Computer-Assisted Gradual Correction of Charcot Foot Deformities: An In-Depth Evaluation of Stage One of a Planned Two-Stage Approach to Charcot Reconstruction.

The surgical treatment of Charcot foot is a widely debated topic, with issues ranging from when to operate to how to properly correct a deformity. Historically, correction of a severe deformity was attempted in 1 acute surgical procedure that frequently required open reduction and internal fixation through large incisions. This 1-time procedure would often result in complications including under- or overcorrection of the deformity, neurovascular injury, or incision dehiscence leading to possible soft-tissue infection or osteomyelitis. This retrospective case series aims to evaluate stage 1 of a planned 2-stage approach to Charcot deformity correction, consisting of gradual modification with the use of computer-assisted external fixation. The purpose of using gradual correction was to safely and accurately correct the Meary and calcaneal inclination angles, which were measured using preoperative and postoperative digital radiographs. The procedure was performed on 18 Charcot foot deformities in 18 patients. Each of the feet had a notably significant rocker bottom deformity and most contained an ulceration. Complete ulcer healing was noted in 100% (13/13) of feet with an ulcer, and a statistically significant corrected Meary's (p < .05) and calcaneal inclination angle (p < .05) to within a normal range was achieved in all deformity corrections with few postoperative problems and complications noted. Average patient follow-up was 39.6 months with a minimum of at least 12 months necessary for inclusion in the study. Therefore, gradual Charcot deformity correction through the use of computer-assisted hexapod external fixation, demonstrates safe, accurate, and reproducible characteristics that adequately prepares the lower extremity for stage 2, the implantation of rigid internal fixation.

Alcohol and hepatitis virus-dysregulated lncRNAs as potential biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths because of frequent late detection and poor therapeutic outcomes, necessitating the need to identify effective biomarkers for early diagnosis and new therapeutic targets for effective treatment. Long noncoding RNAs (lncRNAs) have emerged as promising molecular markers for diagnosis and treatment. Through analysis of patient samples from The Cancer Genome Atlas database, we identified putative lncRNAs dysregulated in HCC and by its risk factors, hepatitis infection and alcohol consumption. We identified 184 lncRNAs dysregulated in HCC tumors versus paired normal samples, 53 lncRNAs dysregulated in alcohol-drinking patients with hepatitis B, and 5, 456 lncRNAs dysregulated in patients with hepatitis infection. A panel of these candidate lncRNAs' expressions correlated significantly with patient survival, clinical variables, and known genomic alteration in HCC. Two most significantly dysregulated lncRNAs in our computational analysis, lnc-CFP-1:1 and lnc-CD164L2-1:1, were validated in vitro to be dysregulated by alcohol. Our findings suggest that lncRNAs dysregulated by different etiologies of HCC serve as potential disease markers and can be further investigated to develop personalized prevention, diagnosis, and treatment strategies.

A comprehensive study of smoking-specific microRNA alterations in head and neck squamous cell carcinoma.

OBJECTIVE: While tobacco smoking is a well-known risk factor for head and neck squamous cell carcinoma (HNSCC), the molecular mechanisms underlying tobacco-induced HNSCC remain unclear. This study sought to comprehensively identify microRNA (miRNA) alterations and evaluate their clinical relevance in smoking-induced HNSCC pathogenesis and progression. MATERIALS AND METHODS: Using small RNA-sequencing data and clinical data from 145 HNSCC patients, we performed a series of differential expression and correlation analyses to identify a panel of tobacco-dysregulated miRNAs associated with key clinical characteristics in HNSCC. We then examined the expression patterns of these miRNAs in normal epithelial cell lines following exposure to cigarette smoke extract. RESULTS: Our analyses revealed distinct panels of miRNAs to be dysregulated with smoking status and associated with additional clinical features, including tumor stage, metastasis, anatomic site, and patient survival. The differential expression of key miRNAs, including miR-101, miR-181b, miR-486, and miR-1301, was verified in cigarette-treated epithelial cell lines, suggesting their potential roles in the early development of smoking-related HNSCCs. CONCLUSION: Specific alterations in miRNA expression may be traced to tobacco use and are associated with important HNSCC clinical characteristics. Future studies of these miRNAs may be valuable for furthering the understanding and targeted treatment of smoking-associated HNSCC.

Alcohol-dysregulated microRNAs in hepatitis B virus-related hepatocellular carcinoma.

Alcohol consumption and chronic hepatitis B virus (HBV) infection are two well-established risk factors for Hepatocellular carcinoma (HCC); however, there remains a limited understanding of the molecular pathway behind the pathogenesis and progression behind HCC, and how alcohol promotes carcinogenesis in the context of HBV+ HCC. Using next-generation sequencing data from 130 HCC patients and 50 normal liver tissues, we identified a panel of microRNAs that are significantly dysregulated by alcohol consumption in HBV+ patients. In particular, two microRNAs, miR-944 and miR-223-3p, showed remarkable correlation with clinical indication and genomic alterations. We confirmed the dysregulation of these two microRNAs in liver cell lines treated by alcohol and acetaldehyde, and showed that manipulation of miR-223-3p and miR-944 expression induces significant changes in cellular proliferation, sensitivity to doxorubicin, and the expression of both direct-binding and downstream mRNA targets. Together, the results of this study suggest that alcohol consumption in HBV+ HCCs regulates microRNAs that likely play previously uncharacterized roles in the alcohol-associated carcinogenesis of HCC, and future studies of these microRNAs may be valuable for furthering the understanding and treatment of alcohol and HBV-associated HCC.