Use of the double-paddle anterolateral thigh flap for locally advanced tongue carcinoma requiring second site reconstruction

BackgroundAdvanced oral tongue carcinoma can present with extension beyond the oral cavity. Operative defects after resection may involve multiple anatomical sites and significantly impact speech and swallowing. Dependence on long-term enteral feeding is not uncommon for these patients. The anterolateral thigh (ALT) flap is one of the most reliable and flexible flaps used in the reconstruction of total and subtotal tongue defects. The double-paddle flap modification may be a more suitable option for complex oral tongue defects after advanced tumor ablation.MethodsCase series of 31 patients with oral tongue squamous cell carcinoma that were classified as stage IV. The age of patients ranged from 32 to 63 years. We designed the double-paddle ALT flaps to reconstruct the two-site surgical defects (tongue defect and pharynx or neck skin defect). Postoperative viability of the flap was checked by clinical observation. The last examination was performed at 3-months after the completion of adjuvant chemoradiotherapy. The functional capacity of our patients was evaluated by three physicians (Head and Neck Surgeon, Radiation Oncologist, and Physiatrist) using a Speech Intelligibility Score and the Functional Oral Intake Scale.ResultsA total of 31 patients with surgical defects after total or subtotal tongue resection for cancer underwent double-paddle ALT flaps for reconstruction from March 2018 to December 2019. The dimension of flaps from 8 × 12 cm to 10 × 18 cm were divided into double-paddle from 8 × 5 cm to 10 × 10 cm. There was one case of pedicle thrombosis, one case of postoperative bleeding, three cases of neck infection, and six cases of salivary fistula. Our patients were seen in follow up from 6 to 36 months, with median follow-up of 23.5 months. The survival rate of ALT flap was 100%. All of our patients achieved an oral diet by 9 months after surgery. The mean score speech intelligibility was 2.74 ± 0.68 (4-point ordinal scale). The 2-year disease-free survival rate was 61.3%.ConclusionsThe double-paddle ALT flap is a reliable flap suitable for oral defects involving multiple subsites after ablative procedures. The majority of patients demonstrated acceptable functional rehabilitation.Clinical question/ level of evidenceTherapeutic, IV.     

Papel de la yeyunoplastia en la reconstrucción esofágica compleja

IntroductionEsophageal reconstruction is a very complex surgical procedure, burdened by significant morbidity. Gastroplasty and coloplasty have classically been used. Free jejunal plasty has shown to be a very good option in the treatment of cervical esophagus pathology, but the role of supercharged jejunoplasty in thoracic esophagus reconstruction is still controversial.MethodsA retrospective study of esophageal reconstructions with jejunoplasties performed in our unit between January 2011 and December 2019. Epidemiological data, indications, surgical technique, and morbidity and mortality were analyzed.Results67 procedures of esophageal reconstruction were performed, 10 of which were jejunoplasties: 5 free jejunums and 5 supercharged. Morbidity, mortality, mean stay and withdrawal time from enteral feeding were lower in free than in supercharged jejunums.ConclusionsSupercharged jejunoplasty was the last option for reconstruction of the thoracic esophagus. Median sternotomy access provides an excellent approach to the anterior mediastinum and the internal mammary vessels. The free jejunum would be the first choice, with the indemnity of the rest of the esophagus, in the reconstruction of the cervical esophagus.     

Exploring a 7-gene prognostic model based on ferroptosis for efficiently guiding immunotherapy in melanoma patients

PurposeAlthough skin cutaneous melanoma (SKCM) is a relatively immunotherapy-sensitive tumor type, there is still a certain fraction that benefits less from treatment. Ferroptosis has been demonstrated to modulate tumor progression in many cancer types. This study focused on ferroptosis-related genes to construct a prognostic model for SKCM patients.Materials and methodsGene expression profiles of SKCM samples were obtained from public databases. Unsupervised consensus clustering was used to determine molecular subtypes related to ferroptosis. Least absolute shrinkage and selection operator (LASSO) and stepwise Akaike information criterion (stepAIC) were applied to construct a prognostic model based on differentially expressed genes between two molecular subtypes.ResultsC1 and C2 subtypes were identified with differential prognosis and immune infiltration. A 7-gene prognostic model was constructed to classify samples into high-FPRS and low-FPRS groups. Low-FPRS group with favorable prognosis had higher immune infiltration and more enriched immune-related pathways than the high-FPRS group. The two groups showed distinct sensitivity to immunotherapy, with the low-FPRS group predicted to have more positive response to immunotherapy than the high-FPRS group. A nomogram based on the FPRS score and clinical features was built for more convenient use.ConclusionsThe critical role of ferroptosis involved in SKCM development was further validated in this study. The prognostic model was efficient and stable to be applied in clinical conditions to support clinicians in determining personalized therapy for SKCM patients especially those with metastasis.     

Are TRPA1 and TRPV1 channel-mediated signalling cascades involved in UVB radiation-induced sunburn?

Burn injuries are underappreciated injuries associated with substantial morbidity and mortality. Overexposure to ultraviolet (UV) radiation has dramatic clinical effects in humans and is a significant public health concern. Although the mechanisms underlying UVB exposure are not fully understood, many studies have made substantial progress in the pathophysiology of sunburn in terms of its molecular aspects in the last few years. It is well established that the transient receptor potential ankyrin 1 (TRPA1), and vanilloid 1 (TRPV1) channels modulate the inflammatory, oxidative, and proliferative processes underlying UVB radiation exposure. However, it is still unknown which mechanisms underlying TRPV1/A1 channel activation are elicited in sunburn induced by UVB radiation. Therefore, in this review, we give an overview of the TRPV1/A1 channel-mediated signalling cascades that may be involved in the pathophysiology of sunburn induced by UVB radiation. These data will undoubtedly help to explain the various features of sunburn and contribute to the development of novel therapeutic approaches to better treat it.     

The infant health effects of starting universal child benefits in pregnancy: Evidence from England and Wales

Child benefits are typically paid from birth. This paper asks whether starting universal child benefits in pregnancy leads to improvements in infant health. Leveraging administrative birth registry and hospital microdata from England and Wales, I study the effects of the Health in Pregnancy Grant, a universal conditional cash transfer equivalent to three months of child benefit (190 GBP) as a lump sum to pregnant mothers from 2009 to 2011. I exploit quasi-experimental variation in eligibility with a regression discontinuity design in the date of birth of the baby. I find that the policy increased birth weight by 8–12 grams on average, reduced low birth weight ($<$2500 g) by 3-6 percent and decreased prematurity by 9–11 percent. Younger mothers, particularly those living in deprived areas, benefit the most. I present evidence that the mechanisms are unlikely to be antenatal care, nutrition or smoking, with reductions in stress remaining a possible explanation.     

种植手术同期根向复位瓣附着龈重建的临床研究

目的探索一种简单高效的手术方法,用于增加种植体周围的附着龈宽度并且能缩短种植修复的疗程。探讨根向复位瓣附着龈重建术的效果。方法收集有种植修复需求的患者8例,但种植位点处附着龈宽度小于2 mm,行种植手术同期利用根向复位瓣技术进行附着龈重建。术后2周拆线。8周后常规种植上部修复并负荷。分别观察手术前、术后8周、修复完成即刻、修复完成1年时附着龈宽度的变化情况。结果所有患者种植体周围的附着龈宽度明显增加,修复完成1年后未见明显附着龈退缩。术后2周拆线,除1个种植位点在术后第2天因缝合线脱落致黏膜仍有炎症外,其余位点黏膜愈合良好。结论根向复位瓣附着龈重建术创伤小,并且同期种植手术可以缩短种植修复疗程,术后患者恢复效果较好。可以作为增加种植体周围附着龈宽度的简单高效的方法。     

养精种玉汤辅助体外受精-胚胎移植对排卵障碍性不孕患者的影响

目的：探究养精种玉汤辅助体外受精-胚胎移植（IVF-ET）对排卵障碍性不孕患者的影响。方法：选取2016年12月至2017年3月邯郸市中心医院收治的排卵障碍性不孕患者82例作为研究对象，按照随机数字表法随机分为对照组与观察组，每组41例。对照组给予促性腺激素释放激素激动剂（Gn）+控制性促排卵+IVF-ET治疗，观察组在此基础上联合养精种玉汤治疗，至HCG日停止服用。治疗后统计2组Gn使用情况、取卵数及妊娠率；检测并比较HCG日2组子宫内膜容受性指标；比较2组妊娠结局及治疗期间相关不良反应发生情况。结果：观察组Gn使用天数及使用剂量均低于对照组，而妊娠率高于对照组（P<0.05或P<0.01）；观察组子宫内膜类型为A型患者比例高于对照组，而子宫内膜类型为C型患者比例低于对照组（P<0.05或P<0.01）；观察组子宫内膜厚度大于对照组，而子宫内膜动脉血流参数PI及RI均低于对照组（P<0.01）；2组不良反应发生率差异无统计学意义（P>0.05），且治疗期间2组血清肝功能指标及血尿常规检测均未发现异常。结论：养精种玉汤辅助IVF-ET可有效增强排卵障碍性不孕患者子宫内膜容受性，提高患者妊娠率并改善其妊娠结局，具有良好的安全性。     

Optimizing T-cell receptor avidity with somatic hypermutation

Adoptive transfer of T cells that have been genetically modified to express an antitumor T-cell receptor (TCR) is a potent immunotherapy, but only if TCR avidity is sufficiently high. Endogenous TCRs specific to shared (self) tumor-associated antigens (TAAs) have low affinity due to central tolerance. Therefore, for effective therapy, anti-TAA TCRs with higher and optimal avidity must be generated. Here, we describe a new in vitro system for directed evolution of TCR avidity using somatic hypermutation (SHM), a mechanism used in nature by B cells for antibody optimization. We identified 44 point mutations to the Pmel-1 TCR, specific for the H-2D^b-gp100_25-33 melanoma antigen. Primary T cells transduced with TCRs containing two or three of these mutations had enhanced activity in vitro. Furthermore, the triple-mutant TCR improved in vivo therapy of tumor-bearing mice, which exhibited improved survival, smaller tumors and delayed or no relapse. TCR avidity maturation by SHM may be an effective strategy to improve cancer immunotherapy.     

游离腓肠内侧动脉穿支皮瓣修复前臂及足部软组织缺损

目的 探讨应用腓肠内侧动脉穿支皮瓣(MSAP)修复前臂及足部软组织缺损的临床效果.方法 自2015年5月至2017年9月,应用MSAP修复前臂及足部软组织缺损创面13例,其中男9例,女4例,年龄19~57岁,平均41岁;其中前臂6例,足部7例,足部创面均位于前中足.皮瓣切取面积为3.0 cm×4.0 cm^7.0 cm×15.0 cm.修复足部创面时均选用同侧小腿,小腿供区创面均进行一期直接缝合.术后通过门诊复查及微信方式,对皮瓣外形、感觉及供区恢复情况进行定期随访.结果 13例皮瓣全部成活,无血管危象发生及坏死,3例术后存在感染,给予换药及抗炎治疗后创面逐渐愈合.术后随访11例(2例外省患者失访),随访时间4~18个月,平均12个月,未发现供区明显功能障碍,受区皮瓣外形良好;7例感觉恢复至S2~S3,TPD 6~9 mm.结论 游离MSAP不损伤主干血管,血管蒂长,穿支恒定,皮下脂肪相对较薄,游离移植修复前臂及足部创面效果良好.     

Can a conditional cash transfer reduce teen fertility? The case of Brazil’s Bolsa Familia

In 2008, Brazil's conditional cash transfer program expanded to cover a wider range of ages. Poor families are now given stipends for their children's school attendance up to age seventeen, whereas prior the maximum age was fifteen. Using a nationally representative household survey, we estimate the impact of this policy on teen fertility with a triple difference analysis on the fertility outcomes of treated cohorts vs. non-treated cohorts based on income eligibility, age eligibility, and timing of program implementation. We find a three percentage point drop in fertility among eligible teens within five years of program implementation. This offsets the difference in fertility between poor and non-poor teens. The impact is concentrated in urban areas, with no program effects found in rural areas. We are able to replicate these findings using National Birth Registry Data.