Integrating Palliative Care Into the Management of Genitourinary Malignancies.

Palliative care (PC) plays a critical role in managing the difficulties associated with genitourinary malignancies. Its primary aim is to improve the overall health of patients, provide support to both patients and their caregivers, and help individuals to navigate the complex decisions about treatment and end-of-life care. PC takes a holistic approach to patient care, recognizing that genitourinary malignancies affect multiple aspects of a person's life. By addressing physical, emotional, social, and spiritual needs, PC aims to provide comprehensive support that is consistent with the patient's values and preferences. The goal is to optimize comfort, minimize distress, and enhance the patient's quality of life throughout the course of the illness. PC is not a one-off intervention, but an ongoing source of support. This article aims to provide a thorough overview of the critical elements involved in addressing the challenges posed by genitourinary cancers, emphasizing the importance of palliative interventions. We will highlight the multifaceted aspects of care and explore strategies to optimize the overall well-being of patients throughout the course of treatment for genitourinary malignancies.

Patients' and professionals' perspectives on the consideration of patients' convenient therapy periods as part of personalised rehabilitation: a focus group study with patients and therapists from inpatient neurological rehabilitation.

BACKGROUND: Research on the optimal period for administering health services, especially rehabilitation interventions, is scarce. The aims of this study were to explore the construct of patients' convenient therapy periods and to identify indicators based on the perspectives of patients and different health professionals from inpatient neurological rehabilitation clinics. METHODS: This study was part of a larger project on patients' convenient therapy periods following a mixed methods approach. In the current study a grounded theory approach was employed based on the use of focus group interviews. Focus group interviews were conducted in three different inpatient neurological rehabilitation clinics. Patients and therapists from inpatient neurological rehabilitation clinics who were able to speak and to participate in conversations were included. RESULTS: A total of 41 persons, including 23 patients and 18 therapists, such as music and occupational therapists, participated in a total of six focus group interviews. The analysis of the focus group interviews resulted in the identification of a total of 1261 codes, which could be summarised in fifteen categories. However, these categories could be divided into five indicators and ten impact factors of convenient therapy periods. Identified indicators were verbal and non-verbal communication, mental functions, physiological needs, recreational needs, and therapy initiation. CONCLUSIONS: The results provide initial evidence that convenient therapy periods are clinically relevant for patients and therapists. Different states of patients' ability to effectively participate in a rehabilitation intervention exist. A systematic consideration of patients' convenient therapy periods could contribute to a personalised and more efficient delivery of intervention in neurological rehabilitation. To our knowledge, this study is one of the first attempts to research convenient therapy periods.

Assessment of Temporal Bone Thickness for Implantation of a New Active Bone-Conduction Transducer.

OBJECTIVE: To investigate the minimum bone thickness in adults and children in the area of the skull affected by implantation of a new bone conduction device in patients without known medical history that indicates anatomical malformations. STUDY DESIGN: Retrospective, non-interventional study on computer tomography (CT) scans on file at a university medical center. STUDY METHODS: A digital model of the new bone conduction implant was virtually implanted in 3D reconstructions of temporal bones based on 197 CT scans, 132 from adults and 65 from children (evenly distributed in five different age groups). The bone thickness was measured in a total of 11 designated positions; five measurement points for the transducer (recess area), and six for the fixation screws, corresponding to three different positions for the fixation band holding the implant in place (screw area). RESULTS: The minimum bone thickness in the combined recess and screw area for adults was 5.55 ±â€Š1.46 mm, with a 95% CI of 5.30 to 5.80 mm. For children, the thickness was 4.34 ±â€Š2.29 mm (95% CI: 3.77-4.91 mm), increasing from 1.92 mm (0-4 yr) to 6.41 mm (12-14 yr). For all ages, the bone in the recess area was generally thicker compared with the screw area.With an implantation depth of 3 mm the transducer fitted in all of the adult temporal bones (100%) and 99.2% (131/132) of the adults had a bone thickness of at least 2.7 mm in all six measured screw positions. In all children from the age of 5 the transducer fitted at an implantation depth of 3 mm, and in all children from the age of 9, the fixation screws fitted at a depth of 2.7 mm. In all CT scans except for a 6-month-old child the new bone conduction device could be implanted in at least one of the fixation band positions analyzed. CONCLUSIONS: In adults and many children without known medical history that indicates anatomical malformations, the average minimum bone thickness was thicker than both the maximum transducer depth of 3 mm and the 2.7 mm bone involvement of the osseointegrating fixation screws. The results indicate implant fit of the new bone conduction implant in all adult patients. The risks of compromising the sigmoid sinus and the dura as considered with larger implants are thus significantly reduced. Preoperative planning with CT would still be recommended for children below 9 years old.

Impact on place of death in cancer patients: a causal exploration in southern Switzerland.

BACKGROUND: Most terminally ill cancer patients prefer to die at home, but a majority die in institutional settings. Research questions about this discrepancy have not been fully answered. This study applies artificial intelligence and machine learning techniques to explore the complex network of factors and the cause-effect relationships affecting the place of death, with the ultimate aim of developing policies favouring home-based end-of-life care. METHODS: A data mining algorithm and a causal probabilistic model for data analysis were developed with information derived from expert knowledge that was merged with data from 116 deceased cancer patients in southern Switzerland. This data set was obtained via a retrospective clinical chart review. RESULTS: Dependencies of disease and treatment-related decisions demonstrate an influence on the place of death of 13%. Anticancer treatment in advanced disease prevents or delays communication about the end of life between oncologists, patients and families. Unknown preferences for the place of death represent a great barrier to a home death. A further barrier is the limited availability of family caregivers for terminal home care. The family's preference for the last place of care has a high impact on the place of death of 51%, while the influence of the patient's preference is low, at 14%. Approximately one-third of family systems can be empowered by health care professionals to provide home care through open end-of-life communication and good symptom management. Such intervention has an influence on the place of death of 17%. If families express a convincing preference for home care, the involvement of a specialist palliative home care service can increase the probability of home deaths by 24%. CONCLUSION: Concerning death at home, open communication about death and dying is essential. Furthermore, for the patient preference for home care to be respected, the family's decision for the last place of care seems to be key. The early initiation of family-centred palliative care and the provision of specialist palliative home care for patients who wish to die at home are suggested.

Changes in Bone Conduction Implant Geometry Improve the Bone Fit in Mastoids of Children and Young Adults.

OBJECTIVES: In 2012 the first active bone conduction implant was introduced, but did not fit into the mastoids of some adults and many children. Thus, a geometry change of the transducer was proposed (BCI 602). In this study, we aimed to determine whether these changes improved the mastoid cavity fit of the implant in children and young adults. DESIGN: We retrospectively analyzed computed tomography scans of 151 mastoids from 81 children and adolescents (age range, 5 mo to 20 yr) and 52 control mastoids from 33 adults. After three-dimensional reconstruction of the temporal bone from computed tomography, we virtually implanted the BCI 602 into the mastoids, and compared the bone fit with that of the BCI 601. RESULTS: The BCI 602 could be virtually implanted in 100% of patients ≥12 years old, while the BCI 601 transducer could be completely embedded in the bone of only 70% of these mastoids. Moreover, virtual implantation of the BCI 602 was possible in 75% of children 3 to 5 years of age, while the BCI 601 did not fit in the mastoids of any patients under 5 years old without the use of lifts. CONCLUSIONS: Compared to the BCI 601, placement of the BCI 602 allegedly requires less bone removal. The newer BCI 602 transducer is more likely than its predecessor to be completely accommodated in the mastoid bone among all age groups and indications. Preoperative planning is still recommended to avoid exposure of delicate structures.

Transcriptional Regulation of Cysteine and Methionine Metabolism in Lactobacillus paracasei FAM18149.

Lactobacillus paracasei is common in the non-starter lactic acid bacteria (LAB) community of raw milk cheeses. This species can significantly contribute to flavor formation through amino acid metabolism. In this study, the DNA and RNA of L. paracasei FAM18149 were sequenced using next-generation sequencing technologies to reconstruct the metabolism of the sulfur-containing amino acids cysteine and methionine. Twenty-three genes were found to be involved in cysteine biosynthesis, the conversion of cysteine to methionine and vice versa, the S-adenosylmethionine recycling pathway, and the transport of sulfur-containing amino acids. Additionally, six methionine-specific T-boxes and one cysteine-specific T-box were found. Five of these were located upstream of genes encoding transporter functions. RNA-seq analysis and reverse-transcription quantitative polymerase reaction assays showed that expression of genes located downstream of these T-boxes was affected by the absence of either cysteine or methionine. Remarkably, the cysK2-ctl1-cysE2 operon, which is associated with te methionine-to-cysteine conversion and is upregulated in the absence of cysteine, showed high read coverage in the 5'-untranslated region and an antisense-RNA in the 3'-untranslated region. This indicates that this operon is regulated by the combination of cis- and antisense-mediated regulation mechanisms. The results of this study may help in the selection of L. paracasei strains to control sulfuric flavor formation in cheese.

Comparative Genomics of Completely Sequenced Lactobacillus helveticus Genomes Provides Insights into Strain-Specific Genes and Resolves Metagenomics Data Down to the Strain Level.

Although complete genome sequences hold particular value for an accurate description of core genomes, the identification of strain-specific genes, and as the optimal basis for functional genomics studies, they are still largely underrepresented in public repositories. Based on an assessment of the genome assembly complexity for all lactobacilli, we used Pacific Biosciences' long read technology to sequence and de novo assemble the genomes of three Lactobacillus helveticus starter strains, raising the number of completely sequenced strains to 12. The first comparative genomics study for L. helveticus-to our knowledge-identified a core genome of 988 genes and sets of unique, strain-specific genes ranging from about 30 to more than 200 genes. Importantly, the comparison of MiSeq- and PacBio-based assemblies uncovered that not only accessory but also core genes can be missed in incomplete genome assemblies based on short reads. Analysis of the three genomes revealed that a large number of pseudogenes were enriched for functional Gene Ontology categories such as amino acid transmembrane transport and carbohydrate metabolism, which is in line with a reductive genome evolution in the rich natural habitat of L. helveticus. Notably, the functional Clusters of Orthologous Groups of proteins categories "cell wall/membrane biogenesis" and "defense mechanisms" were found to be enriched among the strain-specific genes. A genome mining effort uncovered examples where an experimentally observed phenotype could be linked to the underlying genotype, such as for cell envelope proteinase PrtH3 of strain FAM8627. Another possible link identified for peptidoglycan hydrolases will require further experiments. Of note, strain FAM22155 did not harbor a CRISPR/Cas system; its loss was also observed in other L. helveticus strains and lactobacillus species, thus questioning the value of the CRISPR/Cas system for diagnostic purposes. Importantly, the complete genome sequences proved to be very useful for the analysis of natural whey starter cultures with metagenomics, as a larger percentage of the sequenced reads of these complex mixtures could be unambiguously assigned down to the strain level.

Comparative genomics to explore phylogenetic relationship, cryptic sexual potential and host specificity of Rhynchosporium species on grasses.

BACKGROUND: The Rhynchosporium species complex consists of hemibiotrophic fungal pathogens specialized to different sweet grass species including the cereal crops barley and rye. A sexual stage has not been described, but several lines of evidence suggest the occurrence of sexual reproduction. Therefore, a comparative genomics approach was carried out to disclose the evolutionary relationship of the species and to identify genes demonstrating the potential for a sexual cycle. Furthermore, due to the evolutionary very young age of the five species currently known, this genus appears to be well-suited to address the question at the molecular level of how pathogenic fungi adapt to their hosts. RESULTS: The genomes of the different Rhynchosporium species were sequenced, assembled and annotated using ab initio gene predictors trained on several fungal genomes as well as on Rhynchosporium expressed sequence tags. Structures of the rDNA regions and genome-wide single nucleotide polymorphisms provided a hypothesis for intra-genus evolution. Homology screening detected core meiotic genes along with most genes crucial for sexual recombination in ascomycete fungi. In addition, a large number of cell wall-degrading enzymes that is characteristic for hemibiotrophic and necrotrophic fungi infecting monocotyledonous hosts were found. Furthermore, the Rhynchosporium genomes carry a repertoire of genes coding for polyketide synthases and non-ribosomal peptide synthetases. Several of these genes are missing from the genome of the closest sequenced relative, the poplar pathogen Marssonina brunnea, and are possibly involved in adaptation to the grass hosts. Most importantly, six species-specific genes coding for protein effectors were identified in R. commune. Their deletion yielded mutants that grew more vigorously in planta than the wild type. CONCLUSION: Both cryptic sexuality and secondary metabolites may have contributed to host adaptation. Most importantly, however, the growth-retarding activity of the species-specific effectors suggests that host adaptation of R. commune aims at extending the biotrophic stage at the expense of the necrotrophic stage of pathogenesis. Like other apoplastic fungi Rhynchosporium colonizes the intercellular matrix of host leaves relatively slowly without causing symptoms, reminiscent of the development of endophytic fungi. Rhynchosporium may therefore become an object for studying the mutualism-parasitism transition.

PFP1, a gene encoding an Epc-N domain-containing protein, is essential for pathogenicity of the barley pathogen Rhynchosporium commune.

Scald caused by Rhynchosporium commune is an important foliar disease of barley. Insertion mutagenesis of R. commune generated a nonpathogenic fungal mutant which carries the inserted plasmid in the upstream region of a gene named PFP1. The characteristic feature of the gene product is an Epc-N domain. This motif is also found in homologous proteins shown to be components of histone acetyltransferase (HAT) complexes of fungi and animals. Therefore, PFP1 is suggested to be the subunit of a HAT complex in R. commune with an essential role in the epigenetic control of fungal pathogenicity. Targeted PFP1 disruption also yielded nonpathogenic mutants which showed wild-type-like growth ex planta, except for the occurrence of hyphal swellings. Complementation of the deletion mutants with the wild-type gene reestablished pathogenicity and suppressed the hyphal swellings. However, despite wild-type-level PFP1 expression, the complementation mutants did not reach wild-type-level virulence. This indicates that the function of the protein complex and, thus, fungal virulence are influenced by a position-affected long-range control of PFP1 expression.

Aripiprazole for the treatment of Tourette syndrome: a case series of 100 patients.

OBJECTIVE: Aripiprazole is an atypical neuroleptic with agonistic and antagonistic dopaminergic and serotonergic effects. Because preliminary data obtained from uncontrolled studies suggest that aripiprazole may be effective in the treatment of tics, we performed a retrospective study with a large group of patients with Tourette syndrome. METHODS: One hundred patients (78 men and 22 women; mean ± SD age, 27.1 years (± 11.5) years) who had been treated with daily doses of 5 to 45 mg (mean, 17.0 ± 9.6 mg) aripiprazole at our specialized Tourette syndrome outpatient clinic were included. Ninety-five patients with insufficient pretreatment (one or more neuroleptics) were switched to aripiprazole. RESULTS: Eighty-two patients exhibited a considerable reduction in tic severity. In 48 patients, effective treatment lasted for more than 12 months. Five patients reported additional beneficial effects on behavioral comorbidities such as depression, anxiety, and autoaggression. Altogether, 31 patients (31%) dropped out of the treatment owing to inefficacy (n = 7), adverse effects (n = 15: drowsiness, agitation, weight gain, and sleep disturbances), both (n = 4) or other reasons (n = 5). CONCLUSION: This is the largest case series on the treatment of tics with aripiprazole so far. Overall, our results corroborate previous data suggesting that aripiprazole is effective and safe in most patients. In particular, our data confirm effectiveness in adult patients and clarify that beneficial effects sustain. However, in contrast to previous data, in 1 of 3 of our highly selected patients, aripiprazole was ineffective or not well tolerated. Optimal dose seems to be individually different and may range from 5 to 45 mg.

Oligoclonal bands in cerebrospinal fluid in patients with Tourette's syndrome.

Since a postinfectious or autoimmune etiology is suggested to be involved in the pathogenesis of Tourette's syndrome (TS), we investigated oligoclonal bands (OB) of immunoglobulin G (IgG) in cerebrospinal fluid (CSF), indicating a humoral immune response in the central nervous system. CSF examinations including isoelectric focusing to analyze the presence of OB were performed in 21 TS patients [17 men/4 women, mean age = 29 ± 12 (SD) years]. Isoelectric focusing showed the presence of positive OB in 6, borderline bands in 2, and serum and CSF bands ("mirrored pattern") in another 2 patients. Clinical data did not correlate with CSF findings. Thus, 38% (8 of 21) of our patients exhibited pathological CSF bands. Since none of them suffered from another disease known to be associated with OB, our results suggest an association with the pathogenesis of TS itself and point to an involvement of immunological mechanisms in TS pathology.

Reirradiation of recurrent breast cancer with and without concurrent chemotherapy.

BACKGROUND: Treatment options for loco-regional recurrent breast cancer after previous irradiation are limited. The efficacy of chemotherapy might be hampered because of impaired tissue perfusion in preirradiated tissue. Thus, mastectomy or local excision and reconstructive surgery are the preferred treatments. However, in recent years evidence accumulates that a second breast conserving approach with reirradiation as part of the treatment might be feasible and safe and, furthermore, reirradiation might be an option for palliation. Here we report on the experience of a single community centre in reirradiation of recurrent breast cancer. METHODS: The report is based on 29 patients treated with reirradiation. All data were prospectively collected. The median age was 63 years (range 35 to 82 yrs). The interval between initial diagnosis and diagnosis before start of reirradiation was 11.6 months to 295.5 months. The mean total dose (initial dose and reirradiation dose) was 106.2 Gy (range 80.4 to 126 Gy) and the mean BED3 Gy 168,5 Gy (range 130,6 to 201,6). The mean interval between initial radiotherapy and reirradiation was 92.9 months (range 8.7 to 290.1). Inoperable or incompletely resected patients were offered concurrent chemotherapy with either 5-FU or capecitabine. All patients received 3D-conformal radiotherapy with 1.6 to 2.5 Gy/fraction five times weekly. The treatment volume comprised all visible lesions or lesions detectable on CT/MRI/FDG-PET/CT or the tumour bed or recurrent tumour. RESULTS: The local progression-free survival of all patients at one and two years was 81% and 63%. Patients who had no surgery of the recurrence (16/29) had local progression-free survival at one and two years of 72% and 25% with a median progression-free survival time of 17 months. Partial remission and good symptom relief was achieved in 56% (9/16) or complete response of symptoms and/or tumour in 44% (7/16). Patients who had no distant metastases and had at least an R1-resection had a local progression-free survival of 90% after 2 years. The disease-free survival after 2 years was 43% and the median disease-free survival time was 24 months. In four patients a second breast conserving operation was performed and the cosmetic results in all four patients are good to excellent. Acute side effects were mild to moderate with no grade 3 or 4 toxicity. Accordingly, no grade 3 or 4 late effects were observed so far. No grade 3 or 4 plexopathy was observed. CONCLUSION: In this heterogeneous group of patients reirradiation of locoregional recurrences of breast cancer showed low to moderate acute toxicity. In our experience, local control rates are high and palliation is good.