Papillary thyroid carcinoma with a high tumor mutation burden has a poor prognosis

BackgroundTumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).MethodsBased on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.ResultsHigh TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8⁺ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.ConclusionsPTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected.     

Long-term follow-up of camouflage effects following resin infiltration of post orthodontic white-spot lesions in vivo

Objectives:To reassess the long-term camouflage effects of resin infiltration (Icon, DMG, Hamburg, Germany) of white spot lesions (WSL) and sound adjacent enamel (SAE) achieved in a previous trial. The null hypothesis was tested that there were no significantly different CIE-L*a*b*-ΔE-values between WSL and SAE areas of assessment after at least 24 months (T24) compared to those at baseline (T0).Materials and Methods:Of twenty subjects who received previous resin infiltration treatment of n_teeth = 111 nonrestored, noncavitated postorthodontic WSL after multibracket treatment during a randomized controlled trial and were contacted 20 months after baseline, eight subjects (trial teeth n_teeth = 40; m/f ratio 1/7; age range (mean; SD) 12–17 [15.25; 2.12] years); response rate: 40%) were available for follow-up after at least 24 months (T24). CIE-L*a*b* differences between summarized color and lightness values (ΔE_WSL/SAE) of WSL and SAE were assessed using a spectrophotometer and compared to baseline data assessed prior to infiltration (T0), and those after 6 (T6), and 12 (T12) months using paired t tests at a significance level of α = 5%.Results:T24 assessments were performed after a mean 33.86 (SD: 8.64; Min: 24; Max: 45) months following T0. Mean (SD) ΔE_WSL/SAE units of available teeth were 8.76 (5.33) at baseline; 5.5 (2.75) at T6; 5.2 (2.41) at T12; and 5.57 (2.6) at T24. Comparisons of T6, T12, and T24 with T0 yielded highly significant differences, whereas T6–T24 and T12–T24 differences were found to be not significant.Conclusions:Assimilation of infiltrated WSL to the color of adjacent enamel by resin infiltration is considered to be suitable for the long-term improvement in the esthetic appearance of postorthodontic WSL.     

Optimizing Rapid Recovery After Anterior Hip Arthroplasty Surgery: A Comparative Study of Fascia Iliaca Compartment Block and Local Infiltration Analgesia

BackgroundMultimodal pain therapy combining analgesics, local infiltration analgesia (LIA) and peripheral nerve blocks, such as fascia iliaca compartment block (FICB), can improve postoperative pain, nausea and vomiting (PONV) and ambulation in patients undergoing total hip arthroplasty (THA). We hypothesized that addition of FICB would decrease opioid requirements and length of stay (LOS) but could create a motor block.MethodsThis is a single center, prospective, blinded randomized controlled study of 152 patients undergoing elective THA via direct anterior approach from October 2019 till August 2021. Three patient groups were defined: patients receiving only spinal anesthesia (control group, n = 53); spinal anesthesia with LIA perioperatively (n = 50); and spinal anesthesia with FICB on the recovery unit (n = 49). Outcome measures consisted of postoperative pain scores, PONV, length of hospital stay, opioid requirements and mobility.ResultsOverall pain scores were low for all patient groups, with a lower pain score for LIA in comparison to the control group until 4 hours postoperatively (P < .05). Length of hospital stay, postoperative pain, nausea and vomiting (PONV) scores and quadriceps muscle strength did not differ significantly between groups. The control group showed higher scores at 12 hours postoperatively in comparison to FICB regarding rehabilitation potential, use of walking aids and activities of daily living (P < .05), but all groups reached the same endpoint 48 hours postoperatively. The LIA and FICB groups required less opioids until 24 hours postoperatively.ConclusionLIA is a beneficial adjuvant therapy to spinal anesthesia in THA patients as it may decrease pain scores and the need for opioid consumption. Adjuvant FICB only provided lower opioid requirements.     

Large volume injection and infiltration system

Summary A system which can be used for injection or infiltration of large volumes of fluid is described. This consists of a syringe which fills automatically from a reservoir through an inlet/outlet valve.     

局部浸润麻醉在隆乳术中的应用

目的 探讨局部浸润麻醉方法在隆乳术中的应用效果。方法 将2％利多卡因20ml加0．5％布匹卡因5ml配制成120ml局部麻醉液，采用局部浸润麻醉方法为568例受术者行隆乳手术，根据胸部神经、肌肉的解剖特点，行合理的分布药量和准确有效的注射。结果 568例隆乳术者，局部浸润麻醉方法均有效，且麻醉效果良好。无一例受术者因分离腔穴时产生疼痛而影响手术操作或停止手术。结论 局部麻醉效果理想可靠，方法简单易行，适用于任何术式的隆乳术。而在分离腔穴时产生的疼痛主要是因注射层次不当和药量分布不均所致。与麻醉方法无关；其麻醉效果与假体置入层次或乳腺胸大肌是否发达无因果关系。     

Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism

Background The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo. Methods Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.Results Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. Conclusions Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.     

人类转移癌间质淋巴样细胞漫润及其意义的探讨

观察126例人类转移癌,分析比较淋巴样细胞浸润(LI)程度与患者年龄、病理类型、组织分化和核异型程度的关系。结果表明:患者年龄及病理类型与LI程度无关;组织分化程度在LI上虽有差别,但无对应性关系;而核异型程度与LI关系密切。核异型性愈明显,LI程度愈高,反之亦然。这说明核分级不仅可以反映宿主免疫反应的高低,也可提示转移癌抗原性的强弱。     

胎肌条件培养液对白血病细胞的体外效应

以髓系(HL-60)与淋系(Molt-4)细胞为观察对象,用细胞计数、细胞集落培养、台酚蓝拒染及溴化二甲噻唑二苯四唑试验为观察手段,研究胎肌条件培养液(FMCM)对白血病细胞的影响.实验标本分为4组:①对照组.②20%FMCM处理组.③阿糖胞苷(Ara-C,1×10~(-7)M/L)处理组.④混合处理组(经FMCM与Ara-C二者的处理).发现:①FMCM对两个细胞株均无明显的直接作用.②当HL-60细胞经FMCM预处理或在用Ara-C处理同时加入FMCM,Ara-C对其抑制作用可为FMCM加强,已受Ara-C抑制的HL-60细胞则无此现象.③Ara-C对Molt-4的抑制作用不受FMCM的影响.由此而初步认为:①FMCM对白血病细胞似无明显直接作用.②某些(非全部)白血病细胞对Ara-C的敏感性可为FMCM加强.③在己受抑制的细胞中不呈现这种致敏现象.①提示FMCM有可能用于白血病临床治疗.     

MRI gadolinium enhancement of bone marrow: age-related changes in normals and in diffuse neoplastic infiltration

 Objective: To quantify gadolinium-related enhancement in the bone marrow of the spine in normals and in patients with homogeneous diffuse malignant bone marrow infiltration. Design and patients: The patients consisted of two groups: group 1 comprised 94 healthy adults (18–86 years) without bone marrow disease and group 2 comprised 30 patients with homogeneous diffuse malignant bone marrow infiltration due to myeloma (n=20) or breast carcinoma (n=10). All patients received intravenous gadopentetate dimeglumine (Gd-DTPA), 0.1 mmol/kg body weight. Pre- and postcontrast signal intensity (SI) on T1-weighted spin-echo (SE) images (TR/TE: 572 ms/15 ms) was measured over a region of interest (ROI) and the percentage SI increase was calculated. The results were confirmed by bone marrow biopsy (n=20) and clinical parameters (n=10). Dynamic contrast-enhanced studies using a spoiled gradient-recalled-echo (GRE) sequence (TR/TE/α: 68 ms/6 ms 75°) were performed in 10 controls with normal bone marrow. Results and conclusion: Contrast material enhancement in healthy persons can vary greatly (range 3–59%, mean 21%, SD 11%). With increasing age there is a significant decrease in contrast enhancement (Pearson’s correlation, P<0.01). The percentage SI increase in patients with intermediate-grade (biopsy 20–50 vol%) and high-grade (biopsy >50 vol%) diffuse malignant bone marrow infiltration was significantly higher than in normals (mean 67%, SD 34%, P<0.001). Low-grade (biopsy <20 vol%) diffuse malignant bone marrow infiltration can not be assessed by non-enhanced T1-weighted SE images or Gd-DTPA application. In conclusion, contrast material enhancement in healthy persons can vary greatly and is dependent on age, while intermediate-grade and high-grade diffuse malignant bone marrow infiltration can be objectively assessed with SI measurements.