Evaluating the Feasibility, Acceptance, and Beneficial Effects of Online Occupational Therapy for Post-COVID-19 Condition: Protocol for a Randomized Controlled Trial (ErgoLoCo Study).

BACKGROUND: Post-COVID-19 syndrome (PCS; also known as "long COVID") is a relatively novel disease comprising physical, psychological, and cognitive complaints persisting several weeks to months after acute infection with SARS-CoV-2. Approximately 10% of patients with COVID-19 are affected by long-term symptoms. However, effective treatment strategies are lacking. The ErgoLoCo (Occupational Therapy [Ergotherapie] for Long COVID) study was designed to develop and evaluate a novel occupational therapy (OT) concept of online delivery of therapy for long COVID. OBJECTIVE: The primary study objective is to assess the feasibility of the online OT intervention in PCS. Secondary aims include the evaluation of online OT concerning cognitive problems, occupational performance, and social participation. METHODS: This randomized controlled interventional pilot study involves parallel mixed methods process analyses and a realist evaluation approach. A total of 80 clients with PCS aged at least 16 years will be recruited into two interventional groups. The control cohort (watch and wait) comprises 80 clients with long COVID. Treatment is provided through teletherapy (n=40) or delivery of prerecorded videos (n=40) using the same standardized OT concept twice weekly over 12 weeks. Analyses of quantitative questionnaires and qualitative interviews based on the theoretical framework of acceptability will be performed to assess feasibility. Focus group meetings will be used to assess how acceptable and helpful the intervention was to the participating occupational therapists. Standardized tests will be used to assess the initial efficacy of the intervention on neurocognitive performance; limitations in mobility, self-care, and everyday activities; pain; disabilities; quality of life (QoL); social participation; and anxiety and depression in PCS, and the possible effects of online OT on these complaints. RESULTS: The German Ministry of Education and Research provided funding for this research in March 2022. Data collection took place from October 2022 to August 31, 2023. Data analysis will be completed by the end of April 2024. We anticipate publishing the results in the fall of 2024. CONCLUSIONS: Despite the enormous clinical need, effective and scalable treatment options for OT clients who have PCS remain scarce. The ErgoLoCo study will assess whether online-delivered OT is a feasible treatment approach in PCS. Furthermore, this study will assess the effect of the intervention on cognitive symptoms, QoL, and occupational performance and participation in everyday life. Particular emphasis will be placed on the experiences of clients and occupational therapists with digitally delivered OT. This study will pave the way for novel and effective treatment strategies in PCS. TRIAL REGISTRATION: German Clinical Trial Registry DRKS00029990; https://drks.de/search/de/trial/DRKS00029990. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50230.

Parenting and Gender as Impact Factors for Social Participation, Quality of Life, and Mental Health in Long COVID.

OBJECTIVES: This study aims to investigate the impact of gender and parental tasks on social participation, health-related quality of life (hrQoL), and mental health in persons with long COVID. METHODS: A mixed-methods approach was followed including a cross-sectional web-based survey and semi-structured interviews. Multivariable linear regressions were used to quantify the effect of gender and parenting tasks on social participation, hrQoL, and mental health. Qualitative data from interviews with participants experiencing long COVID symptoms was analyzed using content analysis. RESULTS: Data from 920 participants in the quantitative study and 25 participants in the qualitative study was analyzed. Parenting tasks were associated with increased impairments in family and domestic responsibilities in persons with long COVID compared to lower impairments in persons without long COVID (P = .02). The qualitative data indicate that coping with long COVID and pursuing parenting tasks limit participants' ability to perform leisure activities and attend social gatherings. In long COVID, men had higher anxiety symptoms than women, and in those without long COVID, the opposite was observed (P < .001). In the qualitative study, participants expressed feelings of dejection and pessimism about their future private, occupational, and health situations. No differences between the genders could be observed. CONCLUSIONS: Long COVID is associated with impairments in family and domestic responsibilities in individuals who have parenting tasks. Among participants with long COVID, anxiety symptoms are higher in men than women.

Association of long COVID with health-related Quality of Life and Social Participation in Germany: Finding from an online-based cross-sectional survey.

Purpose: This study aims to examine the health-related Quality of Life (hrQoL) and social participation in participants with Long COVID compared to participants without symptoms after COVID-19 and participants with no prior SARS-CoV-2 infection. Methods: A cross-sectional online survey was conducted in Germany. The non-random sample consists of participants 18 years or older. Participants were divided in three groups: Lg COVID with a prior SARS-CoV-2 infection and new or persistent symptoms 28 days after infection, ExCOVID with a prior SARS-CoV-2 infection and without new or persistent symptoms after 28 days, and NoCOVID when participants had no prior SARS-CoV-2 infection. EQ-5D-3L was used as hrQoL measure and the Index for the Assessment of Health Impairments (IMET) to reflect social participation. Descriptive and inferential statistics were performed. Results: A total of 3188 participants were included in the analysis (1421 Lg COVID, 260 ExCOVID, 1507 NoCOVID). Lg COVID was associated with the lowest EQ-5D-3L index values (p < 0.001), Visual Analogue Scale (VAS) scores (p < 0.001), and IMET (p < 0.001) scores followed by NoCOVID and ExCOVID. After adjusting for sociodemographic and medical conditions in a multivariable model Long COVID was still associated with lower hrQoL compared to NoCOVID (p < 0.001). About 10% of Lg COVID participants showed no health impairments in all EQ-5D dimensions while 51.1% of NoCOVID and 60% of ExCOVID participants showed no health impairments. Conclusion: This study highlights the impairments of persons with Long COVID on hrQoL and social participation compared to individuals without Long COVID in Germany. Trial registration: German Clinical Trial Registry, DRKS00026007.

Expression of Nectin-4 in Chromophobe Renal Cell Carcinoma in a multicenter cohort - early prognostic and therapeutic considerations.

INTRODUCTION: Nectin-4 is a member of the nectin family and a calcium-independent immunoglobuline-like transmembrane protein that contributes to tumor growth and angiogenesis in malignant tumors. A Nectin-4 directed antibody drug conjugate, Enfortumab vedotin-ejf, has recently been approved for treatment in urothelial cancer and is currently under investigation in other tumor entities such as breast, lung, and prostate cancer. In non-clear cell renal cell carcinoma (RCC) vascular endothelial growth factor (VEGF)-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. However, due to the rarity of disease treatment recommendations for chromophobe RCC (chRCC) are limited and new therapeutic agents urgently needed. In this study, we investigated the expression and prognostic impact of Nectin-4 in a large cohort of chRCC. METHODS: patients who underwent renal surgery due to chRCC were recruited. Clinical data was retrospectively evaluated. Tumor specimen were analyzed for Nectin-4 expression by immunohistochemistry. RESULTS: 81 chRCC patients were eligible for analysis. In 15 (18.5 %) samples tumors were positive for Nectin-4. No significant associations were found for Nectin-4 expression and clinical attributes in patients with chRCC. Kaplan-Meier analysis disclosed a 5 year- overall survival for Nectin-4-negative and Nectin-4-positive tumors of 91.8% versus 100.0% (p=0.316, log rank). CONCLUSIONS: In chRCC a small subset of tumors expresses Nectin-4 potentially amenable to Nectin-4 directed treatment. Expression of Nectin-4 is not associated with parameters of aggressiveness or survival. Due to the rare incidence of chRCC further studies with larger cohorts are warranted.

Evaluation of the National Competence Based Catalogue of Learning Objectives (NKLM 2.0) for undergraduate medical education at the Medical School Hannover.

Background: The National Competence-Based Catalogue of Learning Objectives for Undergraduate Medical Education (NKLM) serves as the foundation for curricular development in undergraduate medical education in Germany. A new version of the NKLM was launched in 2021, and medical faculties are now evaluating the learning objectives (LOs). This paper describes the evaluation process used at Hannover Medical School. Methods: The evaluation process was structured in three steps. LOs were rated as "keep", "modify" or "delete". First, the 1133 LOs were compared with the mapping of the Hannover curriculum from 2017. Then, a small team from the Curricular Development Department conducted a pre-evaluation of the 1133 LOs. Finally, a group of clinical experts and students discussed and agreed on the ratings. Results: For 868 LOs, one or more counterparts were found in the mapping, but 265 new LOs were not found and thus, classified as new. In the first rating, 779 LOs were kept, 300 were modified (172 due to wording), 45 were deleted, and there was no rating for 9 LOs. The expert group changed 47 of the pre-evaluation decisions. The final rating was to keep 738 LOs, modify 356, and delete 39 LOs. Conclusion: This method effectively evaluated the LOs from NKLM 2.0 while balancing expert knowledge and an overview of the curriculum.

Circulating and Urinary Concentrations of Malondialdehyde in Aging Humans in Health and Disease: Review and Discussion.

(1) Background: Malondialdehyde (MDA) is a major and stable product of oxidative stress. MDA circulates in the blood and is excreted in the urine in its free and conjugated forms, notably with L-lysine and L-serine. MDA is the most frequently measured biomarker of oxidative stress, namely lipid peroxidation. Oxidative stress is generally assumed to be associated with disease and to increase with age. Here, we review and discuss the literature concerning circulating and excretory MDA as a biomarker of lipid peroxidation in aging subjects with regard to health and disease, such as kidney disease, erectile dysfunction, and COVID-19. (2) Methods: Scientific articles, notably those reporting on circulating (plasma, serum) and urinary MDA, which concern health and disease, and which appeared in PubMed were considered; they formed the basis for evaluating the potential increase in oxidative stress, particularly lipid peroxidation, as humans age. (3) Results and Conclusions: The results reported in the literature thus far are contradictory. The articles considered in the present study are not supportive of the general view that oxidative stress increases with aging. Many functions of several organs, including the filtration efficiency of the kidneys, are physiologically reduced in men and women as they age. This effect is likely to result in the apparent "accumulation" of biomarkers of oxidative stress, concomitantly with the "accumulation" of biomarkers of an organ's function, such as creatinine. How free and conjugated MDA forms are transported in various organs (including the brain) and how they are excreted in the urine via the kidney is not known, and investigating these questions should be the objective of forthcoming studies. The age- and gender-related increase in circulating creatinine might be a useful factor to be taken into consideration when investigating oxidative stress and aging.

Social participation during the COVID-19 pandemic in persons with a high risk for a severe course of COVID-19 - results of a longitudinal, multi-center observational study in Germany.

Objective: The COVID-19 pandemic has affected how people go about their daily lives, often in various and substantial ways. This study aims to prospectively evaluate the changes in social participation during the COVID-19 pandemic in persons with a high risk for a severe COVID-19 course in Germany. Methods: A paper-pencil-based survey was conducted starting at March 2021. Participants filled out questionnaires at four time points based on their COVID-19 vaccination status: before COVID-19 vaccination, one month, six months and twelve months after COVID-19 vaccination. Social participation measures included the Pandemic Social Participation Questionnaire (PSP-Q) and the Index for measuring participation restrictions (IMET). Repeated measures ANOVA and paired t-test were used to test for changes between time-points. Repeated measures correlation was used to assess the relationship between social participation and local COVID-19 incidences. Results: Data from 245 participants was analyzed before and one month after COVID-19 vaccination. In addition, data from 156 participants was analyzed at time points one, six and twelve months after COVID-19. PSP-Q and IMET scores changed significantly after participants received a COVID-19 vaccination. Between one month and twelve months after vaccination, social participation improved significantly measured by PSP-Q. Social participation was negatively correlated with regional COVID-19 incidences before and after COVID-19 vaccination. Social participation was positively correlated with COVID-19 incidences between one month and twelve months after COVID-19 vaccination. Conclusions: Social participation improved in persons with a high risk for a severe COVID-19 course during the pandemic. The local COVID-19 incidence showed a negative association with social participation only until the fall of 2021 when it was used as the sole metric to regulate COVID-19 protective measures. Although our data describes the trends in social participation, further studies are needed to identify the influencing factors for the observed increase in social participation.

Migrant healthcare workers during COVID-19: bringing an intersectional health system-related approach into pandemic protection. A German case study.

Introduction: Migrant healthcare workers played an important role during the COVID-19 pandemic, but data are lacking especially for high-resourced European healthcare systems. This study aims to research migrant healthcare workers through an intersectional health system-related approach, using Germany as a case study. Methods: An intersectional research framework was created and a rapid scoping study performed. Secondary analysis of selected items taken from two COVID-19 surveys was undertaken to compare perceptions of national and foreign-born healthcare workers, using descriptive statistics. Results: Available research is focused on worst-case pandemic scenarios of Brazil and the United Kingdom, highlighting racialised discrimination and higher risks of migrant healthcare workers. The German data did not reveal significant differences between national-born and foreign-born healthcare workers for items related to health status including SARS-CoV-2 infection and vaccination, and perception of infection risk, protective workplace measures, and government measures, but items related to social participation and work conditions with higher infection risk indicate a higher burden of migrant healthcare workers. Conclusions: COVID-19 pandemic policy must include migrant healthcare workers, but simply adding the migration status is not enough. We introduce an intersectional health systems-related approach to understand how pandemic policies create social inequalities and how the protection of migrant healthcare workers may be improved.

Amino acids, post-translational modifications, nitric oxide, and oxidative stress in serum and urine of long COVID and ex COVID human subjects.

In this study, we investigated the status of amino acids, their post-translational modifications (PTM), major nitric oxide (NO) metabolites and of malondialdehyde (MDA) as a biomarker of oxidative stress in serum and urine samples of long COVID (LoCo, n = 124) and ex COVID (ExCo, n = 24) human subjects collected in 2022. Amino acids and metabolites were measured by gas chromatography-mass spectrometry (GC-MS) methods using stable-isotope labelled analogs as internal standards. There were no differences with respect to circulating and excretory arginine and asymmetric dimethylarginine (ADMA). LoCo participants excreted higher amounts of guanidino acetate than ExCo participants (17.8 ± 10.4 µM/mM vs. 12.6 ± 8.86 µM/mM, P = 0.005). By contrast, LoCo participants excreted lower amounts of the advanced glycation end-product (AGE) NG-carboxyethylarginine (CEA) than ExCo participants did (0.675 ± 0.781 µM/mM vs. 1.16 ± 2.04 µM/mM, P = 0.0326). The serum concentrations of MDA did not differ between the groups, indicating no elevated oxidative stress in LoCo or ExCo. The serum concentration of nitrite was lower in LoCo compared to ExCo (1.96 ± 0.92 µM vs. 2.56 ± 1.08 µM; AUC, 0.718), suggesting altered NO synthesis in the endothelium. The serum concentration of nitrite correlated inversely with the symptom anxiety (r = - 0.293, P = 0.0003). The creatinine-corrected urinary excretion of Lys and its metabolite L-5-hydroxy-Lys correlated positively with COVID toes (r = 0.306, P = 0.00027) and sore throat (r = 0.302, P = 0.0003). Our results suggest that amino acid metabolism, PTM and oxidative stress are not severely affected in long COVID. LoCo participants may have a lower circulating NO reservoir than ExCo.

Evaluation of Gas 6 as a Prognostic Marker in Papillary Renal Cell Carcinoma.

INTRODUCTION: Growth arrest-specific protein 6 (Gas 6) is a ligand that plays a role in proliferation and migration of cells. For several tumor entities, high levels of Gas 6 are associated with poorer survival. We examined the prognostic role of Gas 6 in renal cell carcinoma (RCC), especially in papillary RCC (pRCC), which is still unclear. METHODS: The patients' sample collection is a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of Gas 6 was determined by immunohistochemistry. RESULTS: In total, Gas 6 staining was evaluable in 180 of 240 type 1 and 110 of 128 type 2 pRCC cases. Kaplan-Meier analysis disclosed no significant difference in 5-year overall survival for all pRCC nor either subtype. Also, Gas+ and Gas- groups did not significantly differ in any tumor or patient characteristics. CONCLUSION: Gas 6 was not found to be an independent prognostic marker in pRCC. Future studies are warranted to determine if Gas 6 plays a role as prognostic marker or therapeutic target in pRCC.

Feasibility of self-organized blood sample collection in adults for study purposes in a primary care setting.

BACKGROUND/AIMS: The COVID-19 pandemic situation poses new challenges for research. Ethical issues might arise if especially vulnerable individuals for severe COVID-19 course expose themselves because of participation in studies to a higher risk of infection for study purposes. How is the feasibility and acceptance of self-organized blood sample collections to measure anti-SARS-CoV-2 Spike IgG antibodies in persons with a high risk for a severe COVID-19 disease progression? METHODS: Persons with a high risk for a severe COVID-19 disease progression (immunocompromised, oncology patients or over 80 years old) were recruited between January and September 2021 to send in blood samples (at least 500 µl) 1 month and 6 months after second COVID-19 vaccination. Participants were given the choice of drawing capillary or venous blood themselves or having blood drawn by health professionals belonging to either the study's own research team or the personnel found in local practices or clinics. Participants were surveyed via a telephone interview in December 2021 and January 2022 about their choice of blood sampling methods and influence of blood collection choice upon study participation. RESULTS: Data from 360 participants was collected via telephone follow-up. First blood samples were collected by the participants themselves (35.8%), local practices or clinics (31.9%) and the research team (22.5%). Second blood samples were mostly collected in local practices or clinics (35.6%) followed by participants themselves (25.9%) and the research team (11.5%). Blood samples were not collected in 2.5% and 19.1% of persons during first and second blood draw, respectively. Only 2% of blood samples did not reach the laboratory or were not analyzable. About one-fourth (26%) of participants stated that they would not have participated in the study if it would have been required to travel to the university hospital to give their blood sample. CONCLUSIONS: Participants were able to self-organize blood collection, making use of several different blood sample methods. Nearly all blood samples were analyzable when self-collected and sent in by post. One-fourth of the participants would not have participated in the study if required to give their blood sample in the study location. TRIAL REGISTRATION: German Clinical Trial Registry, DRKS00021152.

Immunohistochemical expression of the hepatocyte growth factor in chromophobe renal cell carcinoma.

BACKGROUND: The prognostic value of Hepatocyte growth factor (HGF) in non-clear cell renal cell carcinoma (RCC) is still unclear. The aim of this study is to evaluate the prognostic impact of HGF expression in a large cohort of chromophobe RCC (chRCC). METHODS: Patients who underwent renal surgery due to chRCC were recruited. Clinical data was retrospectively evaluated. Tumor specimen were analyzed for HGF expression by immunohistochemistry. RESULTS: 81 chRCC patients were eligible for analysis, thereof 37 (45.7%) patients were positive for HGF. No significant associations were found for HGF expression and clinical attributes in patients with chRCC. Kaplan-Meier analysis revealed no differences in 5-year overall survival (OS) for patients with HGF- compared to HGF+ tumors (95.0% versus 90.9%; p = 0.410). CONCLUSIONS: In chRCC HGF expression is not associated with parameters of aggressiveness or survival.

[Social participation and melanoma during the COVID-19 pandemic]. / Soziale Teilhabe und Hautkrebs während der COVID-19-Pandemie.

BACKGROUND: Measures used to contain the spread of coronavirus disease 2019 (COVID-19) have impaired the social participation of many people. Especially people with chronic or oncologic conditions were affected. In this observational study, we aimed to assess social participation in melanoma patients with immune checkpoint therapy. Therefore, we investigated social participation in a very specific group and consider this a basis for further studies in a growing collective of long-term survivors in an era of infectious diseases. MATERIALS AND METHODS: Cross-sectional assessment via the index to measure social participation and health associated quality of life ("Index zur Messung von Einschränkungen der Teilhabe", IMET). Results are compared with published norm data. RESULTS: In all, 47 melanoma patients (mean age 58.5 years, standard deviation 13.2) were included: 18 patients had advanced melanoma stage III and received adjuvant Immunotherapy, while 29 patients were treated because of metastatic melanoma (stage IV). Results of the IMET showed no significant impairments in social participation when regarding the total score and when being compared to prepandemic norm data. Female patients did have significantly impaired participation. CONCLUSION: The endpoints health-related quality of life and social participation are important in long-term survivors with melanoma. During the pandemic, women of our collective were especially at risk for impairment of social participation. Differences between pandemic and disease-specific influences on social participation cannot be derived from our data. Nevertheless, this study will be part of growing and necessary research on long-term cancer survivors diseases.

[Immunosuppressed people's beliefs, expectations, and experiences with COVID-19 vaccinations : Results of a longitudinal study]. / Impfeinstellung, Erwartungen und Impferfahrung von Immunsupprimierten bei COVID-19-Impfungen : Ergebnisse einer Längsschnittstudie.

BACKGROUND: Immunocompromised people are less likely to be vaccinated, despite an increased benefit of many vaccinations in terms of benefit-risk assessment, including the vaccines against SARS CoV-2 (COVID-19). Attitudes, expectations, and experiences with previous vaccinations influence the decision to get vaccinated. OBJECTIVE: To explore the attitudes of immunocompromised people towards vaccinations in general and COVID-19 vaccination in particular and their experiences with COVID-19 vaccinations. MATERIAL AND METHODS: As part of the CoCo Immune study, immunocompromised participants were surveyed in the spring and summer of 2021 (1 November 2021-7 September 2021) using questionnaires. Initially, they were asked about their expectations concerning a COVID-19 vaccination and followed up about their experience after COVID-19 vaccination. In addition, sociodemographic data, general attitudes toward vaccinations and experiences with previous vaccinations were collected. Analysis was performed using descriptive and bivariate statistics. RESULTS: The 243 participants mostly approved vaccinations and expected the COVID-19 vaccination to be effective and well-tolerated. Women were more concerned about the safety of vaccinations and were more often worried about side effects. Older persons felt better informed than younger persons. Participants who reported subjective side effects of previous vaccinations were more skeptical about vaccinations as well as the government institutions that recommend vaccinations. They less often agreed with the statement "in retrospect, the COVID-19 vaccination has been harmless for me so far". DISCUSSION: The participants mostly expressed a positive attitude and anticipation towards COVID-19 vaccinations; however, the age and sex differences found suggest that there are different information needs which should be addressed when educating individuals about vaccinations or designing vaccination campaigns.

The role of claudin-6 in chromophobe renal cell carcinoma.

BACKGROUND: The prognostic value of Claudin-6 (CLDN6) in non clear cell renal cell carcinoma (RCC) is still unclear. AIM: To evaluate the prognostic impact of CLDN6 expression in a large cohort of chromophobe RCC (chRCC). MATERIAL AND METHODS: Patients who underwent renal surgery due to chRCC were recruited. Clinical data were retrospectively evaluated. Tumor specimens were analyzed for CLDN6 expression by immunohistochemistry. RESULTS: 81 chRCC patients were eligible for analysis, thereof 10 (12.3%) patients were positive for CLDN6. No significant associations were found for CLDN6 expression and clinical attributes in patients with chRCC. Kaplan-Meier analysis revealed no differences in overall survival (OS) for patients with CLDN6⁻ compared to CLDN6⁺ tumors (87.0% versus 62.5%; p=0.174). CONCLUSION: In chRCC CLDN6 expression is not associated with parameters of aggressiveness or survival. Due to the rare incidence of chRCC further studies with larger cohorts are warranted.

Long-term Consequences of COVID-19 and the Pandemic: Protocol for a Web-Based, Longitudinal Observational Study (DEFEAT).

BACKGROUND: With population-wide vaccination availability, the global COVID-19 pandemic entered a new phase. Despite vaccination status, some people who were infected with SARS-CoV-2 experience long-term symptoms. OBJECTIVE: In this study, we aim to characterize the long-term effects of SARS-CoV-2 infection and the pandemic. We also aim to build symptom clusters and determine risk factors for developing long COVID symptoms. Furthermore, we assess social participation and health-related quality of life in patients with long COVID and in the general population during a global pandemic. METHODS: With a mixed-methods, web-based approach, we aim to recruit 2000 people in Germany who are older than 18 years and can provide informed consent. In the quantitative arm of the study, we identify symptoms of and predictive factors for long COVID manifestations with cluster analysis and assess social participation during the pandemic with standardized questionnaires. The qualitative arm of the study uses individual interviews and focus group discussions to better understand the illness experience of persons who experience long COVID. RESULTS: Recruitment started in September 2021. Up until July 2022, we recruited approximately 4500 participants via our web-based database. CONCLUSIONS: This study aims to build an innovative, patient-centered, web-based research platform appropriate for the pandemic by minimizing physical contact between study personnel and participants. All study activities are designed to better understand the long COVID syndrome, social participation during the pandemic, and the illness experiences of persons affected by long COVID. TRIAL REGISTRATION: German Clinical Trial Registry DRKS00026007; https://tinyurl.com/yh282fkt. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38718.

Expression of nectin-4 in papillary renal cell carcinoma.

BACKGROUND: Nectin-4 contributes to tumor proliferation, lymphangiogenesis and angiogenesis in malignant tumors and is an emerging target in tumor therapy. In renal cell carcinoma (RCC) VEGF-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. Enfortumab vedotin-ejf (EV) is an antibody drug conjugate that targets Nectin-4. The aim of our study was to investigate the expression of Nectin-4 in a large cohort of papillary RCC specimens. PATIENTS AND METHODS: Specimens were derived from the PANZAR consortium (Erlangen, Heidelberg, Herne, Homburg, Mainz, Mannheim, Marburg, Muenster, LMU Munich, TU Munich, and Regensburg). Clinical data and tissue samples from n = 190 and n = 107 patients with type 1 and 2 pRCC, respectively, were available. Expression of Nectin-4 was determined by immunohistochemistry (IHC). RESULTS: In total, Nectin-4 staining was moderately or strongly positive in of 92 (48.4%) of type 1 and 39 (36.4%) type 2 of pRCC cases. No associations between Nectin-4 expression and age at diagnosis, gender, grading, and TNM stage was found. 5 year overall survival rate was not statistically different in patients with Nectin-4 negative versus Nectin-4 positive tumors for the overall cohort and the pRCC type 2 subgroup, but higher in patient with Nectin-4 positive pRCC type 1 tumors compared to Nectin-4 negative tumors (81.3% vs. 67.8%, p = 0.042). CONCLUSION: Nectin-4 could not be confirmed as a prognostic marker in pRCC in general. Due to its high abundance on pRCC specimens Nectin-4 is an interesting target for therapeutical approaches e.g. with EV. Clinical trials are warranted to elucidate its role in the pRCC treatment landscape.

Effects of Pre-Existing Mental Conditions on Fatigue and Psychological Symptoms Post-COVID-19.

BACKGROUND: Patients who are post-COVID-19 will require more treatment soon. Therefore, it is important to understand the root cause of their psychological and somatic conditions. Previous studies showed contradictory results on the influence of pre-existing mental conditions. The present study examines the influence of these pre-existing conditions and their pre-treatment on the severity of post-COVID-19 symptoms. METHODS: This analysis employs questionnaire data from a large study sample in Germany. Overall, 801 participants were included. All participants rated their health status on a scale from 0 to 100. Fatigue, depression, and anxiety were measured using the FAS, PHQ-9, and GAD-7 scales. RESULTS: All pre-pandemic values showed no significant differences between the groups. The current health status was rated similarly by the recovered patients (µ = 80.5 ± 17.0) and the control group (µ = 81.2 ± 18.0) but significantly worse by acutely infected (µ = 59.0 ± 21.5) and post-COVID-19 patients (µ = 54.2 ± 21.1). Fatigue, depression, and anxiety were similar for recovered patients and the control group. By contrast, there were significant differences between the control and the post-COVID-19 groups concerning fatigue (45.9% vs. 93.1%), depression (19.3% vs. 53.8%), and anxiety (19.3% vs. 22.3%). CONCLUSION: Fatigue and psychological conditions of post-COVID-19 patients are not associated with pre-existing conditions.

N-Acetyl-L-cysteine in human rheumatoid arthritis and its effects on nitric oxide (NO) and malondialdehyde (MDA): analytical and clinical considerations.

N-Acetyl-L-cysteine (NAC) is an endogenous cysteine metabolite. The drug is widely used in chronic obstructive pulmonary disease (COPD) and as antidote in acetaminophen (paracetamol) intoxication. Currently, the utility of NAC is investigated in rheumatoid arthritis (RA), which is generally considered associated with inflammation and oxidative stress. Besides clinical laboratory parameters, the effects of NAC are evaluated by measuring in plasma or serum nitrite, nitrate or their sum (NOx) as measures of nitric oxide (NO) synthesis. Malondialdehyde (MDA) and relatives such as 4-hydroxy-nonenal and 15(S)-8-iso-prostaglandin F2α serve as measures of oxidative stress, notably lipid peroxidation. In this work, we review recent clinico-pharmacological studies on NAC in rheumatoid arthritis. We discuss analytical, pre-analytical and clinical issues and their potential impact on the studies outcome. Major issues include analytical inaccuracy due to interfering endogenous substances and artefactual formation of MDA and relatives during storage in long-term studies. Differences in the placebo and NAC groups at baseline with respect to these biomarkers are also a serious concern. Modern applied sciences are based on data generated using commercially available instrumental physico-chemical and immunological technologies and assays. The publication process of scientific work rarely undergoes rigorous peer review of the analytical approaches used in the study in terms of accuracy/trueness. There is pressing need of considering previously reported reference concentration ranges and intervals as well as specific critical issues such as artefactual formation of particular biomarkers during sample storage. The latter especially applies to surrogate biomarkers of oxidative stress, notably MDA and relatives. Reported data on NO, MDA and clinical parameters, including C-reactive protein, interleukins and tumour necrosis factor α, are contradictory in the literature. Furthermore, reported studies do not allow any valid conclusion about utility of NAC in RA. Administration of NAC patients with rheumatoid arthritis is not recommended in current European and American guidelines.