveillance. However, due to the impossibility to carry out extensive sequencing in resource-limited hospitals, other PCR-based strategies could be applied to efficiently monitor the circulating variants without the need to greatly expand the sequencing capacity. In our case, overpassing the technical limitations inherent to a second level hospital, we were able to characterize the weekly distribution of SARS-CoV-2 by the RT-qPCR amplification patterns visualization, single nucleotide polymorphism genotyping, and sequencing of randomly selected samples. All these molecular approaches allowed us to trace the epidemiology of SARS-CoV-2 viruses circulating in Ibiza and Formentera (Balearic Islands, Spain) during the third to the sixth pandemic waves (January 2021-July 2022), in which three major lineages that were considered as VOCs (Alpha, Delta, and Omicron), and many other non-VOC variants were detected and tracked.

Correction to: Genome Analysis and Genomic Comparison of the Novel Species Arthrobacter ipis Reveal Its Potential Protective Role in Its Bark Beetle Host.

A Correction to this paper has been published: https://doi.org/10.1007/s00248-021-01811-x.

Management of mixed acute rejection driven by a de novo donor-specific complement-binding anti-DQB1*03:01 antibody and intraepithelial CD8 T-cells in a kidney recipient: a case report.

Mixed acute rejection is a clinicopathological entity that is difficult to accurately diagnose, and so may be under-reported. Allografts are lost more often than in either humoral or cellular rejection. The diagnosis requires both histological and immunological studies on renal biopsy and blood specimens from the transplant recipient to provide the required rescue therapy to abolish the allogeneic response against the graft. We present a clinical case report of an active mixed acute rejection driven by a de novo donor-specific complement-binding anti-DQB1*03:01 antibody and intraepithelial CD8 T-cells in a patient with a kidney transplant. The patient was diagnosed, treated, and followed up as per the local institution's procedure with a full recovery of graft function. Our case emphasises the challenge of a mixed acute rejection and supports the need to improve the post-transplant outcome of recipients and their grafts.

[De novo sporadic mutation in the KCND3 gene in a patient with early onset chronic ataxia]. / Mutacion puntual de novo en el gen KCND3 en un paciente con ataxia cronica de inicio precoz.

TITLE: Mutacion puntual de novo en el gen KCND3 en un paciente con ataxia cronica de inicio precoz.

Four Years' Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in Infants Detected in Three Spanish Newborn Screening Centers.

Identification of very long-chain acyl-CoA dehydrogenase deficiency is possible in the expanded newborn screening (NBS) due to the increase in tetradecenoylcarnitine (C14:1) and in the C14:1/C2, C14:1/C16, C14:1/C12:1 ratios detected in dried blood spots. Nevertheless, different confirmatory tests must be performed to confirm the final diagnosis. We have revised the NBS results and the results of the confirmatory tests (plasma acylcarnitine profiles, molecular findings, and lymphocytes VLCAD activity) for 36 cases detected in three Spanish NBS centers during 4 years, correlating these with the clinical outcome and treatment. Our aim was to distinguish unambiguously true cases from disease carriers in order to obtain useful diagnostic information for clinicians that can be applied in the follow-up of neonates identified by NBS.Increases in C14:1 and of the different ratios, the presence of two pathogenic mutations, and deficient enzyme activity in lymphocytes (<12% of the intra-assay control) identified 12 true-positive cases. These cases were given nutritional therapy and all of them are asymptomatic, except one. Seventeen individuals were considered disease carriers based on the mild increase in plasma C14:1, in conjunction with the presence of only one mutation and/or intermediate residual activity (18-57%). In addition, seven cases were classified as false positives, with normal biochemical parameters and no mutations in the exonic region of ACADVL. All these carriers and the false positive cases remained asymptomatic. The combined evaluation of the acylcarnitine profiles, genetic results, and residual enzyme activities have proven useful to definitively classify individuals with suspected VLCAD deficiency into true-positive cases and carriers, and to decide which cases need treatment.

The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome.

We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined oxidative phosphorylation deficiency) syndrome. Whole-exome sequencing (WES) of the three patients and the healthy sister of one of them was used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant.

Assessment of resting energy expenditure in pediatric mitochondrial diseases with indirect calorimetry.

BACKGROUND & AIMS: Mitochondrial diseases (MD) are the most frequent inborn errors of metabolism. In affected tissues, MD can alter cellular oxygen consumption rate leading to potential decreases in whole-body resting energy expenditure (REE), but data on pediatric children are absent. We determined, using indirect calorimetry (IC), whole-body oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient (RQ) and REE in pediatric patients with MD and healthy controls. Another goal was to assess the accuracy of available predictive equations for REE estimation in this patient population. METHODS: IC data were obtained under fasting and resting conditions in 20 MD patients and 27 age and gender-matched healthy peers. We determined the agreement between REE measured with IC and REE estimated with Schofield weight and FAO/WHO/UNU equations. RESULTS: Mean values of VO2, VCO2 (mL·min-1·kg-1) or RQ did not differ significantly between patients and controls (P = 0.085, P = 0.055 and P = 0.626 respectively). Accordingly, no significant differences (P = 0.086) were found for REE (kcal·day-1 kg-1) either. On the other hand, although we found no significant differences between IC-measured REE and Schofield or FAO/WHO/UNU-estimated REE, Bland-Altman analysis revealed wide limits of agreement and there were some important individual differences between IC and equation-derived REE. CONCLUSIONS: VO2, VCO2, RQ and REE are not significantly altered in pediatric patients with MD compared with healthy controls. The energy demands of pediatric patients with MD should be determined based on IC data in order to provide the best possible personalized nutritional management for these children.

Serratia myotis sp. nov. and Serratia vespertilionis sp. nov., isolated from bats hibernating in caves.

During the study of bacteria associated with bats affected by white-nose syndrome hibernating in caves in the Czech Republic, we isolated two facultatively anaerobic, Gram-stain-negative bacteria, designated strains 12(T) and 52(T). Strains 12(T) and 52(T) were motile, rod-like bacteria (0.5-0.6 µm in diameter; 1-1.3 µm long), with optimal growth at 20-35 °C and pH 6-8. On the basis of the almost complete sequence of their 16S rRNA genes they should be classified within the genus Serratia; the closest relatives to strains 12(T) and 52(T) were Serratia quinivorans DSM 4597(T) (99.5 % similarity in 16S rRNA gene sequences) and Serratia ficaria DSM 4569(T) (99.5% similarity in 16S rRNA gene sequences), respectively. DNA-DNA relatedness between strain 12(T) and S. quinivorans DSM 4597(T) was only 37.1% and between strain 52(T) and S. ficaria DSM 4569(T) was only 56.2%. Both values are far below the 70% threshold value for species delineation. In view of these data, we propose the inclusion of the two isolates in the genus Serratia as representatives of Serratia myotis sp. nov. (type strain 12(T) =CECT 8594(T) =DSM 28726(T)) and Serratia vespertilionis sp. nov. (type strain 52(T) =CECT 8595(T) =DSM 28727(T)).

Respiratory distress syndrome caused by influenza H1N1 in a patient with a simultaneous pancreas-kidney transplantation.

Adult respiratory distress syndrome is a severe respiratory failure due to noncardiogenic pulmonary edema with high mortality rates (50-70%). The most common etiology of respiratory distress is sepsis, but it may also be caused by several of the immunosuppressants prescribed in transplantation. In the last year, influenza H1N1 virus infection has become more relevant. It has shown a greater incidence among immunosuppressed patients as well as those with chronic kidney disease or diabetes mellitus. We present the case of a patient with simultaneous pancreas-kidney transplantation who presented respiratory distress after the second dose of thymoglobulin. Initially, we interpreted that the thymoglobulin was the cause, so it was replaced with basiliximab. Empirical treatment was started with 3 doses of 6-methylprednisolone (250 mg), with a favorable response. After 7 days, we received the results of the reverse-transcriptase polymerase chain reaction of a nasal smear and blood culture, which were positive for H1N1 virus. In our knowledge, this is the first reported case of a patient with simultaneous pancreas-kidney transplantation and respiratory distress secondary to H1N1 virus infection who showed a favorable response to corticosteroid therapy.

Tuberous sclerosis associated with polycystic kidney disease: effects of rapamycin after renal transplantation.

Tuberous sclerosis is rarely associated with autosomal dominant polycystic kidney disease in the so-called tuberous sclerosis complex. This association leads to an increased frequency of end-stage renal disease. We present a patient suffering from both syndromes, who received a renal graft and anticalcineurinic drugs as immunosuppressive agents. Progressive titration of the drug was necessary in order to attain the effective doses due to the enzymatic induction caused by concomitant treatment with antiepileptic drugs. These high doses resulted in nephrotoxicity. Immunosuppressor treatment was switched to rapamycin, whereby an improvement in renal function and other signs of tuberous sclerosis and polycystic kidney disease was observed. This case report highlights both the efficacy and safety of rapamycin as an immunosuppressor treatment and its capacity for controlling other symptoms of these genetic-related disorders.

Nutritional and Pharmacological Management during Chemotherapy in a Patient with Propionic Acidaemia and Rhabdomyosarcoma Botryoides.

We present the nutritional and pharmacological management of a 2-year-old girl with a severe form of propionic acidaemia and a genitourinary embryonal rhabdomyosarcoma. This association has not been described before, nor the utilization of chemotherapy in patients with propionic acidaemia.The patient is a girl with neonatal onset of propionic acidaemia, homozygous for the c.2041-2924del3889 mutation in PCCA gene. At 23 months of age she was diagnosed with genitourinary embryonal rhabdomyosarcoma. Conservative surgery, brachytherapy and nine cycles of chemotherapy with iphosphamide, vincristine and actinomycin were recommended by oncologists. Due to the possibility that the child could present decompensations, we elaborated three different courses of treatment: when the patient was stable (treatment 1), intermittent bolus feeding through gastrostomy, containing 70 kcal/kg/day and 1.4 g/kg/day of total protein (0.6 g/kg/day of natural protein and 0.8 g/kg/day of amino acid-based formula) was prescribed; on the chemotherapy-days (treatment 2), diet consisted on continuous feeding, with the same energy and amino acid-based formula but half of natural protein intake; in case of decompensation (treatment 3), we increased by 10% the energy intake, and completely stopped natural protein in the diet but maintaining the amino acid-based formula. On chemotherapy- days carnitine was increased from 100 mg/kg/day to 150 mg/kg/day, and N-carbamylglutamate was added.Through the 7 months with chemotherapy the patient did not suffer decompensations, while she maintained good nutritional status.Enteral continuous feeding by gastrostomy, amino acid-based formula, and preventive use of N-carbamylglutamate during chemotherapy-days are the principal measures we propose in these situations.

[Niemann-Pick type C disease: From neonatal cholestasis to neurological degeneration. Different phenotypes]. / Enfermedad de Niemann-Pick tipo C: desde una colestasis neonatal hacia un deterioro neurológico. Variabilidad fenotípica.

INTRODUCTION: Niemann-Pick type C is a lysosomal storage disorder caused by a defect in intracellular trafficking of cholesterol. It is a rare disease, usually caused by mutations in NPC1 gene, but in some cases by mutations in NPC2 gene. Usually it is present in the paediatric age with a great variability of clinical manifestations. This disease leads to neurological degeneration with various age-related symptoms. Transient neonatal cholestasis, the appearance of splenomegaly and/or hepatomegaly may occur years before the neurological symptoms. PATIENTS AND METHODS: We report 6 cases diagnosed in our unit in the last 20 years. We reviewed the clinical manifestations, neuroradiological findings (MRI) and molecular analysis of all of them. RESULTS: The disease began before 6 years of age and 5 cases had liver dysfunction and cholestasis in the neonatal period. Ascites was detected in 2 cases in prenatal period. Five cases have or had splenomegaly. Mutations in NPC1 gene were detected in all of them. CONCLUSIONS: It is important to understand this disease and the identification of early clinical symptoms to make an early diagnosis, leading to appropriate treatment and avoiding unnecessary tests. Moreover, it is important to suitably advise families and provide them with genetic counselling.

[Squamous cell carcinoma arising on an epidermal inclusion cyst: a case presentation and review of the literature]. / Carcinoma epidermoide desarrollado sobre quiste de inclusión epidérmica cutáneo. Presentación de un nuevo caso y revisión de la literatura.

Epidermal inclusion cysts are very common lesions that very rarely undergo malignant transformation-in the English-language literature we have only found 18 adequately documented cases. We present the case of a man with a 2-month history of a retroauricular skin lesion in which histological study revealed squamous cell carcinoma arising on an epidermal inclusion cyst. Cysts that grow rapidly, reach a large size, ulcerate, develop a fistula, or that do not respond to medical treatment, and those that recur should be excised completely and histological study performed of the whole lesion.

Non-skin solid tumors as a cause of morbidity and mortality after liver transplantation.

The use of immunosuppressive agents in renal transplant recipients increases the risk of tumor development. The global incidence of tumors in renal transplant recipients is 4% to 18% and is especially high for skin lesions, non-Hodgkin lymphoma, and genital malignancy but not for lung, breast, prostate gland, or colorectal lesions. Between May 1983 and May 2008, we performed 663 renal transplantation procedures; 85.5% were first transplantation procedures. Mean patient age was 46.93 years. Patients received treatment with combinations of immunosuppressive agents including corticosteroids, cyclosporine, OKT3, mycophenolate mofetil, tacrolimus, azathioprine, and basiliximab or daclizumab. The incidence of nonskin tumors was 4.07%. Mean age at diagnosis was 61.41 years, mean interval between transplantation and diagnosis of tumor was 6.04 years, and mean duration of graft function was 7.59 years. Mortality was due to tumor in 20.14% of patients, and of those with cancer, 74.07% died; all patients who died had a functioning graft. The most common malignant lesions were lung cancer in men and breast cancer in women. The incidence of nonskin tumors was lower than that in published series, probably because of routine screening of patients while on the waiting list and in transplant recipients with functioning grafts.

[LC-MS/MS analysis of herbicide residues in waters from Navarre]. / Análisis de residuos de herbicidas en aguas procedentes de Navarra mediante LC-MS/MS.

BACKGROUND: The aim of the study was to obtain information on the residues of herbicides (imazametabenz, simazine, isoproturon, clortoluron, metribuzine, atrazine, cianazine, terbutrin, propanil, terbutilazine, alachlor and pendimetalin) present in water proceeding from Navarre. MATERIAL AND METHODS: A total of 465 samples of water were taken: 378 were taken from 141 water supplies; the remaining 87 proceeded from fountains, springs and borings in agricultural areas in the south of Navarre. The technique employed was LC-MS/MS. RESULTS: Herbicide residues were detected in 33% of the water supplies, and their concentration exceeded the normative limit in 8% of them. Herbicide residues were found in 86% of the samples from wells and fountains of the agricultural areas of the south of Navarre. The number of water supplies with herbicide residues increased from north to south. However, the percentage of water supplies in which the concentration of herbicides exceeded the limits was greater in the centre of Navarre than in the north and south. Imazametabenz was the herbicide most detected in the samples from the northern, central and southern areas. Atrazine, terbutilazine and imazametabenz were most detected in the samples of the southern area. CONCLUSIONS: The differences amongst the three areas of Navarre can be explained as being due to the different agricultural practices of each area. Concentrations of herbicides exceeding the normative limits were not detected in any of the water samples proceeding from the larger towns of Navarre.