Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism.

PURPOSE: CDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 mutation. We aimed to describe novel germline mutations of these genes in patients with primary hyperparathyroidism (PHPT). METHODS: During genetic screening for familial hyperparathyroidism, three novel CDKIs germline mutations in three unrelated cases between January 2019 and November 2021 were identified. In this report, we describe clinical features, DNA sequence analysis, and familial segregation studies based on these patients and their relatives. Genome-wide DNA study of loss of heterozygosity (LOH), copy number variation (CNV), and p27/kip immunohistochemistry was performed on tumour samples. RESULTS: DNA screening was performed for atypical parathyroid adenomas in cases 1 and 2 and for cystic parathyroid adenoma and young age at diagnosis of PHPT in case 3. Genetic analysis identified likely pathogenic variants of CDKN1B in cases 1 and 2 and a variant of the uncertain significance of CDKN2C, with uniparental disomy in the tumour sample, in case 3. Neoplasm screening of probands showed other non-endocrine tumours in case 1 (colon adenoma with dysplasia and atypical lipomas) and case 2 (aberrant T-cell population) and a non-functional pituitary adenoma in case 3. CONCLUSION: Germline mutations in CDKIs should be included in gene panels for genetic testing of primary hyperparathyroidism. New germline variants here described can be added to the current knowledge.

Glucagon stimulation test to assess growth hormone status in Prader-Willi syndrome.

PURPOSE: Growth hormone deficiency (GHD) must be confirmed before starting treatment in adults with Prader-Willi syndrome (PWS). Most studies use the growth-hormone-releasing hormone plus arginine (GHRH-arginine) test. No data are available on the glucagon stimulation test (GST) in PWS. We compared the utility of fixed-dose (1 mg) GST versus GHRH-arginine test in diagnosing GHD. METHODS: Adults and late adolescents with PWS underwent both tests on separate days. In the GHRH-arginine test, GHD was defined according to body mass index. In the GST, two cutoffs were analyzed: peak GH concentration < 3 ng/mL and < 1 ng/mL. For analyses, patients were divided into two groups according to body weight (≤ 90 kg and > 90 kg). RESULTS: We analyzed 34 patients: 22 weighing ≤ 90 kg and 12 weighing > 90 kg. In patients weighing ≤ 90 kg, the two tests were concordant in 16 (72.72%) patients (k = 0.476, p = 0.009 with GST cutoff < 3 ng/mL, and k = 0.450, p = 0.035 with GST cutoff < 1 ng/mL). In patients weighing > 90 kg, the two tests were not concordant with GST cutoff < 3 ng/mL, but were concordant in 11 (91.6%) patients (k = 0.833, p = 0.003) with GST cutoff < 1 ng/mL. GH peaks on the two tests correlated (r = 0.725, p = 0.008). CONCLUSION: Fixed-dose (1 mg) GST using a peak GH cutoff of < 3 ng/mL or < 1 ng/mL promises to be useful for screening for GHD in adults and late adolescents with PWS. However, in those weighing > 90 kg, the < 1 ng/mL cutoff seems better. Larger studies are necessary to establish definitive glucagon doses and cutoffs, especially in extremely obese patients.

Prognostic implications of Anemia in patients with acute heart failure in emergency departments. ANEM-AHF Study.

INTRODUCTION: The presence of anaemia leads to a worse prognosis in patients with heart failure (HF). There are few data on the impact of anaemia on mortality in patients with acute heart failure (AHF), and the studies available are mainly retrospective, and include hospitalised patients. OBJECTIVE: Evaluate the role of anaemia on 30-day and 1-year mortality in patients with AHF attended in hospital emergency departments (HEDs). METHODS: We performed a multicentre, observational study of prospective cohorts of patients with AHF. The study variables were: Anaemia (haemoglobin < 12g/dL in women and <13g/dL in men), mortality at 30 days and at 1 year, risk factors, comorbidity, functional impairment, basal functional grade for dyspnoea, chronic and acute treatment, clinical and analytical data of the episode, and patient destination. STATISTICAL ANALYSIS: Bivariate analysis and survival analyses using Cox regression. RESULTS: A total of 13 454 patients were included, 7662 (56.9%) of whom had anaemia. Those with anaemia were older, had more comorbidity, a worse functional status and New York Heart Association class, greater renal function impairment, and more hyponatraemia. The mortality was higher in patients with anaemia at 30 days and 1 year: 7.5% vs 10.7% (P < .001) and 21.2% vs 31.4% (P < .001), respectively. The crude and adjusted hazard ratios of anaemia for 30-day mortality were: 1.46 (confidence interval [CI] 95% 1.30-1.64); P < .001 and 1.20 (CI 95% 1.05-1.38); P = .009, respectively, and 1.57 (CI 95% 1.47-1.68) and 1.30 (CI 95% 1.20-1.40) for mortality at 1 year. The weight of anaemia on mortality was different in each follow-up period. CONCLUSIONS: Anaemia is an independent predictor of mortality at 30 days and 1 year in patients with AHF attended in HEDs. It is important to study the aetiology of AHF since adequate treatment would reduce mortality.

Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study.

BACKGROUND: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. PATIENTS AND METHODS: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA-IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. RESULTS: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799-1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458-1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690-1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. CONCLUSION: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. CLINICAL TRIALS IDENTIFIER: NCT04037124.

Processing and mechanical characteristics of magnesium-hydroxyapatite metal matrix biocomposites.

Magnesium/hydroxyapatite composites were produced by conventional extrusion and their mechanical behavior studied under uniaxial compression at room temperature. The results evidence the capability of the HA for strengthening the Mg material, lowering its microstructural anisotropy and inhibiting deformation twinning. They also reveal that the ECAP processing is effective for improving the grain structure and reducing the crystallographic texture of these composites, giving rise to a significant enhancement of their yield strength and microhardness although the ultimate compressive stress worsens. The analysis of the strain hardening rate of the flow curves demonstrates that the HA addition and the ECAP processing are also effective in inhibiting non-basal dislocation slip.

Latin American Study of Nutrition and Health (ELANS): rationale and study design.

BACKGROUND: Obesity is growing at an alarming rate in Latin America. Lifestyle behaviours such as physical activity and dietary intake have been largely associated with obesity in many countries; however studies that combine nutrition and physical activity assessment in representative samples of Latin American countries are lacking. The aim of this study is to present the design rationale of the Latin American Study of Nutrition and Health/Estudio Latinoamericano de Nutrición y Salud (ELANS) with a particular focus on its quality control procedures and recruitment processes. METHODS/DESIGN: The ELANS is a multicenter cross-sectional nutrition and health surveillance study of a nationally representative sample of urban populations from eight Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Perú and Venezuela). A standard study protocol was designed to evaluate the nutritional intakes, physical activity levels, and anthropometric measurements of 9000 enrolled participants. The study was based on a complex, multistage sample design and the sample was stratified by gender, age (15 to 65 years old) and socioeconomic level. A small-scale pilot study was performed in each country to test the procedures and tools. DISCUSSION: This study will provide valuable information and a unique dataset regarding Latin America that will enable cross-country comparisons of nutritional statuses that focus on energy and macro- and micronutrient intakes, food patterns, and energy expenditure. TRIAL REGISTRATION: Clinical Trials NCT02226627.

Effect of highly dispersed yttria addition on thermal stability of hydroxyapatite.

The capability of the colloidal method to produce yttria (Y(2)O(3)) dispersed hydroxyapatite (HA) has been investigated as an alternative method to the conventional method of mechanical mixing and sintering for developing HA-based materials that could exhibit controllable and enhanced functional properties. A water based colloidal route to produce HA materials with highly dispersed Y(2)O(3) has been applied, and the effect of 10 wt.% Y(2)O(3) addition to HA investigated by thermal analysis, X-ray diffraction and Fourier transform infrared spectroscopy. These measurements evidence a remarkable effect of this Y(2)O(3) addition on decomposition mechanisms of synthetic HA. Results show that incorporation of Y(2)O(3) as dispersed second phase is beneficial because it hinders the decomposition mechanisms of HA into calcium phosphates. This retardation will allow the control of the sintering conditions for developing HA implants with improved properties. Besides, substitution of Ca(2+) with Y(3+) ions appears to promote the formation of OH(-) vacancies, which could improve the conductive properties of HA favorable to osseointegration.

Robotic radical hysterectomy. A literature review.

Advanced laparoscopic procedures are increasingly being used as an alternative to laparotomy in gynecologic surgery. Several reviews have been completed that examine the advantages and drawbacks of this technique. Robotic technology offers the promise of overcoming many of the shortcomings of laparoscopy, while preserving classic operative techniques. This review article summarizes some of the most recent literature provided in the arena of robotic assisted radical hysterectomy for the treatment of cervical or endometrial cancer.

Cefalea en un paciente joven. Neurocisticercosis / Migraine in a young patient. Neurocysticercosis

La cisticercosis cerebral es una forma de presentación de parasitosis cerebral causada por Tenia Soleum. A pesar de la escasa prevalencia lejos de las zonas endémicas, el incremento de los movimientos migratorios obliga a un mayor estado de alerta por parte del médico ante síntomas frecuentes como es una cefalea, sobre todo en pacientes con factores de riesgo epidemiológicos. El diagnóstico debe ser precoz y el tratamiento instaurarse lo antes posible, de lo contrario las consecuencias pueden ser fatales para el enfermo (AU)

[BCG and radiotherapy: the compatibility of 2 conservative treatments for cancer of the urinary bladder]. / BCG y radioterapia: compatibilidad de dos tratamientos conservadores frente al cancer de vejiga urinaria.

OBJECTIVE: To review the efficacy of radiotherapy and BCG in the treatment of transitional cell carcinoma of the urinary bladder in its different forms of presentation, with special reference to patients with infiltrating bladder tumors receiving radiotherapy and those in whom the lesion recurs as a high grade superficial bladder tumor. METHODS/RESULTS: 10 patients who previously received radiotherapy for T2-4 infiltrating bladder tumor that recurred as a high grade superficial tumor were treated with BCG. Four patients are alive and disease-free with a preserved bladder at 2-8 years follow-up. Four other patients who required cystectomy for persistence or progression of the tumor to the bladder wall, are alive and disease free at 3-7 years follow-up. The remaining two patients who were not amenable to major surgery died from the disease more than two years after treatment with BCG. BCG was well-tolerated by 70% of the patients and the rest showed minor complications. CONCLUSIONS: 28.3% of recurrences after radiotherapy are superficial tumors and 7% are carcinoma in situ. The appearance of carcinoma in situ or T1 G3 lesions following radiotherapy of the bladder questions its efficacy against these superficial forms for which cystectomy is reserved. BCG has been found to be effective in high grade superficial bladder tumors that have not been previously irradiated, therefore it would be acceptable to extend its application to those patients in whom radiotherapy has achieved control of the infiltrating tumor but not the high grade superficial tumor. The 40-70% of patients who are alive with a preserved bladder appears to be sufficient to recommend BCG salvage for high grade superficial bladder tumors post-radiotherapy. BCG therapy does not entail major complications or compromise patient survival, including those cases that will require cystectomy.

Decline in sexually transmitted disease prevalence in female Bolivian sex workers: impact of an HIV prevention project.

OBJECTIVE: To implement an HIV prevention intervention among female commercial sex workers (CSW), and to monitor key outcomes using routinely collected clinical and laboratory data. DESIGN: Cross-sectional and longitudinal analysis of data from an open-enrollment cohort. SETTING: One public sexually transmitted disease (STD) clinic and about 25 brothels in La Paz, Bolivia. PARTICIPANTS: A total of 508 female CSW who work at brothels and attend a public STD clinic. INTERVENTION: Improved STD clinical care, supported by periodic laboratory testing, and behavioral interventions performed by a local non-governmental organization. MAIN OUTCOME MEASURES: Prevalence of gonorrhea, syphilis (reactive plasma reagin titer > or = 1 : 16), genital ulcer disease, chlamydial infection, and trichomoniasis; self-reported condom use in the previous month; and HIV seroprevalence. RESULTS: From 1992 through 1995, prevalence of gonorrhea among CSW declined from 25.8 to 9.9% (P < 0.001), syphilis from 14.9 to 8.7% (P = 0.02), and genital ulcer disease from 5.7 to 1.3% (P = 0.006); trends in prevalence of chlamydial infection and trichomoniasis were not significant. Self-reported condom use during vaginal sex in the past month increased from 36.3 to 72.5% (P < 0.001). In a multivariate analysis, condom use was inversely associated with gonorrhea [odds ratio (OR), 0.63; 95% confidence interval (Cl), 0.41-0.97], syphilis (OR, 0.39; 95% Cl, 0.23-0.64), and trichomoniasis (OR, 0.44; 95% Cl, 0.32-0.71). In 1995, HIV seroprevalence among CSW was 0.1%. CONCLUSION: Effective prevention interventions for female CSW can be implemented through public services and non-governmental organizations while HIV rates are still low, and key outcomes can be monitored using data obtained from periodic screening examinations.

[Lumbar ureteral fistula after aortobifemoral bypass in a patient with ileal conduit and pelvic irradiation]. / Fístula ureteral lumbar después de un by-pass aortobifemoral en un paciente con conducto ileal e irradiación pélvica.

Contribution of a complex case of lumbar ureteral fistula with secondary abscess after aortobifemoral bypass in a patient with a background of radical cystectomy with ileal conduit and pelvic radiotherapy. A nephrostomy was established and the retroperitoneal collection was drained so that in a second phase ureteral replacement with ileum could be performed using uretero-ileal terminoterminal and ileum-ileal terminolateral by-pass with good therapeutic and functional results.

Incidence of tumoural pathology in horseshoe kidneys.

OBJECTIVES: To know the incidence of tumoural pathology among our cases of horseshoe kidney (HK), a congenital anomaly occurring in 0.25% of the population, as well as their prognostic factors and follow-up. METHODS: A total of 82 patients admitted at our Centre between 1967 and 1996 with an HK diagnosis were retrospectively reviewed. We have collected a total of 10 cases of HK tumours. We analyse the clinical, diagnostic, surgical and evolutionary peculiarities of the different HK tumour aetiologies, as compared with those described in literature. RESULTS: Our experience is based on 10 patients-5 adenocarcinomas, 4 transitional cell carcinomas and a Wilms' tumour. CONCLUSIONS: We have observed that in the case of transitional cell carcinomas, the diagnosis is generally made at an advanced stage. The prognosis of the tumorous disease depends upon the same prognostic factors as in the case of normal kidneys. Renal adenocarcinoma is the kind of tumour most frequently associated with HKs. Its incidence among the HK cases is not greater than among the normal population. Conservative local treatment criteria for adenocarcinoma should be valid for HKs as well.

[Orthotopic bladder substitution: II. Types and complications]. / Sustitución vesical ortotópica: II. Tipos y complicaciones.

OBJECTIVE: In the last two decades, attention has been focused on the design of continent urinary diversion and orthotopic neobladder in an attempt to find the ideal bladder substitute. The more commonly utilized techniques of orthotopic bladder replacement are described and the urodynamic aspects and complications are analyzed. METHODS: The series of Studer, Hautmann, Kock, Pagano, Thuroff (Mainz Pouch) and Goldwasser and the relevant literature on this subject were reviewed. RESULTS/CONCLUSION: To date, similar functional results have been achieved by the different techniques of bladder substitution, although different intestinal segments are utilized. A longer follow-up is warranted to determine which is the ideal technique of bladder substitution.

[Orthotopic bladder replacement: II. Functional results and complications in patients with Studer-type ileal neobladder]. / Sustitución vesical ortotópica: III. Resultados funcionales y complicaciones en los pacientes con neovejiga ileal tipo Studer.

OBJECTIVE: Since 1988, 100 Studer ileal low pressure urinary reservoirs have been performed at our institution. The functional results and the complications observed in these patients are presented. METHODS: Patients submitted to radical cystectomy and lower urinary tract reconstruction with the Studer technique from 1988 to 1994 were retrospectively studied. All patients were males, their mean age was 60 years (37-75) and the mean follow-up was 18 months (6-72). The isoperistaltic ileal segment as antireflux mechanism was utilized in 97 cases and intussusception of the ileal segment to which the ureters were anastomosed in 3 cases. Reinsertion of the ureter was done using the Wallace technique in 90 cases and by direct fixation according to a personal technique (H.V.) in 10 cases. Anastomosis of the neobladder and the urethra was done with the end of the second suture of the orthotopic reservoir. The neurovascular bands were preserved in 21 patients less than 60 years old with tumor stage T2-T3a, according to the technique described by Walsh and Mostwin (1984). RESULTS: One patient died early postoperatively from sepsis. The early complications included urinoma (4%), urinary fistula (3%), intestinal fistula (2%), pulmonary complications (4%), pelvic hematoma (1%) and intestinal obstruction (3%). Only 4 of these patients required surgical resolution of the complication. The late complications included stricture of neobladder-urethra anastomosis (6%), lithiasis in neobladder (4%), ureteroileal stricture (8%), 5 renal units were lost, chronic urinary retention (5%), symptomatic metabolic acidosis (1%) and urinary infection (14%). Thirteen of these patients with late complications required surgery. At 6 months' minimum follow-up, 90% of the patients were continent during the day and 60% during the night. Overall, 36% of the patients recovered erection postoperatively; 76% of the patients with preserved neurovascular bands recovered erection. Forty-four percent of the patients claimed they had a satisfactory sexual activity postoperatively. CONCLUSION: The Studer neobladder permits voiding through the urethra, preservation of the upper urinary tract, the urinary infection rate is acceptable, the complication rate is low and it offers patients continence rates that allow them to have a good quality of life.

[Orthotopic bladder replacement: I. Physiopathology of orthotopic bladder replacement with intestine]. / Sustitución vesical ortotópica: I. Fisiopatología de la sustitución vesical ortotópica con intestino.

OBJECTIVE: To analyze the physiopathological principles of utilizing the bowel for orthotopic bladder substitution and their effects on metabolism, function and continence. METHODS: The world literature is reviewed and our experience of 100 cases is described in the third part of this study. RESULTS/CONCLUSION: To reduce the metabolic changes, utilization of colonic or ileal segments with a maximum length of about 40 cm is advocated. This length of detubulized intestinal segment permits creating an ample, low pressure reservoir with an antireflux mechanism. The precise incidence of neoplastic degeneration of the ileal and colonic reservoirs is not known, but appears to be lower for the ileal neobladder.

[Vesico-ureteral reflux associated with detrusor instability]. / Reflujo vesicoureteral asociado a inestabilidad del detrusor.

OBJECTIVE: The aim of this study was to determine the urodynamic characteristics of patients with vesico-ureteral reflux (VUR) and detrusor instability (DI) followed by medical treatment. PATIENTS AND METHODS: The urodynamic and cystographic findings in a group of 24 patients between 4 and 18 years of age (mean 7.6 years) with a simultaneous diagnosis of VUR and DI were reviewed. All of them presented with recurrent urinary tract infections. Twenty were female of whom eight also had enuresis and daytime symptoms. Mean follow-up was 40 months (range 18-97 months). VUR was diagnosed by voiding cystourethrogram and classified according to the grades proposed by the "International reflux study on children". RESULTS: All but 6 patients had at least a 15% reduction in age-adjusted capacity. No relationship was observed between the severity of VUR (measured as the addition of reflux grades in both units of each patient) and reduction in bladder capacity or compliance. Seven patients had upper tract damage (either scars or a decrease in size or function on the renogram). Upper tract damage was significantly more frequent in patients with bilateral reflux (regardless of the type of DI). Patients with unilateral reflux and sustained instability had significantly less upper tract damage. Results of treatment are reported separately. CONCLUSIONS: In these patients, the severity of VUR did not seem to have an impact on bladder capacity or compliance. The risk factors for upper tract damage in this series differ from those found by other authors.

[Efficacy of oxybutynin chloride in children with vesico-ureteral reflux and detrusor instability]. / Eficacia del cloruro de oxibutinina en niños con inestabilidad del detrusor y reflujo vesicoureteral.

OBJECTIVE: The purpose of this study was to assess the urodynamic (UD), radiological (VCUG) and clinical outcome in patients with detrusor instability (DI) and vesico-ureteral reflux (VUR). PATIENTS AND METHODS: UD and VCUG findings in 24 patients between 4 and 18 years of age (mean 7.6 years) with a simultaneous diagnosis of VUR and DI were reviewed. All presented with recurrent urinary tract infections (UTI). Twenty were female of whom 8 also had enuresis and daytime symptoms. Ten had bilateral VUR, making a total of 34 units. Mean follow-up was 40 months (range 18-97 months) and at least 2 UD studies were done. Treatment consisted of oxybutinin chloride (OC) and chemoprophylaxis. RESULTS: Treatment lasted an average of 31 months with an average dose of 11 mg/day. There was a statistically significant improvement in UTI rate, enuresis score and UD parameters [CysCap, volume at 1st contraction, maximum contraction and compliance (comp)]. Thirteen patients achieved stable bladders and 9 had some UD improvement (3 with low compliance and 2 with less severe DI), leaving 2 with unchanged DI. Reflux disappeared in 20 units and was downgraded in 6. VUR improvement coincided with the cases of UD improvement. Persistence of DI was always associated with persistent VUR. CONCLUSIONS: Oxybutinin treatment can be long, but UD and VUR improvement run parallel in most cases. The rare discrepant cases point towards a multifactorial ethology in this condition.