Impact of Ureteroscopy Before Nephroureterectomy for Upper Tract Urothelial Carcinoma on Oncologic Outcomes.

OBJECTIVE: To compare the oncologic outcomes of patients with upper tract urothelial carcinoma undergoing nephroureterectomy (NU) with and without prior ureteroscopy (URS). METHODS: We reviewed records of all patients with no prior history of bladder cancer who underwent NU at our institution (n = 201). We compared patients who underwent URS before NU with patients who proceeded directly to NU based on imaging alone. After excluding patients undergoing URS with therapeutic intent, we used multivariable Cox proportional hazards models, adjusting for tumor characteristics with cancer-specific survival (CSS), intravesical recurrence-free survival, metastasis-free survival (MFS), and overall survival (OS) as end points. This study received institutional review board approval. RESULTS: A total of 144 (72%) patients underwent URS before NU, and 57 (28%) patients proceeded directly to NU. The median follow-up time for survivors was 5.4 years from diagnosis. The performance of diagnostic URS before NU was significantly associated with IR (hazard ratio 2.58; 95% CI 1.47, 4.54; P = .001), although it was not associated with CSS, MFS, or OS. The adjusted intravesical recurrence-free survival probability 3 years after diagnosis is 71% and 42% for patients who did not and did receive URS before NU, respectively (adjusted risk difference 30%; 95% CI 13%, 47%). CONCLUSION: We did not find evidence that URS adversely impacts disease progression and survival in patients with upper tract urothelial carcinoma. Although patients are at higher risk for IR after NU when they have undergone prior diagnostic URS, their CSS, MFS, and OS are not significantly affected.

Validation of the lower urinary tract symptom score.

INTRODUCTION: To develop and validate a lower urinary tract symptom score (LUTSS) as a measure of lower urinary tract symptom (LUTS) severity and a treatment outcome tool in adults. MATERIALS AND METHODS: An expert panel was convened to develop the LUTSS questionnaire. Content validity was achieved by obtaining subject and expert feedback from two prospective drafts. Subjects were divided into three groups: normal, LUTS and overactive bladder (OAB). Questionnaire was administered on two separate occasions within 1-2 weeks. Test-retest reliability, internal consistency, discriminant validity, criterion validity and responsiveness to change were also assessed. RESULTS: The questionnaire contains 14 questions with answers scored on a 5-point Likert scale (0-4). It includes 9 storage, 4 voiding and 1 bother question. One hundred ninety-one patients completed it; 80 males and 111 females, mean age 65 years (range 22-91). Seventy-two had OAB, 91 LUTS without OAB and 28 were normal. Test-retest intraclass correlation was 0.96 and Cronbach's-□ was 0.77, indicating strong test-retest reliability and internal consistency, respectively. ANOVA and post-hoc bootstrap-generated adjustments showed significant differences between the three groups (p < 0.001), demonstrating discriminant validity. Responsiveness to change was exhibited by the significant decrease between preop and postop scores and a concurrent patient global impression of improvement (PGI-I) score indicative of symptomatic improvement. CONCLUSION: The 14-question LUTSS is a validated questionnaire that assesses a full range of LUTS in men and women. The ordinal nature of the data with its highly specific description of symptoms makes it ideally suited as a nuanced and comprehensive symptom score and patient reported outcome (PRO) tool.

Prediction of nocturia severity in men: nocturnal urine overproduction vs race or metabolic risk factors.

IMPORTANCE: Nocturia is one of the most common and bothersome of lower urinary tract symptoms. OBJECTIVE: To examine the effect of race and metabolic risk factors on nocturia severity in men as measured by the number of nightly voids. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review from 2011 to 2013 was performed at a Veterans Affairs-based urology clinic in Brooklyn, New York, among 104 adult men 18 years or older who completed a 24-hour frequency and volume chart. Metabolic risk factors included race and a history of diabetes mellitus, hypertension, and obstructive sleep apnea. The 24-hour frequency and volume chart data included the nocturia index (nocturnal urine volume divided by maximal voided volume), the nocturnal polyuria index (nocturnal urine volume divided by 24-hour volume), and nocturnal urine production (nocturnal urine volume per hours slept). A nocturia index of less than 2 vs 2 or higher, a nocturnal polyuria index of less than 33% vs 33% or higher, and nocturnal urine production of less than 90 vs 90 mL/h or higher were chosen as clinically relevant cutoff points for nocturia severity. Nocturia severity was compared by race, the aforementioned variables, and the presence or absence of diabetes mellitus, hypertension, and obstructive sleep apnea. MAIN OUTCOMES AND MEASURES: The number of nightly voids. RESULTS: One hundred four adult men (mean age, 64 years; age range, 24-92 years) completed a 24-hour frequency and volume chart (mean number of nightly voids, 2.93; range, 0-15). The number of nightly voids was not statistically different for white vs black race (3.00 vs 2.93, P = .86) or for the presence vs the absence of diabetes mellitus (3.00 vs 2.88, P = .85), hypertension (2.94 vs 2.80, P = .75), and obstructive sleep apnea (3.29 vs 2.83, P = .50). However, nocturia severity was significantly different based on a nocturia index of less than 2 vs 2 or higher (1.39 vs 3.60), a nocturnal polyuria index of less than 33% vs 33% or higher (1.83 vs 3.65), and nocturnal urine production of less than 90 vs 90 mL/h or higher (2.27 vs 3.77) (P < .001 for all). CONCLUSIONS AND RELEVANCE: Neither race nor metabolic risk factors affect nocturia severity. In contrast, variables that denote nocturnal urine overproduction sharply discriminate the risk of nocturia severity and suggest that variable data may provide useful clinical correlation.

The evaluation and management of persistent nocturia.

Nocturia, or waking at night to void, is a common symptom that leads to substantial morbidity. Men and women are both affected across a wide age range, such that the objective evaluation of nocturia remains a challenge, due largely to its multifactorial etiology. While for some patients, nocturia is caused by common structural conditions such as prostatic obstruction, for others it is due to a complex interplay between multiple underlying systemic diseases. For this reason, persistent nocturia merits particularly careful consideration. The purpose of this review is to describe the most recent salient research in the field of nocturia, with a particular emphasis on its evaluation and management.

Desmopressin in the treatment of nocturia: clinical evidence and experience.

Nocturia is a common and bothersome condition experienced by both men and women. Studies have suggested that nocturia contributes a level of morbidity to those who suffer from the condition, both young and old. Desmopressin has historically been utilized to treat conditions such as central diabetes insipidus, certain bleeding disorders and primary nocturnal enuresis. Recently, interest has increased as to the use of desmopressin (a vasopressin analog) in the treatment of adult nocturia, for whom nocturnal polyuria is prevalent. While desmopressin has been traditionally administered in tablet and bioequivalent high dose melt formulations, newer low-dose orally disintegrating sublingual desmopressin has been recently studied to determine safe and efficacious dosing strategies. In this review, nocturia and its associated morbidities are discussed, followed by a contemporary literature review regarding the safety and efficacy of desmopressin for its treatment.

Moderate transmission but high prevalence of malaria in Madagascar.

Malaria transmission remains poorly documented in areas of low transmission. A study has been carried out over two consecutive years in Analamiranga, a village located at an altitude of 885m on the western edge of the Malagasy highlands, with the aim of generating and updating malariometric indexes for both mosquitoes and schoolchildren. In this village, no vector control measures were performed during the study period nor during previous decades. Mosquitoes were collected monthly when landing on human volunteers and in various resting-places. Blood samples were taken every 3 months from schoolchildren aged 6-12 years and microscopically examined. Of 7,480 mosquitoes collected on human subjects, 5,790 were anophelines. Ten anopheline species were represented and three of these, Anopheles funestus, Anopheles arabiensis and Anopheles mascarensis, accounted for 59.2% of the collection. Of these three species 4,640 were also collected in resting places. The proportion of mosquitoes fed on bovids was high; conversely, the anthropophilic rate (mosquitoes fed on human beings) was especially low: 31%, 7% and 1%, respectively, for A. funestus, A. arabiensis and A. mascarensis. The only confirmed malaria vector was A. funestus with a low sporozoite index (of 6,830 A. funestus, five were positive for Plasmodium falciparum and four for Plasmodium vivax). The annual entomological inoculation rate (number of bites of infected anophelines per adult person) was estimated at 2.49 with low variation over the 2 years. Overall, 909 thick blood smears were tested from blood samples taken from schoolchildren with 30.3% being malaria-positive. The four Plasmodium species infecting human subjects were detected in the following proportions: P. falciparum 78.9%, P. vivax 19.4%, Plasmodium malariae 1.0% and Plasmodium ovale 0.7%. The proportions of children who were infected with any Plasmodium ranged from 10.7% in February to 51.0% in September. Parasitemic children with fever (axillary temperature >37.5 degrees C) accounted for 16.4% of the children sampled. This study demonstrates that there are substantial parasitological consequences of even a relatively low entomological transmission and also recommends including exterior resting-places of mosquitoes in future spraying campaigns in the highlands of Madagascar.

Polyplexes and lipoplexes for mammalian gene delivery: from traditional to microarray screening.

Gene therapy requires the development of non-toxic and highly efficient delivery systems for DNA and RNAi. Polycations, especially dendrimers, have shown enormous potential as gene transfer vehicles, displaying minimal toxicity with a broad range of cell lines. In this paper, a total of 13 dendrimers, up to G3.0, were constructed from AB(3) type isocyanate monomers using solid phase methodology and evaluated for transfection activity. Among the library of compounds prepared, a G3.0 dendrimer displayed comparable activity to Superfect. Gel retardation assays demonstrated that all of the compounds completely bound plasmid DNA, indicating the efficient formation of complexes between DNA and the dendrimers. A "transfection microarray" approach was developed for screening these compounds as well as a panel of lipoplexes (complexes of DNA with cationic lipids) and polyplexes (complexes of DNA with synthetic polycationic polymers), in 3D solution like micro-assay). Five cationic lipids with a cholesterol tail showed stronger or comparable transfection activity relative to Effectene. The new, micro-array screening method was rapid and miniaturized, offering the potential of high throughput screening of large libraries of transfection candidates, with thousands of library members per array, and the ability to rapidly screen a broad range of cell types.

Is the Mbita trap a reliable tool for evaluating the density of anopheline vectors in the highlands of Madagascar?

BACKGROUND: One method of collecting mosquitoes is to use human beings as bait. This is called human landing collection and is a reference method for evaluating mosquito density per person. The Mbita trap, described by Mathenge et al in the literature, consists of an entry-no return device whereby humans are used as bait but cannot be bitten. We compared the Mbita trap and human landing collection in field conditions to estimate mosquito density and malaria transmission. METHODS: Our study was carried out in the highlands of Madagascar in three traditional villages, for 28 nights distributed over six months, with a final comparison between 448 men-nights for human landing and 84 men-nights for Mbita trap, resulting in 6,881 and 85 collected mosquitoes, respectively. RESULTS: The number of mosquitoes collected was 15.4 per human-night and 1.0 per trap-night, i.e. an efficiency of 0.066 for Mbita trap vs. human landing. The number of anophelines was 10.30 per human-night and 0.55 per trap-night, i.e. an efficiency of 0.053. This efficiency was 0.10 for indoor Anopheles funestus, 0.24 for outdoor An. funestus, and 0.03 for Anopheles arabiensis. Large and unexplained variations in efficiency were observed between villages and months. CONCLUSION: In the highlands of Madagascar with its unique, highly zoophilic malaria vectors, Mbita trap collection was poor and unreliable compared to human landing collections, which remains the reference method for evaluating mosquito density and malaria transmission. This conclusion, however, should not be extrapolated directly to other areas such as tropical Africa, where malaria vectors are consistently endophilic.

Sex differences in the incidence of orofacial clefts and the question of primary prevention in families with genetic risk.

Systematic registration of all children with orofacial clefts in Bohemia (Czech Republic) started at the Clinic of Plastic Surgery, Prague in 1964. A sample of 181 affected children with positive family histories (i.e. one of the parents had some type of orofacial cleft) was selected for the present study. The aim of this study was to follow the relation not only between the type of cleft in the child and in its parent, but also between the sex of the child and of the affected parent. Among children of mothers with cleft lip 68% were boys and only 32% were girls with cleft lip or cleft lip and palate. If the mother had cleft lip and palate, the same cleft type was found in 64% of boys and only 15% of girls. If the mother had cleft palate, the same cleft type was found in 37% of boys and 51% of girls. Very similar results were found for affected fathers and their children, with only one exception: among children of fathers with cleft lip and palate, the percentage of boys and girls with CLP was 43% and 40%, respectively. We can conclude that the cleft type in a child depends not only upon the cleft type present in the mother or father, but also upon the sex of the child. There was higher risk to have the orofacial cleft in sons of mothers with CL or CLP or fathers with CL and daughters of mothers or fathers with CP. The combination of the preconception choice of the sex of the baby with the ultrasonography method for the prenatal screening of malformations could decrease the risk delivering a child with an orofacial cleft in families with a genetic predisposition.

The relation of isolated cleft of the hard palate to submucous cleft palate.

The authors report a case of a spontaneous development of a fistula in a nonoperated submucous cleft palate in a male aged 40 years. This observation and the search of the underlying causes are based on their report from 1971 dealing with an analysis of 5 cases of an inborn defect in the hard palate.

Maternal hyperthermia and infection as one of possible causes of orofacial clefts.

It has been proposed that the hyperthermia in pregnant women may be associated with birth defects in their offsprings. We analysed the retrospective interview data on probable febrile illness during critical period of orofacial clefts development in 992 mothers of boys and girls with three types of orofacial clefts--cleft lip, unilateral or bilateral cleft lip and palate and cleft palate. A number of mother that gave the positive answer was relatively high and varied from 24% to 33%. There were no significant differences of the incidence of mother febrile illness between three groups of orofacial clefts in boys and girls. These data support presumption on the harmful effect of febrile illness during early pregnancy on craniofacial development.

[Extensive corium grafts]. / Rozsáhlé koriové stepy.

Even in our times of revolutionary advances in the technology and operative techniques in plastic surgery, the corium is a material with multiple applications and can be found in the patient at varying thickness. The aim of the article is to show that its indication to reinforce flaccid musculature or to cover muscular defects of the abdominal wall is fully justified even in a time of routine use of plastic nets.

Francis Burian--founder of the treatment of facial clefts in Czechoslovakia.

Prof. F. Burian, the founder of Czechoslovak Plastic Surgery, belonged to the world-wide scale among the most prominent pioneers of this field. His main interest and professional concern was devoted to the problems of facial clefts. The present communication reviews the gradual development of surgical repair of cleft lip and palate from the early twenties to the late fifties at the Department for Plastic Surgery in Prague, headed by Prof. F. Burian.

Long-term experiences with the two-stage palatoplasty with regard to the development of maxillary arch.

From our data on 46 patients operated on by one surgeon in 1961 and 1962 who were regularly examined up to adulthood, it may be concluded that the growth results of the two-stage palatoplasty, when the second stage is done before the patient is 7 years of age, are almost identical to the results of one-stage palate repair performed at the age of 3 to 4 years. However, a greater orthodontic effort is needed to achieve a properly aligned dentoalveolar arch with the two-stage palatoplasty.

Extensive corium grafts.

Even in our times of revolutionary advances in the technology and operative techniques in plastic surgery, the corium is a material with multiple applications and can be found in the patient at varying thickness. The aim of the article is to show that its indication to reinforce flaccid musculature or to cover muscular defects of the abdominal wall is fully justified even in a time of routine use of plastic nets.

Aetiological, modifying and lethal factors in cleft lip and palate.

Prenatal factors influencing cleft lip (CL), cleft lip and palate (CLP) and isolated cleft palate (CP) may account for the development of the defect (aetiological factor) for a change in the degree or type of the defect (modifying factor), or for the death of the embryo (lethal factor). Each active factor appears to act in all three directions, all be it at different ratios. This is used for analysis of groups of cleft-effected individuals registered at the Department of Plastic Surgery, Prague, from the catchment area of Bohemia. In terms of cleft defect teratogenesis (aetiology, modification, lethality) a "protective influence" appears probable in female embryos, in blood group A (ABO system), in HLA antigens A9, A11, B35. An "embryotoxic influence" i.e., an increase in all the three influences is seen in male embryos, regional influences, in the B and AB blood groups, in HLA antigens B17, in primiparae, in multiple pregnancies, in older mothers and in cytomegalovirus infections. The Epstein-Barr virus seem to increase, in particular, CLP embryo lethality. The activity of the factors was rated by means of correlations between the cleft frequency in first-degree relatives and the frequency of the factor in six subgroups classified by the cleft defect subtypes, by means of interactions between two and more factors and by a study of the differences between male and female probands. A model of the threshold of CL and CP teratogenesis was proposed, a model in agreement with prenatal reciprocal equilibrium.

[Present trends in the treatment of burn injuries]. / Soucasné trendy v lécbe popáleninového traumatu.

The authors present contemporary experience as regards burn injuries assembled by the Burns Centre of the clinic of Plastic Surgery of the Medical Faculty of Hygiene--Charles University Prague with the treatment of burns with special attention to team work and surgical procedures. The authors discuss all stages of work with the patient starting with his transport, treatment of shock, indications of releasing incisions, necretomies, various types of transplantations to cultivation of autologous and homologous epithelium. Special attention is devoted to treatment of electric injuries.