15-epi-lipoxin A5 promotes neutrophil exit from exudates for clearance by splenic macrophages.

Specialized proresolving mediators (SPMs) promote local macrophage efferocytosis but excess leukocytes early in inflammation require additional leukocyte clearance mechanism for resolution. Here, neutrophil clearance mechanisms from localized acute inflammation were investigated in mouse dorsal air pouches. 15-HEPE (15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid) levels were increased in the exudates. Activated human neutrophils converted 15-HEPE to lipoxin A5 (5S,6R,15S-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), 15-epi-lipoxin A5 (5S,6R,15R-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), and resolvin E4 (RvE4; 5S,15S-dihydroxy-6E,8Z,11Z,13E,17Z-eicosapentaenoic acid). Exogenous 15-epi-lipoxin A5, 15-epi-lipoxin A4 and a structural lipoxin mimetic significantly decreased exudate neutrophils and increased local tissue macrophage efferocytosis, with comparison to naproxen. 15-epi-lipoxin A5 also cleared exudate neutrophils faster than the apparent local capacity for stimulated macrophage efferocytosis, so the fate of exudate neutrophils was tracked with CD45.1 variant neutrophils. 15-epi-lipoxin A5 augmented the exit of adoptively transferred neutrophils from the pouch exudate to the spleen, and significantly increased splenic SIRPa+ and MARCO+ macrophage efferocytosis. Together, these findings demonstrate new systemic resolution mechanisms for 15-epi-lipoxin A5 and RvE4 in localized tissue inflammation, which distally engage the spleen to activate macrophage efferocytosis for the clearance of tissue exudate neutrophils.

The value of combined MRI, enhanced CT and 18F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer.

OBJECTIVE: The purpose of this article was to investigate the value of combined MRI, enhanced CT and 18F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer. METHODS: Ninety-five ovarian cancer patients were selected as the study subjects, all of them underwent surgical treatment, and MRI, enhanced CT and 18F-FDG PET/CT were performed on all of them in the postoperative follow-up, and the pathological results after the second operation were used as the diagnostic "gold standard". The diagnostic value (sensitivity, specificity, accuracy, negative predictive value and positive predictive value) of the three examination methods alone or in combination for the diagnosis of postoperative recurrence and metastasis of ovarian cancer was compared, and the detection rate was calculated when the lesion was the unit of study, so as to compare the efficacy of the three methods in the diagnosis of postoperative recurrent metastatic lesions of ovarian cancer. RESULTS: The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the combined group were higher than those of MRI and enhanced CT for recurrence and metastasis of ovarian cancer after surgery, and the specificity, accuracy and positive predictive value of the combined group were higher than those of the 18F-FDG PET/CT group, and those of the 18F-FDG PET/CT group were higher than those of the enhanced CT group (all P < 0.05). When the postoperative recurrent metastatic lesions of ovarian cancer were used as the study unit, the detection rate of lesions in the combined group was higher than that of the three examinations detected individually, and the detection rate of lesions in 18F-FDG PET/CT was higher than that of enhanced CT and MRI (P < 0.05). CONCLUSION: The combination of MRI, enhanced CT and 18F-FDG PET/CT can accurately diagnose recurrence and metastasis of ovarian cancer after surgery, detect recurrent metastatic lesions as early as possible, and improve patients' prognosis.

Olaparib with or without bevacizumab versus bevacizumab plus a fluoropyrimidine as maintenance therapy in advanced colorectal cancer: The randomized phase 3 LYNK-003 study.

BACKGROUND: The randomized, open-label, phase III LYNK-003 study assessed the efficacy of first-line maintenance olaparib, alone or in combination with bevacizumab, versus bevacizumab plus a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer (mCRC). We present results of the prespecified interim futility analysis. METHODS: Eligible participants were ≥18 years of age with unresectable or mCRC that had not progressed after induction with first-line bevacizumab plus 5-fluorouracil plus oxaliplatin plus leucovorin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX). Participants were randomly assigned 1:1:1 to olaparib plus bevacizumab, olaparib alone, or bevacizumab plus a fluoropyrimidine (5-fluorouracil or capecitabine). The primary end point was progression-free survival (PFS) per RECIST v1.1 by central review. RESULTS: Between August 2020 and May 2022, 309 participants were assigned to olaparib plus bevacizumab (n = 104), olaparib (n = 107), or bevacizumab plus fluoropyrimidine (n = 98). At interim analysis, with a median follow-up of 7.6 months (range 0.1-19.7 months), the median PFS was 3.7 months (95% CI 2.8-5.3) with olaparib plus bevacizumab (HR 1.52; 95% CI 1.02-2.27; P = 0.982) and 3.5 months (95% CI 2.0-3.7) with olaparib (HR 2.11; 95% CI 1.39-3.18; P = 0.999) versus 5.6 months (95% CI 3.8-5.9) with bevacizumab plus fluoropyrimidine. Treatment-related adverse events occurred in 64 (62%), 52 (50%), and 57 (59%) participants, respectively. There were no treatment-related deaths. CONCLUSION: The LYNK-003 study was stopped prematurely as criteria for futility were met. Maintenance olaparib with or without bevacizumab did not demonstrate clinical efficacy compared with bevacizumab plus a fluoropyrimidine. GOV REGISTRATION: NCT04456699.

Use of ultra-high performance liquid chromatography-high-resolution mass spectroscopy to profile the metabolites from the serum of patients with breast cancer.

Breast cancer (BC) is the most common type of malignancy and the leading cause of cancer-associated mortality in women worldwide. As such, assessing the metabolic changes during human breast carcinogenesis is key for developing disease prevention methods and treatment. In the present study, non-targeted metabolomics with chemometrics based on ultra-high performance liquid chromatography-high-resolution mass spectrometry were performed to assess differences in serum metabolite patterns between patients with BC and healthy individuals. A total of 3,246 metabolites in the sera of healthy controls and patients with BC were found. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that arginine, proline, nicotinate, nicotinamide, caffeine and arachidonic acid metabolism, as well as fatty acid biosynthesis were significantly altered in patients with BC in comparison with controls. These results suggested that serum metabolic profiling has potential for discovering molecular biomarkers for the detection of BC. It may also further the understanding of the underlying mechanisms associated with this disease.

Integrative analysis of RNA-sequencing and microarray for the identification of adverse effects of UVB exposure on human skin.

Background: Ultraviolet B (UVB) from sunlight represents a major environmental factor that causes toxic effects resulting in structural and functional cutaneous abnormalities in most living organisms. Although numerous studies have indicated the biological mechanisms linking UVB exposure and cutaneous manifestations, they have typically originated from a single study performed under limited conditions. Methods: We accessed all publicly accessible expression data of various skin cell types exposed to UVB, including skin biopsies, keratinocytes, and fibroblasts. We performed biological network analysis to identify the molecular mechanisms and identify genetic biomarkers. Results: We interpreted the inflammatory response and carcinogenesis as major UVB-induced signaling alternations and identified three candidate biomarkers (IL1B, CCL2, and LIF). Moreover, we confirmed that these three biomarkers contribute to the survival probability of patients with cutaneous melanoma, the most aggressive and lethal form of skin cancer. Conclusion: Our findings will aid the understanding of UVB-induced cutaneous toxicity and the accompanying molecular mechanisms. In addition, the three candidate biomarkers that change molecular signals due to UVB exposure of skin might be related to the survival rate of patients with cutaneous melanoma.

The Outcomes of Mini-Plate Fixation for Unstable Wagstaffe Tubercle Fracture, an Indirect Syndesmosis Injury in Rotational Ankle Fracture.

Background: Wagstaffe fracture constitutes an indirect injury to the AITFL and can precipitate syndesmotic instability. The prevailing fixation methods often involve the use of mini-screws or K-wires, with absorbable suture repair reserved for cases with small or comminuted fragments exhibiting instability. In this study, we devised a mini-plate fixation method capable of securing the fracture fragment irrespective of its size or condition. Methods: A retrospective chart review was conducted on patients who underwent surgery for ankle fractures between May 2022 and October 2023. The surgical technique involved direct fixation of the Wagstaffe fracture using mini-plate fixation. Radiologic evaluation was performed using postoperative CT images, and clinical outcomes were assessed using the OMAS and VAS. Results: Fourteen patients with an average age of 62.5 years were included. Most fractures were associated with the supination-external rotation type. The average preoperative OMAS significantly improved from 5.95 to 83.57 postoperatively. The average VAS score decreased from 7.95 preoperatively to 0.19 postoperatively. Conclusions: The mini-plate technique for Wagstaffe fractures exhibited dependable fixation strength, effective fracture reduction, a minimal complication rate, and judicious surgical procedure duration.

Natural Products for the Management of Asthma and COPD.

Chronic airway inflammatory diseases like asthma, chronic obstructive pulmonary disease (COPD), and their associated exacerbations cause significant socioeconomic burden. There are still major obstacles to effective therapy for controlling severe asthma and COPD progression. Advances in understanding the pathogenesis of the two diseases at the cellular and molecular levels are essential for the development of novel therapies. In recent years, significant efforts have been made to identify natural products as potential drug leads for treatment of human diseases and to investigate their efficacy, safety, and underlying mechanisms of action. Many major active components from various natural products have been extracted, isolated, and evaluated for their pharmacological efficacy and safety. For the treatment of asthma and COPD, many promising natural products have been discovered and extensively investigated. In this chapter, we will review a range of natural compounds from different chemical classes, including terpenes, polyphenols, alkaloids, fatty acids, polyketides, and vitamin E, that have been demonstrated effective against asthma and/or COPD and their exacerbations in preclinical models and clinical trials. We will also elaborate in detail their underlying mechanisms of action unraveled by these studies and discuss new opportunities and potential challenges for these natural products in managing asthma and COPD.

Tongue Metastasis From Renal Cell Carcinoma: A Rare Case Presentation.

Renal cell carcinoma (RCC) is characterized by a marked metastatic potential and is the third most common cancer of metastasis to the head and neck, following breast and lung cancer. We report a rare case of a patient with RCC with metastasis to the tongue. A 72-year-old man visited our otorhinolaryngology clinic complaining of tongue pain and ulcerative lesions which occurred 3 weeks before. The patient had been diagnosed with RCC and received a right radical nephrectomy 3 years previously. Because the lesion was suspected to be malignant, a hemiglossectomy was planned. However, metastatic lesions were suspected on the left upper lung and the left 10th ribs in imaging studies and the result of an incisional biopsy revealed tongue metastasis of RCC. RCC metastasis to the tongue is extremely rare. Only 51 cases were reported worldwide from 1911 to 2017. According to the literature, no case of RCC metastasis to the tongue has been reported to date in Korea. Therefore, we report this case along with a review of the literature.

Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors.

PURPOSE: This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. MATERIALS AND METHODS: In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer. RESULTS: A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%. CONCLUSION: The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer.

PURPOSE: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). MATERIALS AND METHODS: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. RESULTS: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). CONCLUSION: GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Impact of Patient Sex on Adverse Events and Unscheduled Utilization of Medical Services in Cancer Patients Undergoing Adjuvant Chemotherapy: A Multicenter Retrospective Cohort Study.

PURPOSE: The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex. MATERIALS AND METHODS: This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea. RESULTS: A total of 1,170 patients with colorectal, gastric, or non-small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits. CONCLUSION: Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

Prospective assessment of dynamic changes in frailty and its impact on early clinical outcomes following physician-modified fenestrated-branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms.

INTRODUCTION: Frailty, a predictor of poor outcomes, has been widely studied as a screening tool in surgical decision-making. However, the impact of frailty on the outcomes after fenestrated-branched endovascular aortic repairs (FBEVARs) is less well established. In addition, the changes in frailty during recovery after FBEVAR are unknown. We aim to assess the impact of frailty on outcomes of high-risk patients undergoing physician-modified FBEVARs for complex abdominal and thoracoabdominal aortic aneurysms, as well as the changes in frailty during follow-up. METHODS: Consecutive patients enrolled in a single-center prospective Physician-Sponsored Investigational Device Exemption protocol (FDA# G200159) were evaluated. In addition to the baseline characteristics, frailty was assessed using the Hopkins Frailty Score (HFS) and frailty index (FI) measured by the Frailty Meter. Sarcopenia was measured by L3 total psoas muscle area (PMA). These measurements were repeated during follow-up. The follow-up HFS and FI were compared with baseline scores using the Wilcoxon signed-rank test, whereas follow-up PMA measurements were compared with the baseline using the paired t test. The association between baseline frailty and morbidity was evaluated by the Wilcoxon rank-sum test. RESULTS: Seventy patients were analyzed in a prospective Physician-Sponsored Investigational Device Exemption study from February 9, 2021, to June 2, 2023. At baseline, HFS identified 54% of patients as not frail, 43% as intermediately frail, and 3% as frail. Technical success of FBEVAR was 94% with one in-hospital mortality. Early major adverse events were seen in 10 (14.3%) patients. No difference in baseline FI was seen between patients with early morbidity and those without. Patients who were not frail per HFS were less likely to experience early morbidity (P = .033), and there was a significantly lower baseline PMA in patients who experienced early morbidity (P = .016). At 1 month, patients experienced a significant increase in HFS and HFS category (P = .001 and P = .01) and a significant decrease in sarcopenia (mean PMA: -96 mm2, P = .005). At 6 months, HFS and HFS category as well as PMA returned toward baseline (P = .42, P = .38, and mean PMA: +4 mm2, P = .6). CONCLUSIONS: Preoperative frailty and sarcopenia were associated with early morbidity after physician-modified FBEVAR. During follow-up, patients became more frail and sarcopenic by 1 month. Recovery from this initial decline was seen by 6 months, suggesting that frailty and sarcopenia are reversible processes rather than a unidirectional phenomenon of continued decline.

Diagnostic Performance of Modified Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Patients Without Risk Factors for Hepatocellular Carcinoma: Comparison With World Federation for Ultrasound in Medicine and Biology Guideline.

OBJECTIVE: The aim of this study was to assess the ability of the modified contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) to distinguish malignancy in patients without known hepatocellular carcinoma (HCC) risk factors and compare diagnostic accuracy with that of the World Federation for Ultrasound in Medicine and Biology (WFUMB) guideline across radiologists with different levels of CEUS experience. METHODS: A total of 848 individuals with no hepatitis infection presenting with 870 lesions in non-cirrhotic livers were included and divided into the Testing and Validation groups. The modified CEUS LI-RADS was proposed, including downgrading of focal nodular hyperplasia with typical features. Diagnostic performance of the modified CEUS LI-RADS was assessed in the Testing group. In the Validation group, two radiologists with more than 9 y of CEUS experience (Experts) and two radiologists with less than 6 mo of CEUS experience (Novices) used both the modified CEUS LI-RADS and the WFUMB guideline to evaluate performance in diagnosis of the lesions. RESULTS: LR-5 + M (combination of modified LR-5 and modified LR-M) revealed optimal performance with a sensitivity, specificity and area under the curve (AUC) of 99.3%, 81.6% and 0.904, respectively. Novices using the modified CEUS LI-RADS outperformed those using the WFUMB guideline (AUC: 0.858 vs. 0.767, p = 0.005). Additionally, the sensitivity, specificity and AUC of Novices were comparable to those of Experts using the modified CEUS LI-RADS (94.1%, 77.6% and 0.858 vs. 96.1%, 77.6% and 0.868 for experts, respectively). CONCLUSION: The modified CEUS LI-RADS is a valuable method for distinguishing hepatic malignancy in patients without HCC risk factors. This is particularly beneficial for radiologists with limited CEUS expertise.

Efficacy and Safety of Lu-177 DOTATATE Peptide Receptor Radionuclide Therapy in Patients with Unresectable or Metastatic Neuroendocrine Tumors in Korea.

BACKGROUND: Lutetium (Lu)-177 peptide receptor radionuclide therapy (PRRT) is one of the standard treatments for somatostatin receptor-positive well-differentiated neuroendocrine tumors (NETs). However, limited Asian representation in the pivotal NETTER-1 trial and a lack of real-world data for Lu-177 PRRT from Asian regions exist. OBJECTIVE: This retrospective study aimed to evaluate the efficacy and safety of Lu-177 PRRT in Korean patients with advanced NETs. PATIENTS AND METHODS: This study analyzed 64 patients treated with Lu-177 DOTATATE PRRT at the Asan Medical Center, Seoul, Korea, between November 2019 and December 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), and safety profile. RESULTS: The median age of patients was 55 years. Prior to PRRT, patients received a median of two lines (range 0-6) of systemic therapy. Fifty (78%) patients received the planned four cycles of Lu-177 DOTATATE PRRT. The median PFS was 21.7 months (95% confidence interval 16.7-not available) and the ORR was 20%. With a median follow-up of 15.7 months (range 1.0-39.3), the median OS was not reached and the 1-year OS rate was 88%. The median PFS was better in patients with grade 1-2 NETs than in those with grade 3 NET (not reached vs. 14.2 months; hazard ratio 3.15; p = 0.0058). Hematological toxicities were the common adverse events, including grade ≥ 3 anemia (7.8%), neutropenia (10.9%), and thrombocytopenia (9.4%). CONCLUSIONS: In Korean patients with advanced NETs, Lu-177 DOTATATE PRRT showed efficacy and safety outcomes, consistent with those in the NETTER-1 trial and previous Western real-world studies.

ß-endorphin suppresses ultraviolet B irradiation-induced epidermal barrier damage by regulating inflammation-dependent mTORC1 signaling.

Solar ultraviolet B (UVB) radiation triggers excessive inflammation, disrupting the epidermal barrier, and can eventually cause skin cancer. A previous study reported that under UVB irradiation, epidermal keratinocytes synthesize the proopiomelanocortin-derived peptide ß-endorphin, which is known for its analgesic effect. However, little is known about the role of ß-endorphin in UVB-exposed skin. Therefore, in this study, we aimed to explore the protective role of ß-endorphin against UVB irradiation-induced damage to the skin barrier in normal human keratinocytes (NHKs) and on a human skin equivalent model. Treatment with ß-endorphin reduced inflammatory responses in UVB-irradiated NHKs by inactivating the NF-κB signaling pathway. Additionally, we found that ß-endorphin treatment reversed UVB-induced abnormal epidermal proliferation and differentiation in NHKs and, thus, repaired the skin barrier in UVB-treated skin equivalents. The observed effects of ß-endorphin on UVB-irradiated NHKs were mediated via blockade of the Akt/mTOR signaling pathway. These results reveal that ß-endorphin might be useful against UVB-induced skin injury, including the disruption of the skin barrier function.

Guidelines for the Use of Botulinum Toxin in Otolaryngology From the Korean Society of Laryngology, Phoniatrics and Logopedics Guideline Task Force.

The Korean Society of Laryngology, Phoniatrics and Logopedics created a task force to establish clinical practice guidelines for the use of botulinum toxin (BT) in otolaryngology. We selected 10 disease categories: spasmodic dysphonia, essential vocal tremor, vocal fold granuloma, bilateral vocal fold paralysis, Frey's syndrome, sialocele, sialorrhea, cricopharyngeal dysfunction, chronic sialadenitis, and first bite syndrome. To retrieve all relevant papers, we searched the CORE databases with predefined search strategies, including Medline (PubMed), Embase, the Cochrane Library, and KoreaMed. The committee reported 13 final recommendations with detailed evidence profiles. The guidelines are primarily aimed at all clinicians applying BT to the head and neck area. In addition, the guidelines aim to promote an improved understanding of the safe and effective use of BT by policymakers and counselors, as well as in patients scheduled to receive BT injections.

Evaluating the Efficacy of Tension Band Wiring Fixation for Chaput Tubercle Fractures.

BACKGROUND: Chaput tubercle fractures, located at the attachment site of the anterior inferior tibiofibular ligament (AITFL) on the distal tibia, have the potential to destabilize the syndesmosis joint. This study aims to assess the effectiveness of tension band wiring (TBW) as a surgical intervention for managing Chaput fractures and the consequent syndesmosis instability. METHODS: A retrospective review of patient charts was undertaken for those who had undergone ankle fracture surgery from April 2019 through May 2022. The surgical procedure involved direct fixation of the Chaput fractures using the TBW method. Radiological assessments were performed using postoperative simple radiographs and computed tomography (CT) scans, while clinical outcomes were evaluated using the Olerud-Molander Ankle Score (OMAS) and the visual analog scale (VAS). RESULTS: The study included 21 patients. The average OMAS improved significantly, rising from 5.95 preoperatively to 83.57 postoperatively. Similarly, the average VAS score dropped from 7.95 before the surgery to 0.19 thereafter. Minor wound complications were reported by three patients, and one case of superficial infection was resolved with antibiotic therapy. CONCLUSIONS: Our findings suggest that the TBW technique is an effective surgical approach for treating Chaput fractures and associated syndesmosis instability. It provides reliable fixation strength and leads to improved long-term functional outcomes. Further research is needed to compare the TBW technique with alternative methods and optimize the treatment strategies for these complex ankle fractures.

Cause of Death in Patients with Oropharyngeal Carcinoma by Human Papillomavirus Status: Comparative Data Analysis.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinomas (OPSCC) has increased in recent decades, and human papillomavirus (HPV) infection is the main cause of OPSCC. The data regarding causes of death (CODs) are vitally important in informing follow-up strategies and revising treatment strategies to deal with any possible preventable treatment-related COD. However, limited studies have assessed the competing COD by HPV status in patients with OPSCC. OBJECTIVE: We aimed to analyze the distribution of the competing COD according to HPV status in OPSCC. METHODS: We retrospectively included stage I-IVB patients with OPSCC from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. The association between HPV status and head and neck cancer-specific mortality (HNCSM), second primary cancer mortality (SPCM), and noncancer-caused mortality (NCCM) were analyzed. The chi-square test, Kaplan-Meier analysis, and Fine and Gray model were used for statistical analysis. RESULTS: We included 5852 patients in this study and 73.2% (n=4283) of them had HPV-related tumors. A total of 1537 (26.3%) patients died, including 789 (51.3%), 333 (21.7%), and 415 (27%) patients who died from head and neck cancer, second cancer, and noncancer causes, respectively. The 5-year HNCSM, SPCM, NCCM, and overall mortality were 14.7%, 6.5%, 7.7%, and 26.4%, respectively. Those with HPV-positive disease had a lower cumulative incidence of HNCSM (subdistribution hazard ratio [sHR] 0.362, 95% CI 0.315-0.417; P<.001), SPCM (sHR 0.400, 95% CI 0.321-0.496; P<.001), and NCCM (sHR 0.460, 95% CI 0.378-0.560; P<.001) than those with HPV-negative disease. The 5-year risk of HNCSM was 26.9% and 10.7% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of SPCM was 12.4% and 4.6% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of NCCM of death was 13.7% and 5.8% in those with HPV-negative and HPV-positive disease, respectively (P<.001). Using the Fine and Gray competing-risks model, our results show that those with HPV-negative tumors had a significantly higher risk of HNCSM (P<.001), SPCM (P<.001), and NCCM (P<.001) than those with HPV-negative tumors. CONCLUSIONS: HPV-positive OPSCC has a lower NCSM, SPCM, and NCCM as compared to those with HPV-negative OPSCC. HPV positivity is a favorable prognostic factor in the context of overcoming cancer as well as in terms of reducing the risk of other CODs in OPSCC. Our finding supports the need to tailor patient follow-up based on the HPV status of patients with OPSCC.

Primary cilia: Structure, dynamics, and roles in cancer cells and tumor microenvironment.

Despite the initiation of tumor arises from tumorigenic transformation signaling in cancer cells, cancer cell survival, invasion, and metastasis also require a dynamic and reciprocal association with extracellular signaling from tumor microenvironment (TME). Primary cilia are the antenna-like structure that mediate signaling sensation and transduction in different tissues and cells. Recent studies have started to uncover that the heterogeneous ciliation in cancer cells and cells from the TME in tumor growth impels asymmetric paracellular signaling in the TME, indicating the essential functions of primary cilia in homeostasis maintenance of both cancer cells and the TME. In this review, we discussed recent advances in the structure and assembly of primary cilia, and the role of primary cilia in tumor and TME formation, as well as the therapeutic potentials that target ciliary dynamics and signaling from the cells in different tumors and the TME.

TFF3 promotes clonogenic survival of colorectal cancer cells through upregulation of EP4 via activation of STAT3.

Background: While growing evidence indicates the importance of TFF3 in cancer, the molecular mechanism of its action in cancer remains largely unknown. Clonogenic survival is a key ability for tumor cells, which is interpreted as a trait of cancer cells with tumor-initiating capabilities. We investigated the effect and the underlying mechanisms of TFF3 on the clonogenic survival of colorectal cancer (CRC) cells. Methods: Expression of TFF3 in CRC tissues and matched paracancerous tissues was determined by western blotting. Colony formation assays were performed to evaluate the clonogenic survival ability of CRC cells. PTGER4 mRNA expression was detected by quantitative polymerase chain reaction. PTGER4 promoter activity was determined by luciferase reporter assay. STAT3 nuclear localization was investigated using immunofluorescence staining. Expression of TFF3 and EP4 in CRC tissues was determined by immunohistochemistry. Results: TFF3 knockout led to decreased clonogenic survival of CRC cells, while overexpression of TFF3 resulted in the opposite effect. EP4 was found to be upregulated by TFF3 at both the mRNA and protein level. Moreover, EP4 antagonist abrogated TFF3-mediated clonogenic survival of CRC cells. PGE2 and EP4 agonist could restore the effect of TFF3 knockout on the clonogenic survival of CRC cells. Furthermore, TFF3 promoted STAT3 activation and nuclear localization. Activated STAT3 bound to PTGER4 promoter, the gene encoding for EP4, and facilitated PTGER4 transcription. Conclusions: TFF3 promotes clonogenic survival of CRC cells via upregulating EP4 expression.