Cohort Of Patients Research Articles

Ixekizumab Improves Nail, Scalp, and Skin Response and Quality of Life Independent of Baseline Psoriasis Severity: Results From the Psoriasis in Special Areas (PSoSA) Study

Background: Ixekizumab has shown impressive efficacy among patients with nail, skin, and scalp psoriasis. Here, we present real-world data from the PSoSA study evaluating effectiveness of ixekizumab by cohorts of patients with mild and moderate/severe nail psoriasis. Methods: PSoSA is an ongoing, prospective, multicenter, single-arm, observational study enrolling adult patients with confirmed diagnosis of moderate-to-severe psoriasis and nail involvement, with or without scalp involvement, initiating ixekizumab in a US dermatology clinic. Assessment of improvements in nail (by modified Nail Psoriasis Severity Index [mNAPSI], with scoring range 0–130), skin (by Psoriasis Area and Severity Index [PASI], with scoring range 0–72), and scalp (by Psoriasis Scalp Severity Index [PSSI], with scoring range 0–72) response and in quality of life (by Dermatology Life Quality Index [DLQI], with scoring range 0–30) were collected at weeks (W) 4, 12, 24, and 52. Percent change was calculated for patients with non-missing baseline values. Data were stratified by nail psoriasis severity at baseline; patients with mNAPSI scores <20 were categorized as mild while those with scores ≥20 were categorized as moderate/severe. In our second interim analysis, we will be reporting data to W24. Results: Of 182 patients included in the analysis, 101 patients had baseline mNAPSI scores <20 and 81 had scores ≥20. Median percent changes from baseline in mNAPSI response at W4, W12, and W24 were −12.2, −33.3, and −71.9, respectively, for patients with baseline scores <20 and −6.1, −38.7, and −68.6, respectively, for patients with scores ≥20. Median percent changes from baseline in PASI response at W4, W12, and W24 were −60.0, −91.2, and −100.0, respectively, for patients with baseline mNAPSI scores <20 and −62.7, −91.4, and −96.7, respectively, for patients with scores ≥20. Median percent changes from baseline in PSSI response at W4, W12, and W24 were −79.3, −100.0, and −100.0, respectively, for patients with baseline mNAPSI scores <20 and −87.5, −100.0, and −100.0, respectively, for patients with scores ≥20. Median percent changes from baseline in DLQI response at W4, W12, and W24 were −66.7, −77.8, and −89.7, respectively for patients with baseline mNAPSI scores <20, and −57.1, −70.0, and −88.7, respectively, for patients with scores ≥20. Conclusions: In a real-world setting, patients with moderate-to-severe psoriasis initiating ixekizumab saw major improvements in nail, skin, and scalp response as well as quality of life as early as 4 weeks and sustained through 24 weeks, independent of nail psoriasis severity at baseline.

Demographics and Disease Characteristics of Patients with Alopecia Areata with Comorbid Atopic Dermatitis, Vitiligo or Anxiety/Depression: TARGET-DERM AA

Introduction Alopecia areata (AA) is a chronic autoimmune disease. Common AA comorbidities include atopic dermatitis (AD), vitiligo, anxiety and depression (AnxDep). TARGET-DERM AA is an ongoing longitudinal, real-world study of United States and Canadian AA patients. The purpose of this analysis is to assess characteristics among AA patients with and without the above comorbidities. Methods At enrollment (December 2021-June 2024), patients reported outcomes (including comorbidities, Patient Global Impression of Severity-AA, and clinician-reported outcome measures: Severity of Alopecia Tool, Measure for Eyebrow/Eyelash Hair Loss). Characteristics were compared across subgroups. Results Of the 267 AA patients with completed patient questionnaires at enrollment, 61.4% were female; 24.4% were aged <12 years, 13.7% 12-17, and 61.7% 18 or older. Overall, 21.0% self-reported an AD diagnosis (19.7% of pediatric, 11.1% of adolescent, and 25.4% of adult AA patients), 7.1% vitiligo (7.0% of pediatric, 3.7% of adolescent, and 8.5% of adult AA patients) and 44.9% AnxDep (21.1% of pediatric, 40.7% of adolescent, and 58.5% of adult AA patients). 42.1% of patients with comorbid vitiligo had severe AA disease (SALT>50) and 27.8% patients without comorbid vitiligo had SALT>50. 28.6% of those with comorbid AD had SALT>50 compared to 28.9% of those not reporting AD, with 30.0% of AnxDep and 27.9% of non-AnxDep having SALT>50, all p>0.2. 42.1% of patients with comorbid vitiligo reported PGIS-AA ‘severe/very severe’ disease, with 41.1% of patients with comorbid AD and 42.5% of patients with comorbid AnxDep reporting severe/very severe AA disease, all numerically higher than patients without comorbid vitiligo (36.3%), AD (35.6%), and AnxDep (31.9%), all p>.07. Among those with and without vitiligo, 42.1% vs 37.9% had eyebrow involvement, 36.8% vs 30.2% eyelash; considering AD, 35.7% vs 38.9% had eyebrow involvement, 28.6% vs 31.3% eyelash; for AnxDep 39.2% vs 37.4% had eyebrow involvement, 30.8% v 30.6% eyelash, all p>0.5. Discussion In this real-world cohort of AA patients, the presence of specific comorbidities was not associated with statistically significant differences in clinician reported AA severity, eyebrow or eyelash involvement. Comorbid AnxDep was associated with increased patient-reported AA disease severity. Additional research characterizing how dermatologic and psychiatric comorbidities impact health-related quality of life and patient burden has the potential to inform management decisions.

A Novel Technique for Top Surgery in Small-Breasted Individuals Who Experience Gender Dysphoria – Concentric Periareolar Mastectomy, Interlocking Suture and Waterjet-Assisted-Liposuction

Background: In small-breasted individuals, who experience gender dysphoria, the concentric periareolar approach is typically the preferred method for mastectomy. However, this method carries a notable risk of hypertrophic scars and changes in the areolar dimensions. This study introduces the periareolar interlocking suture (PIS) as a new scar-minimizing procedure, with a low complication rate and high patient satisfaction. Patients and Methods: We performed a concentric periareolar mastectomy (CPM) combined with PIS and waterjet-assisted liposuction (WAL) in patients with small breasts (A to B-Cup) and good skin quality/elasticity. Outcome measures included complication rates, patient satisfaction (assessed via the BODY-Q Chest and Nipples Scale and scar appearance), nipple sensitivity, and the rate of surgical corrections. Results: Between April 2017 and December 2023, we conducted 2312 mastectomies in 1156 people who experience gender dysphoria, with 410 breasts treated using CPM combined with PIS and WAL. The mean patient age was 23 years, mean hospital stay was 4 days, and mean operation time was 96.1 minutes. The overall complication rate was 7.8%, with acute hematomas occurring in 4.6% of the cases. Secondary revisions were necessary in only 2.2% of cases. Patient satisfaction, measured using the BODY-Q scale, was statistically significant and very high. Conclusion: Individuals with gender dysphoria are well-informed and increasingly demand aesthetic outcomes. Whenever feasible, procedures with minimal scarring are preferred. The technique presented here resulted in very high patient satisfaction, preserved nipple sensitivity, and a low rate of complications and secondary aesthetic corrections in a carefully selected cohort of patients with small breasts.

Predictors of Mortality and Neurological Complications in a Large Cohort of Patients With COVID-19

Objectives: This study aimed to investigate the association between the baseline clinical and laboratory characteristics of patients with COVID-19 and their risk of subsequent development of neurological complications and mortality. Methods: This retrospective, single-center cohort study included patients with COVID-19 who presented to the Emergency Department of Razi Hospital. Patients’ charts were reviewed to collect baseline clinical and laboratory data. Results: Of 2205 patients with COVID-19, 1473 (66.8%) developed various neurological complications in addition to other symptoms. Among the 168 patients who died, 66.66%, 43.5%, and 25% had a history of neurological disorders, encephalopathy, and stroke, respectively. Disease severity was significantly associated with comorbidities, hypoxemia, hypoalbuminemia, hypophosphatemia, elevated ESR, hypomagnesemia, stroke, and encephalopathy (P<0.05). The risk of death remained strongly linked to older age, comorbidities, severe infection, ICU admission, and extended hospitalization (P<0.05), even after adjustments, indicating they are potential confounders for other variables. More importantly, in non–critically ill patients, there was no significant association between the risk of death and hypoxemia, anemia, thrombocytopenia, hypomagnesemia, stroke, and encephalopathy (P>0.05). Moreover, the association between encephalopathy and other factors was greatly influenced by disease severity. Nonetheless, older age, comorbidities, and anemia remained significant predictors of stroke even after adjusting for confounders (P<0.05). Conclusions: The high rates of neurological disorders among deceased patients with COVID-19 underscores the need for early prediction and management of these complications. Moreover, neurological disorders were linked to an increased risk of death because they tend to be present in critically ill patients admitted to the ICU with extended hospitalization.

Retrospective Analysis of the Impact of Screening for Psoriatic Arthritis (PsA) with the Psoriasis Epidemiology Screening Tool (PEST) in Clinical Dermatology Practice

Introduction: Patients with plaque psoriasis (PSO) have an increased risk of developing PsA as the disease severity progresses. While it is estimated that 30% of patients with PSO have PsA, nearly 16% of patients with PSO may have undiagnosed PsA.1,2 Implementing the PEST questionnaire for PsA screening in dermatologic practice may increase early intervention by improving rates of timely diagnosis.3 This observational study aimed to assess the proportion of patients with PSO and no previous PsA diagnosis who screened positive on the PEST and were then diagnosed with PsA by a healthcare provider in the PEST deployment period within the Advanced Dermatology and Cosmetic Surgery (ADCS) specialty dermatology network. Procedure/Study: De-identified, real-world patient data [2018–2019 and 2021–2022] were sourced from electronic health records within the ADCS network of outpatient facilities across 14 states in the United States. Patients were included in the analysis if they received care at an ADCS facility where the PEST was deployed, had ≥1 encounter with a diagnosis code for PSO, and never had a diagnosis code for PsA before their first diagnosis code for PSO. For outcomes directly related to PEST evaluations, data from 1/1/2021–12/31/2022 (PEST deployment period) were used. For outcomes not directly related to PEST results, data from 1/1/2018–12/31/2019 (period before PEST deployment) were evaluated. Descriptive statistics, including frequencies, percentages, and 95% confidence intervals (CIs) for categorical variables, were used to characterize the patient cohorts by study period. Results: Among ADCS facilities using the PEST during the deployment period (44% of practices in the network), the final study population included 14,308 and 21,142 patients with PSO in the period before PEST deployment and during the PEST deployment period, respectively. In the PEST deployment cohort, 1,100 (5.2%; 95% CI: 4.9–5.5) patients were screened using the PEST. In the period before PEST deployment, 327 (2.3%; 95% CI: 2.0–2.5) patients with PSO and no previous PsA diagnosis were subsequently diagnosed with PsA. During the PEST deployment period, 449 (2.1%; 95% CI: 1.9–2.3) patients with PSO and no previous PsA diagnosis received a subsequent PsA diagnosis without PEST screening. Of all patients with PSO who screened positive for PsA on the PEST (score ≥3; n=296), 10.8% (n=32; 95% CI: 7.6–15.1) subsequently received a formal PsA diagnosis during the PEST deployment period. Conclusion: These results suggest that a meaningful proportion of patients with PsA may be underdiagnosed in the dermatology setting. Deployment of the PEST in the clinical dermatologic workflow may provide an opportunity to diagnose PsA earlier and improve patient outcomes.

Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment

AbstractCutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.

Abstract IA020: Deciphering the mechanisms of neutrophil immune response in bone metastatic prostate cancer

Abstract Metastatic disease of prostate cancer (PCa) is currently incurable. Bone is the most common tissue site for prostate cancer metastasis and progression in bone is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that bone marrow neutrophils inhibit bone metastatic PCa growth, however metastatic PCa becomes resistant to neutrophil response and progresses within the bone compartment. It is unclear how these findings translate to a clinical setting. Further, the mechanisms associated with tumor resistance to neutrophil immune response remain unknown and presents a new avenue for therapeutic intervention. Thus, the goals of this study were: 1) to define the impact of metastatic PCa on neutrophil function throughout prostate cancer progression and 2) to determine the potential of neutrophils as predictive biomarkers of PCa disease progression. To do this, peripheral blood polymorphonuclear neutrophils (PMNs) were collected from 4 patient cohorts (localized PCa, metastatic hormone-sensitive PCa (mHSPC), metastatic castration-resistant (mCRPC) and healthy men) and PMN molecular and functional properties assessed, including: cancer cell cytotoxicity and cell surface markers. There was a significant decrease with disease progression in PMN expression of CD10, a marker for differentiation, while in tandem, there was an increase in pro-inflammatory marker, CD88 (complement receptor) in mCRPC men compared to mHSPC. PMNs from all disease stages were equally cytotoxic to human PCa cell lines (LNCaP, C42B, and PC3). However, second generation androgen deprivation therapy (ADT) suppressed patient PMN cytotoxicity against mCRPC cells (C42B, PC3). This suppression was due to androgen receptor (AR)-mediated regulation of the pleotropic and immune suppressant cytokine, transforming growth factor beta receptor I (TβRI). PMNs from mCRPC patients who received 2nd generation ADT, expressed significantly more TβRI than patients who only received 1st line ADT. Further, we found that PMNs in CRPC patient bone metastases express more TβRI than PMNs in matched liver metastases, which express little to no TβRI. Treatment of mouse bone marrow neutrophils with enzalutamide, increased neutrophil TβRI expression in a dose dependent manner and blocked cytotoxicity against PCa cells. Exogenous testosterone treatment in vivo, pharmacologic inhibition (using Repsox, a small molecule kinase inhibitor of TβRI) or genetic deletion (using conditional TβRI knockout mice) rescued enzalutamide-mediated neutrophil suppression and restored neutrophil cytotoxicity. These data collectively suggest that AR inhibition suppresses anti-tumor neutrophil responses via TβRI however, this study highlights the ability to leverage standard-care ADT to generate neutrophil anti-tumor responses against bone metastatic PCa. Citation Format: Leah M Cook. Deciphering the mechanisms of neutrophil immune response in bone metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA020.

Quality of life and functional outcomes after ileocystoplasty for microcystis of tuberculous etiology

BACKGROUND: The outcome of tuberculous bladder lesions is its irreversible shrinkage, persistent disorder of accumulative function and a significant decline in the quality of patient’s life. Supratrigonal augmentation ileocystoplasty and replacement ileocystoplasty are standard treatments for microcystis of tuberculous etiology. Currently, the advantages and disadvantages of these methods have not been sufficiently studied. AIM: To conduct a comparative assessment of the quality of life and functional outcomes of patients with tuberculosis etiology microcystis after supratrigonal augmentation and replacement ileocystoplasty. MATERIALS AND METHODS: The patients of the study were divided into two groups. The first group included 19 patients who underwent supratrigonal bladder resection with augmentation ileocystoplasty, the second group included 20 patients treated with replacement ileocystoplasty. In the period from one to six years after the surgery, quality of life was assessed and a complex urodynamic study was carried out. RESULTS: Analysis of the “General health” measure according to the King’s Health Questionnaire demonstrated the worst quality of life in the patient group after bladder resection (p = 0.013). In this group, the QoL scale indicated the worst measures of “Quality of Life due to Dysuria” (p = 0.019). The measures of the filling enterocystometry were consistent between the patient cohorts and varied in the satisfactory range. All key criteria reflecting the voiding function were significantly worse in group I: larger volume of residual urine (p = 0.001), lower maximum emptying rate (p = 0.034), and higher frequency of intermittent self-catheterization (p = 0.001). Calculation of the obstruction index showed a high prevalence of chronic urinary retention in the specified patient group (p = 0.015). Thus, abdominal pressure had to be increased several-fold for the patients underwent augmentation ileocystoplasty to initiate (p = 0.001) and maintain (p = 0.036) emptying of the intestinal urinary reservoir. The incidence of reservoir-ureteral reflux and incontinence is consistent in both groups (p 0.05). CONCLUSIONS: Cystectomy with replacement ileocystoplasty, as an intervention with the best quality of life and functional results, is the optimal choice in patients with microcystis of tuberculous etiology.

Abstract C028: Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence

Abstract There have been improvements in clinical risk stratifications for oral cavity squamous cell carcinoma (OSCC) with the AJCC 8th edition staging system. Other studies suggest the addition of a metric of specific immune interactions in and around the tumor may be helpful to further stratify patients, with mixed findings. The advent of spatial imaging has allowed a global view for assessing tumor features in the context of all surrounding cell interactions. We hypothesize that the lack of architectural information could contribute to varied clinical outcomes in previous studies, such as tumor recurrence. This highlights how spatial technologies could aid in understanding the role of tissue architecture and its influence on biology and medicine. To study tissue remodeling spatially, we focused on multiplexed-ion beam imaging (MIBI), a spatial proteomics platform to visualize 40 immuno-onco proteins simultaneously. Our banked patient cohort consists of 20 recurrent and 49 non-recurrent OSCC primary surgery samples. Clinical metadata capturing pathologic stage, alcohol use, smoking history, survival data, and more were also collected. With our pathologist, we curated 290 field-of-views (FOVs) of matched primary tumors, uninvolved lymph nodes, and metastatic lymph nodes (if any). Downstream computational analysis using existing MIBI codebases augmented with in-house spatial analytics has revealed a robust spatial dataset. After using machine-learning algorithms to cell segment our images, we validated these assigned cells and marker staining to further annotate cell populations. When we analyzed direct cell interactions, there was a decrease in heterogeneity in immune interactions within recurrent patients compared to non-recurrent patients. To ascertain how the loss of these interactions affected recurrence prognosis, we investigated their prevalence within the tumor border vicinity. We hypothesize that the proximity and cell-cell interactions near the border will promote a tumor-suppressive environment. Utilizing centroid-to-centroid distance measurements, we distilled the top 30 cell-cell interactions within a 100-micron distance from the tumor border. Cell pairs involving macrophage tissue-resident memory cells and CD8 T memory resident cells were more abundant in recurrent patients, while pairs involving CD4 T regulatory and CD8 cells were found in non-recurrent patients. Reassuringly, cell pairings involving myeloid cells were upregulated in the recurrent cohort as expected. Interestingly, cancer-associated fibroblast cell pairings were upregulated indiscriminately in both patient sub- cohorts. This suggests that the impact of certain known immunosuppressive changes may contribute in varying amounts to disease control. Our data demonstrates differences in the architecture of tumors with known divergent outcomes, which suggests global tissue-level changes could be a predictive factor. Clinically, interrogating these interactions of interest could guide treatment escalation or de-escalation in the future. Citation Format: Connie J. Zhou, Jane Lee, Rebecca Jaszczak, Steven R. Long, Patrick K. Ha, Matthew H. Spitzer. Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C028.

Abstract B004: Identification of distinct subpopulations of cancer associated fibroblasts in oral squamous cell carcinoma by imaging mass cytometry

Abstract Background: Although cancer associated fibroblast (CAF) heterogeneity is recognized in oral squamous cell carcinoma (OSCC), the phenotype and role of CAF subpopulations in OSCC is still unknown. Objectives: This study aimed to dissect CAF heterogeneity and spatial location by using imaging mass cytometry on formalin fixed paraffin embedded (FFPE) tissues from primary OSCC. Methods: Imaging mass cytometry (Hyperion technology) was used to identify 24 markers (E-cadherin, EGFR, Ki-67, α-SMA, CD140β, FAP, FSP-1/S100A4, CD90/Thy-1, integrin α-11, collagen-1, tenascin-C, caveolin-1, CD4, CD8a, CD16, CD20, CD68, CD163, FoxP3, granzyme B, CD31, podoplanin, CD146, and YAP-1) in HPV-negative OSCC lesions (n=10). Tissue images were segmented employing the Steinbock framework. Unsupervised clustering of single-cell data was carried out using a bioinformatics pipeline developed in R language. Results: Unsupervised clustering identified several major cell types, with E-cadherin+ cells being the most abundant (30%) and CD146+ being the least abundant cell type (0.62%). Within the immune compartment CD4+ cells were most abundant (11.72%) followed by CD8+ cells (10.6%) and CD68+ cells (10.25%). Cells negative for other major lineage markers and positive for stromal markers were considered as CAFs and they clustered in 6 clusters defined as CAF1 to CAF6. CAF1-3 were high in FAP and CD140β while CAF 4-6 were low expressing FAP and CD140β. CAF1 and 6 expressed high αSMA, while CAF 3 and 5 expressed high collagen-1. CAF6 had high expression of integrin α-11. CAF1 and 3 subtypes were found closer to immune cells whereas CAF2 and 6 were closely located to cancer cells. Conclusions: We identified six distinct subpopulations of CAFs in OSCC by using imaging mass cytometry. Their clinical implications can be further revealed by using this method on larger patient cohorts with FFPE tissues available in diagnostic biobanks. Citation Format: Stian Tornaas, Siren Fromreide, Dimitrios Kleftogiannis, Hans Jørgen Aarstad, Olav K. Vintermyr, Lars Akslen, Harsh Dongre, Daniela Elena Costea. Identification of distinct subpopulations of cancer associated fibroblasts in oral squamous cell carcinoma by imaging mass cytometry [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B004.

Genetic, Clinical, and Biochemical Characterization ofa Large Cohort of Palestinian Patients With Fanconi-Bickel Syndrome.

This study aims to investigate the clinical, biochemical, and genetic characteristics of Fanconi-Bickel syndrome (FBS) in a cohort of 20 individuals from Palestine and to identify novel pathogenic variants. A retrospective analysis was conducted on medical records from Al-Makassed Hospital's pediatric department spanning 2015 to 2023. Individuals diagnosed with FBS via molecular genetic testing were included in the study. Among the 20 genetically confirmed FBS patients, hepatomegaly was prevalent in 95%, whereas 70% exhibited both developmental delay and hypophosphatemic rickets, and 68.4% experienced growth retardation. Hypertriglyceridemia (HTG) was universal. Elevated liver enzymes and alkaline phosphatase were common, along with hypophosphatemia (95%) and urinary abnormalities. Genetic analysis revealed five distinct SLC2A2 pathogenic variants, including three previously unreported variants: p.Gln23Arg (c.68A > G), p.Thr353Arg (c.1058_1059delinsGG), and an exon 7 deletion. This study presents the largest single-center cohort of FBS patients, expanding our understanding of the disorder's phenotypic and genotypic spectrum. Despite FBS generally carrying a favorable prognosis, timely diagnosis remains crucial to prevent severe complications.

Disease activity at the onset of diagnosis as a predictor of disease outcomes in a cohort of patients with systemic lupus erythematosus: A post hoc retrospective analysis of the COMOSLE-EGYPT study.

Systemic lupus erythematosus (SLE) has a non-uniform course directly reflected in changes in disease activity and anticipation of damage. To determine the impact of disease activity at the onset of disease diagnosis, measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) disease activity score, on different disease parameters and outcomes. This multicentre, retrospective cohort study included 823 SLE patients. Disease damage was measured by the Systemic Lupus International Collaborating Clinics Damage Index (SLICC), and comorbidities were measured by the Charlson Comorbidity Index (CCI). According to the mean SLEDAI at onset of disease diagnosis, patients were classified into two groups: I included patients with a mean SLEDAI ≤ 10 (non-severe disease activity), and II included patients with a mean SLEDAI > 10 (severe disease activity). SLEDAI at onset of disease diagnosis was a predictor of damage and comorbidities. A higher SLEDAI score at onset of disease diagnosis was associated with damage accrual. Patients who are younger at disease onset are more likely to have more severe disease. Severe disease activity at the onset of disease diagnosis was also associated with future comorbidity occurrences, but it was not significantly associated with mortality. SLEDAI at the onset of disease diagnosis could be a prognostic marker predicting the damage, which may help in the identification of patients who are at higher risk of adverse outcomes. Special care should be directed towards patients who are younger at disease onset as they may have a higher disease activity at diagnosis. Key Points • This is a unique study as it is the first to focus on the impact of SLE disease activity at the onset of disease diagnosis measured by SLEDAI disease activity score on different disease parameters and outcomes. • Previous studies, though these are scarce, have highlighted the impact of disease activity throughout the disease course and not specifically at the beginning of the SLE disease.

The prognostic implications and oncogenic role of NSUN5 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC), a predominant form of urinary malignancy, requires the identification of reliable biomarkers to enhance both prognostic outcomes and therapeutic developments specific to ccRCC. NSUN5, a member of the NOL1/NOP2/SUN domain (NSUN) family, plays a critical role in RNA stabilization and exhibits widespread expression across various tumor types. However, the exact function of NSUN5 in ccRCC remains insufficiently understood. Data were collated from cohorts of ccRCC patients who underwent nephrectomy, including those from the Cancer Genome Atlas (TCGA) and the Sun Yat-sen University Cancer Center (SYSUCC), to evaluate the clinical relevance of NSUN5. Integrative models based on NSUN5 expression were subsequently developed to predict the prognosis of ccRCC within the TCGA and SYSUCC cohorts. Furthermore, the impact of NSUN5 on RCC cells and its association with cellular senescence were corroborated through in vitro experimental analyses. NSUN5 exhibited elevated expression in both ccRCC patients and renal cancer cell lines, whose upregulation significantly correlated with age, tumor size, TNM stage, WHO/International Society of Urological Pathology (ISUP) grade, presence of necrosis, and a poor prognosis. An accessible nomogram, incorporating NSUN5 along with various clinicopathological parameters, was adept at predicting outcomes for ccRCC patients. Additionally, in vitro findings indicated that reduced expression of NSUN5 enhanced tumor cell senescence and simultaneously inhibiting cell proliferation and migration. These observations suggest that elevated NSUN5 expression is linked to poorer overall survival (OS) and progression-free survival (PFS), positioning NSUN5 as a viable diagnostic and prognostic biomarker in ccRCC.

Endoscopic revision surgery for ossicular chain reconstruction: intraoperative findings and functional outcomes.

To report the intraoperative observations and hearing outcomes in patients undergoing endoscopic revision ossiculoplasty. A retrospective cohort of patients who had undergone revision ossiculoplasty were enrolled in this study. Intraoperative findings were documented. Follow-up visits were scheduled from 3 to 12 months post-surgery to assess hearing levels and record any potential complications. Between April 2020 and May 2023, a total of 26 cases were enrolled, with 11 male patients represented. The mean age of the patients was 40.5 ± 9.4 years, ranging from 18 to 66 years. During the revision surgeries, various intraoperative findings were noted, including adhesive tissues affecting the activity of ossicular chain (observed in 37.0% of cases), tympanosclerosis of the ossicular chain (also in 37.0% of cases), dislocation of ossicular prosthesis (33.3%), erosion of the ossicular chain (33.3%), and identified cholesteatoma (11.1%). In terms of hearing outcomes, a significant improvement was observed. Overall, only 37.0% of patients achieved an air-bone gap of 20 dB or less, indicating the inferior outcome in revision ossiculoplasty. This study highlight the role of inflammatory responses (adhesion, tympanosclerosis), stapes erosion, and prosthesis dislocation, as contributing factors to the failure of primary tympanoplasty. Endoscopic revision ossiculoplasty emerges as a reliable and effective approach.

Higher healthcare cost and utilization before and after diagnosis of AATD in the United States.

Patients with alpha-1 antitrypsin deficiency (AATD) often experience substantial delays from the onset of symptoms to a diagnosis. We explored the impact of delayed diagnosis of AATD on healthcare costs and utilization by assessing costs/utilization before and after diagnosis. Retrospective claims data was used to conduct a longitudinal analysis of a cohort of patients with follow-up over four years in a commercial claims database was conducted. Patients with at least four years of claims experience between the years 2011 - 2017 were included in this study. Outcome measures were calculated for each year (Year 1 pre-index diagnosis, and Years 1, 2, and 3 post-index follow-up). Measures included healthcare costs (pharmacy and medical costs), medical costs, inpatient events, and emergency room visits. Unadjusted measures in the follow-up Year 1, Year 2, and Year 3 were compared to Year 1 pre-index. A separate multivariate analysis adjusting for age, sex, and comorbidities was conducted. Among 1258 patients, mean adjusted healthcare costs were significantly higher in Year 1 post-index compared to Year 1 pre-index ($51,785 vs $41,441, p = < 0.05). In Year 2 ($36,937 vs $41,441, p = < 0.05) and 3 ($28,558 vs $41,441, p = < 0.05) post-index, mean adjusted healthcare costs decreased compared to Year 1 pre-index. Adjusted medical costs were similar in Year 1 ($25,034) post-index compared to Year 1 ($22,952) pre-index but were significantly lower in Year 2 ($15,242 vs $25,034, p = < 0.05) and Year 3 ($8,779 vs $25,034, p = < 0.05) post-index. The frequency of inpatient and emergency room events was significantly lower in all three observation periods following diagnosis in the unadjusted analysis. The adjusted analysis showed similar findings, except for emergency room visits, which were similar across all observation periods. Patients with AATD had substantial healthcare costs/utilization in the year before diagnosis. Costs were significantly higher in the first year following diagnosis. However, subsequent years showed cost reductions to levels below pre-diagnosis. These data support the need for strategies to reduce the time from symptom onset to diagnosis.

Estimated clinical utility of multi-gene pharmacogenetic testing in a retrospective cohort of gynecology patients.

This study aimed to estimate the clinical utility of performing multi-gene pharmacogenetic testing on patients undergoing gynecologic surgery/procedure by evaluating the prescribing rate of Clinical Pharmacogenetics Implementation Consortium (CPIC) level A medications and frequency of drug-gene interactions (DGIs). The electronic health record was queried for 76 current procedural terminology codes to identify gynecologic surgeries/procedures that occurred between 1 January 2015 to 31 December 2020 in patients with at least one of 152 international classification of disease codes. Prescription data for CPIC level A medications was extracted. Those enrolled in the Penn Medicine Biobank were assessed for DGIs. The cohort consisted of 7798 female patients and 682 were in the biobank. Up to 6 years following their surgery or procedure, 80% were ordered ≥1 CPIC level A medication. Over half (54%) of these medications were ordered within 3 days after their surgery or procedure. The most common CPIC level A medications ordered were ibuprofen (57%) and ondansetron (42%). Overall, 7% of the cohort had ≥1 known or predicted DGI with medications they were prescribed. Multi-gene pharmacogenetic testing may be beneficial to gynecologic surgery/procedure patients by assisting clinicians with prescribing postoperative analgesics and future medications.

The effect of cancer and cancer treatment on attention control: evidence from anti-saccade performance.

Cancer and cancer treatment have been associated with cognitive changes in survivorship, with forgetfulness and distractibility reported years post-treatment. Deficits in attention control may explain these difficulties. We assessed breast cancer survivors using a primary measure of attention control, the saccade/antisaccade task, to assess the effects of diagnosis and treatment. Saccade performance was studied in a cohort of breast cancer patients at two time points, (1) after surgery before adjuvant treatment and (2) approximately 2years after enrollment, and compared to non-cancer controls. Saccade performance was assessed in a prosaccade task as well as in visually guided and unguided antisaccade tasks. We assessed the frequency of directional errors and saccadic reaction time. Survivors were more likely than controls to make directional errors in an unguided antisaccade task, with older survivors exhibiting the most significant difficulties following adjuvant treatment. Survivor and control performance were much more similar in a visually guided antisaccade task. These results indicate a main effect of cancer diagnosis on attention control, with greater deficits following treatment and in older survivors. Deficits in attention control may lead to greater difficulties in the initial learning of information, explaining reports of forgetfulness in survivors. These findings underscore the enduring impact of cancer and its treatment on attention control, particularly highlighting that older breast cancer survivors may experience more pronounced difficulties with inhibitory control in daily life. Antisaccade performance may provide a useful metric for quantifying this impact.

Complications on the feeding artery after an arterio-venous fistula closure in patients after kidney transplantation - a national cohort study

Abstract Background Arteriovenous fistulas (AVFs) in kidney transplant recipients are sometimes closed, either as a policy or due to complications. We collected data on the incidence of complications after AVF closure in a national cohort of transplanted patients. Methods Patients who received a kidney transplant between 2000-2015 and had a functional AVF that was later ligated or extirpated were included. Medical records were searched for arterial complications on the arm with the closed AVF. Furthermore, all patients who were still alive in January 2023 were invited for a follow-up arterial ultrasound examination. Results Sixty patients were included; mean follow-up was 9.3±3.8 years. There were 5 (8% cumulative incidence) patients with symptomatic arterial thrombosis and 3 (5% incidence) with symptomatic feeding artery aneurysm. Prospective ultrasound exam was performed in 50 patients; mean diameter of brachial artery was almost doubled on the arm with closed AVF (8.1±3.2 vs. 4.7±0.7 mm, p &amp;lt; 0.001). Additional asymptomatic complications were found in 9 patients (18% incidence): 7 cases (14% incidence) of arterial thrombosis, some extending up to the axillary artery, and 3 (6% incidence) brachial artery aneurysms. All patients in whom the thrombosis spread to the brachial artery had large brachial arteries (&amp;gt; 10 mm) or an aneurysm. Conclusion We observed a high cumulative incidence of arterial thrombosis (20%) and brachial artery aneurysms (10%), sometimes developing several years after AVF closure. These complications should be taken into account when contemplating closure of a well-developed AVF and an AVF preserving approach with flow-reduction surgery might be preferred in some cases.

Early prediction of acute-on-chronic liver failure development in patients with diverse chronic liver diseases.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days.Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT < 100, 109/L; 1 or 0] × 0.44 + [TBIL ≥ 35, µmol/L; 1 or 0] × 0.05 + [HDL-C < 0.5, mmol/L; 1 or 0] × 1.04 - Ln[Hb, g/L] × 0.89 + [BUN > 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P < 0.001). Additionally, the new score improved in predictive accuracy, time-dependent receiver operating characteristics, probability density function evaluations, and calibration curves, making it highly predictive for the onset of ACLF at all time points. The optimal cut-off value of 9.6 effectively distinguished between high- and low-risk patients for ACLF onset. These findings were further validated in a separate cohort of patients. A new progressive score, based on seven predictors, has been developed to accurately forecast the occurrence of ACLF within 7, 14, and 28 days in patients with various chronic liver diseases. This tool may be utilized to identify high-risk patients, tailor follow-up management, and guide the escalation of care, prognostication, and transplant evaluation.

Clinical Outcomes According to Aortic Stenosis Management: Insights From Real-World Practice.

Real-world data regarding clinical outcomes according to aortic stenosis (AS) management are scarce. Therefore, we aimed to investigate long-term management across the spectrum of outpatients with AS. Between May 2016 and December 2017, consecutive outpatients with mild (peak aortic velocity, 2.5-2.9 m/s), moderate (3-3.9 m/s), and severe AS (≥4 m/s) were included by 117 cardiologists in the VALVENOR (Follow-Up of a Cohort of Patients With Valvular Aortic Stenosis in the Nord-pas-de-Calais Region) study and followed-up for aortic valve replacement (AVR) and modes of death. Among 2704 patients included, 1156 (42.7%) had mild, 1121 (41.5%) moderate, and 427 (15.8%) severe AS. After a median follow-up of 5 years, 993 AVRs (488 surgical and 505 transcatheter) and 1098 deaths occurred. The 5-year cumulative incidence of AVR or of the composite of death or AVR was 13.3% and 45.2% in mild AS, 45.5% and 75.3% in moderate AS, and 62.8% and 90.6% in severe AS, respectively. Of the 292 patients who met the criteria for AVR but were not treated, AVR was considered futile in 137 patients and 155 patients refused AVR. Mortality rates after 3 years were high: 86% for anticipated futility and 72.3% for refusal. While patients at anticipated futility showed a well-balanced proportion of cardiovascular and noncardiovascular deaths, cardiovascular deaths predominated among those who refused AVR. At 5-year follow-up, only two thirds of patients with severe AS underwent AVR. Patients with untreated severe AS experienced high mortality rates, mostly cardiovascular for patients who declined AVR. This advocates for better patient education based on shared decision making and for optimizing AS quality of care, from diagnosis to treatment.