Evaluating a Sustained-Release Dexamethasone Insert as Adjunctive Therapy for Inflammation and Pain Post-Corneal Transplantation.

Purpose: To assess the efficiency and safety of an intracanalicular dexamethasone insert (Dextenza, Ocular Therapeutix, Inc) supplemented with a reduced-frequency topical drop regimen in mitigating pain and inflammation post-penetrating keratoplasty (PKP), Descemet stripping endothelial keratoplasty (DSEK), and Descemet membrane endothelial keratoplasty (DMEK), compared to standard topical corticosteroid therapy. Patients and Methods: Eyes were categorized within the DSEK, DMEK, or PKP groups based on ocular characteristics and surgical indications. Randomized in a 1:1 ratio, the intervention group received Dextenza alongside a lowered drop frequency, while the control group followed a conventional drop protocol with no Dextenza. Primary outcomes included average pain scores and absence of anterior chamber cell and flare. Secondary outcomes included delayed re-epithelialization, corneal rejection episodes, instances of intraocular pressure (IOP) elevation >10mmHg above baseline, cystoid macular edema (CME) occurrence, and the necessity for steroid rescue. Results: The study included 30 eyes (10 PKP, 10 DSEK, 10 DMEK). Mean pain scores (0-100 scale; (0-39 = mild pain, 40-69 = moderate pain, 70-100 = severe pain) in the Dextenza group were 3.6 (PKP), 12 (DSEK), 8 (DMEK), compared to 1.2 (PKP), 0 (DSEK), and 4 (DMEK) in controls. PKP control (n=5): 1 delayed re-epithelialization, 1 IOP elevation, 2 CME. DSEK control (n=5): 1 corneal rejection, 1 IOP elevation, 1 CME. DMEK control (n=5): 1 IOP elevation, 1 CME. DMEK Dextenza (n=5): 1 delayed re-epithelialization, 1 CME. No cases required steroid rescue, and no cell or flare was observed one-week post-surgery. There were no statistically significant differences in pain, delayed re-epithelialization, IOP elevation, corneal rejection, or CME between the Dextenza and control groups regardless of the type of corneal transplantation performed. Conclusion: Dextenza, when combined with a lower-frequency drop regimen, demonstrates a safety profile comparable to that of a traditional higher-frequency drop protocol in terms of pain management and the adverse events explored in this study, potentially enhancing postoperative drop adherence.

Efficacy of lumbar and abdominal muscle rehabilitation training on degree of osteoporosis, pain and anxiety in elderly patients with osteoporotic vertebral compression fracture after PKP and compliance analysis.

Purpose: To explore the rehabilitation effect and compliance of lumbar and abdominal muscle rehabilitation training in patients with osteoporotic vertebral compression fracture (OVCF) after percutaneous balloon vertebroplasty (PKP). Methods: A total 177 elderly patients with OVCF were divided into rehabilitation group (n = 104) and control group (n = 73) according to whether they received psoas and abdominal muscle rehabilitation training for 3 months after PKP. The differences of general data, orthopaedic rehabilitation, prognosis and bone metabolism were compared between the two groups. All the patients were divided into compliance group (68 cases) and non-compliance group (36 cases) according to compliance. Orthopaedic rehabilitation indicators, prognostic indicators of PKP, and bone metabolism-related parameters were collected for analysis of Chi-square test and Logistic regression. ROC curve was used to analyze the predictive value of bone metabolism related indicators in the compliance of lumbar and abdominal muscle rehabilitation training. Results: There was no significant difference in the general data between the rehabilitation training group and the control group (All p > 0.05). Compared with the control group, the Berg balance scale score was significantly increased, while the Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) score and the proportion of new fractures were significantly decreased in the rehabilitation training group (All p < 0.05). Compared with the control group, the bone mineral density (BMD) T value, osteocalcin (OCN) and 25-hydroxyvitamin D (25 (OH) D) levels were significantly increased and the levels of type I N-propeptide (P1NP) and ß-isomerized C-terminal telopeptides (ß-CTX) were significantly decreased in the rehabilitation training group compared with the control group (All p < 0.05). Chi-square test and Logistic regression analysis showed that age > 75 years, severe anxiety, severe pain and postoperative complications were significantly associated with the compliance of psoas and abdominal muscle rehabilitation training in patients with OVCF after PKP. ROC curve analysis showed that BMD T value, OCN, P1NP, ß-CTX, or 25-OH-D levels predicted the AUC of rehabilitation training compliance in patients with OVCF after PKP were 0.821, 0.835, 0.736, 0.715, and 0.748, respectively. Conclusion: Rehabilitation training of lumbar and abdominal muscles can significantly improve the efficacy of PKP, reduce the degree of osteoporosis and improve the prognosis of patients with OVCF. Age, anxiety, pain and postoperative complications were independent risk factors affecting the compliance of psoas and abdominal rehabilitation training in patients with OVCF after PKP.

Descemet Membrane Endothelial Keratoplasty for Penetrating Keratoplasty.

Background: Descemet membrane endothelial keratoplasty (DMEK) has been utilized more frequently during recent years to treat penetrating keratoplasty (PKP) graft failures. The perioperative evaluation technique of anterior segment optical coherence tomography (AS-OCT) is increasingly significant. Our goal is to discuss DMEK surgical and clinical for subsequent PKP graft failure, along with significant surgical modifications and adjustments in accordance with preoperative assessment utilizing AS-OCT. Materials and Methods: Patients' records who performed DMEK for PKP failure were retrospectively reviewed. Demographic information, PKP graft size determined by postoperative problems, corneal donor endothelial cell density (ECD), AS-OCT, central pachymetry, visual acuity (VA) evaluated in Snellen units, intraoperative surgical procedure modifications, and postoperative ECD were all included in the data collection. Results: The observation was conducted with 16 patients with 16 eyes, nine males and seven females. The observation period is 18 months. DMEK was performed at an average age of 63. Preoperative AS-OCT was performed on all patients, and based on cases, surgical plans were created. Before processing DMEK, the mean VA is 0.04, and central pachymetry is 685 m. They improved considerably to 0.3 (P value = 0.001) and 542 m (P value = 0.008) at the most recent follow-up. About 93.75% of the grafts were adhered to after the procedure. Late decompensation caused a 6.25% graft failure rate. Graft detachment rates and cases requiring rebubble rates were respectively 18.75%. Conclusion: In DMEK for failed PKP, a good case-specific preoperative assessment by AS-OCT is essential. As a result, it relies on developing a surgical strategy that can improve surgical outcomes, lower the risk of complications, and quicken visual recovery.

PKP2 induced by YAP/TEAD4 promotes malignant progression of gastric cancer.

Gastric cancer (GC) exhibits significant heterogeneity and its prognosis remains dismal. Therefore, it is essential to investigate new approaches for diagnosing and treating GC. Desmosome proteins are crucial for the advancement and growth of cancer. Plakophilin-2 (PKP2), a member of the desmosome protein family, frequently exhibits aberrant expression and is strongly associated with many tumor types' progression. In this study, we found upregulation of PKP2 in GC. Further correlation analysis showed a notable association between increased PKP2 expression and both tumor stage and poor prognosis in individuals diagnosed with gastric adenocarcinoma. In addition, our research revealed that the Yes-associated protein1 (YAP1)/TEAD4 complex could stimulate the transcriptional expression of PKP2 in GC. Elevated PKP2 levels facilitate activation of the AKT/mammalian target of rapamycin signaling pathway, thereby promoting the malignant progression of GC. By constructing a mouse model, we ultimately validated the molecular mechanism and function of PKP2 in GC. Taken together, these discoveries suggest that PKP2, as a direct gene target of YAP/TEAD4 regulation, has the potential to be used as an indication of GC progression and prognosis. PKP2 is expected to be a promising therapeutic target for GC.

Unveiling the Binding between the Armadillo-Repeat Domain of Plakophilin 1 and the Intrinsically Disordered Transcriptional Repressor RYBP.

Plakophilin 1 (PKP1), a member of the p120ctn subfamily of the armadillo (ARM)-repeat-containing proteins, is an important structural component of cell-cell adhesion scaffolds although it can also be ubiquitously found in the cytoplasm and the nucleus. RYBP (RING 1A and YY1 binding protein) is a multifunctional intrinsically disordered protein (IDP) best described as a transcriptional regulator. Both proteins are involved in the development and metastasis of several types of tumors. We studied the binding of the armadillo domain of PKP1 (ARM-PKP1) with RYBP by using in cellulo methods, namely immunofluorescence (IF) and proximity ligation assay (PLA), and in vitro biophysical techniques, namely fluorescence, far-ultraviolet (far-UV) circular dichroism (CD), and isothermal titration calorimetry (ITC). We also characterized the binding of the two proteins by using in silico experiments. Our results showed that there was binding in tumor and non-tumoral cell lines. Binding in vitro between the two proteins was also monitored and found to occur with a dissociation constant in the low micromolar range (~10 µM). Finally, in silico experiments provided additional information on the possible structure of the binding complex, especially on the binding ARM-PKP1 hot-spot. Our findings suggest that RYBP might be a rescuer of the high expression of PKP1 in tumors, where it could decrease the epithelial-mesenchymal transition in some cancer cells.

Identification and validation of prognostic and immunotherapeutic responses in esophageal squamous carcinoma based on hypoxia phenotype-related genes.

The study aimed to investigate the clinical significance of the interaction between hypoxia and the immune system in esophageal squamous cell carcinoma (ESCC) microenvironment. A comprehensive evaluation of 13 hypoxia phenotype-related genes (HPRs) was conducted using data from TCGA-ESCC and two GEO cohorts. Three distinct HPRclusters were identified, and the HPRscore was established as an independent prognostic factor (p = 0.001), with higher scores indicating poorer prognosis. The HPRscore was validated in various immunotherapy cohorts, demonstrating its efficacy in evaluating immunotherapy and chemotherapy outcomes. Additionally, phenome-wide association study (PheWAS) analysis showed that PKP1 had no significant correlation with other traits at the gene level. PKP1 was identified as a potential prognostic marker for ESCC, with upregulated expression observed in ESCC patients. In vitro experiments showed that the knockdown of PKP1 inhibited ESCC cell proliferation and migration. These findings suggest that the novel HPRscore and PKP1 may serve as prognostic tools and therapeutic targets for ESCC patients.

A Retrospective Study of 91 Patients Treated with Percutaneous Kyphoplasty for Mild Osteoporotic Vertebral Compression Fractures and a New Evaluation Scale of Shape and Filling Effect of Cement.

BACKGROUND: Percutaneous kyphoplasty (PKP) is commonly used to treat severe osteoporotic vertebral compression fractures (OVCFs) by restoring vertebral height. However, its application in mild cases is not frequently discussed. METHODS: The study retrospectively included 100 treated vertebral bodies of the 91 patients mentioned before, and efficacy was evaluated using visual analog scale (VAS) and Oswestry Disability Index (ODI) scores preoperatively, 2 days postoperatively, and at 1 and 6 months after treatment, as well as mean variation in vertebral body height. The study also examined complications such as pain recurrence, delayed vertebral fracture, and loss of vertebral height, and developed a scale to assess the shape and filling effect of cement (SFEC) and its impact on complications. RESULTS: The results showed significant reductions in mean VAS and ODI scores from pre-to post-surgery and an increase in vertebral body height. However, complications occurred in 10 patients who received treatment for 11 vertebral bodies, including pain recurrence, fractures, and loss of vertebral height. Among the 10 patients with complications, 7 (63.6%) vertebral bodies had dissatisfied SFEC scores, compared with 22 (24.7%) vertebral bodies with dissatisfied SFEC scores in 81 patients without complications (89 vertebral bodies). CONCLUSIONS: PKP is a safe and effective method for treating mild OVCFs, but attention should be paid to the shape and filling effects of cement during surgery to prevent later complications. The developed SFEC scale provides a specific and quantitative standards for evaluating the recovery status after PKP, which need further validations.

Are Sandwich Vertebrae Prone to Refracture After Percutaneous Vertebroplasty or Kyphoplasty? A Meta-Analysis.

BACKGROUND: The formation of sandwiched vertebrae (SDVs) after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) has become a common phenomenon. Whether SDVs are more likely to fracture is still controversial. Therefore, we conducted a meta-analysis to provide medical evidence for whether SDVs are more prone to refracture than non-SDVs (NSDVs) after PVP or PKP. METHODS: This study was conducted in accordance with the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Several databases, including PubMed, Embase, Medline databases, China National Knowledge Infrastructure, Wanfang, and Weipu, were thoroughly searched for relevant studies included from any point up until June 2022. Statistical analyses were performed using Revman 5.4. RESULTS: A total of 4052 individuals from 9 studies were enrolled. Overall, patients with SDV presented more risk to have refracture than patients with NSDV (OR = 1.57, P = 0.04). The incidences of refracture were comparable between the 2 cohorts in studies with a follow-up time less than 3 years (OR = 1.28, P = 0.49). However, patients with SDV were more prone to have refracture than patients with NSDV in studies with a follow-up time longer than 3 years (OR = 1.92, P = 0.009). Moreover, patients with SDV were more likely to have refracture than patients with NSDV in studies that involved both PVP and PKP (OR = 1.62, P = 0.002). In addition, age, low bone density, and postoperative kyphosis angle of sandwich fracture segments >10° were independent factors to predict refracture. CONCLUSIONS: Patients with SDV were more likely to have refracture after PVP or PKP, especially when the follow-up time was longer than 3 years.

Detection of gene mutation in the prognosis of a patient with arrhythmogenic right ventricular cardiomyopathy: a case report.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC), or more recently known as arrhythmogenic cardiomyopathy (ACM), is an heritable disorder of the myocardium characterized by progressive fibrofatty replacement the heart muscle and risk of ventricular arrhythmias and sudden cardiac death (SCD). We report a case study to demonstrate the role of gene mutation detection in risk stratification for primary prevention of SCD in a young patient diagnosed with ARVC. CASE PRESENTATION: A 15-year-old Asian (Vietnamese) male patient with no history of documented tachyarrhythmia or syncope and a family history of potential SCD was admitted due to palpitations. Clinical findings and work-up including cardiac magnetic resonance imaging (MRI) were highly suggestive of ARVC. Gene sequencing was performed for SCD risk stratification, during which PKP2 gene mutation was found. Based on the individualized risk stratification, an ICD was implanted for primary prevention of SCD. At 6 months post ICD implantation, the device detected and successfully delivered an appropriate shock to terminate an episode of potentially fatal ventricular arrhythmia. ICD implantation was therefore proven to be appropriate in this patient. CONCLUSIONS: While gene mutations are known to be an important factor in the diagnosis of ARVC according to the 2010 Task Force Criteria and recent clinical guidelines, their role in risk stratification of SCD remains controversial. Our case demonstrated that when used with other clinical factors and family history, this information could be helpful in identifying appropriate indication for ICD implantation.

FERMT1 promotes cell migration and invasion in non-small cell lung cancer via regulating PKP3-mediated activation of p38 MAPK signaling.

BACKGROUND: Fermitin family member 1 (FERMT1) is highly expressed in many tumors and acts as an oncogene. Nonetheless, the precise function of FERMT1 in non-small cell lung cancer (NSCLC) has not been clearly elucidated. METHODS: Bioinformatics software predicted the FERMT1 expression in NSCLC. Transwell assays facilitated the detection of NSCLC cell migration and invasion. Western blotting techniques were employed to detect the protein levels regulated by FERMT1. RESULTS: FERMT1 exhibited high expression levels in NSCLC and was linked to the patients' poor prognosis, as determined by a variety of bioinformatics predictions combined with experimental verification. FERMT1 promoted the migration and invasion of NSCLC and regulated epithelial to mesenchymal transition (EMT) -related markers. Further studies showed that FERMT1 could up-regulate the expression level of plakophilin 3(PKP3). Further research has indicated that FERMT1 can promote cell migration and invasion via up-regulating PKP3 expression. By exploring downstream signaling pathways, we found that FERMT1 has the capability to activate the p38 mitogen-activated protein kinases (p38 MAPK) signaling pathway, and knocking down PKP3 can counteract the activation induced by FERMT1 overexpression. CONCLUSIONS: FERMT1 was highly expressed in NSCLC and can activate the p38 MAPK signaling pathway through up-regulation of PKP3, thus promoting the invasion and migration of NSCLC.

Percutaneous kyphoplasty combined with pediculoplasty for the surgical treatment of osteoporotic thoracolumbar burst fractures.

OBJECTIVE: This study introduces a minimally invasive technique for efficient three-column reconstruction, augmentation, and stabilization of osteoporotic thoracolumbar burst fractures (OTLBFs). METHODS: Sixty-eight patients with OTLBFs and no neurological deficits were included from July 2019 to September 2020. The patients were divided into two groups: the simple percutaneous kyphoplasty (PKP) group (n = 32) and the percutaneous kyphoplasty combined with pediculoplasty (PKCPP) group (n = 36). The clinical and radiological outcomes were assessed during a minimum 1-year follow-up period. Clinical outcomes were assessed via the visual analog scale (VAS) and modified MacNab grading criteria. The radiological outcomes included the Cobb angle (CA), anterior wall height (AWH), and posterior wall height (PWH). The surgery duration, postoperative analgesic dosage, length of hospital stay, and complications were recorded. RESULTS: Surgery duration was not significantly different between the two groups (P > 0.05). The PKCPP group had a lower analgesic dosage and shorter hospital stay (P < 0.05). Postoperatively, the PKCPP group exhibited better VAS scores and modified MacNab scale scores (P < 0.05), but the differences at the last follow-up assessment were not significant (P > 0.05). Postoperative CA, AWH, and PWH correction were not significantly different on the first postoperative day (P > 0.05). However, the PKCPP group had significantly less CA and PWH loss of correction at the last follow-up visit (P < 0.05). The PKCPP group had significantly fewer complications (P < 0.05). CONCLUSIONS: The PKCPP technique complements simple PKP for OTLBFs. It quickly relieves pain, maintains the vertebral body height and Cobb angle, ensures cement stabilization, and offers more stable three-column support.

The role of PKP1 in tumor progression in melanoma: Analysis of a cell adhesion-related model.

The incidence rate of melanoma varies across regions, with Europe, the United States, and Australia having 10-25, 20-30, and 50-60 cases per 1 00 000 people. In China, patients with melanoma exhibit different clinical manifestations, pathogenesis, and outcomes. Current treatments include surgery, adjuvant therapy, and immune checkpoint inhibitors. Nonetheless, complications may arise during treatment. Melanoma development is heavily reliant on cell adhesion molecules (CAMs), and studying these molecules could provide new research directions for metastasis and progression. CAMs include the integrin, immunoglobulin, selectin, and cadherin families, and they affect multiple processes, such as maintenance, morphogenesis, and migration of adherens junction. In this study, a cell adhesion-related risk prognostic signature was constructed using bioinformatics methods, and survival analysis was performed. Plakophilin 1 (PKP1) was observed to be crucial to the immune microenvironment and has significant effects on melanoma cell proliferation, migration, invasion, and the cell cycle. This signature demonstrates high reliability and has potential for clinical applications.

Downregulated expression of plakophilin-2 gene in patients with colon adenocarcinoma predicts an unfavorable prognosis and immune infiltrate.

BACKGROUND: Plakophilin 2 gene (PKP2) has been revealed to be differentially expressed in various cancer types and is correlated with prognosis. However, the role of PKP2 in colon adenocarcinoma remains indistinct. METHODS: Differences in transcriptional expression of PKP2 between colon adenocarcinoma tissues and normal adjacent tissues were acquired from the publicly available dataset-the Cancer Genome Atlas. A receiver operating curve (ROC) was constructed to differentiate colon adenocarcinoma tissues from adjacent normal tissues. The Kaplan-Meier plot method was performed to evaluate the effect of PKP2 on survival. The correlation between mRNA expression of PKP2 and immune infiltrating was determined by the Tumor Immune Estimation Resource and Tumor-Immune System Interaction databases. RESULTS: The expression of PKP2 in colon adenocarcinoma tissues was significantly downregulated compared with corresponding adjacent normal tissues. Decreased PKP2 mRNA expression was associated with lymph node metastases and advanced pathological stage. The ROC curve analysis indicated that with a cutoff value of 6.034, the sensitivity and specificity for PKP2 differentiating the colon adenocarcinoma tissues from the adjacent normal tissues were 90.2 and 66.5% respectively. Kaplan-Meier plot survival analysis revealed that colon adenocarcinoma patients with low-PKP2 had a worse prognosis than those with high-PKP2 (68.2 vs. 101.4 months, p = 0.028). Correlation analysis showed that mRNA expression of PKP2 was correlative with immune infiltrates. CONCLUSIONS: Downregulated PKP2 is significantly correlated with unfavorable immune infiltrating and survival in colon adenocarcinoma. This research indicates that PKP2 can be selected as a novel biomarker of potential immunotherapy targets and unfavorable prognosis in colon adenocarcinoma.

Intraoperative pain prediction of percutaneous kyphoplasty under local anesthesia by preoperative experimental pain assessment.

BACKGROUND: Percutaneous kyphoplasty (PKP) is the preferred treatment for osteoporotic vertebral compression fractures (OVCF) Currently, the preoperative anesthesia methods for PKP are mainly local anesthesia and tracheal intubation general anesthesia. OBJECTIVE: To assess whether patient sensitivity to pain measured preoperatively could predict the patients' pain response during PKP treatment under local anesthesia, to facilitate the development of an optimal preoperative anesthesia plan for patients. METHODS: Fifty-five female patients diagnosed with osteoporotic single vertebral fracture who were treated with PKP under local anesthesia were selected. The patients' pain sensitivities, including pain threshold and pain tolerance threshold, were evaluated with a pain test device on the day before the operation in the ward. Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SpO2) were recorded before anesthesia, post-anesthesia, after needle puncture, and after balloon dilatation. At the same time, blood was drawn at the above time points to determine the level of norepinephrine (NA) as an indicator of intraoperative pain stress response. The numerical rating scale (NRS) during surgery was recorded at the end of the surgery. RESULTS: The preoperative pain tolerance threshold of 55 surgical patients was correlated with the intraoperative NRS score (r=-0.768, P< 0.001), as well as with the preoperative and intraoperative changes in HR (r=-0.791, P< 0.001), MAP (r=-0.819, P< 0.001), and NA (r=-0.553, P< 0.001). Thus, the lower the preoperative pain tolerance threshold, the more severe the patient's response to pain during PKP treatment under local anesthesia, and the greater the hemodynamic changes. Consequently, the intraoperative experience becomes worse. However, there was no correlation between preoperative pain threshold and NRS scores (r=-0.069, P= 0.616) nor between the preoperative and intraoperative changes in HR (r= 0.103, P= 0.453), MAP (r= 0.086, P= 0.535), and NA (r=-0.058, P= 0.674). CONCLUSION: The results indicated that preoperative pain assessment could predict the level of pain response in OVCF patients during PKP surgery under local anesthesia.

Influence of sarcopenia on surgical efficacy and mortality of percutaneous kyphoplasty in the treatment of older adults with osteoporotic thoracolumbar fracture.

BACKGROUND: Sarcopenia is an age-related condition that causes loss of skeletal muscle mass and disability. Sarcopenia is closely related to the prognosis of patients suffering osteoporotic thoraco-lumbar compression fractures (OTLCF). The purpose of this study was to investigate the effect of sarcopenia on the efficacy of percutaneous kyphoplasty (PKP) in the treatment of older adults with OTLCF surgery and postoperative mortality. METHODS: From February 2016 to June 2019, 101 patients who met the inclusion and exclusion criteria were included in this study. The grip strength of the dominant hand was measured using an electronic grip tester. The diagnostic cutoff value of grip strength for sarcopenia was <27 kg for males and <16 kg for females. The cross-sectional area (cm2) of the musculature at the level of the pedicle of the thoracic 12th vertebra (T12) was measured by chest CT. The skeletal muscle index (SMI) was calculated by dividing the muscle cross-sectional area at the T12 pedicle level by the square of the height. The diagnostic cut-off value of SMI at T12 level is 42.6 cm2/m2 for males and 30.6 cm2/m2 for females. Sarcopenia was diagnosed when the grip strength and SMI values were both lower than the diagnostic cut-off value. All included patients received PKP treatment for OTLCF. The age, gender, operation time, bleeding volume, time to ground, length of hospital stay, visual analog scale (VAS) score before operation and one month after operation, Oswestry Disability Index (ODI) one month after operation and the incidence of refracture within 36 months after operation were compared between the two groups. The survival curves of the two groups were analyzed by Kaplan Meier. Chi-square test was used to compare the differences in survival rates between the two groups at 12, 24, and 36 months after operation. Univariate and multivariate Cox regression analysis compared multivariate factors on OTLCF postoperative mortality. RESULTS: There was no significant difference in gender, operation time, blood loss and preoperative VAS score between the two groups (χ2 = 1.750, p = 0.186; t = 1.195, p = 0.235; t = -0.582, p = 0.562; t = -1.513, p = 0.133), respectively. The patients in the sarcopenia group were older (t = 3.708, p = 0.000), and had longer postoperative grounding time and hospitalization time (t = 4.360, p = 0.000; t = 6.458, p = 0.000). The VAS scores and ODI scores one month postoperatively were also higher in sarcopenia group (t = 5.900, p = 0.000; t = 7.294, p = 0.000), and there was a statistical difference between the two groups. Interestingly, there was no significant difference in the incidence of spinal refracture within 36 months between the two groups (χ2 = 1.510, p = 0.219). The sarcopenia group had a higher mortality rate at 36 months after operation, and the difference was statistically significant (p = 0.002). Sarcopenia is an independent risk factor for long-term mortality in OTLCF patients received PKP surgery. CONCLUSIONS: Patients with sarcopenia combined with OTLCF have poor postoperative recovery of limb function and a high risk of death in the long-term (36 months) after surgery. Active and effective intervention for sarcopenia is required during treatment.

Vector Analysis and Prognostic Factors for Femtosecond Arcuate Keratotomy in Post-Keratoplasty Astigmatism.

Purpose: To analyze different tomographic and refractive parameters for predicting successful visual outcome following femtosecond laser-assisted arcuate keratotomy (FSAK) for post-keratoplasty astigmatism. Design: Retrospective. Methods: Retrospective study evaluating patients with astigmatism following penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK) who underwent FSAK. Vector analysis using the Alpins method was done to calculate surgically induced astigmatism (SIA). An improvement of 3 lines of Early Treatment Diabetic Retinopathy Study (ETDRS) lines was used for successful outcome. Outcome was measured at 3 months and 17 months. Results: This study included 106 eyes from 104 patients (65 males and 39 females). Mean age was 31.8±8.6 years, and 89.4% (n=93) of cases were keratoconus (KC), 3.8% (n=4) scar, 3.8% (n=4) granular dystrophy, 1.9% (n=2) post-LASIK ectasia, and 1.0% (n=1) macular dystrophy. Uncorrected visual acuity (UCVA) improved from 1.02±0.53 logarithm minimal angle of resolution (logMAR) to 0.87±0.49 logMAR (p=0.01) at 3 months and to 0.92±1.08 logMAR (p=0.57) at 17 months. Best spectacle-corrected visual acuity (BSCVA) improved from 0.41±0.30 logMAR to 0.31±0.19 logMAR (p<0.01) at 3 months and to 0.23±0.27 logMAR (p<0.01) at 17 months. Success was achieved in 50% (n=53) and 49% (n=52) at 3 and 17 months follow-up, respectively. Success group showed worse preoperative UCVA (1.21±0.56 vs 0.83±0.44 logMAR; p<0.01), worse preoperative BSCVA (0.50±0.36 vs 0.33±0.19 logMAR; p=0.01). Preoperative UCVA had an area under the curve of 0.721 (95% CI: 0.622-0.820; p< 0.01). The Youden's optimal cutoff point was 0.90 logMAR (equivalent Snellen 20/159) with 76.9% sensitivity and 35.2% specificity. Flattening index (FI) was 87% in DALK and 73% in PKP (p=0.14). Correction index (CI) was 99% and 86% (p=0.18) for DALK and PKP, respectively. Success of the astigmatic surgery for DALK and PKP was 44% vs 42% (p=0.29), respectively. Conclusion: Improvement of at least three lines was achieved in 49% of patients who underwent FSAK following PKP or DALK; this improvement was achieved in patients who had a worse preoperative UCVA.

Clinical and Genetic Characteristics of Arrhythmogenic Right Ventricular Cardiomyopathy Patients: A Single-Center Experience.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited progressive cardiomyopathy. We aimed to define the long-term clinical outcome and genetic characteristics of patients and family members with positive genetic tests for ARVC in a single tertiary care cardiac center in Saudi Arabia. Methods: We enrolled 46 subjects in the study, including 23 index-patients (probands) with ARVC based on the revised 2010 ARVC Task Force Criteria (TFC) and 23 family members who underwent a genetic test for the ARVC between 2016 and 2020. Results: Of the probands, 17 (73.9%) were males with a mean age at presentation of 24.95 ± 13.9 years (7 to 55 years). Predominant symptoms were palpitations in 14 patients (60.9%), and syncope in 10 patients (43.47%). Sustained ventricular tachycardia (VT) was documented in 12 patients (52.2%). The mean left ventricular ejection fraction (LVEF) by echocardiogram was 52.81±6.311% (30-55%), and the mean right ventricular ejection fraction (RVEF) by cardiac MRI was 41.3±11.37% (23-64%). Implantable cardioverter-defibrillator (ICD) implantation was performed in 17 patients (73.9%), and over a mean follow-up of 13.65 ± 6.83 years, appropriate ICD therapy was noted in 12 patients (52.2%). Genetic variants were identified in 33 subjects (71.7%), 16 patients and 17 family members, with the most common variant of plakophilin 2 (PKP2) in 27 subjects (81.8%). Conclusions: ARVC occurs during early adulthood in Saudi patients. It is associated with a significant arrhythmia burden in these patients. The PKP2 gene is the most common gene defect in Saudi patients, consistent with what is observed in other nations. We reported in this study two novel variants in PKP2 and desmocollin 2 (DSC2) genes. Genetic counseling is needed to include all first-degree family members for early diagnosis and management of the disease in our country.

Comprehensive Analysis Identifies PKP3 Overexpression in Pancreatic Cancer Related to Unfavorable Prognosis.

Plakophilin 3 (PKP3) affects cell signal transduction and cell adhesion and performs a crucial function in tumorigenesis. The current investigation evaluated the predictive significance and underlying processes of PKP3 within pancreatic cancer (PC) tissues. The assessment of differences in PKP3 expression was conducted through an analysis of RNA-seq data acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, clinical samples were collected to validate the findings. The predictive significance of PKP3 was investigated by analyzing survival data derived from TCGA and clinical specimens. PKP3's biological function was assessed via phenotypic experiments after the suppression of PKP3 expression within PC cells. Functional enrichment analysis, encompassing KEGG, GO, and GSEA, was employed to assess the underlying mechanism of PKP3. Immune infiltration analysis was conducted in the present investigation to determine the association between PKP3 and tumor-infiltrating immune cells (TICs). In PC tissues, PKP3 expression was abnormally upregulated and correlated with a negative prognosis in individuals with PC. PKP3 can promote the progression, migration, and invasive capacity of PC cells and is relevant to the regulation of the PI3K-Akt and MAPK signaling pathways. Immune infiltration analysis demonstrated that PKP3 impeded CD8+ T-cell infiltration and immune cytokine expression within the tumor microenvironment. The PKP3 protein was identified as a prospective independent predictive indicator and represents a viable approach for immunotherapy in the context of PC. PKP3 may impact prognosis by broadly inhibiting immune cell infiltration and promoting the activation of tumor-associated signaling pathways.

The role of genetic testing in suspected fulminant myocarditis: A case report.

ACM is a rare hereditary heart disease characterized by a progressive fibro-fatty replacement of the myocardium that can affect either the right or the left ventricle or both. It is mainly caused by variants in the desmosome genes with autosomal dominant transmission and incomplete penetrance. The disease shows a wide spectrum of clinical manifestations, including ventricular arrhythmias, HF and myocarditis. The latter is considered a 'hot phase' in the natural history of the disease and must therefore be distinguished from the isolated AM, which is frequently due to viral infections. Our case report is an example of how an AM, as the first manifestation of the disease, helped to reach a diagnosis of ACM through the genetic analysis. In fact, the multi-parametric investigation, which also included CMR and EMB, revealed controversial aspects that led us to perform the genetic test. The latter revealed a heterozygous pathogenic variant in the PKP2 that was considered definitive proof of ACM.