Investigating mortality and morbidity associated with UrINary incontinence during Older Womens Secondary Care Admissions and exploring nurses experiences of delivering related care (U-INconti): a mixed methods research protocol.

INTRODUCTION: Urinary incontinence (UI) is associated with increasing age and is more frequently experienced by women. Despite 40% prevalence in the community, little is known about the prevalence/incidence of UI in older women during hospital admission. UI during hospital admissions, within this group, has also been under-researched in terms of its relationship to specific clinical conditions and mortality rates. Given that UI has serious implications for both patient care and women's general health and well-being on discharge, this protocol describes a planned research project which aims to determine mortality, morbidity, prevalence and incidence of UI in older women (≥55 years) during hospital admission to inform nursing practice. Additionally, it aims to explore the experience of nurses who deliver women's care. METHODS AND ANALYSIS: This is an explanatory mixed-methods study consisting of two phases: (1) retrospecitive analysis of electronic patient care records (EPCR) to determine prevalence/incidence of UI, clinical conditions most likely associated with UI and any associations between UI and death, (2) nurse interviews to explore views, knowledge and perceptions of performing the nursing assessment and providing care for older women (≥55 years) with UI during admission. EPCR will be gained from a National Health Service (NHS) teaching hospital. Nurse interviews will be conducted with nurses from an alternative but similar-sized NHS hospital. ETHICS AND DISSEMINATION: Ethical approval is provided by the University of Salford Ethics Committee and regulatory approval by the NHS Health Research Authority (Integrated Research Application System project ID: 303118). Local NHS trust approval to access electronic care records for the purposes of analysis of anonymised data has been provided by one of the two collaborating NHS hospitals. Findings will be disseminated through open-access geriatric or urogynaecology journals and presented to relevant stakeholders at local, national and international meetings including scientific meetings such as the UK Continence Society and International Continence Society.

Urinary incontinence in women 55 years and older: A scoping review to understand prevalence, incidence, and mortality of urinary incontinence during secondary care admission.

BACKGROUND: Up to 40% of older women living in the community experience urinary incontinence. In community settings, urinary incontinence impacts the quality of life, morbidity, and mortality rates. However, little is known about urinary incontinence and its impact on older women admitted to hospitals. OBJECTIVES: This scoping review aims to establish the current knowledge of urinary incontinence during hospital admission for women (⩾ 55 years of age) with three key objectives: (a) What is the prevalence/incidence of urinary incontinence? (b) What health conditions are associated with urinary incontinence? (c) Is there an association between urinary incontinence and mortality? ELIGIBILITY CRITERIA: Empirical studies were included in assessing the incidence/prevalence of urinary incontinence during hospital admissions and its related morbidities and mortality rates. Studies which only included men or younger women (< 55 years of age) were excluded. Only articles written in English and conducted between 2015 and 2021 were included. SOURCES OF EVIDENCE: A search strategy was developed, and CINAHL, MEDLINE, and Cochrane databases were searched. CHARTING METHODS: Data from each article meeting the criteria were pulled into a table, including study design, study population, and setting, aims, methods, outcome measures, and significant findings. A second researcher then reviewed the populated data extraction table. RESULTS: Overall, 383 papers were found: 7 met inclusion/exclusion criteria. Prevalence rates ranged from 22% to 80% depending on the study cohort. Several conditions were associated with urinary incontinence, including frailty, orthopaedics, stroke, palliative care, neurology, and cardiology. There was a potential positive association between mortality and urinary incontinence, although only two papers reviewed reported mortality. CONCLUSION: A dearth of literature determined the prevalence, incidence, and mortality rates for older women admitted to hospitals. Limited consensus on associated conditions was found. Further research is needed to fully explore urinary incontinence in older women during hospital admissions, particularly concerning prevalence/incidence and its association with mortality.

Spatial and molecular profiling of the mononuclear phagocyte network in classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSCs) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNPs) in the vicinity of HRSCs express similar regulatory mechanisms in parallel, and their presence in tissue is associated with inferior patient outcomes. MNPs in cHL have hitherto been identified by a small number of canonical markers and are usually described as tumor-associated macrophages. The organization of MNP networks and interactions with HRSCs remains unexplored at high resolution. Here, we defined the global immune-cell composition of cHL and nonlymphoma lymph nodes, integrating data across single-cell RNA sequencing, spatial transcriptomics, and multiplexed immunofluorescence. We observed that MNPs comprise multiple subsets of monocytes, macrophages, and dendritic cells (DCs). Classical monocytes, macrophages and conventional DC2s were enriched in the vicinity of HRSCs, but plasmacytoid DCs and activated DCs were excluded. Unexpectedly, cDCs and monocytes expressed immunoregulatory checkpoints PD-L1, TIM-3, and the tryptophan-catabolizing protein IDO, at the same level as macrophages. Expression of these molecules increased with age. We also found that classical monocytes are important signaling hubs, potentially controlling the retention of cDC2 and ThExh via CCR1-, CCR4-, CCR5-, and CXCR3-dependent signaling. Enrichment of the cDC2-monocyte-macrophage network in diagnostic biopsies is associated with early treatment failure. These results reveal unanticipated complexity and spatial polarization within the MNP compartment, further demonstrating their potential roles in immune evasion by cHL.

The use of temozolomide in paediatric metastatic phaeochromocytoma/paraganglioma: A case report and literature review.

There is increasing evidence to support the use of temozolomide therapy for the treatment of metastatic phaeochromocytoma/paraganglioma (PPGL) in adults, particularly in patients with SDHx mutations. In children however, very little data is available. In this report, we present the case of a 12-year-old female with a SDHB-related metastatic paraganglioma treated with surgery followed by temozolomide therapy. The patient presented with symptoms of palpitations, sweating, flushing and hypertension and was diagnosed with a paraganglioma. The primary mass was surgically resected six weeks later after appropriate alpha- and beta-blockade. During the surgery extensive nodal disease was identified that had been masked by the larger paraganglioma. Histological review confirmed a diagnosis of a metastatic SDHB-deficient paraganglioma with nodal involvement. Post-operatively, these nodal lesions demonstrated tracer uptake on 18F-FDG PET-CT. Due to poor tumour tracer uptake on 68Ga-DOTATATE and 123I-MIBG functional imaging studies radionuclide therapy was not undertaken as a potential therapeutic option for this patient. Due to the low tumour burden and lack of clinical symptoms, the multi-disciplinary team opted for close surveillance for the first year, during which time the patient continued to thrive and progress through puberty. 13 months after surgery, evidence of radiological and biochemical progression prompted the decision to start systemic monotherapy using temozolomide. The patient has now completed ten cycles of therapy with limited adverse effects and has benefited from a partial radiological and biochemical response.

Epidermal choristoma: a case series and review of the literature.

Epidermal choristoma is a rare, congenital lesion in which islands of ectopic skin are found within the oral cavity. They present as pigmented macules or papules on the tongue. Histologic appearances are characteristic and benign. We present three cases review the current literature and recommend observation of the lesion rather than complete excision should be considered as a reasonable management option.

Single cell derived mRNA signals across human kidney tumors.

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.

Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours.

Malignant rhabdoid tumour (MRT) is an often lethal childhood cancer that, like many paediatric tumours, is thought to arise from aberrant fetal development. The embryonic root and differentiation pathways underpinning MRT are not firmly established. Here, we study the origin of MRT by combining phylogenetic analyses and single-cell mRNA studies in patient-derived organoids. Comparison of somatic mutations shared between cancer and surrounding normal tissues places MRT in a lineage with neural crest-derived Schwann cells. Single-cell mRNA readouts of MRT differentiation, which we examine by reverting the genetic driver mutation underpinning MRT, SMARCB1 loss, suggest that cells are blocked en route to differentiating into mesenchyme. Quantitative transcriptional predictions indicate that combined HDAC and mTOR inhibition mimic MRT differentiation, which we confirm experimentally. Our study defines the developmental block of MRT and reveals potential differentiation therapies.

SRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular Tumors.

Pericytic tumors encompass several entities sharing morphologic and immunohistochemical features. A subset of perivascular myoid tumors associated with the SRF-RELA fusion gene was previously described. Herein, we report a series of 13 tumors belonging to this group, in which we have identified new fusion genes by RNA-sequencing, thus expanding the molecular spectrum of this entity. All patients except 1 were children and infants. The tumors, frequently located in the head (n=8), had a mean size of 38 mm (range 10 to 150 mm) and were mostly (n=9) well-circumscribed. Exploration of the follow-up data (ranging from 3 to 68 mo) confirmed the benign behavior of these tumors. These neoplasms presented a spectrum of morphologies, ranging from perivascular patterns to myoid appearance. Tumor cells presented mitotic figures but without marked atypia. Some of these tumors could mimic sarcoma. The immunohistochemical profiles confirmed a pericytic differentiation with the expression of the smooth muscle actin and the h-caldesmon, as well as the frequent positivity for pan-cytokeratin. The molecular analysis identified the expected SRF-RELA fusion gene, in addition to other genetic alterations, all involving SRF fused to CITED1, CITED2, NFKBIE, or NCOA2. The detection of SRF-NCOA2 fusions in spindle cell rhabdomyosarcoma of the infant has previously been described, representing a risk of misdiagnosis, although the cases reported herein did not express MyoD1. Finally, clustering analyses confirmed that this group of SRF-fused perivascular myoid tumors forms a distinct entity, different from other perivascular tumors, spindle cell rhabdomyosarcomas of the infant, and smooth muscle tumors.

Embryonal precursors of Wilms tumor.

Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the H19 locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.

Conservative or radical surgery for pediatric papillary thyroid carcinoma: A systematic review of the literature.

BACKGROUND: Pediatric papillary thyroid carcinoma (PTC) is characterized by an aggressive clinical course. Early diagnosis is a challenge and treatment consists principally of partial or total thyroidectomy±neck dissection and radioactive iodine therapy. Due to the rarity of PTC in children, there is no consensus on optimal surgical treatment. METHODS AND RESULTS: A literature search was carried out using PubMed, Embase, Medline, Cochrane and Web of Science. Seven studies (489 patients) investigating the outcome of surgically managed pediatric PTC were identified. No clear advantage in survival or recurrence rate was found for total thyroidectomy compared to other surgical approaches. CONCLUSION: Despite the aggressive behavior of PTC, prognosis is good, with low mortality. After removal of disease and prevention of recurrence, reduction of iatrogenic complications are a priority in this age group. Due to the paucity of available evidence, this review cannot recommend conservative or radical surgery for pediatric papillary thyroid carcinoma. To answer this question, we recommend the establishment of a randomized controlled trial with adequately matched baseline variables.

Relationship between placental morphology and histological findings in an unselected population near term.

Whilst individual histological features are well described, there are no universally agreed criteria as to what constitutes a clinically significant histological lesion of the placenta in an uncomplicated pregnancy, nor has the presence of such histological findings been systematically related to quantitative morphological characteristics of the placenta (such as placental shape, cord insertion and cord coiling). This study aims to explore this relationship and further to describe the incidence of predefined categories of histological lesions of the placenta in an unselected obstetric population recruited prior to delivery. The study is based upon the placental examination of 1,156 women with singleton pregnancies recruited prospectively in a single unit. Placentas were analysed where deliveries occurred between 34-43 weeks. The incidence of normal histological findings and specific histological categories, such as ascending genital tract infection, chronic placental underperfusion, intervillous thrombus and villitis of unknown aetiology, were noted. The relationship between placental morphological indices: coiling index, cord centrality index (distance of cord insertion on the chorionic plate from the centre) and eccentricity (shape of the placenta) and histological lesions was investigated. There were no significant differences between cord centrality and eccentricity between placentas with and without histological lesions except an association between hypercoiling of the umbilical cord and intervillous thrombosis and villitis of unknown aetiology (p = 0.024 and p = 0.009, respectively). The macroscopic morphological features of the placenta cannot predict the presence or absence of the histological placental lesions, nor are these lesions in general associated with differences in cord centrality, placental eccentricity or cord coiling.

Placental weight, digitally derived placental dimensions at term and their relationship to birth weight.

OBJECTIVE: A few recent studies have investigated the relationship between birth weight and digitally derived placental dimensions, and no standardised methodology has been used. The aims of this study are to compare manually derived placental measurements with those derived digitally and to establish the relationship of birth weight to the placental weight and circumference. METHODS: Three hundred fifty-one consecutive unselected women with singleton pregnancy delivering in a tertiary maternity unit at 37-42 weeks were recruited. Manual and digital placental axis measurements (using calibrated digital imaging and 'Image J' software) were obtained and the circumference derived. The relationship between the two methods was assessed using a Bland-Altman plot analysed. The relationship between z-scores of birth weight, placental weight and placental circumference was investigated. RESULTS: Manually and digitally obtained placental long axis, short axis and circumference measurements show close correlation (r=0.70, 0.70 and 0.83, respectively). The z score of birth weight is significantly correlated with the z score of placental weight (r=0.59, p<0.001) and z score placental digital circumference (r=0.40, p<0.001). Birth weight:placental weight ratio is 7.20 and birth weight:placental circumference=64.57 g/cm. CONCLUSION: There is close though not perfect agreement between the manual and digital placental measurements. Birth weight is strongly correlated with placental weight and circumference at term.