Problems and Opportunities of a Smartphone-Based Care Management Platform: Application of the Wald Principles to a Survey-Based Analysis of Patients' Perception in a Pilot Center.

(1) Background: Mobile health (mHealth) solutions can become a means of improving functional recovery and reducing the peri-operative burden and costs associated with arthroplasty procedures. The aim of this study is to explore the objectives, functionalities, and outcomes of a platform designed to provide personalized surgical experiences to qualified patients, along with the associated problems and opportunities. (2) Methods: A survey-based analysis was conducted on patients who were prescribed the use of a specific care management platform and underwent primary robotic total knee arthroplasty (rTKA) between January 2021 and February 2023. (3) Results: Patients registered on the platform who have undergone primary robotic TKA (rTKA) were considered. The mean age of registered patients is 68.6 years. The male (M)/female (F) ratio is 45.1%/54.9%. The patients interviewed were at an average distance of 485 days from the intervention, with a standard deviation of 187.5. The survey highlighted appreciation for the app and its features, but also limitations in its use and in its perception by the patients. All these data were evaluated according to the Wald principles and strategies to improve patient recruitment, enhance adherence, and create a comprehensive patient journey for optimized surgical experiences. (4) Conclusions: This patient care platform may have the potential to impact surgical experiences by increasing patient engagement, facilitating remote monitoring, and providing personalized care. There is a need to emphasize the importance of integrating the recruiting process, improving adherence strategies, and creating a comprehensive patient journey within the platform.

Role of systemic immunosuppression on subglottic stenosis in granulomatosis with polyangiitis: Analysis of a single-centre cohort.

PURPOSE: Subglottic stenosis (SGS) is a potentially life-threatening manifestation of granulomatosis with polyangiitis (GPA). Endoscopic dilation is effective, but relapses are frequent and the benefit of systemic immunosuppression in this setting is still controversial. We aimed to investigate the role of immunosuppressive treatment on SGS relapse risk. METHODS: This is a retrospective observational study based on review of medical charts among our cohort of patients with GPA. RESULTS: Twenty-one patients with SGS-GPA were identified, with a prevalence of 20% among our entire GPA cohort (n = 105). Compared to patients without SGS, patients with SGS-GPA had an earlier disease onset (mean age 30.2 vs. 47.3 years, p<0.001), and lower BVAS (mean 10.5 vs 13.5; p = 0.018). Five patients didn't receive systemic immunosuppression for SGS and they all (100%) relapsed after the first procedure, while among medical treatment group relapse rate was 44% (p = 0.045). When single treatment regimens are considered, rituximab (RTX) and cyclophosphamide (CYC) yielded a protective role towards the need of subsequent dilation procedure after the first if compared with absence of medical treatment. Patients with SGS and generalized disease, who initially received either a RTX- or a CYC-based induction treatment, and higher cumulative doses of glucocorticoids, showed a delayed median time to SGS relapse (36 vs. 12 months, p = 0.024). CONCLUSIONS: Subglottic stenosis is highly prevalent in patients with GPA and may define a milder systemic disease subset occurring more frequently in younger patients. Systemic immunosuppression provides benefit in preventing recurrence of SGS in GPA patients and regimens based on cyclophosphamide or rituximab might have a non-redundant role in this setting.

Caffeine and rheumatoid arthritis: A complicated relationship.

The current ideal goal of rheumatoid arthritis (RA) management is to resolve joint and systemic inflammation by using pharmacological interventions, assuming this will correspondingly lead to overall well-being. Nonetheless, it has emerged that a substantial number of RA patients do not reach optimal disease control, thus suggesting the holistic management of subjective symptoms might be overlooked. This poses significant medical challenges; hence the proposal of incorporating lifestyle interventions as part of a multidimensional approach. Among these aspects, both patients and physicians perceive the important role of nutrition. This review shall examine how caffeine, one of the most studied bioactive components of the most widely consumed beverages, may potentially interfere with RA management. In particular, the mechanism by which caffeine affects RA pathogenesis, as a trigger for RA onset or flare, including its influence on rheumatic drug metabolism and the most common RA comorbidities and constitutional symptoms are outlined, highlighting important knowledge gaps and unmet research needs.

Central role of mitochondria and p53 in PUVA-induced apoptosis in human keratinocytes cell line NCTC-2544.

Despite strong evidence concerning the high efficiency of PUVA therapy (psoralen plus UVA light), its mechanism of action has not yet been fully elucidated. In this study, we have evaluated in a cell line of human keratinocytes (NCTC-2544) the effects of two linear psoralen derivatives, 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP), that are widely used in PUVA therapy and two angular derivatives, Angelicin (ANG) and 4,6,4'-trymetyl angelicin (TMA). All derivatives photoinduce cellular death, TMA being the most active compound. The cell cycle analysis showed that the four derivatives induce, 24 h after irradiation, a cell cycle arrest in G1 phase later followed by massive apoptosis. The G1 arrest is correlated to an increase in the expression of p21(Waf1/Cip1), a protein associated with the cell cycle block and apoptosis. Furthermore, treatment of NCTC-2544 resulted in p53 activation by 5-MOP, 8-MOP, and ANG but not TMA and its phosphorylation at serine-15. The levels of p21(Waf1/Cip1) paralleled p53 protein staining pattern suggesting that p53 activation correlated with p21(Waf1/Cip1) induction. Simultaneous to p53 activation, psoralens induced mitochondrial depolarization, cytochrome c release, mitochondrial production of reactive oxygen species, as well as caspase-3 and -9 activation. Thus these results strongly indicate the necessity of p53 activation and the induction of the apoptotic machinery downstream of mitochondria.

Two consecutive immunophenotypic switches in a child with MLL-rearranged acute lymphoblastic leukemia.

An 18-month-old girl was diagnosed with pre-pre-B ALL/t(4;11) leukemia, which during the treatment and after matched bone marrow transplantation (BMT), underwent two consecutive switches from lymphoid to myeloid lineage and vice versa. The high expression of HOXA9 and FLT3 genes remaining genotypically stable in a leukemia throughout phenotypic switches, suggests that this leukemia may have originated as a common B/myeloid progenitors.

Immunogenotype changes prevail in relapses of young children with TEL-AML1-positive acute lymphoblastic leukemia and derive mainly from clonal selection.

PURPOSE: Variations of the immunogenotype and TEL deletions in children with TEL-AML1+ acute lymphoblastic leukemia support the hypothesis that relapses derive from a persistent TEL-AML1+ preleukemic/leukemic clone rather than a resistant leukemia. We aimed at elucidating the relationship between the immunogenotype patterns at diagnosis and relapse as well as their clinical and biological relevance. PATIENTS AND METHODS: Immunoglobulin and T-cell receptor gene rearrangements were analyzed in 41 children with a TEL-AML1+ acute lymphoblastic leukemia and an early (up to 30 months after diagnosis; n = 12) or late (at 30 months or later; n = 29) disease recurrence by a standardized PCR approach. RESULTS: In 68% of the patients (group I), we identified differences in the immunogenotype patterns, whereas no changes were observed in the remaining 32% (group II). The divergence resulted more often from clonal selection than clonal evolution and consisted predominantly of losses (0-6, median 5) and/or gains (0-4, median 1) of rearrangements. The frequency and number of clonal immunoglobulin/T-cell receptor rearrangements in group I was higher at diagnosis (2-13, median 5) than at relapse (2-7, median 4), whereas it was the lowest in group II (1-5, median 3). Although group I children were younger at diagnosis, there was no correlation between particular immunogenotype patterns and remission duration. CONCLUSION: These findings imply that the clonal heterogeneity in younger children most likely reflects an ongoing high recombinatorial activity in the preleukemic/leukemic cells, whereas the more uniform repertoire observed in older children mirrors end-stage rearrangement patterns of selected cell clones that evolved during the prolonged latency period.