MCID achievement in staged bilateral total knee arthroplasty: Are both joints created equal?

BACKGROUND: A notable portion of unilateral total knee arthroplasty (TKA) patients undergo arthroplasty of the contralateral knee. The aims of this study were to describe the Minimal Clinically Important Difference for Improvement (MCID-I) and Worsening (MCID-W) in staged bilateral TKAs (BTKAs) and identify factors associated with these outcomes. METHODS: Patients with staged BTKA were retrospectively reviewed. Demographics, surgery details, and Patient-Reported Outcome Measurement Information System Physical Function Short Form 10a (PROMIS PF10a) were collected. MCID-I and MCID-W were defined for PROMIS PF10a. Patients were stratified into nine groups based on the MCID achievement of the first and second TKA: (A) MCID-I, MCID- I, (B) MCID-I, Neutral, (C) MCID-I, MCID-W, (D) Neutral, MCID-I, (E) Neutral, Neutral, (F) Neutral, MCID-W, (G) MCID- W, MCID-I, (H) MCID-W, Neutral, (I) MCID-W, MCID-W. Neutral patients did not achieve either MCID-I or MCID-W. RESULTS: The final cohort consisted of 59 staged BTKA patients. In patients who achieved MCID-I in the first TKA, 39.1% achieved MCID-I again in the second TKA (A), 39.1% were neutral (B), and 21.7% achieved MCID-W (C) in the second TKA. However, 77.8% of those who achieved MCID-W in the first joint (n = 9) went on to achieve MCID-I (G) in the second TKA. Those who achieved MCID-I after both TKAs (A) had a longer staged interval than those who achieved first MCID-I, then MCID-W (C) (15 months vs 8 months, P = 0.0113). CONCLUSION: In staged BTKA, MCID achievement of the first TKA may not be associated with the outcome of the second TKA.

Bridging the Gap: The Impact of Bowel Management Programs on Daily Life in Pediatric Colorectal Disease.

BACKGROUND: This commentary discusses the social impact of bowel management programs (BMPs) on children with colorectal diseases, including anorectal malformations (ARM), Hirschsprung disease (HD), functional constipation (FC), and spina bifida. Previous studies focused on functional outcomes, but this study bridges the gap to daily life experiences. METHODS: The study examined children's experiences in BMPs, focusing on school participation, vacation ability, and overall patient experience. Cleanliness, defined as fewer than one stool soiling episode per week, was achieved by 70% of participants. RESULTS: Positive patient experiences were linked to achieving stool cleanliness, regardless of the management method. Invasive methods like enemas did not negatively affect experiences if cleanliness was maintained. Validated patient-reported experience measures (PREMs) and patient-reported outcomes measures (PROMs) were used, though the median age of 8.9 years posed limitations. CONCLUSION: The commentary highlights the significance of stool cleanliness in improving patient experiences and supports the effectiveness of various BMP methods. Future research should include longitudinal follow-ups to assess BMP durability and gather data from older children.

Identification of patient-reported outcomes measures (PROMs) and patient-reported experiences measures (PREMs) in Gaucher disease in Spain.

BACKGROUND: Patient-reported outcome measures (PROMs) and patient-reported experiences measures (PREMs) are crucial for understanding the impact of GD on quality of life and patient's perceptions on care, but also to guide decision-making processes. Nevertheless, no specific PREMs in GD have been published, neither PROMs for Spanish GD patients have been developed. METHODS: Two project coordinators selected key-points to be included in a PROMs/PREMs questionnaire, and the scientific committee and a group of expert patients contributed to the initial draft. Then, 9 meetings with experts were held to discuss controversial points. After, a questionnaire with 103 items regarding symptomatology, aspects of daily life and care experience was developed. Finally, it was conducted a Delphi survey among a multidisciplinary group of experts in GD. RESULTS: Consensus was reached on 85 out of the 103 items. Recommendations on PROMs and PREMs regarding symptomatology, aspects of daily life and care experience were obtained. Consensus was reached on the importance of considering fatigue, concentration problems, and communication issues in GD patients using 5-step analog scales. Panelists recommended asking GD patients about the impact on social functioning and work/school performance. Finally, consensus was reached on considering care experiences, such as treatment satisfaction, treatment interruptions or transitions and healthcare professionals involved in patient's management to perceive patient's perceptions. CONCLUSION: This expert consensus may help developing GD-specific PROMs/PREMs for improving GD management. Properly developed and validated PROMs/PREMs may help decision-making, establishing patient-tailored therapeutic and follow-up goals.

Evaluating the Population-Based Usage and Benefit of Digitally Collected Patient-Reported Outcomes and Experiences in Patients With Chronic Diseases: The PROMchronic Study Protocol.

BACKGROUND: Chronic diseases are associated with a high disease burden. Under- and overprovision of care as well as quality variation between health care providers persists, while current quality indicators rarely capture the patients' perspective. Capturing patient-reported outcome measures (PROMs) as well as patient-reported experience measures (PREMs) is becoming more and more important to identify gaps in care provision, prioritize services most valuable to patients, and aid patients' self-management. OBJECTIVE: This study aims to measure the potential benefits and effectiveness of using electronic patient-reported outcome measures (ePROMs) and electronic patient-reported experience measures in a structured and population-based manner to enhance health care for chronic disease patients in Germany. METHODS: This prospective cohort study aims to evaluate the potential benefits of PROM usage in patients with chronic diseases. We evaluate whether (1) digitally collected PROMs and PREMs can be used for health system performance assessment by generating a representative response of chronically diseased individuals with asthma, chronic obstructive pulmonary disease, diabetes, and coronary artery disease across Germany, and (2) based on the PROMs and PREMs, low-value care can be identified. As patient-reported outcomes (PROs) are rarely presented back to patients, (3) this study also examines patients' reactions to their PROM scores in the form of digital PRO feedback. For these purposes, randomly selected patients from a nationwide German insurer are digitally surveyed with generic and disease-specific PROMs and PREMs, as well as additional questions on their health-related behavior, 4 times over 1 year. Individual PRO feedback is presented back to patients longitudinally and compared to a peer group after each survey period. Patient-reported data is linked with health insurance data. Response rates, changes in health and experience outcomes over time, self-reported changes in health behavior, and health care system usage will be analyzed. RESULTS: The PROMchronic study explores the usage of PROMs in patients with chronic diseases. Data collection began in October 2023, after the initial invitation letter. All the 200,000 potential patients have been invited to participate in the study. Data have not yet been analyzed. Publication of the interim results is planned for the autumn of 2024, and the results are planned to be published in 2025. CONCLUSIONS: We aim to fill the research gap on the population-based usage of PROMs and PREMs in patients with chronic diseases and add to the current understanding of PROM data-sharing with patients. The study's results can thereby inform whether a health care system-wide approach to collecting PROMs and PREMs can be used to identify low-value care, assess quality variation within and across chronic conditions, and determine whether PRO feedback is helpful and associated with any changes in patients' health behaviors. TRIAL REGISTRATION: German Clinical Trials Register DRKS00031656; https://drks.de/search/en/trial/DRKS00031656. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56487.

Immediate Impact of a Patient-Reported Outcome Measure Visual Dashboard on Cleft lip and Palate Care Provision.

Cleft-related Patient Reported Outcome Measure (PROM) results were formatted into graphical displays for children scoring below the 25th percentile on one or more scales. Reports were piloted in a multidisciplinary clinic where providers reviewed them, and their impact was qualitatively recorded. Graphical PROM reports informed discussions, led to treatment plan changes, and raised awareness of unmet psychosocial needs. Because of the success of this quality improvement pilot, visual PROM reports will become a regular part of our multidisciplinary cleft care. More broadly, graphical PROM data display facilitates better understanding of the patient's perspective and leads to more informed visits.

Quality of Life in Patients Affected by Facial Basal Cell Carcinoma: Prospective Longitudinal Pilot Study and Validation of Skin Cancer Index in Lithuanian Language.

Purpose: Facial basal cell carcinoma (BCC) poses significant challenges due to its potential for local destruction and impact on quality of life (QoL). Continuous research is necessary to identify novel factors influencing the quality of life within this demographic across diverse cultural settings. The aims of this study were to translate, culturally adapt, and validate the Lithuanian version of Skin Cancer Index, subsequently utilizing this questionnaire in the pilot phase of the study to achieve the following: (1) identify the differences in short- and long-term QoL, (2) establish empirical correlations between SCI scores and aesthetic facial regions, evaluate the potential differences between age, gender, and tumor size groups. Patients and Methods: A prospective longitudinal study was conducted with 100 consecutive patients. The SCI was translated into Lithuanian language, with a rigorous assessment of its psychometric properties to confirm validity. Alongside hypothesis testing, a detailed analysis of variables was conducted. Statistical techniques, including t-tests and ANOVA, were employed to compare scores across demographic and clinical groups, with effect size calculations for further interpretation. Results: Our findings demonstrate that the Lithuanian SCI successfully fulfills the criteria established by the COSMIN checklist. Surgical treatment for facial BCC notably enhances QoL, particularly evident six months post-surgery. Analysis of SCI scores identified demographic and clinical factors associated with lower QoL, including female gender, treatment with skin plasty, and tumor sites in aesthetically sensitive areas like the cheek, nose, and eyelid. Conclusion: The Lithuanian version of the SCI is a reliable and valid tool for assessing QoL in facial BCC patients. Our findings underscore the global relevance of understanding the multifactorial influences on QoL in BCC patients. Early diagnosis, less invasive treatment approaches, and tailored post-operative care are crucial in minimizing the psychological, social, and appearance-related burdens of facial BCC.

The gap between statistical and clinical significance: time to pay attention to clinical relevance in patient-reported outcome measures of insomnia.

BACKGROUND: Appropriately defining and using the minimal important change (MIC) and the minimal clinically important difference (MCID) are crucial for determining whether the results are clinically significant. The aim of this study is to survey the status of randomized controlled trials (RCTs) for insomnia interventions to assess the inclusion and interpretation of MIC/MCID values. METHODS: We conducted a cross-sectional study to survey the status of RCTs for insomnia interventions to assess the inclusion and appropriate interpretation of MIC/MCID values. A literature search was conducted by searching the main sleep medicine journals indexed in PubMed, the Excerpta Medica Database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify a broad range of search terms. We included RCTs with no restriction on the intervention. The included studies used the Insomnia Severity Index (ISI) or the Pittsburgh Sleep Quality Index (PSQI) questionnaire as the outcome measures. RESULTS: 81 eligible studies were identified, and more than one-third of the included studies used MIC/MCID (n = 31, 38.3%). Among them, 21 studies with ISI as the outcome used MIC defined as a relative decrease ranging from 3 to 8 points. The most frequently used MIC value was a 6-point decrease (n = 7), followed by 8-point (n = 6) and 7-point decrease (n = 4), a 4 to 5-points decrease (n = 3), and a 30% reduction from baseline; 6 studies used MCID values, ranging from 2.8 to 4 points. The most frequently used MCID value was a 4-point decrease in the ISI (n = 4). 4 studies with PSQI as the outcome used a 3-point change as the MIC (n = 2) and a 2.5 to 2.7-point difference as MCID (n = 2). 4 non-inferiority design studies considered interval estimation when drawing clinically significant conclusions in their MCID usage. CONCLUSIONS: The lack of consistent MIC/MCID interpretation and usage in outcome measures for insomnia highlights the urgent need for further efforts to address this issue and improve reporting practices.

Serum CD133-Associated Proteins Identified by Machine Learning Are Connected to Neural Development, Cancer Pathways, and 12-Month Survival in Glioblastoma.

Glioma is the most prevalent type of primary central nervous system cancer, while glioblastoma (GBM) is its most aggressive variant, with a median survival of only 15 months when treated with maximal surgical resection followed by chemoradiation therapy (CRT). CD133 is a potentially significant GBM biomarker. However, current clinical biomarker studies rely on invasive tissue samples. These make prolonged data acquisition impossible, resulting in increased interest in the use of liquid biopsies. Our study, analyzed 7289 serum proteins from 109 patients with pathology-proven GBM obtained prior to CRT using the aptamer-based SOMAScan® proteomic assay technology. We developed a novel methodology that identified 24 proteins linked to both serum CD133 and 12-month overall survival (OS) through a multi-step machine learning (ML) analysis. These identified proteins were subsequently subjected to survival and clustering evaluations, categorizing patients into five risk groups that accurately predicted 12-month OS based on their protein profiles. Most of these proteins are involved in brain function, neural development, and/or cancer biology signaling, highlighting their significance and potential predictive value. Identifying these proteins provides a valuable foundation for future serum investigations as validation of clinically applicable GBM biomarkers can unlock immense potential for diagnostics and treatment monitoring.

ATF1 promotes ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2.

BACKGROUND: Ferroptotic proteins are promising therapeutic targets for lung cancer. The PROM2 is upregulated in lung cancer and known to suppress ferroptosis. This study examined the molecular mechanisms for PROM2-induced ferroptosis resistance in lung cancer. METHODS: Ferroptosis in lung cancer was assessed by iron kit, and transmission electron microscopy was applied to observe the changes in mitochondrial morphology. BODIPY™ was applied to test the lipid ROS, and MeRIP was performed to test the m6A modification of PROM2. RIP assay was employed for confirming the binding between METTL3 and PROM2. In addition, dual luciferase assay was employed for exploring the transcriptional regulation of ATF1 to METTL3, and the binding relation between ATF1 and METTL3 promoter region was explored by ChIP assay. RESULTS: Expression levels of PROM2 were significantly higher in lung cancer cell lines than a noncancerous control line, and PROM2 knockdown significantly reduced both cancer cell viability and proliferation rate. In addition, PROM2 knockdown reduced xenograft tumor growth and exacerbated erastin-induced ferroptosis. Compared to PROM2 mRNA from control cells, transcripts in lung cancer cells exhibited enhanced m6A levels, and showed greater binding with METTL3. Further, ATF1 upregulated METTL3 transcription, thereby stabilizing PROM2 mRNA and increasing ferroptosis resistance. CONCLUSION: ATF1 could promote ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2. Thus, our work might shed novel insights on discovering therapeutic strategy for lung cancer.

Clinically most relevant psychometric properties of the Lower Extremity Functional Scale: a systematic review.

PURPOSE: To systematically review and summarize the literature on minimal detectable change (MDC) and minimal clinically important difference (MCID) values for the Lower Extremity Functional Scale (LEFS). METHODS: The databases that were searched included PubMed, Embase, Medline, and CINAHL, from database inception to August 2023. The inclusion criteria were studies that examined the MDC or MCID of the LEFS in various patient populations and languages. The data extracted included information regarding test-retest reliability, MDC, MCID, and the intervals between assessments. RESULTS: Twenty-four studies defined MDC and five studies MCID values for the LEFS. They review reported a wide range of MDC values, spanning 11 language versions and a variety of diagnoses, with testing intervals ranging from 1 day to 12 months. MCID values were defined with corresponding area under curve, specificity, and sensitivity metrics for three language versions and a variety of diagnoses across timeframes from 4 weeks to 12 months. CONCLUSIONS: The review defined MDC and MCID values that can be applied in clinical practice for the LEFS across a variety of timeframes, diagnoses, and languages. The findings of this study allow clinicians use the identified MDC and MCID values of the LEFS when interpreting clinical outcome data.

The systematic review identified 24 studies on the minimal detectable change (MDC) and five on the minimal clinically important difference (MCID) of the Lower Extremity Functional Scale (LEFS) across different timeframes, diagnoses, and language versions that can be applied in clinical practice.Clinicians can use the MDC and MCID values of the LEFS to make decisions regarding changes in patient scores over time.Clinicians should be cautious about interpreting the MDC and MCID values contextually, considering factors such as language, timeframe, and specific diagnoses.

Parent reported outcomes for idiopathic clubfoot children treated with the Ponseti technique: An analysis of 140 feet followed minimum 5 years.

Objective: The treated clubfoot children are often evaluated clinically during follow-up. However, patient reported outcomes (PROM) are seldom analysed for these children. We investigated 87 idiopathic clubfoot children (140 feet) treated by the Ponseti method and followed minimum 5 years to study their clinical outcomes and PROM. Material and methods: This was a cross-sectional study, based on evaluating treated clubfoot children clinically (Pirani score) and PROM (Oxford Ankle and Foot Questionnaire - Parent Version) and comparing them with the age-matched healthy controls (n = 60). The questionnaire has four main domains related to the child's physical, school and play, emotional and footwear profile. The children having persistent deformity (residual/relapse) were specifically studied for their PROM scores. Results: The mean child age at initial treatment was 2.3 months and the mean follow-up duration was 6.9 years. The PROM score of clubfoot children was statistically lower than the healthy controls (p < 0.001). Of the individual domains, the physical domain was the most affected. On calculating the Pirani scores, 10 out of 140 feet (7 %) had some form of persistent deformity. The children with persistent deformity had lower Oxford scores than healthy children or those with corrected feet. The physical domain followed by the emotional domain scored low when persistent deformity was present. Conclusions: Most children (98 %) had a plantigrade foot following Ponseti treatment at follow-up. However, PROM score of the clubfoot children did not correspond to the clinical outcome. Persistent deformity, even minor, was a cause of parental concern and resulted in a low PROM score.

Development of a Vitamin B12 Deficiency Patient-Reported Outcome Measure for Clinical Practice and Research.

BACKGROUND: It is difficult to recognize vitamin B12 deficiency and to evaluate the effect of B12 treatment due to a broad range of variable clinical symptoms overlapping with other diseases and diagnostic biomarkers that quickly normalize during treatment. This poses a risk of delay in diagnosis and a challenge to uniformly monitor the effect of B12 treatment. There is a need for a new clinical outcome measure suitable for clinical practice and clinical evaluation studies. OBJECTIVE: To develop a Patient-Reported Outcome Measure (PROM) which measures the severity of vitamin B12 deficiency symptoms. METHODS: The B12 PROM was developed by (1) gathering input from experts and literature review to define a construct and develop a conceptual model, (2) processing input from health care providers, scientists, and patients to develop items and response options, and (3) improving items based on the feedback from laypersons, test interviews, semi-structured cognitive interviews with patients, and forward and backward translation (ENG-NL). RESULTS: The B12 PROM includes 62 items grouped into 8 categories of symptoms related to vitamin B12 deficiency (General, Senses, Thinking, In limbs and/or face, Movement, Emotions, Mouth & Abdomen, Urinary tract & Reproductive organs). Cognitive interviews demonstrated good comprehensibility and comprehensiveness. CONCLUSIONS: This study is the first step in the development of a disease-specific PROM for vitamin B12 deficiency to measure the burden of symptoms. Further validation and reliability testing are necessary before the PROM can be applied in clinical practice and research.

Plain language titleDevelopment of a Vitamin B12 Deficiency Questionnaire for Clinical Practice and ResearchPlain language summaryThis study is the first step in the development of a questionnaire for vitamin B12 deficiency to measure the severity of vitamin B12 deficiency symptoms. The questionnaire includes 62 items grouped into 8 categories of symptoms related to vitamin B12 deficiency (General, Senses, Thinking, In limbs and/or face, Movement, Emotions, Mouth & Abdomen, Urinary tract & Reproductive organs). Interviews with patients demonstrated good comprehensibility and comprehensiveness of the questionnaire. Further testing is necessary before the questionnaire can be applied in clinical practice and research.

Performing region-specific tasks does not improve lower extremity patient-reported outcome scores.

BACKGROUND: Patient-reported outcome measures quantify outcomes from patients' perspective with validated instruments. QuickDASH (Quick Disability of Arm, Shoulder and Hand, an upper extremity PROM) scores improve after completing instrument tasks, suggesting patient-reported outcome results can be modified. We hypothesized that performing lower extremity tasks on the knee injury and osteoarthritis outcome score for joint reconstruction (KOOS-JR) and hip disability and osteoarthritis outcome score for joint reconstruction (HOOS-JR) instruments would similarly improve the scores. METHODS: Forty seven hip and 62 knee osteoarthritis patients presenting to a suburban academic center outpatient osteoarthritis and joint replacement clinic were enrolled and randomized to an intervention or a control group. Inclusion criteria were age over 18 years and English competency. Patients completed a HOOS-JR or KOOS-JR instrument, completed tasks similar to those of the instrument (intervention) or the QuickDASH (control), and then repeated instruments again. Paired and unpaired t-tests were used to compare the intervention and control group scores before and after tasks. RESULTS: There was no significant difference in total or individual scores after task completion compared to baseline in either the HOOS-JR or the KOOS-JR groups. There was no significant difference in the scores between the intervention or control groups. CONCLUSIONS: Disability may be less modifiable in the lower extremity than in the upper extremity, perhaps because upper extremity activities are more easily compensated by the contralateral limb, or because lower extremity activities are more frequent. Thorough evaluation of factors influencing patient-reported outcome measures is necessary before their extensive application to quality control and reimbursement models.

Trends in reported outcomes and patient reported outcome measures (PROMs) in humeral shaft fracture literature: a systematic review.

PURPOSE: With a lack of standardization among outcome measures in fracture literature, cross-study comparisons remain limited. This systematic review aimed to identify trends in outcome measures reported by studies of the treatment of humeral shaft fractures. METHODS: A systematic review was performed of studies reporting clinical outcomes of humeral shaft fractures indexed in PubMed. Extracted data included demographics, fracture characteristics, treatment modalities, outcomes, patient reported outcome measures (PROMs), and journal characteristics. Cochran-Armitage tests and linear regressions were used to identify data trends. Pearson chi-square and Kruskal-Wallis tests were used for comparisons between studies. RESULTS: This review included 197 studies with outcomes of 15,445 humeral shaft fractures. 126 studies reported PROMs and 37 different PROMs were used. The Constant Score was most commonly reported (34% of studies), followed by ASES Score (21%), MEPS (21%), and DASH Score (20%). There was a significant increase in PROM usage over time (p = 0.016) and in articles using three or more PROMs (p = 0.005). The number of PROMs were significantly greater in prospective cohort studies and RCTs (p = 0.012) compared to retrospective cohort studies and case series (p = 0.044 for both). Post-treatment shoulder motion was reported in 43% of studies and 34% reported elbow motion. 86% of studies reported complications as an outcome parameter. Time to union and nonunion rate were published in 69% and 88% of studies, respectively. CONCLUSION: This study identified increasing PROM usage over time and disparities in the reporting of outcomes in humeral shaft fracture literature requiring further validation and standardization of available outcome measures.

Patient-Reported Outcome Measures in Rhinitis and Chronic Rhinosinusitis.

Patient-Reported Outcome Measures (PROMs) are valuable in the assessment and management of rhinitis and chronic rhinosinusitis [CRS]. They measure outcomes which may include symptoms, disease control, well-being, and health-related quality of life (QOL). PROMS for rhinitis and rhinosinusitis are often used before and after an intervention, e.g., medication, therapeutic procedure or, in allergic rhinitis (AR), allergen immunotherapy. Although widely used in clinical trials for AR and conjunctivitis, symptom score PROMs are less validated than disease control or QOL measures. The best validated PROM for AR is the RQLQ (Rhinitis Quality of Life Questionnaire), but there is no universally accepted criterion standard for symptom and disease control PROMs. For CRS, at least 15 different criteria have been used to assess disease control in clinical studies, but what CRS disease control means and how it should be measured are concepts in evolution. The most used QOL measure for CRS is the SNOT-22 Sinonasal Outcome Test (SNOT-22). The use of PROMs to support clinical decisions and for shared decision making for rhinitis and rhinosinusitis still has many challenges, including selection of the preferred instrument, when and how to administer, the impact of co-morbidities, and questionnaire fatigue for both patient and provider.

Patient-Rated Wrist Evaluation Threshold for Successful Open Surgery of the Triangular Fibrocartilage Complex.

Purpose To determine thresholds in patient-reported outcome measures at baseline in patients electing to undergo triangular fibrocartilage complex (TFCC) surgery to select patients with clinically improved outcomes. Methods The study cohort comprised consecutive patients who underwent open TFCC repair between December 2011 and December 2018 in various clinics in the Netherlands. All patients were asked to complete the patient-rated wrist evaluation (PRWE) questionnaire at baseline as well as at 12 months postoperatively. The minimal clinically important difference (MCID) for the PRWE was calculated to be 24 using an anchor-based method. We compared patient, disease, and surgical characteristics between patients who did and did not reach the MCID. The t -tests and chi-square tests were undertaken to test differences between outcomes and satisfaction in patients who did or did not reach the MCID. Results Patients (34%) who did not reach MCID had a longer history of complaints. The chances of reaching the MCID for patients with a low PRWE score at baseline were slim. Of patients with a PRWE score <34 at baseline, only 14% reached the MCID, whereas in patients with a PRWE score of ≥34, 69% reached the MCID. Conclusion A PRWE total score at baseline <34 is a strong signal to reconsider open surgery of the TFCC because the chance of reaching a clinically meaningful outcome is slim. Level of Evidence II. Type of Study Therapeutic.

Clinical exome analysis and targeted gene repair of the c.1354dupT variant in iPSC lines from patients with PROM1-related retinopathies exhibiting diverse phenotypes.

BACKGROUND: Inherited retinal dystrophies (IRD) are one of the main causes of incurable blindness worldwide. IRD are caused by mutations in genes that encode essential proteins for the retina, leading to photoreceptor degeneration and loss of visual function. IRD generates an enormous global financial burden due to the lack of understanding of a significant part of its pathophysiology, molecular diagnosis, and the near absence of non-palliative treatment options. Patient-derived induced pluripotent stem cells (iPSC) for IRD seem to be an excellent option for addressing these questions, serving as exceptional tools for in-depth studies of IRD pathophysiology and testing new therapeutic approaches. METHODS: From a cohort of 8 patients with PROM1-related IRD, we identified 3 patients carrying the same variant (c.1354dupT) but expressing three different IRD phenotypes: Cone and rod dystrophy (CORD), Retinitis pigmentosa (RP), and Stargardt disease type 4 (STGD4). These three target patients, along with one healthy relative from each, underwent comprehensive ophthalmic examinations and their genetic panel study was expanded through clinical exome sequencing (CES). Subsequently, non-integrative patient-derived iPSC were generated and fully characterized. Correction of the c.1354dupT mutation was performed using CRISPR/Cas9, and the genetic restoration of the PROM1 gene was confirmed through flow cytometry and western blotting in the patient-derived iPSC lines. RESULTS: CES revealed that 2 target patients with the c.1354dupT mutation presented monoallelic variants in genes associated with the complement system or photoreceptor differentiation and peroxisome biogenesis disorders, respectively. The pluripotency and functionality of the patient-derived iPSC lines were confirmed, and the correction of the target mutation fully restored the capability of encoding Prominin-1 (CD133) in the genetically repaired patient-derived iPSC lines. CONCLUSIONS: The c.1354dupT mutation in the PROM1 gene is associated to three distinct AR phenotypes of IRD. This pleotropic effect might be related to the influence of monoallelic variants in other genes associated with retinal dystrophies. However, further evidence needs to be provided. Future experiments should include gene-edited patient-derived iPSC due to its potential as disease modelling tools to elucidate this matter in question.

Feasibility of weekly cisplatin and radiotherapy for localized anal cancer - A Danish anal cancer group report.

BACKGROUND: Chemoradiotherapy (CRT) with flourouracil and mitomycin is the standard treatment for squamous cell carcinomas of the anus (SCCA), however the associated acute toxicity often hinders compliance. Although weekly cisplatin is a well-established treatment for other squamous cell carcinomas, it has not been explored in SCCA. PURPOSE: To investigate if radiotherapy (RT) with weekly cisplatin is a feasible option for SCCA and to report the acute toxicity. MATERIAL/METHODS: Patients were treated with RT and weekly cisplatin 40 mg/m2 between 1998-2020. Retrospective data from medical records (n=65) and prospectively collected data from an observational study (n=51) comprising physician assessed toxicity (NCI-CTCAE 4.0), patient-reported outcomes (EORTC-QlQC30 + CR29) baseline, mid-therapy, end of treatment and 2-4 weeks post-treatment were included. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: We included 116 patients. T-stages were T1:4%, T2: 71%, T3: 17%, T4: 8% and 47% has N+ disease. RT doses were 53.75-64 Gy/45-51.2 Gy and the mean cumulative dose of cisplatin was 307.5 mg. The median overall treatment time was 43 days. Within 6 months after CRT 88.9 % had complete response. The median follow-up time was 4.5 years and 5-year DFS and OS were 77% (95%CI 68.7;84.5%) and 86.4% (95%CI 78.3;91.7%), respectively. Hospitalization occured in 20% with 2.6% being admitted due to febrile neutropenia. Hematological toxicity was low with 13.7% grade 3 and 3.9% grade 4. Anal pain, skin, gastrointestinal and urogenital toxicity were mild. CONCLUSION: RT and weekly cisplatin for SCCA showed good outcome results and an acceptable acute toxicity profile.

Patient-reported assessment of compassion in Spanish: a systematic review.

Aims and objectives: This systematic review aims to: (1) explore which tools have been used in Spanish to measure compassion; (2) know which of these tools could be used to assess compassion in healthcare settings from the perspective of patients; (3) evaluate the quality of these patient-reported measures in Spanish contexts; and (4) determine which of these instruments would be best suited to be used in healthcare settings. Background: Compassion has been recognized as a fundamental dimension of quality healthcare. Methods: Several scientific databases were consulted for relevant records published up to December 16th, 2021. In accordance with PRISMA guidelines, 64 studies were included. Results and conclusions: while existing instruments, validated in Spanish, allow for the measurement of self-compassion or compassion to others, there are no valid and reliable measures currently available in Spanish to measure patient-reported compassion. Relevance to clinical practice: In order to ensure and promote compassion in the health care context, it is essential to have a valid and reliable tool to measure this construct in a patient-informed way, and this is currently not possible in the Spanish-speaking context because of the lack of such an instrument in Spanish.