Obstructive urinary tract diseases and prenatal diagnosis. Timing of surgical correction]

The Authors are reviewing their experience of Obstructive Uropathies diagnosed and treated surgically in neonates, the last 8 years in their Institution. 67 cases were reviewed, in which 37 presented with ureteropelvic junction obstruction (UPJ). 13 with posterior urethral valves, 11 with primary megaureter and 6 with ureterocele. Prenatal ultrasonography allowed the diagnosis to be made in two third of the patients. UPJ is the most common obstructive uropathy observed. Posterior urethral valves the most severe because of high pulmonary and renal (dysplasia) complication rate. Surgery, when indicated, has no more complications to be expected than in general population, if oriented prophylactic measures are taken in the early peri- and postoperative period.     

Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

A simple theoretical verification of monitor unit calculation for intensity modulated beams using dynamic mini-multileaf collimation.

A spreadsheet based program is presented to perform an independent Monitor Unit (MU) calculation verification for the Quality Assurance (QA) of Intensity Modulated Radiation Therapy (IMRT) using Dynamic MultiLeaf Collimation (DMLC). The computed dose value is compared to the planned dose by calculating the percent dose difference per Intensity Modulated Beam (IMB) and absolute dose difference per IMB. The proposed acceptability levels are +/-5.0% or +/-2.0 cGy for the percent dose difference per IMB and the absolute dose difference per IMB, respectively. For percent dose difference per treatment, an acceptability level of +/-2.0% is proposed. The presented program is considered adequate for checking the treatment plans calculated for IMRT treatments using DMLC as a part of the QA procedure.     

CD83 expression on dendritic cells and T cells: correlation with effective immune responses

Human CD83 is a marker molecule for mature dendritic cells (DC) and is also expressed on activated B and T cells. Although CD83 has been implicated in immune responses, its function on DC and T cells remains unclear. In this study, we wanted to assess the role of CD83 expressed on DC and T cells in the immune response. Down-regulation of CD83 expression on human DC through RNA interference (RNAi) results in a less potent induction of allogeneic T cell proliferation, reduced IFN-gamma secretion by established T cells and decreased capacity in the priming of functional tumor antigen-specific CD8+ T lymphocytes. In addition, CD83 mRNA-electroporated DC are stronger T cell stimulators. However, CD83 overexpression on Melan-A/MART-1-specific tumor-infiltrating lymphocytes (TIL) circumvents the need for CD83 expression on DC. Co-culture of immature DC with TIL or K562 cells overexpressing CD83 results in the production of enhanced levels of pro-inflammatory cytokines, whereas this production is less pronounced or even absent in co-cultures with non-modified TIL or K562 cells. In conclusion, we demonstrate that CD83 expression on T cells and DC modulates the immune response by activating DC and by delivering costimulatory signals for the stimulation of naive and memory T cells, respectively.     

A comprehensive map of genetic relationships among diagnostic categories based on 48.6 million relative pairs from the Danish genealogy

For more than half a century, Denmark has maintained population-wide demographic, health care, and socioeconomic registers that provide detailed information on the interaction between all residents and the extensive national social services system. We leverage this resource to reconstruct the genealogy of the entire nation based on all individuals legally residing in Denmark since 1968. We cross-reference 6,691,426 individuals with nationwide health care registers to estimate heritability and genetic correlations of 10 broad diagnostic categories involving all major organs and systems. Heritability estimates for mental disorders were consistently the highest across demographic cohorts (average h² = 0.406, 95% CI = [0.403, 0.408]), whereas estimates for cancers were the lowest (average h² = 0.130, 95% CI = [0.125, 0.134]). The average genetic correlation of each of the 10 diagnostic categories with the other nine was highest for gastrointestinal conditions (average r_g = 0.567, 95% CI = [0.566, 0.567]) and lowest for urogenital conditions (average r_g = 0.386, 95% CI = [0.385, 0.388]). Mental, pulmonary, gastrointestinal, and neurological conditions had similar genetic correlation profiles.

Denmark, like other Nordic countries (1–4), has maintained for more than half a century population-wide demographic, health care, and socioeconomic registers that provide detailed information on the interaction between all residents and the extensive national social services system (5, 6), including familial information via parental links (7, 8). This has allowed population-based studies of the causes and consequences of disease at an unprecedented scale and detail (9).Several studies in the Nordic countries have leveraged diagnostic information from cross-referenced civil and health care registers on pairs of close relatives for quantitative genetic studies—that is, co-occurrence and familial coaggregation, heritability and genetic correlation, and nonrandom mating (10–14). However, the dynamics of a population (e.g., changes in mating patterns and family structure, health care provision, clinical practice, and diagnostic systems) may compromise such initiatives and bias quantitative genetic estimates and inference on human behavior. Thus, realizing the potential of Nordic population and health care registers depends on insights into the structure and network properties of the entire genealogy and accounting for underlying changes in the frequencies of human traits, notably in population demographics and disease frequencies.Here, we reconstruct the Danish genealogy using the population-wide Danish Civil Registration System that holds information on family relationships for all individuals with at least 1 d of legal residence in Denmark since 1968 (7, 8). We describe the size, structure, and network properties of the genealogy along 116 y. We leverage the cross-reference to the nationwide, public, and health care registers to estimate occurrence, heritability, and genetic correlations for 10 broad categories of medical conditions across eight consecutive demographic cohorts.     

Initial clinical experience with infrared-reflecting skin markers in the positioning of patients treated by conformal radiotherapy for prostate cancer

PURPOSE: To evaluate an infrared (IR) marker-based positioning system in patients receiving conformal radiotherapy for prostate cancer. METHODS AND MATERIALS: During 553 treatments, the ability of the IR system to automatically position the isocenter was recorded. Setup errors were measured by means of orthogonal verification films and compared to conventional positioning (using skin drawings and lasers) in 184 treatments. RESULTS: The standard deviation of anteroposterior (AP) and lateral setup errors was significantly reduced with IR marker positioning compared to conventional: 2 vs. 4.8 mm AP (p < 0.01) and 1.6 vs. 3.5 mm laterally (p < 0.01). Longitudinally, the difference was not significant (3.5 vs. 3.0 mm). Systematic errors were on the average smaller AP and laterally for the IR method: 4.1 vs. 7.8 mm AP (p = 0.01) and 3.1 vs. 5.6 mm lateral (p = 0.07). Longitudinally, the IR system resulted in somewhat larger systematic errors: 5.0 vs. 3.4 mm for conventional positioning (p = 0.03). The use of an off-line correction protocol, based on the average deviation measured over the first four fractions, allowed virtual elimination of systematic errors. Inability of the IR system to correctly locate the markers, leading to an executional failure, occurred in 21% of 553 fractions. CONCLUSION: IR marker-assisted patient positioning significantly improves setup accuracy along the AP and lateral axes. Executional failures need to be reduced.     

Mycobacterium marinum causing tenosynovitis. 'Fish tank finger'

Mycobacterium marinum is an unusual atypical mycobacterium with low pathogenicity for humans in comparison with Mycobacterium tuberculosis. Among the non-tuberculous mycobacterial pathogens, Mycobacterium marinum is the most common pathogen to cause skin infections. Mycobacterium marinum infection causes chronic cutaneous lesions and in some cases deeper infections such as tenosynovitis, septic arthritis and rarely osteomyelitis. We report the case of a male patient presenting with tenosynovitis of the distal upper extremity secondary to Mycobacterium marinum infection.