Preimplantation Genetic Testing within the Public Healthcare System in Slovenia.

Preimplantation genetic testing (PGT) is the earliest form of prenatal diagnosis that has become an established procedure for couples at risk of passing a severe genetic disease to their offspring. At UMC Ljubljana, we conducted a retrospective register-based study to present 15 years of PGT service within the public healthcare system in Slovenia. We collected the data of the PGT cycles from 2004 to 2019 and compared clinical outcomes for chromosomal and monogenic diseases using different embryo biopsy and testing approaches. In addition, we assessed the extent to which PGT has become the preferred option compared to classic prenatal diagnostics. We treated 211 couples, 110 with single gene disorder, 88 with structural chromosome rearrangement and 13 for numerical chromosome aberration. There were 375 PGT cycles with oocyte retrieval, while embryo transfer was possible in 263 cases resulting in 78 deliveries and 84 children. Altogether, the clinical pregnancy rate per embryo transfer was 31% in 2004-2016 (blastomere biopsy) and 43% in 2017-19 (blastocyst biopsy), respectively. We assessed that approximately a third of couples would opt for PGT, while the rest preferred natural conception with prenatal diagnosis. Our results show that providing a PGT service within the public healthcare system has become a considerable option in pregnancy planning for couples at risk of transmitting a severe genetic disease to their offspring. In Slovenia, approximately a third of couples would opt for PGT. Although the number of cycles is small, our clinical results are comparable to larger centres.

Magnetoelastic properties and behaviour of 4C pyrrhotite, Fe7S8, through the Besnus transition.

Pyrrhotite, Fe7S8, is a commonly occurring carrier of magnetic remanence and has a low temperature transition, the Besnus transition, involving a change in spin state. Variations of the thermodynamic, magnetic and elastic properties through this transition at ∼33 K in a natural sample of 4C pyrrhotite have been tested against a group theoretical model for coupling between order parameters relating to Fe/vacancy ordering (irrep U 1(1/2,0,1/4)) and magnetic ordering (irreps m[Formula: see text] and m[Formula: see text]). Magnetoelastic coupling is weak but the pre-existing microstructure of ferroelastic and magnetic domains, that develop as a consequence of Fe/vacancy and ferrimagnetic ordering during slow cooling in nature (P63/mmc → C2'/c'), causes subtle changes in the low temperature transition (C2'/c' → P [Formula: see text]). The Besnus transition involves a rotation of magnetic moments out of the a-c plane of the monoclinic structure, but it appears that the transition temperature might vary locally according to whether it is taking place within the pre-existing domain walls or in the domains that they separate. Evidence of metamagnetic transitions suggests that the magnetic field-temperature phase diagram will display some interesting diversity. Low temperature magnetic transitions in minerals of importance to the palaeomagnetism community have been used to identify the presence of magnetite and haematite in rocks and the Besnus transition is diagnostic of the existence of pyrrhotite, Fe7S8.

Modeling Water Quality in Watersheds: From Here to the Next Generation.

In this synthesis, we assess present research and anticipate future development needs in modeling water quality in watersheds. We first discuss areas of potential improvement in the representation of freshwater systems pertaining to water quality, including representation of environmental interfaces, in-stream water quality and process interactions, soil health and land management, and (peri-)urban areas. In addition, we provide insights into the contemporary challenges in the practices of watershed water quality modeling, including quality control of monitoring data, model parameterization and calibration, uncertainty management, scale mismatches, and provisioning of modeling tools. Finally, we make three recommendations to provide a path forward for improving watershed water quality modeling science, infrastructure, and practices. These include building stronger collaborations between experimentalists and modelers, bridging gaps between modelers and stakeholders, and cultivating and applying procedural knowledge to better govern and support water quality modeling processes within organizations.

A Systematic Clinical Review of Prenatally Diagnosed Tetrasomy 9p.

Tetrasomy 9p was first described in 1973 and approximately 68 cases with a variable phenotype have been reported to date with 22 of them being detected prenatally. The objective of this study was to review prenatally-reported cases of tetrasomy 9p thus far and to identify ultrasound phenotypes that may be suggestive of this specific syndrome. A PubMed database search was done in February 2018 without any restriction of publication date orjournals, with the use of the following keywords: tetrasomy 9p, tetrasomy 9p prenatal, mosaic tetrasomy 9p, mosaic tetrasomy 9p prenatal, isochromosome 9p, duplication 9p prenatal, trisomy 9p prenatal. Reported cases were included if the clinical presentation and diagnostic approach of each case was clearly described. The most common characteristics of prenatally-detected tetrasomy 9p are intrauterine growth retardation (IUGR, 57.0%), central nervous system (CNS) abnormalities (59.0%), skeletal anomalies (29.0%), genitourinary and renal anomalies (29.0%) and cardiac defects (29.0%). The phenotypic spectrum of tetrasomy 9p is rather unspecific as these findings are commonly associated with other chromosome anomalies, as well as microdeletion/microduplication or monogenic syndromes. The combination of early fetal morphology and diagnostic genetic testing enables a definite tetrasomy 9p diagnosis and effective further pregnancy management.

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation.

The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

Imaging Features of Juvenile Xanthogranuloma of the Pediatric Head and Neck.

BACKGROUND AND PURPOSE: Juvenile xanthogranuloma is a non-Langerhans cell histiocytosis primarily affecting children. The purpose of this study was to characterize the imaging features of histologically confirmed pediatric head and neck juvenile xanthogranuloma. MATERIALS AND METHODS: A retrospective review was performed of medical records and imaging of histologically confirmed head and neck juvenile xanthogranuloma. RESULTS: Ten patients (6 girls, 4 boys) 1 month to 12 years of age were imaged with ultrasound only (n = 1), CT only (n = 2), CT and ultrasound (n = 1), MR imaging only (n = 3), or MR imaging and CT (n = 3). Masses were solitary in 9 patients and multiple in 1. Solitary masses were located in the external auditory canal, infra-auricular region, infratemporal fossa with intracranial extension, frontal scalp, and subperiosteal space eroding the calvaria and along the dura. One patient with disseminated disease had scalp-, calvarial-, and dural-based masses. Clinical presentation included a mass or alteration in function. On sonography, juvenile xanthogranuloma appeared hypoechoic. On contrast-enhanced CT, masses appeared homogeneous and isoattenuating with muscle and sometimes eroded bone. On MR imaging, compared with the cerebral cortex, the masses appeared hyper- or isointense on T1 and hypo- or isointense on T2, had decreased diffusivity, and enhanced homogeneously. Juvenile xanthogranuloma was not included in the differential diagnosis in any case. CONCLUSIONS: Head and neck juvenile xanthogranuloma has varied manifestations. Mild hyperintensity on T1, hypointensity on T2 compared with the cerebral cortex, decreased diffusivity, and homogeneous enhancement are characteristic. Awareness of these features should prompt radiologists to include juvenile xanthogranuloma in the differential diagnosis of pediatric head and neck masses.

[What are the Prerequisites for a Successful Cooperation between Nursing Homes and Physicians? - Results of a Mixed-methods Cross-Sectional Study in Bavarian Nursing Homes]. / Was sind die Voraussetzungen für eine erfolgreiche Zusammenarbeit zwischen Pflegeeinrichtung und Ärzten? ­ Ergebnisse einer Mixed Methods Querschnittserhebung in bayerischen Pflegeeinrichtungen.

Aim: This mixed-methods cross-sectional study examined the cooperation between nursing home staff and physicians in Bavarian nursing homes in order to understand which organisational and communication measures are resulting in satisfying teamwork among professional groups in nursing homes. Methods: In 3 interview rounds nursing home staff, general practitioners, medical specialists, dentists, nursing home residents, and relatives in 52 nursing homes were interviewed using a questionnaire that was enhanced after every round. Additionally, focus group interviews have been performed in 2 nursing homes. Results: 443 persons involved in patient care, 50 residents and 47 relatives participated in the structured interviews. 22 persons attended the focus group interviews. 65% of the nursing homes required regular visits of general practitioners and 36% or, respectively, 27% required regular or on demand visits of specialists. 47% of the nursing home staff that was asked about this issue stated that it would make their work easier if only a small number of physicians were in charge of their institution. Measures for improvement of medical care in nursing homes most frequently suggested by interview partners responsible for patient care were: better communication (9%), better remuneration of physicians' nursing home visits (7%, nurses and physicians) and less bureaucracy and regular physicians' visits (5% in each question). Conclusion: Because of the composition of our study sample it cannot be assumed that the results are representative for all Bavarian nursing homes. Confidence in one another, low number of persons in charge, binding agreements and regular physicians' nursing home visits are essential for a successful cooperation between providing physicians and nursing home staff.

[PREDICTING FACTORS OF THE LIFE SPAN IN PATIENTS, SUFFERING METASTATIC COLORECTAL CANCER AND SYNCHRONOUS HEPATIC AFFECTION AFTER SURGICAL TREATMENT].

The results of treatment of 125 patients, suffering metastatic hepatic affection in colorectal cancer (pT1--4N0--2M1--in colonic cancer and pT1--3N0--2M1--in cancer recti), to whom in 2008-2015 yrs a one-staged (Group 1) or two-staged (Group II) surgical treatment was done. In affection of 4 regional lymph nodes and more (pN2) late results were less favorable, than in pN1 or pN0, not depending from surgical approach choosed. In 48 (38.4%) patients with one syndromal hepatic metastatic focus, the indices of general three-year and five-year cumulative survival were the best, than in other groups--82 and 63% (p = 0.001) accordingly; in monolobar affection--68 and 49%, and in bilobar--23 and 0%, not depending from method of surgical treatment (p < 0.001) choosed. Predictive factors were established, which impact negatively the indices of general survival in patients, suffering metastatic hepatic affection in colorectal cancer: hepatic metastatic foci number 4 and more, bilobar hepatic metastatic affection.

Hormone Therapy and its Effect on the Prognosis in Breast Cancer Patients.

Introduction: Use of hormone therapy (HT) has declined dramatically in recent years. Some studies have reported that HT use before a diagnosis of breast cancer (BC) may be a prognostic factor in postmenopausal patients. This study aimed to examine the prognostic relevance of HT use before BC diagnosis. Methods: Four BC cohort studies in Germany were pooled, and 4492 postmenopausal patients with HT use data were identified. Patient data and tumor characteristics were compared between users and nonusers, along with overall survival (OS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Cox proportional hazards models were stratified by study center and adjusted for age at diagnosis, tumor stage, grading, nodal status, and hormone receptors. Results: Women with HT use before the diagnosis of BC were more likely to have a lower tumor stage, to be estrogen receptor-negative, and to have a lower grading. With regard to prognosis there were effects seen for OS, DMFS and LRFS, specifically in the subgroup of women with a positive hormone receptor. In these subgroups, BC patients had a better prognosis with previous HT use. Conclusions: HT use before a diagnosis of BC is associated with a more favorable prognosis in women with a positive hormone receptor status. It may be recommended that the prognostic factor HT should be documented and analyzed as a confounder for prognosis in studies of postmenopausal hormone-responsive breast cancers.

A critical update on endothelial nitric oxide synthase gene variations in women with idiopathic recurrent spontaneous abortion: genetic association study, systematic review and meta-analyses.

A number of case-control studies investigated the association between idiopathic recurrent spontaneous abortion (IRSA) and variations in the gene encoding endothelial nitric oxide synthase (NOS3), but yielded contradictory results. Our aim was to test the association of the NOS3 variable number of tandem repeats (VNTR) in intron 4 and +894 G/T single-nucleotide polymorphism (SNP) with IRSA in Slovenian women (148 IRSA and 149 control women), conduct a systematic review of literature on the association between NOS3 gene variations and IRSA, and perform meta-analyses of studies that met the inclusion criteria, defined by virtue of the European Society for Human Reproduction and Embryology evidence-based guidelines for recurrent spontaneous abortion. Genotyping was performed using PCR and restriction fragment length polymorphism methods. The systematic review of literature (English language) was conducted using PubMed and Scopus databases, to 1 November 2014. We determined no association of IRSA with the VNTR in intron 4 and +894 G/T SNP in Slovenian women. Furthermore, 16 case-control studies were identified on the association between 15 NOS3 gene variations and IRSA. However, significant inconsistencies exist in the selection criteria of patients and controls between studies. The meta-analysis of VNTR in intron 4 was performed on five studies (894 patients, 944 controls), whereas the meta-analysis of +894 G/T SNP included six studies (1111 patients, 1121 controls). The association with IRSA was significant for the +894 G/T SNP under the dominant genetic model (GT+TT versus GG) based on fixed (odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.28-1.86, P = <0.01) and random effects models (OR = 1.54, 95% CI = 1.03-2.31, P = 0.03). In conclusion, the GT and TT genotypes of the +894 G/T SNP in women might contribute to a predisposition to IRSA. Additional genetic association and functional studies in different populations with larger numbers of participants and a uniformly defined IRSA are needed to clarify the contribution of NOS3 +894 G/T gene variation to IRSA.

[The influence of fibroblast growth factor (FGF2) on cardiomyocytes differentiation of mesenchymal stem cells of bone marrow ex vivo].

The influence of FGF2 on the efficiency of cardiomyocytes differentiation of mesenchymal stem cells (MSC) of bone marrow induced by 5-azacetidine (5-aza) was studied. The effect of FGF2 developing by the 14th day after the combined action of a differentiating agent and growth factor was manifested in an increase in Mef2A, Mef2D and gene transcription and a rise of ionized Ca2+ concentration in cytoplasm keeping cell viability and proliferation activity. In the presence of FGF2 this approach provided cardiomyogenesis and the increase in the formation of early precursors of cardiomyocytes.

[Challenges for medical staff and local authorities in an aging population in a German rural area]. / Medizinische und kommunale Herausforderungen einer alternden Gesellschaft im ländlichen Bereich.

OBJECTIVE: The aim of this survey is the assessment of health and social situation of elderly persons in rural regions as well as their requests and needs concerning accommodation and medical care in the old age. METHODS: In a cross-sectional survey, inhabitants of the rural commune Markt Heiligenstadt, Upper Franconia, aged over 50 years were interviewed. Sixty-eight questions were asked regarding wishes and needs concerning accommodation and living in the old age. RESULTS: 513 (39%) inhabitants participated. Their mean age was 66 years (± 11 years) and 53% were female. 49% are suffering from hypertension and 17% from diabetes mellitus. Reduced autonomy in everyday life is predominantly caused by diseases of the musculoskeletal system. 40% of the respondents aged over 70 years reported hearing and visual impairments. Most of the participants are living in their privately owned home (81%) despite their comparatively low income and express their wish to live and be cared for in their own home in old age (90%). 75% of the respondents are married or living in a partnership. 90% have children and in 55% the children are living in the same house or in the commune. There are 2 local family doctors' practices, but no specialists' practices and no hospitals in the commune. Almost all the respondents (98%) have a regular family doctor. 17% of the participants would relocate if there was no family doctor nearby, 6% if there was no specialist and 4% if there was no hospital nearby. CONCLUSION: Health problems and functional limitations among the inhabitants of Markt Heiligenstadt are similar to those reported in German nationwide surveys. Medical care is strongly depending on general practitioners. The strong social networks of the participants and the predominant presence of residential property are important resources needed to accomplish the preference for home care in old age. This implies increasing challenges for the primary care providers. In future, the general practitioner will be a central coordinator of medical care and professional nursing together with the care by family members.

Sentinel lymph node detection in patients with vulvar carcinoma; Feasibility of intra-operative mapping with technetium-99m-labeled nanocolloid.

AIMS: Sentinel lymph node (SLN) mapping appears to be feasible in patients with primary vulvar cancer. Previous protocols describe the injection of the technetium-99m-nanocolloid at least 3 h before surgery which involves two invasive procedures for the patient. In this study, we assessed the feasibility, safety, and accuracy of an intra-operative rather than preoperative SLN mapping in patients with primary vulvar cancer. METHODS: Patients with histologically confirmed squamous cell vulvar cancer and clinically FIGO stage Ib disease underwent intra-operative SLN mapping by intradermal injection of the nanocolloid around the tumor. SLN were identified and removed before a complete inguinofemoral lymphnode dissection was performed. Surgical and pathologic data on all patients were prospectively entered into a database. RESULTS: An SLN procedure was performed in 16 patients; 3 patients received unilateral lymphadenectomy, and 13 women underwent surgery on both groins. In all groins but 4 at least one SLN was clearly identified (detection rate 25/29, 86%). A median number of 2 SLN and 4 non-SLN per groin were removed. 3 of 16 patients (19%) had metastatic disease in the lymph nodes. There was no false negative SLN result. CONCLUSION: Intra-operative SLN detection seems feasible in patients with early stage vulvar cancer. More patients need to be enrolled in this ongoing study before this more convenient technique can be considered safe.

Variation in organ quality between liver transplant centers.

A wide spectrum of quality exists among deceased donor organs available for liver transplantation. It is unknown whether some transplant centers systematically use more low quality organs, and what factors might influence these decisions. We used hierarchical regression to measure variation in donor risk index (DRI) in the United States by region, organ procurement organization (OPO) and transplant center. The sample included all adults who underwent deceased donor liver transplantation between January 12, 2005 and February 1, 2009 (n = 23,810). Despite adjusting for the geographic region and OPO, transplant centers' mean DRI ranged from 1.27 to 1.74, and could not be explained by differences in patient populations such as disease severity. Larger volume centers and those having competing centers within their OPO were more likely to use higher risk organs, particularly among recipients with lower model for end-stage liver disease (MELD) scores. Centers using higher risk organs had equivalent waiting list mortality rates, but tended to have higher post-transplant mortality (hazard ratio 1.10 per 0.1 increase in mean DRI). In conclusion, the quality of deceased donor organ patients receive is variable and depends in part on the characteristics of the transplant center they visit.

Evaluation of FDG-PET for detecting lymph node metastasis in uterine corpus cancer.

BACKGROUND: In order to decrease surgery-related morbidity, we evaluated the reliability of the evaluation of lymph node metastasis in patients with uterine corpus cancer by positron-emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) before surgical staging. MATERIALS AND METHODS: Patients with newly diagnosed uterine corpus cancer scheduled for surgical staging, including lymphadenectomy, underwent PET imaging within 30 days before surgery. PET results and postoperative histopathology were compared for each patient and each nodal site. Sensitivity, specificity, positive and negative predictive value (PPV/NPV) as well as accuracy of FDG-PET in predicting nodal disease was determined by joined meta-analysis of the present data and the data available in the literature. RESULTS: Of 21 patients examined, 13 patients were eligible to enter this pilot study. Only one patient had lymph node metastasis, which was preoperatively detected by FDG-PET scan. Additionally, another patient was considered to have lymph node metastasis according to increased focal FDG uptake; however, all lymph nodes were free of malignant disease upon final pathology. In contrast, all other patients without lymph node metastasis upon final pathology showed negative preoperative FDG-PET scans. The meta-analysis yielded a sensitivity, specificity, PPV, NPV and accuracy of 0.53, 0.91, 0.57, 0.90 and 0.84, respectively. CONCLUSION: In patients with uterine corpus cancer, FDG-PET had an insufficient positive predictive value in detecting lymph node metastases, indicating that this method cannot replace surgical staging. However, due to its high NPV, FDG-PET might be beneficial in selected patients who are poor candidates for surgical staging.

Estimation of the harm to the waiting list as a crucial factor in the selection of patients with hepatocellular carcinoma for liver transplantation.

BACKGROUND: Long-term survival rates after orthotopic liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) of any size and number may now be predicted using the Metroticket calculator. The aim of this study was to evaluate the minimum post-OLT survival threshold that would justify the selection of a patient with HCC for OLT. METHODS: We used a Markov model, recently developed at the University of Michigan, which assumes that a patient with HCC should undergo OLT if his or her transplant benefit is greater than the cumulative harm to the rest of the waiting list (WL). In the base case, we considered a patient with a low survival perspective without OLT (5-year survival rate, 10%). The data sources to construct and validate the model were as follows: the Organ Procurement and Transplantation Network report, and our prospective database. RESULTS: Our center was generally characterized by lower WL mortalities, although there were lower transplant probabilities for both HCC and non-HCC patients than the average US center. The proportion of HCC patients on the WL was higher in Padua (25%) than in the United States (10%). The calculated harm to the WL was 434 quality-adjusted days of life in Padua, and 957 in the United States (P < .01). The OLT benefit outweighed the harm to the WL when the 5-year post-OLT survival rate was higher than 30% in Padua, and 61% in the United States. CONCLUSIONS: In a decision model including the concepts of transplantation benefit and harm to the WL, the minimum 5-year post-OLT survival threshold justifying the selection of a patient with HCC for OLT in Padua was 30%.

Foreigners traveling to the U.S. for transplantation may adversely affect organ donation: a national survey.

The aims of this study were (1) to determine attitudes among the American public regarding foreigners coming to the United States for the purposes of transplantation, and (2) to investigate the impact this practice might have on the public's willingness to donate organs. A probability-based national sample of adults age > or =18 was asked whether people should be allowed to travel to the United States to receive a transplant, and whether this practice would discourage the respondents from becoming an organ donor. Among 1049 participants, 30% (95% CI 25-34%) felt that people should not be allowed to travel to the United States to receive a deceased donor transplant, whereas 28% felt this would be acceptable in some cases. Thirty-eight percent (95% CI 33-42%) indicated that this practice might prevent them from becoming an organ donor. In conclusion, deceased-donor transplantation of foreigners is opposed by many Americans. Media coverage of this practice has the potential to adversely affect organ donation.