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Lancet (London, England) Jun 2024
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Immune Checkpoint Inhibitors; Purpura Fulminans; Male; Middle Aged; Female; Aged
PubMed: 38944528
DOI: 10.1016/S0140-6736(24)01178-4 -
Advances in Pediatrics Aug 2024Patients with differences of sex development (DSDs) have complex anatomy and surgical needs related to both Mullerian and non-Mullerian structures. Approaches to vaginal... (Review)
Review
Patients with differences of sex development (DSDs) have complex anatomy and surgical needs related to both Mullerian and non-Mullerian structures. Approaches to vaginal reconstruction for these conditions are guided by individual anatomy, with the goal of establishing unobstructed outflow for the reproductive, urinary, and gastrointestinal tracts. Patients may have anatomy requiring vaginoplasty for either outflow tract obstruction or chosen sexual function. In this article, the authors focus on management of differences in vaginal anatomy with delayed vaginoplasty for the newborn with DSD.
Topics: Humans; Female; Disorders of Sex Development; Vagina; Infant, Newborn; Plastic Surgery Procedures; Male
PubMed: 38944480
DOI: 10.1016/j.yapd.2024.04.002 -
Oral Oncology Jun 2024Different fibula osteocutaneous free flap (FOCFF) configurations have been described with a double-skin paddle (DSP) to address composite through-and-through...
BACKGROUND
Different fibula osteocutaneous free flap (FOCFF) configurations have been described with a double-skin paddle (DSP) to address composite through-and-through oromandibular defects: division of the skin paddle using different perforators (div-FOCFF) or a de-epithelialized DSP FOCFF (deEpi-FOCFF). This study aimed to compare the surgical outcomes using these two methods (deEpi-FOCFF/div-FOCFF).
METHODS
Patients who underwent segmental mandibulectomy and reconstruction with a DSP FOCFF between 2011 and 2014 were included. We compared postoperative outcomes of patients undergoing reconstruction with deEpi-FOCFF versus div-FOCFF implementing propensity score matching.
RESULTS
Of the 245 patients, 156 cases (78 pairs) were 1:1 matched. Demographic and oncologic variables were comparable between groups. The average age was 57.68 years. A higher number of perforators per flap was evident in the div-FOCFF group (p < 0.001). The deEpi-FOCFF group exhibited a higher total flap loss rate when compared to the div-FOCFF group (15 % versus 5 % p = 0.03). On multivariate analysis, number of perforators per flap (OR 0.31, p = 0.02), using the deEpi-FOCFF (OR 3.88, p = 0.03), and an increased reconstructive time (OR 1.01, p = 0.01) independently affected the likelihood of free flap failure.
CONCLUSION
If the number and location of perforators are optimal, div-FOCFF improves reconstructive outcomes for composite oromandibular defects versus the deEpi-FOCFF.
PubMed: 38943871
DOI: 10.1016/j.oraloncology.2024.106910 -
Journal of Plastic, Reconstructive &... Jun 2024Assessment of breast volume is essential in preoperative planning of immediate breast reconstruction (IBR) surgery to achieve satisfactory cosmetic outcome. This study...
BACKGROUND
Assessment of breast volume is essential in preoperative planning of immediate breast reconstruction (IBR) surgery to achieve satisfactory cosmetic outcome. This study introduced a breast volume measurement tool that can be used to perform automatic segmentation of magnetic resonance images (MRI) and calculation of breast volume. We compared the accuracy and reliability of this measurement method with four other conventional modalities.
METHODS
Patients who were scheduled to undergo mastectomy with IBR between 2016 and 2021 were enrolled in the study. Five different breast volume assessments, including automatic segmentation of MRI, manual segmentation of MRI, 3D surface imaging, mammography, and the BREAST-V formula, were used to evaluate different breast volumes. The results were validated using water displacement volumes of the mastectomy specimens.
RESULTS
In this pilot study, a total of 50 female patients met the inclusion criteria and contributed 54 breast specimens to the volumetric analysis. There was a strong linear association between the MRI and water displacement methods (automatic segmentation: r = 0.911, p < 0.001; manual segmentation: r = 0.924, p < 0.001), followed by 3D surface imaging (r = 0.858, p < 0.001), mammography (r = 0.841, p < 0.001), and Breast-V formula (r = 0.838, p < 0.001). Breast volumes measured using automatic and manual segmentation of MRI had lower mean relative errors (30.3% ± 22.0% and 28.9% ± 19.8, respectively) than 3D surface imaging (38.9% ± 31.2), Breast-V formula (44.8% ± 25.8), and mammography (60.3% ± 37.6).
CONCLUSION
Breast volume assessment using the MRI methods had better accuracy and reliability than the other methods used in our study. Breast volume measurement using automatic segmentation of MRI could be more efficient compared to the conventional methods.
PubMed: 38943699
DOI: 10.1016/j.bjps.2024.05.029 -
Biomolecules & Biomedicine Jun 2024Liver fibrosis, a common characteristic in various chronic liver diseases, is largely influenced by glycolysis. Quercetin (QE), a natural flavonoid known to regulate...
Liver fibrosis, a common characteristic in various chronic liver diseases, is largely influenced by glycolysis. Quercetin (QE), a natural flavonoid known to regulate glycolysis, was studied for its effects on liver fibrosis and its underlying mechanism. Results showed that QE effectively improved liver injury and fibrosis caused by carbon tetrachloride (CCl4). This was supported by evidence of improved pathological features and reduced levels of serum markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), hyaluronic acid (HA), laminin (LN), and procollagen type III. QE also decreased lactate production and downregulated the expression of glycolysis-related enzymes - pyruvate kinase M2 (PKM2), phosphofructokinase platelet (PFKP), and hexokinase 2 (HK2) - at both the mRNA and protein levels. In liver sinusoidal endothelial cells (LSECs), QE reduced the expression and activity of these enzymes, resulting in reduced glucose consumption, ATP production, and lactate generation. Further analysis revealed that QE inhibited the production of chemokine (C-X-C motif) ligand 1 (CXCL1) and suppressed neutrophil recruitment. Overall, QE showed promising therapeutic potential for liver fibrosis by targeting LSEC glycolysis and reducing neutrophil infiltration.
PubMed: 38943679
DOI: 10.17305/bb.2024.10530 -
Journal of Burn Care & Research :... Jun 2024Finding a perfect epidermal transplant remains a holy grail of burn surgery. The epidermis is a site of stem cells that allows for the epithelial regeneration. The use...
Finding a perfect epidermal transplant remains a holy grail of burn surgery. The epidermis is a site of stem cells that allows for the epithelial regeneration. The use of CEA for the treatment of major burns was first reported in 1981. CEA requires specialized skills; thus, reports from different burn-centers have shown mixed results. Comparing our modern data with past data shows how this field has advanced while maintaining institutional control. We performed a retrospective analysis of all patients admitted between 01/01/1988-12/31/2021 for massive burns that were managed with CEA. Patients were divided into pre-defined groups: G1(early-era)=1988-1999, G2(pre-modern-era)=2000-2010, and G3(modern-era)=2011-2021. We compared demographics, %TBSA, presence of inhalation-injury, LOS, complications, and mortality. We treated 52 patients with CEA during the study period. In the modern-era, we found 11 patients; in the pre-modern-era, 10; and in the early-era, 31. Injury characteristics, including %TBSA and the presence of inhalation-injury, were not significantly different between the groups. We observed lower mortality rates in G1 and G3 (G1:20% vs. G2:42% vs. G3:27%, p<0.05), although the predicted mortality was not significantly different between the groups (G1:50% vs. G2:47% vs. G3:49%, NS). Patients in G1 also had a shorter hospital LOS, in days, (G1:90 vs. G2:127 vs. G3:205, p<0.05). Finally, the surface-area grafted per patient was the highest in G2 (G1:2,000cm2 vs. G2:4,187cm2 vs. G3:4,090cm2, p<0.01). CEA has not gained popularity despite proven positive outcomes. Our retrospective analysis showed that CEA should be considered as a treatment option for patients with large burns, given proper training and infrastructure.
PubMed: 38943557
DOI: 10.1093/jbcr/irae132 -
Microsurgery Jul 2024This study is an economic evaluation comparing virtual surgical planning (VSP) utilization to free hand mandibular reconstruction (FHR) for advanced oral cavity cancer,...
OBJECTIVE
This study is an economic evaluation comparing virtual surgical planning (VSP) utilization to free hand mandibular reconstruction (FHR) for advanced oral cavity cancer, for which the cost effectiveness remains poorly understood. The proposed clinical benefits of VSP must be weighed against the additional upfront costs.
METHODS
A Markov decision analysis model was created for VSP and FHR based on literature review and institutional data over a 35-year time horizon. Model parameters were derived and averaged from systematic review and institutional experience. VSP cost and surgical time saving was incorporated. We accounted for long-term risks including cancer recurrence and hardware failure/exposure. We calculated cost in US dollars and effectiveness in quality-adjusted-life-years (QALYs). A health care perspective was adopted, discounting costs and effectiveness at 3%/year. Deterministic and probabilistic sensitivity analyses tested model robustness.
RESULTS
In the base case scenario, total VSP strategy cost was $49,498 with 8.37 QALYs gained while FHR cost was $42,478 with 8.27 QALY gained. An incremental cost-effectiveness ratio (ICER), or the difference in cost/difference in effectiveness, for VSP was calculated at $68,382/QALY gained. VSP strategy favorability was sensitive to variations of patient age at diagnosis and institutional VSP cost with one-way sensitivity analysis. VSP was less economically favorable for patients >75.5 years of age or for institutional VSP costs >$10,745. In a probabilistic sensitivity analysis, 55% of iterations demonstrated an ICER value below a $100,000/QALY threshold.
CONCLUSIONS/RELEVANCE
VSP is economically favorable compared to FHR in patients requiring mandibular reconstruction for advanced oral cancer, but these results are sensitive to the patient's age at diagnosis and the institutional VSP cost. Our results do not suggest if one "should or should not" use VSP, rather, emphasizes the need for patient selection regarding which patients would most benefit from VSP when evaluating quality of life and long-term complications. Further studies are necessary to demonstrate improved long-term risk for hardware failure/exposure in VSP compared to FHR.
Topics: Humans; Cost-Benefit Analysis; Mandibular Reconstruction; Quality-Adjusted Life Years; Markov Chains; Mouth Neoplasms; Surgery, Computer-Assisted; Treatment Outcome; Male; Decision Support Techniques; Female; Cost-Effectiveness Analysis
PubMed: 38943374
DOI: 10.1002/micr.31206 -
Journal of Burn Care & Research :... Jun 2024
PubMed: 38943312
DOI: 10.1093/jbcr/irae125 -
Stem Cells and Development Jun 2024Adipose stem cells are considered one of the primary drivers of autologous fat graft biologic activity and survival. We have previously demonstrated that hormonally...
Adipose stem cells are considered one of the primary drivers of autologous fat graft biologic activity and survival. We have previously demonstrated that hormonally active VD3 improved adipose stem cell viability in ex vivo and in vivo fat grafting models. In this study, we evaluated the inactive form of VD3 (cholecalciferol) on adipose stromal cell (ASC) phenotype during hypoxia and the subsequent effect on human fat graft retention in the xenograft model. Lipoaspirate collected from six human donors was used for ex-vivo particle culture studies and isolated ASC studies. Adipose particles were treated with increasing doses of VD3 to determine impact on ASC survival. Expanded stromal cells were treated with VD3 during hypoxic culture and assessed for viability, apoptosis, mitochondrial activity, and nitric oxide release via caspase, DAF-FM, or TMRM. Finally, forty Nu/J mice receiving bilateral dorsal human lipoaspirate were treated thrice weekly with 1) Vehicle control, 2) 50ng calcitriol, 3) 50ng VD3, 4) 500ng VD3, and 5) 5000ng VD3 for 12 weeks, n=8 per group. Graft weight, volume, and architecture were analyzed. Adipose particles treated with dose escalating VD3 had significantly increased ASC viability compared to control (p<0.01). Under hypoxia, ASCs treated with 1nM VD3 had significantly greater viability than untreated and pre-treated cells (p<0.01, p<0.01) and significantly lower apoptosis-to-viability ratio (p<0.01). ASCs pre-treated with 1nM VD3 had significantly lower nitric oxide release (p<0.05) and lower mitochondrial polarization (p<0.05) compared to controls. In vivo results showed mice receiving 5000ng VD3 had significantly greater graft weight (p<0.05) and volume (p<0.05) after 12 weeks of treatment compared to controls. Grafts had enhanced neovascularization, intact adipocyte architecture, and absence of oil cysts. VD3 is an over-the-counter nutritional supplement with a known safety profile in humans. Our xenograft model suggests administering VD3 at the time of surgery may significantly improve fat graft retention.
PubMed: 38943277
DOI: 10.1089/scd.2024.0056 -
Cellular and Molecular Life Sciences :... Jun 2024Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes...
Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes cetuximab resistance, especially microRNA (miRNA) regulation, remains unclear. Growing evidence suggests that miRNAs may act as "nuclear activating miRNAs" for targeting promoter regions or enhancers related to target genes. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, quantitative real-time polymerase chain reaction (qRT‒PCR) and fluorescence in situ hybridization (FISH) results provided compelling evidence of miR-451a nuclear enrichment in response to cetuximab treatment. Chromatin isolation via RNA purification, microarray analysis, and bioinformatic analysis revealed that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It has also been demonstrated that the activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Logistic regression analyses of 87 HNSCC samples indicated the significance of miR-451a and KDM7A in the development of cetuximab resistance. These discoveries support the potential of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear-activating miRNAs.
Topics: Humans; MicroRNAs; Cetuximab; Drug Resistance, Neoplasm; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Jumonji Domain-Containing Histone Demethylases; Argonaute Proteins; Animals; Mice; Cell Nucleus; Female; Mice, Nude
PubMed: 38943031
DOI: 10.1007/s00018-024-05324-x