High Burden Research Articles

Internal Psychometric Validation of an International Burden of Illness Survey for Idiopathic Multicentric Castleman Disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare, chronic, debilitating lymphoproliferative disorder where the mainstay of treatment is symptom management. Our recent international patient survey showed that patients with iMCD have a high symptom burden that has a significant negative patient-reported impact on several aspects of daily life. As part of our ongoing work towards the development of an iMCD symptom burden scale, assessing the survey's psychometric properties is a critical step in understanding its adequacy, relevance, and usefulness. As iMCD is a rare disease, there are challenges to conducting such psychometric analyses which we describe. As part of the exploratory psychometric analysis, three a priori hypothesis sets (HS) were generated by interviewing an iMCD-experienced clinician, a patient, and a caregiver to explore the iMCD patient survey's internal construct validity, given no gold standard iMCD measure exists for external construct validation. HS-1hypothesized that a convergent or discriminant relationship exists with the patients' self-assessment of symptom effect on daily life between two potentially related or unrelated symptoms, respectively. HS-2hypothesized that having a greater number of symptoms has a positive convergent relationship with the patients' assessment of symptoms' effect on daily life. Finally, HS-3hypothesized that patients receiving treatment versus no treatment was associated with patients reporting less effect of symptom burden on their daily life. Spearman's rank absolute correlation strength (ACS) was used for HS-1 and HS-2 (convergent relationship, ACS ≥ 0.3 and pvalue < 0.05; divergent relationship, ACS < 0.3), and Cohen's d to quantify standardized absolute effect sizes (AES) for HS-3 (AES ≥ 0.5 and pvalue < 0.05). Our analyses partially supported HS-1. None of the three positive convergent relationships were supported. Of the six discriminant relationships, only dizziness with impaired cognitive function and tiredness with dizziness were supported. HS-2 analyses showed there was convergent validity between the number of symptoms and their effect on aspects of daily life. HS-3 analyses did not provide evidence to support the hypothesis. These internal psychometric construct analyses provide initial support for the bespoke iMCD patient survey and will guide additional work towards the development of the first iMCD-specific symptom burden scale.

Anticholinergic burden and health-related quality of life among adult patients in a resource-limited setting: a cross-sectional study.

Anticholinergic medications are now widely acknowledged for their unfavorable risk-to-benefit profile owing to their adverse effects. Health-related quality of life (HRQoL) is commonly regarded as a crucial person-centered outcome. This study aimed to investigate the association between anticholinergic burden and HRQoL in hospitalized and ambulatory patients seen in Ethiopia. This cross-sectional study utilized a questionnaire and medical records to collect data from a convenience sample of adult patients attending both inpatient wards and ambulatory clinic of University of Gondar Comprehensive Specialized Hospital between April and September 2022. Anticholinergic burden was measured by anticholinergic cognitive burdens scale (ACBS), while HRQoL was measured using EQ5D-index (Euroqol-5 dimensions-5-Levels index) and EQ5D-VAS (visual analogue scale). Linear regression was used to assess the influence of high anticholinergic burden (ACBS score ≥ 3) on EQ5D-index and EQ5D-VAS, with adjustments made for sociodemographic and clinical confounders. A total of 828 patients participated in this study (median (IQR) age was 45.0 (30, 60) and 55.9% were female). On multiple linear regression analysis, high anticholinergic burden was associated with a statistically significant decline in HRQoL, as evidenced by reductions in both EQ5D index (- 0.174 (- 0.250, - 0.098)) and EQ5D-VAS scores (- 9.4 (- 13.3, - 5.2)). A significant association between high anticholinergic burden and diminished HRQoL was found among a relatively younger cohort in a resource-limited setting, even after adjustment for important confounding variables. Clinicians should be cognizant of the cumulative impact of anticholinergic burden on HRQoL outcomes and strive to minimize anticholinergic burden.

Challenges in Prognostication of an Older Adult with Severe Obesity and End-Stage Heart Failure: A Case Study.

In this report, we present the case of an older adult with severe obesity and multiple comorbidities, including heart failure with preserved ejection fraction (HFpEF), who experienced a prolonged decline complicated by recurrent hospitalizations and skilled nursing facility stays during the two years preceding death. This case highlights challenges in prognostication attributed to severe obesity complicated by HFpEF, which likely delayed goals of care conversations, and access to palliative care and hospice, despite high symptom burden. We discuss prognostic uncertainty among those with severe obesity and outline potential future directions.

An alcohol-related liver disease multi-stakeholder hub (ARMS-Hub) to enhance research activity in underserved communities in the UK

Background Alcohol use is the third leading risk factor of death and disability in the UK and costs the NHS £3.5 billion per year. Despite the high prevalence and healthcare burden of Alcohol-related Liver Disease (ArLD), there has been minimal research addressing prevention, morbidity and mortality. Reasons for this include stigma and lack of interest from public, charitable and commercial funding bodies. The objectives of this project were to identify and develop interdisciplinary partnerships, to explore stigma in ArLD, to develop a representative Patient and Public Involvement and Engagement (PPIE) group, to build research capacity, and to develop interdisciplinary research proposals targeting key research priorities. Methods ArLD networks were identified by members of the Project Steering Group. Health Care Professionals (HCPs) from different backgrounds were invited to join the ARMS-Hub. PPIE representatives were invited through charities and support groups. Research areas were identified, discussed, prioritised and ranked. Research questions were refined during an in-person symposium. A mentorship programme was created to encourage and facilitate networking and knowledge exchange for early career researchers. Results We established the ARMS-Hub with 31 HCPs and 40 PPIE members. There were five stakeholder meetings, which included PPIE representation. Three virtual and three in-person PPIE meetings took place. Topics relevant to stigma in ARLD identified during the meetings were education and awareness, language, and access. Priorities identified were the disconnect between mental health and liver services, education around the wider harms of alcohol, and education of HCPs regarding stigma. We established a mentorship network that regularly meets to support development of new research ideas. Conclusions Stigma is central to lack of research engagement from professionals and PPIE. The main priority identified relates to the disconnect between mental health and liver services. This collaborative study has allowed development of a research agenda to address this priority.

Antenatal care utilisation and receipt of its components in Nigeria: Assessing disparities between rural and urban areas-A nationwide population-based study.

Antenatal care (ANC) is crucial for positive pregnancy outcomes, but it is underutilised in Nigeria, suggesting unmet needs, and potentially contributing to the country's high burden of maternal and neonatal mortalities. This study comprehensively assesses ANC utilisation and receipt of its components in Nigeria, focusing on disparities between rural and urban areas. We used the data disaggregation approach to analyse the Nigeria Demographic and Health Survey 2018. We estimated ANC utilisation, assessed the receipt of ANC components, and identified factors associated with eight or more (≥ 8) ANC contacts nationally and across rural and urban residences. Nationwide, only 20.3% of women had ≥ 8 ANC contacts, with a significant disparity (P < 0.001) between urban (35.5%) and rural (10.4%) areas in Nigeria. The North-East region had the lowest ANC utilisation nationally (3.7%) and in urban areas (3.0%), while the North-West had the lowest in rural areas (2.7%). Nationally, 69% of mothers received iron supplements, 70% had tetanus injections, and 16% received medicines for intestinal parasites, with urban residents having higher proportions across all ANC components. Maternal and husband education, health insurance, and maternal autonomy were associated with increased ANC odds at the national, rural, and urban residences. However, differences exist, with all ethnicities having higher ANC odds than the Hausa/Fulanis in urban areas and the Yorubas demonstrating greater odds than other ethnicities in rural settings. Internet use was significant only in the national context, watching television only in urban settings, while maternal working status, wealth, birth type, religion, and radio listenership were significant in rural areas. Our study reveals significant disparities in ANC utilisation and components across Nigeria, with rural residents, particularly in northern regions, as well as socioeconomically disadvantaged and teenage mothers facing notable challenges. A multifaceted approach prioritising the interplay of intersectional factors like geography, socioeconomic status, education, religion, ethnicity, and gender dynamics is essential. Key strategies should include targeted interventions to promote educational opportunities, expand health insurance coverage, leverage internet and context-specific media, and foster socioeconomic empowerment, with priority for underserved populations.

Long-term outcomes among survivors of childhood osteosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).

Treatment strategies for osteosarcoma evolving between 1970 and 1999 improved 5-year survival and continue as standard of care today. This report evaluates the impact of these evolving therapies on long-term health outcomes. Five-year survivors of childhood osteosarcoma in CCSS treated from 1970 to 1999 were evaluated for late (>5years from diagnosis) mortality, chronic health conditions (CHCs), and health status using piecewise-exponential and logistical models. Comparisons were made between survivors and siblings without cancer, and among survivors examining historical and current standard chemotherapies (e.g., methotrexate/doxorubicin/cisplatin [MAP] vs. others), specific chemotherapy agents and surgical approaches (amputation vs. limb salvage [LS]). Models were evaluated adjusting for attained age, sex, race, ethnicity, and age at diagnosis. A total of 1257 survivors of osteosarcoma were followed on average for 24.4years. Twenty-year all-cause late mortality was 13.3% (95% confidence interval [CI]: 11.7%-14.9%) overall and 11.7% (95% CI: 6.9%-16.5%) for the subset treated with MAP plus LS. Survivors were at higher risk of CHCs (rate ratio [RR] 3.7, 95% CI: 3.2-4.3) than the sibling cohort, most notably having more serious cardiac, musculoskeletal, and hearing CHCs. Within the survivor cohort, the risk of severe CHCs was twice as high with MAP versus no chemotherapy (RR 2.1, 95% CI: 1.3-3.4). Compared with primary amputation, serious musculoskeletal CHCs were higher after LS (RR 6.6, 95% CI: 3.6-13.4), without discernable differences in health status. Contemporary osteosarcoma therapy with MAP plus LS, while improving 5-year disease-free survival, continues to be associated with a high burden of late mortality, CHCs, and health status limitations.

Utility of the WHO dengue guidelines in pediatric immunological studies.

Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.

High Demand for Psychological Support in Patients Who Have Periprosthetic Hip and Knee Joint Infections: An Analysis of 13,976 Patients

BACKGROUNDThere is only sparse knowledge on the psychological burden of patients who have periprosthetic joint infections (PJI). The aim of our study was to assess the need for psychological support following total joint arthroplasty of the hip and knee. A special focus was set on patients who had aseptic and septic complications. METHODSA total of 13,976 patients who underwent total hip (THA, n = 6,926) or total knee arthroplasty (TKA, n = 7,050) between January 1st, 2012 and December 31st, 2019 at a single institution were retrospectively evaluated for the postoperative need for a psychological consultation. Data was collected on age, sex, type of surgery, and indications for revision procedures. The need for a psychological consultation was assessed during the daily postoperative visits, which were further coordinated by two institutional psychologists. RESULTSThe average age was 68 years (range, 12 to 100), and there were 63.5% women. The overall rate of psychological consultations was 1.7%. Patients who had a septic indication for revision surgery had an 18.7-fold higher rate of postoperative psychological consultations compared to patients following primary surgery and a 5.4-fold higher rate compared to patients who had an aseptic indication. In detail, this rate was 1.0% in the primary subgroup, compared to 7.7% following revision arthroplasty (P < 0.001). In the revision subgroup, the rate was 17.9% for septic and 3.3% for aseptic revision arthroplasty cases (P < 0.001). Postoperative psychological consultations were twice as frequent in women (2.1%) compared to men (1.0%), P < 0.001. CONCLUSIONSThe present study raises awareness of the markedly high psychological burden in revision arthroplasty cases, in the view of the high estimated number of unknown cases. There is a significant correlation between PJI and the postoperative need for a psychological consultation, with women being at an even higher risk. Health care providers should aim at offering psychological support for patients who have a septic complication, with affected patients being at risk for psychological stress.

Prognostic significance of refractory thrombus in STEMI patients and the role of red cell distribution width: A case-control study.

The high thrombus burden of the infarct-related artery (IRA) is associated with the adverse prognosis in ST-segment elevation myocardial infarction (STEMI) patients. Our objectives were to investigate the predictors and evaluate the prognosis of refractory thrombus in STEMI patients. A total of 1305 consecutive patients with STEMI who underwent primary percutaneous coronary intervention (pPCI) were screened. The refractory thrombus group (n = 15) was defined as IRA thrombolysis in myocardial infarction flow < grade 2 after multiple thrombus aspiration (TA). The control group (n = 45) was age- and sex-matched and was selected from the same batch of patients. Baseline hematologic indices were measured before the pPCI. The major adverse cardiovascular events (MACE) were recorded during follow-up. The refractory thrombus group had significantly higher red cell distribution width (RDW) at baseline compared with the control group (13.1 [12.4-13.7] vs 12.6 [12.3-12.8], P = .008). In multivariate logistic regression analysis, RDW was an independent predictor of refractory thrombus (odds ratio: 8.799, 95% CI: 1.240-62.454, P = .030). The area under the receiver-operating characteristic curve of the RDW was 0.730 (95%CI: 0.548-0.912, P = .008). During a mean period of 26 months follow-up, patients in the refractory thrombus group tended to have higher percent MACEs compared with patients in the control group (53.3% vs 6.7%, P < .001). In the present study, we found that the refractory thrombus in STEMI patients was associated with the worse prognosis and the increased RDW might be a potential independent predictor.

Chronic Venous Disease: Pathophysiological Aspects, Risk Factors, and Diagnosis.

Chronic venous disease (CVD) is highly prevalent in the general population and encompasses a range of pathological and hemodynamic changes in the veins of the lower extremities. These alterations give rise to a variety of symptoms, with more severe forms resulting in venous ulceration, which causes morbidity and high socioeconomic burden. The origins and underlying mechanisms of CVD are intricate and multifaceted, involving environmental factors, genetics, hormonal factors, and immunological factors that bring about structural and functional alterations in the venous system. This review offers the latest insights into the epidemiology, pathophysiology, and risk factors of CVD, aiming to provide a comprehensive overview of the current state of knowledge. Furthermore, the diagnostic approach for CVD is highlighted and current diagnostic tools are described.

Local FK506 delivery induces osteogenesis in rat bone defect and rabbit spine fusion models

Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and increase surgical costs, adding to patients' already high economic and mental burden. Recent studies have identified that FDA-approved immunosuppressant drug, FK506 (Tacrolimus), can also activate the BMP pathway by binding to its inhibitors. This study tested the hypothesis that FK506, as a standalone treatment, could induce osteogenic differentiation of human mesenchymal stromal cells (hMSCs), as well as functional bone formation in a rat segmental bone defect model and rabbit spinal fusion model. FK506 enhanced osteogenic differentiation and mineralization of hMSCs in vitro. Standalone treatment with FK506 delivered on a collagen sponge produced consistent bone bridging of a critically sized rat femoral defect with functional mechanical properties comparable to naïve bone. In a rabbit single level posterolateral spine fusion model, treatment with FK506 delivered on a collagen sponge successfully fused the L5-L6 vertebrae at rates comparable to rhBMP-2 treatment. These data demonstrate the ability of FK506 to induce bone formation in human cells and two challenging in vivo models, and indicate FK506 can be utilized to treat a variety of spine disorders.

Burden of illness in patients with pulmonary hypertension due to interstitial lung disease: a real-world analysis

BackgroundPulmonary hypertension due to interstitial lung disease (PH-ILD) is associated with high rates of respiratory failure and death. Healthcare resource utilization (HCRU) and cost data are needed to characterize PH-ILD disease burden.MethodsA retrospective cohort analysis of the Truven Health MarketScan® Commercial Claims and Encounters Database and Medicare Supplemental Database between June 2015 to June 2019 was conducted. Patients with ILD were identified and indexed based on their first claim with a PH diagnosis. Patients were required to be 18 years of age on the index date and continuously enrolled for 12-months pre- and post-index. Patients were excluded for having a PH diagnosis prior to ILD diagnosis or the presence of other non-ILD, PH-associated conditions. Treatment patterns, HCRU, and healthcare costs were compared between the 12 months pre- versus 12 months post-index date.ResultsIn total, 122 patients with PH-ILD were included (mean [SD] age, 63.7 [16.6] years; female, 64.8%). The same medication classes were most frequently used both pre- and post-index (corticosteroids: pre-index 43.4%, post-index 53.5%; calcium channel blockers: 25.4%, 36.9%; oxygen: 12.3%, 25.4%). All-cause hospitalizations increased 2-fold, with 29.5% of patients hospitalized pre-index vs. 59.0% post-index (P < 0.0001). Intensive care unit (ICU) utilization increased from 6.6 to 17.2% (P = 0.0433). Mean inpatient visits increased from 0.5 (SD, 0.9) to 1.1 (1.3) (P < 0.0001); length of stay (days) increased from 5.4 (5.9) to 7.5 (11.6) (P < 0.0001); bed days from 2.5 (6.6) to 8.0 (16.3) (P < 0.0001); ICU days from 3.8 (2.3) to 7.0 (13.2) (P = 0.0362); and outpatient visits from 24.5 (16.8) to 32.9 (21.8) (P < 0.0001). Mean (SD) total all-cause healthcare costs increased from $43,201 ($98,604) pre-index to $108,387 ($190,673) post-index (P < 0.0001); this was largely driven by hospitalizations (which increased from a mean [SD] of $13,133 [$28,752] to $63,218 [$75,639] [P < 0.0001]) and outpatient costs ($16,150 [$75,639] to $25,604 [$93,964] [P < 0.0001]).ConclusionPH-ILD contributes to a high HCRU and cost burden. Timely identification, management, and treatment are needed to mitigate the clinical and economic consequences of PH-ILD development and progression.

It Takes a Village: Bringing Palliative Care to Ethiopia.

In Ethiopia, there is a great need for culturally relevant, sustainable palliative care. Profound poverty and limited health care resources magnify the impact of disease in Ethiopia, one of the poorest countries in the world. The impacts of high burden of disease and poor access to health care include physical suffering, and detrimental economic effects. Thus, the potential for palliative care to improve health care allocation and reduce suffering is substantial. An immediate action could include harnessing the infrastructure of the iddir, which are centuries-old, indigenous neighborhood organizations that provide care and support for families during the time of a death. We propose a model of community-based palliative care instantiated within iddirs, in which they are trained as volunteers to deliver basic palliative care. Shifting the gaze of global health research towards local solutions in Ethiopia may reveal sustainable, effective strategies to improve care for millions in this vulnerable population.

High STI burden among a cohort of adolescents aged 12-19 years in a youth-friendly clinic in South Africa.

Adolescents face a higher risk for HIV, STIs, and unintended pregnancy than any other age group in sub-Saharan Africa, and have unique health care needs as they navigate this period of growth and developmental milestones. We conducted the Youth Friendly Services study among adolescents in Rustenburg, South Africa to address some of these concerns. Participants aged 12-19 were followed quarterly for 12 months, asked at baseline about demographics, their sexual behavior, and tested for HIV, STIs, and pregnancy (girls). Report of sexual activity was not a requirement for enrollment. Assent and parental consent were obtained for participants under 18. Some follow up visits fell during COVID-mandated shutdowns, and we worked with participants to reschedule and extend follow up as appropriate. Here we present data on reported behaviors, participant attrition, risk of HIV, other STI, and pregnancy. From May 2018 to August 2019, we enrolled 223 HIV-negative, non-pregnant adolescents (64% girls). The median age was 17 (IQR: 14-18). Among the 119 (53%) participants who reported being sexually active at baseline, the median age at first sex was 16 years (IQR: 15-17). During follow-up, an additional 16 (7%) participants reported having their first sexual encounter. Among the sexually active participants, the incidence of HIV was 1.5 cases / 100 person-years at risk (PYAR, 95% CI: 0.4-6.0), the incidence of chlamydia was 15.7 cases (95% CI: 10.1-24.4), gonorrhea was 4.7 cases (95% CI: 2.1-10.5), and HSV was 6.3 cases (95% CI: 3.1-12.6); we observed no cases of incident syphilis. The incidence of pregnancy among sexually active girls was 15.0 pregnancies / 100 PYAR (95% CI: 8.5-26.5). Despite small numbers, the incidence of most STIs was significantly higher in females compared to males. We also observed two pregnancies and 5 incident STIs among participants who reported never having had sex, these tended to be younger participants. From March to September 2020, the clinic was shut down for COVID-19, and 53 study visits were postponed. Follow up was concluded in November 2020, a total of 19 participants were lost to follow up, however only one participant dropped off-study during COVID-19 shutdowns. Retention at the final visit was 91.5%. We successfully completed a prospective study of adolescents to learn more about the risks they face as they navigate sexual debut in the context of a program of youth-friendly counseling and services. Among self-reported sexually active participants, we observed a high rate of HIV, STI and pregnancy, however we also observed pregnancy and STIs among those who reported no sexual activity.

“Not me!” a qualitative, vignette-based study of nurses’ and physicians’ reactions to spiritual distress on neuro-oncological units

PurposePeople with primary malignant brain tumors experience serious health-related suffering caused by limited prognosis and high symptom burden. Consequently, neuro-oncological healthcare workers can be affected emotionally in a negative way. The aim of this study was to analyze the attitudes and behavior of nurses and physicians when confronted with spiritual distress in these patients.MethodsNeurospirit-DE is a qualitative vignette–based, multicenter, cross-sectional online survey that was conducted in Bavaria, Germany. Reflexive thematic analysis was used for data analysis.ResultsA total of 143 nurses and physicians working in neurological and neurosurgical wards in 46 hospitals participated in the survey. The participants questioned if the ability to provide spiritual care can be learned or is a natural skill. Spiritual care as a responsibility of the whole team was highlighted, and the staff reflected on the appropriate way of involving spiritual care experts. The main limitations to spiritual care were a lack of time and not viewing spiritual engagement as part of the professional role. Some were able to personally benefit from spiritual conversations with patients, but many participants criticized the perceived emotional burden while expressing the imminent need for specific training and team reflection.ConclusionsMost neuro-oncological nurses and physicians perceive spiritual care as part of their duty and know how to alleviate the patient’s spiritual distress. Nonetheless, validation of spiritual assessment tools for neuro-oncology and standardized documentation of patients’ distress, shared interprofessional training, and reflection on the professional and personal challenges faced when confronted with spiritual care in neuro-oncology require further improvement and training.

Next-generation sequencing as a valuable tool for mutational spectrum in advanced-stage NSCLC patients

Background and aim. Lung cancer remains one of the most threatening malignancies, ranking as the second most diagnosed cancer, and it continues to be the leading cause of cancer-related deaths worldwide. Challenges persist with late diagnosis and the high mutational burden characteristic of lung cancer. Methods. Our study focuses on identifying the mutational spectrum of a cohort of advanced-stage non-small cell lung cancer (NSCLC) patients using a minimally invasive method through blood collection. To analyze the mutational landscape of these patients, we employed plasma DNA for the next-generation sequencing (NGS) cancer panel Ion Torrent, which contains 50 of the most mutated genes in lung cancer. All protocols for extraction, quality and quantity control, and library preparation follow the manufacturer’s rules. Bioinformatics analysis was performed to select pathogenic mutations versus non-pathogenic-benign ones. Results. This approach is particularly valuable for patients in advanced stages (III and IV, n=10) of lung adenocarcinoma and lung squamous cell carcinoma, who lack surgical options and limited therapeutic avenues. The comprehensive sequencing analysis revealed that nine of the ten lung cancer patients carried a TP53 mutation. Also, several other mutations exist in various cases, showing heterogeneous profiling. Conclusions. Our findings demonstrate the potential of liquid biopsies in providing crucial genetic insights that can guide personalized treatment strategies, improving the management and outcomes for patients with advanced lung cancer.

“Not me!” a qualitative, vignette-based study of nurses’ and physicians’ reactions to spiritual distress on neuro-oncological units

PurposePeople with primary malignant brain tumors experience serious health-related suffering caused by limited prognosis and high symptom burden. Consequently, neuro-oncological healthcare workers can be affected emotionally in a negative way. The aim of this study was to analyze the attitudes and behavior of nurses and physicians when confronted with spiritual distress in these patients.MethodsNeurospirit-DE is a qualitative vignette–based, multicenter, cross-sectional online survey that was conducted in Bavaria, Germany. Reflexive thematic analysis was used for data analysis.ResultsA total of 143 nurses and physicians working in neurological and neurosurgical wards in 46 hospitals participated in the survey. The participants questioned if the ability to provide spiritual care can be learned or is a natural skill. Spiritual care as a responsibility of the whole team was highlighted, and the staff reflected on the appropriate way of involving spiritual care experts. The main limitations to spiritual care were a lack of time and not viewing spiritual engagement as part of the professional role. Some were able to personally benefit from spiritual conversations with patients, but many participants criticized the perceived emotional burden while expressing the imminent need for specific training and team reflection.ConclusionsMost neuro-oncological nurses and physicians perceive spiritual care as part of their duty and know how to alleviate the patient’s spiritual distress. Nonetheless, validation of spiritual assessment tools for neuro-oncology and standardized documentation of patients’ distress, shared interprofessional training, and reflection on the professional and personal challenges faced when confronted with spiritual care in neuro-oncology require further improvement and training.

Endourological society fellowship program: a real contribution to improve surgical outcomes of stone patients treated with ureteroscopy.

We assessed the impact of the one-year endourological society fellowship program (ESFP) on the achievement of optimal surgical outcomes (OSO) in stone patients treated with ureteroscopy (URS). We identified 303 stone patients treated with URS from January 2018 to June 2022 by five experienced surgeons (ES). Of those, two attended ESFP. OSO was defined as the presence of residual fragments ≤ 4mm at 1-month post-operative imaging (Ultrasound + X - Ray or CT scan). Descriptive statistics explored patients' characteristics and the rate of OSO according to the attendance of ESFP. Uni- and multivariate logistic regression analyses (UVA and MVA) tested the impact of stone characteristics, surgical data, ESFP, and imaging technique on the rate of OSO. The LOWESS curve explored the graphical association between stone size and the multivariable-adjusted probability of OSO in the two groups of surgeons. Of 303 patients, 208 (69%) were treated by the two surgeons who attended ESFP. OSO was achieved in 66% and 52% of patients treated by ES with and without ESFP, respectively (p = 0.01). At UVA, ESFP (OR = 1.78; 95% CI = 1.09-2.90), stone diameter (OR = 0.92; 95% CI = 0.88-0.96), stone location (kidney vs. ureter; OR = 0.34; 95% CI = 0.21-0.58), imaging technique (CT scan vs. Ultrasound + X-Ray; OR = 0.28; 95% CI = 0.16-0.47) predicted OSO achievement (all p < 0.05). At MVA analyses, ESFP was associated with OSO (OR = 2.24; 95% CI = 1.29-3.88; p < 0.05), along with the other aforementioned variables. The LOWESS curve showed that the greater the stone size, the greater the difference in OSO in the two groups of surgeons. ESFP positively affects OSO achievement after URS, especially in patients with a high stone burden.

SciMET-cap: high-throughput single-cell methylation analysis with a reduced sequencing burden

DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap). Accumulated off-target coverage enables genome-wide differentially methylated region (DMR) calling for clusters with as few as 115 cells. We characterize sciMET-cap on human PBMCs and brain (middle frontal gyrus).

Endourological society fellowship program: a real contribution to improve surgical outcomes of stone patients treated with ureteroscopy.

We assessed the impact of the one-year endourological society fellowship program (ESFP) on the achievement of optimal surgical outcomes (OSO) in stone patients treated with ureteroscopy (URS). We identified 303 stone patients treated with URS from January 2018 to June 2022 by five experienced surgeons (ES). Of those, two attended ESFP. OSO was defined as the presence of residual fragments ≤ 4mm at 1-month post-operative imaging (Ultrasound + X - Ray or CT scan). Descriptive statistics explored patients' characteristics and the rate of OSO according to the attendance of ESFP. Uni- and multivariate logistic regression analyses (UVA and MVA) tested the impact of stone characteristics, surgical data, ESFP, and imaging technique on the rate of OSO. The LOWESS curve explored the graphical association between stone size and the multivariable-adjusted probability of OSO in the two groups of surgeons. Of 303 patients, 208 (69%) were treated by the two surgeons who attended ESFP. OSO was achieved in 66% and 52% of patients treated by ES with and without ESFP, respectively (p = 0.01). At UVA, ESFP (OR = 1.78; 95% CI = 1.09-2.90), stone diameter (OR = 0.92; 95% CI = 0.88-0.96), stone location (kidney vs. ureter; OR = 0.34; 95% CI = 0.21-0.58), imaging technique (CT scan vs. Ultrasound + X-Ray; OR = 0.28; 95% CI = 0.16-0.47) predicted OSO achievement (all p < 0.05). At MVA analyses, ESFP was associated with OSO (OR = 2.24; 95% CI = 1.29-3.88; p < 0.05), along with the other aforementioned variables. The LOWESS curve showed that the greater the stone size, the greater the difference in OSO in the two groups of surgeons. ESFP positively affects OSO achievement after URS, especially in patients with a high stone burden.