Nitrogen dioxide pollution increases vulnerability to COVID-19 through altered immune function.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

SRD5A2 gene mutations and polymorphisms in Spanish 46,XY patients with a disorder of sex differentiation.

One hundred and forty-six index patients with 46,XY DSD in whom gonads were confirmed as testes were consecutively studied for a molecular diagnosis during the period 2002-2010. AR gene was analysed in all patients as the first candidate gene, yielding a mutation in 42.5% of cases and SRD5A2 gene was analysed as the second candidate gene, resulting in the characterization of 10 different mutations (p.Y91D, p.G115D, p.Q126R, p.R171S, p.Y188CfsX9, p.N193S, p.A207D, p.F219SfsX60, p.R227Q and p.R246W) in nine index patients (6.2% of the total number of 46,XY DSD patients). One of the mutations (p.Y188CfsX9) has never been reported. In addition, we genotyped SRD5A2 gene p.V89L and c.281+15T>C polymorphisms in 46,XY DSD and in 156 normal adult males and found that patients with SRD5A2 mutations or without a known molecular diagnosis presented a higher frequency of homozygous p.L89, homozygous TT and combined CCTT genotypes compared with controls. This result suggests that 46,XY DSD patient phenotypes may be influenced by SRD5A2 polymorphism genotypes. SRD5A2 gene mutations may not be as infrequent as previously considered in 46,XY DSD patients with variable degrees of external genitalia virilization at birth and normal T production and appears to be the second aetiology in our series.

Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

BACKGROUND: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). OBJECTIVE: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. SETTING: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. METHODS: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. RESULTS: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. CONCLUSIONS: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.

[Five years of renal trauma in a paediatric trauma center: new tools in the diagnostic and therapeutic process]. / Cinco años de traumatismo renal en un centro de trauma pediátrico: nuevas herramientas en el proceso diagnóstico y terapéutico.

INTRODUCTION: There is general agreement in the conservative management of most renal traumas, but questions like the role of angiography are still controversial. Our objective is to review the paediatric renal trauma characteristics, propose a therapeutic protocol and suggest new therapeutic tools. MATERIAL AND METHODS: Retrospective review of clinical records (epidemiology, diagnostic methods, renal injury grade according to the AAST Organ Injury Scale, treatment and follow up) of the paediatric renal injuries at Vail d'Hebron Hospital in the last 5 years. Outline of a diagnostic-therapeutic protocol consistent with the literature. RESULTS: Since 2001, 18 cases of paediatric renal trauma have been diagnosed. Median of age was 10 years (range 2-17). Renal injury grade was: I (4), II (5), III (4), IV (4), V (1). Main mechanisms of injury were car and motorcicle accidents (4), fall (3), bicycle (3) and sports (3). There were different severity associated injuries in 10 patients. Abdominal exploration was normal in 6 cases, and in 5 (including the grade V injury) hematuria was absent or was microscopic. Mean hematocrit and hemoglobine were 34.5% y 11.8 g/dl. Abdominal CT was performed in all cases, detecting injuries that were unnoticed with ultrasound exploration. Complications were: renal artery pseudoaneurism (1), urinoma (1), uretero-pelvic joint disruption (1), arterial hypertension (3), renal colic (1). Management was: conservative in 13 cases, angiography in 4 (2 embolizations of bleeding vessels, 1 pseudoaneurism embolization, 1 placement of endovascular stents in an injury of the arterial intima), delayed surgery in 2 (1 nefrectomy, 1 uretero-pyeloplasty). All of them received prophylactic antibiotics; 10 had self-limited fever with negative cultures. Only in 2 cases DMSA at 6 months was inferior to 20%. There were no deaths. CONCLUSIONS: In paediatric patients, there can be severe renal injuries despite absence of hematuria and a normal physical exam and hemogram. Abdominal CT with endovenous contrast is the keystone of diagnosis, and identifies vascular injuries that might need immediate treatment, like renal ischemia. Angiography is an important tool to consider in case of persistent bleeding or renal infarctation.

[Sigmoid colon vaginoplasty: experience with five cases]. / Vaginoplastia con sigma: a propósito de 5 casos.

Vaginal atresia compounds a rare congenital anomaly and results from anomalies in the development of Müller ducts as happens in the Mayer-Rokitansky syndrome or in other cases of intersexual states. Some different tissues have been issued for the creation of a neovagina, but none of them has been accepted as ideal. We have chosen sigmoid colon in order to create a new vagina functionally appropriate. We present five cases affected of vaginal atresia. Two of them were Mayer-Rokitansky syndromes and the other were diagnosed during the study for primary amenorrhea as a result of an intersexual state. In all cases a vaginoplasty was performed according to Baldwin's technique in the ages between 15 and 20 year-old. The follow up has been from 1 to 16 years. No postoperative complications have been observed. The external aspect of the genitalia is normal and a proper sized with length and lubrificated vagina was attained in all cases without any retraction in any patient. Two of the patients maintain sexual relations without problems. In our experience, the cosmetic and functional result of sigmoid vaginoplasty were excellent.

[Good results with Passerini's technique in severely masculinised female pseudohermaphroditism]. / Buenos resultados empleando la técnica de Passerini en pseudohermafroditismos femeninos con virilización severa.

In female pseudohermaphroditism due to congenital adrenal hyperplasia (CAH), some cases develope a very important masculinization degree with a high outlet of the vagina above the outern urethral sphincter. There are several surgical techniques to solve this problem. Our group uses Passerini's thecnique since 1990. 9 Girls with CAH with extreme masculitation (IV and V Prader degree) have been operated with this technique. The age at intervention varies between 9 months and 3 years, with a follow-up between 1 and 12 years. All these patients had hormonal studies, demostrating a deficiency of 21-hydroxilase in 8 cases and a deficiency of 11-B-hydroxilase in one case. To determine the vaginal outlet a genitography was performed in all cases, vaginoscopy in 7 cases and MNR in 2 cases. Passerini's technique consists of two phases: the first step has the objective of forming the distal 2/3 of the vagina using the skin and the urethral mucosa of the phallus. At the second time transtrigonal way is performed to access the vagina which is desinserted from its urethral outlet and anastomosed with the distal neovagina. There were no significative complications in immediate time. The esthetic result is acceptable in all cases, although one case had to be surgically repaired because of a prominent vulvar flap. We use vaginoscopy to prove vaginal permeability in all cases although one of them developed adherences around the anastomosis. This severe genital malformation, very uncommon, has a difficult surgical solution. Passerini's technique allows, with less complications, to create an acceptable outer genitals at early age and only in one surgical time.

[Vesicoureteral reimplantation in infants]. / Reimplante vésico-ureteral en lactantes.

OBJECTIVE: To describe the results and follow-up of 34 vesico-ureteral reimplantations in infants. METHODS: From 1985 to 1994, 34 vesico-ureteral reimplantations (Cohen transtrigonal technique) were performed in 20 infants aged 1-13 months. The indications for surgery were high grade congenital vesico-ureteral reflux and breakthrough pyelonephritis that had presented in some cases despite prophylactic measures. RESULTS: At 4 years mean follow-up, all reimplanted ureters showed no reflux. One case with bilateral reimplantation was lost to follow-up. CONCLUSIONS: Many of the infants with vesico-ureteral reflux can be managed medically and the reflux will cease in some cases. But a few of them with difficult to control infections, can benefit from early surgery.

[Ten years of prenatal diagnosis of uropathies. Study and conclusions]. / Diez anños de diagnóstico prenatal de uropatías. Estudio y conclusiones.

Since uropathy started to be diagnosed by means of ultrasonography during the prenatal period, paediatric urologists have experienced a major increase in neonatal consultations, which involve healthy children without any symptoms of urinary tract infection. Thereby the criteria for an adequate treatment of these uropathies have been modified. With our study, we intend to analyse the changes regarding the management of such cases in our Service for the last 10 years. 294 cases prenatally diagnosed and confirmed by means of postnatal sonography have been reviewed, taking into account the type of explorations carried out in order to obtain a definitive diagnosis. Ultrasonography, cystourethrography, pyelography, scintigraphy and isotopic renography have determined both degree of obstruction and the renal function of the patient so as to value the kidney viability. We have found 169 cases of pelviureteral junction (PUJ) obstruction, 52 of vesicoureteral reflux (VUR), 48 of megaureter, 13 of ureterocele, 8 of ectopic ureter, 5 of urethral valves, 26 of multicystic dysplasic kidney, 35 of renal duplication, 4 of renal cyst, 2 of ectopic kidney, 2 of renal agenesia, 3 of bladder diverticular, 1 of renal hypoplasia and 1 of Bolande's tumour. 32 children were operated upon due to PUJ obstruction, 27 due to VUR, 14 megaureter, 21 due to ureterocele and ectopic ureter, 5 due to valves, 5 multicystic kidneys, 3 vesical diverticula, 2 renal cysts and 1 due to Bolande's tumour. From a total of 367 diagnoses, 109 patients have undergone an operation, which equals a 29.7%. The rest of the patients have been subject to a medical follow-up. Only 3 patients had to be operated on due to an aggravation of their obstruction. To sum up, the main advantage of prenatal diagnosis is that it presents the patient without urinary infection. Double-diuretic scintigraphy has proved to be the best option to explore the obstruction when dilated despite its limitations in the case of deficient renal function. The most frequent diagnosis, which has undergone a major increase in the last few years, is PUJ obstruction in the manner of pyelic dilatation. Many of them are not confirmed postnatally and most of them (more than 70%) do not need surgical treatment.

[Anterior urethral valves]. / Válvulas de uretra anterior.

The valves of the anterior urethra are a rare congenital malformation, but it can cause a significant deterioration of the uppermost urinary system due to their obstructive patterns. It's placed fundamentally in the peno-scrotal union or in the bulbous urethra. They can associate to the diverticula of the anterior urethra. The clinical manifestations can be varied, depending upon the age of the child and the degree of obstruction that provoque. The treatment is always surgical, although in some occasions they suffice the endoscopic resection. We present the 12 cases controlled in our Center, with known ages between 1 month and 7 years, that began with tumefaction urethral at micturition in 7 cases, urinary infection in 6 and sepsis in 2. All of them required open surgery, after the failure of endoscopic resection in one of them. The results have been favorable in 9 cases regarding to the repercussions in the renal function. Two patients had a need of nephrectomy and one had to be subjected to a renal transplantation. The jet at micturition after surgery is good in 10 cases. In one, there persists a subtle jet, although without clinical repercussions, and in one patient there appeared a slight dilation in the posterior urethra.

[Autologous buccal mucosal graft for urethral reconstruction]. / Reconstrucción uretral con injerto autoólogo de mucosa oral.

Proximal hypospadias are a difficult surgical problem, whether it could take place different surgical approaches. One of those is based on the creation of a neourethra using a free buccal mucosal graft, as a patch or a tube, obtained from de lips or cheek. Since 1983 we have been using this technique in 8 patients. The urethral meatus was penoscrotal in 3, scrotal in 3 and perineal in 2. There was a significant chordee in 3 patients. Hormonal treatment was necessary in 5 patients. The average age for surgery was 3.5 years. The graft was tubularized in all the cases. The free buccal mucosal graft was combined with a distal Duckett procedure in 6 patients. Two patients received only a free buccal mucosal graft. The final result is satisfactory in all the cases, with a good urinary jet. The complications were 7 urethrocutaneous fistulas, 5 of whom needed a surgical repair, and 2 stenosis, which also needed surgical repair.

[Management of primary congenital megaureter with early diagnosis]. / Manejo del megauréter congénito primario de diagnóstico precoz.

We present our follow-up protocol of congenital megaureter (PCM) diagnosed early thanks to showing prenatal ultrasound the dilatation in the urinary system. 47 PCM were studied retrospectively in 35 babies, out of 240 cases of prenatal renal dilatation, from 1984 to 1993. The final diagnosis was established with the early use of ultrasound, cystography, intravenous urography (IVU) and isotope test. The latter two gave hints as to the existence of obstruction, which was the main criterion for early surgery to be prescribed. The surgical treatment, when it was necessary, consisted of ureter reimplantation (Cohen type), following the resection of the stenotic segment. When it was necessary short distal tapering (3-4 cm) was performed. For the follow-up ultrasound, IVU and isotope test were used. Out of the 35 patients observed, 11 were girls and 24 boys, 9 (25.7%) of the PCM were from the right side, 14 (40%) from the left side and 12 (34.2%) bilateral. 36 PCM (76.6%) were non-obstructive and only follow-up was performed. 5 of them, in 3 patients, had infections and were operated on together with the 11 obstructed PCM. In total, 16 PCM were reimplanted, and associated tapering was need in 7 of them. Other 3 patients were operated on for associated pathology. The post-surgical complications were 2 cases or reflux and 1 uric stone that did not need surgery. The development of all cases was favorable. The protocol has been useful for the selection for early surgical intervention of the subsidiary megaureters from those that can be develop without risk.(ABSTRACT TRUNCATED AT 250 WORDS)

[Passerini-Glazel technique of vulvovaginoplasty: a solution for upper outlet of the vagina]. / Vulvovaginoplastia según técnica de Passerini-Glazel: una solución para la desembocadura alta de la vagina.

Since 1988, we have performed the Passerini-Glazel technique, in 5 patients, between 7 months and 3 years old. All showed female pseudohermaphroditism with severe signs of masculinization, and consequently, high outlet of the vagina in the urethra, secondary to Congenital Adrenal Hyperplasia (CAH). The technique use is to get a functional and esthetically acceptable vagina at the expense of a urethral flap and two flaps of skin, coming from the hypertrophic clitoris. The results were excellent in all the patients. In one occasion it was necessary to insert a cylinder of vesical mucous to get a suture without tension of both hemivaginas. In one case there appeared a late vaginal stenosis that was solved with dilations. The present technique is indicated in those cases of CAH, with great testosterone impregnation, in which the vagina ends very high and her primary descent is difficult. It is also indicate in those cases in which there exists the risk of hurting the external sphincter, which would damage the urinary continence mechanism.

[Endoscopic treatment of urethral stenoses in children]. / Tratamiento endoscópico de las estenosis uretrales en los niños.

Twenty-nine male children with urethral stenosis, with ages between 7 months and 18 years, were treated by endoscopic surgery. The etiology of their condition was trauma in 21 cases and congenital in 8. Location of the stenosis corresponded in 18 cases to membranous urethra, 7 to bulbar urethra, 2 to penial urethra while 2 were double, membranous and bulbar. The magnitude of the stenosis was under 1 cm in 24 cases, between 1 to 2 cm in 4 cases and over 2 cm in 1 case. Treatment carried out was visually controlled endoscopic urethrotomy and endoscopic resection. The results obtained were rated as good in 21 children (72%), but 38% required more than one operation. The best results corresponded to the so-called congenital stenosis and the worse to those secondary to rectal atresia and urethral valves.

[Urologic complications in renal transplantation in children]. / Complicaciones urológicas en el trasplante renal infantil.

Our results with 105 pediatric renal transplantations, are reviewed. The identified complications were: 4 ureterovesical stenoses, 1 pyeloureteral stenosis, 1 vesical rupture, 1 vesicoureteral reflux on native ureters and 1 acute urinary obstruction. These incidences were scattered among 5 patients of whom 3 had 2 complications each. All were surgically corrected and 4 of the kidneys are well-functioning at present. We analyze the factors possibly involved and suggest that donor and recipient related parameters might not be determinant, save for those patients afflicted with lower urinary tract anomalies, and that ureteral catheters may prevent urinary extravasation or fistulae.

[Bladder psoas hitch. Report of 11 cases]. / Psoización vesical. A propósito de 11 casos.

Bladder psoas hitch is an surgical technique which, in very complicated cases, like repeated failures of vesico-ureteral re-implants or undiversions, allow us to bridge the shortness of the ureter and obtain a good vesico-ureteral reimplant. The surgical maneuver is described and several of the 11 cases operated by this technique are commented. The results are presented.

Ureteral triplication and ureterocele: report of 3 cases and review of the literature.

We report 3 cases of ureterocele associated with ureteral triplication and review the literature. Ureteral triplication was type I in 2 patients and type II in 1. Diagnosis was established preoperatively in 2 cases and intraoperatively in 1. All patients were initially treated by upper pole partial nephrectomy and aspiration of the ureterocele, leaving the ureteral stump open in the retroperitoneum. Subsequent excision of the ureterocele and ureteral reimplantation for persistent ipsilateral vesicoureteral reflux and recurrent urinary tract infections were required in 2 cases.

[Is it necessary to remove polycystic kidneys?]. / Es necesario extirpar los riñones multiquísticos?

The Multicystic Dysplastic Kidney is the most frequent renal congenital anomaly and the second most common cause of an abdominal mass in the newborn. Traditionally, since this pathological entity was described as such by Spene in 1955, early resection has been deemed its best treatment. In the last decade, a conservative approach has been advocated by some authors, except for the patients presenting with concomitant abdominal pain or infection. In our hospital, relying on the support afforded by the echographic assessment of these patients, we have proposed an expectant behaviour in the management of this entity. So far, we have had the opportunity to follow the course of the disease in 15 patients with the diagnosis of Multicystic Dysplastic Kidney, with the result that in no one of them the size of the cystic mass increased, but instead the mass disappeared completely in one case, diminished greatly in three cases, had a moderate decrease in size in eight cases and in just three patients it has not varied in size. No patient has complained of abdominal pain or has become infected. In the face of such findings, we believe that early resection of the multicystic kidney is not warranted if no complications develop.

[Bolande's tumor: significance of its early diagnosis and treatment]. / Tumor de Bolande: importancia de su diagnóstico y tratamiento precoz.

Four patients diagnosed of having a tumor of Bolande and treated at our institution in the past ten years are presented. In two of them, early diagnosis was aided by prenatal echographic techniques; the other two diagnoses were suspected ar three and ten days of age because of an abdominal mass. The four of them underwent a complete study which included: a plain abdominal film, an ultrasound scan and an intravenous urogram; the last three patients were also surveyed by a CT scan of the abdomen. Surgery was undertaken early on all the patients, the time of operation being in every instance within the first month of life. A laparotomy was performed and, once the contralateral kidney had been carefully examined, a nephroureterectomy was implemented, having been able to preserve in all the cases the suprarenal gland in view of the benign nature of the tumor. A histologic study confirmed the diagnosis and revealed the complete delimitation of the tumor by the renal capsule. The authors underscore the importance of this tumor's suspicion in the face of any solid renal mass detected by prenatal echography or in the neonatal period, since early diagnosis and treatment are imperative in order to prevent the ensuing complications in the rare and unfortunate cases that show a malignant tumoral trend.

[Primary bladder diverticula. Study of 47 cases]. / Divertículos vesicales primarios. Estudio de 47 casos.

We report on 47 patients, surveyed and treated by us, diagnosed of primary vesical diverticula, having thus excluded all those secondary to lower obstructive anomalies, such as urethral valves and neurogenic bladder. Only seven out of the 47 patients were females: two of them had a iatrogenic cause and the remainder were of small size and associated with vesicoureteral reflux. All the cases have been documented by means of an intravenous pyelography (IVP), an excretory cystogram and a voiding cystourethrogram (VCUG). Many diverticula may go unnoticed when screened by IVP, whereas the cystogram and preferentially the VCUG are a 100 for 100 diagnostic. A 45 for 100 of these children (22 cases) had an attendant reflux and 23 for 100 (11 cases) had some other concomitant renal disease. Three further cases were iatrogenic, as a result of the methods employed for antireflux ureteral reimplantation. A 77 for 100 of the patients had urinary tract infection demonstrated by a urinary sediment and a positive culture. Surgery was performed on 34 patients, the indication being made on the basis of the big size of the diverticulum, its clinical repercussion, or because of its association with vesicoureteral reflux or any other kidney malformation. We employ an intravesical approach for the small diverticula with attendant reflux, but for resection of the sizeable ones, irrespective of the existence of reflux, we prefer the combined extra and intravesical approach, which allows a most accurate extravesical dissection, as well as the recognition and control of the ureter and the deferes duct, structures both that are usually anatomically distorted.