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.     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

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.     

Higher melatonin secretion is associated with lower leukocyte and platelet counts in the general elderly population: the HEIJO‐KYO cohort

Circulating white blood cell (WBC) and platelet (PLT) counts are widely available and inexpensive cellular biomarkers of systemic inflammation and have been associated with a risk of cardiovascular disease, cancer, and mortality. Melatonin may reduce systemic inflammation through its direct and indirect antioxidative effect; however, the associations of melatonin secretion with systemic inflammation remain unclear. In this cross‐sectional study on 1088 elderly individuals (mean age, 71.8 years), we measured overnight urinary 6‐sulfatoxymelatonin excretion (UME) and WBC and PLT counts as indices of melatonin secretion and systemic inflammation, respectively. UME was naturally log‐transformed for linear regression models because of skewed distribution (median, 6.8 μg; interquartile range, 4.1–10.6 μg). Univariate models revealed that higher log‐transformed UME levels were significantly associated with lower WBC and PLT counts (P = 0.046 and 0.018). After adjusting for potential confounding factors significantly associated with WBC or PLT counts, higher log‐transformed UME levels were significantly associated with lower WBC and PLT counts (WBC: β, ?0.143; 95% confidence interval, ?0.267 to ?0.020; P = 0.023; PLT: β, ?6.786; 95% confidence interval, ?12.047 to ?1.525; P = 0.012). Furthermore, the adjusted mean differences in WBC and PLT counts between the lowest and highest UME tertile groups were 0.225 × 10⁹/L and 9.480 × 10⁹/L, respectively. In conclusion, melatonin secretion was significantly and inversely associated with WBC and PLT counts in the general elderly population. The associations were independent of several major causes of systemic inflammation, including aging, obesity, smoking, hypertension, diabetes, and physical inactivity.     

Immunotherapy for recurrent pregnancy loss

When immunomodulation is used on an unselected population with recurrent miscarriage (RM), there is no improvement in the live birth rate. However, when the population is selected for a poor prognosis, or immune phenomena, immunotherapy has been shown to be effective. This review discusses four immunomodulatory agents, namely, paternal leukocyte immunization, intravenous immunoglobulin (IVIg), intralipid, and filgrastim. The presence of embryonic aneuploidy may confound the results of treatment, therefore creating an impression of futility when treatment may be highly effective in saving pregnancies that can be saved. Additionally, in an unselected population with RM, there is a relatively good prognosis of 60–80% for a subsequent live birth depending on whether the definition of ≥2 or ≥3 miscarriages is used. Hence, spontaneous prognosis must be taken into account, which has not been the case in previous trials.This review discusses the possible immune-mediated mechanisms of pregnancy loss and the means whereby immunotherapy may modulate these mechanisms.     

Preparation of leukocyte-poor platelets by filtration

There is evidence that leukocyte contaminating red blood cells and platelet concentrates are responsible for refractoriness to platelet transfusions. The efficacy of a cotton-wool filter to remove leukocytes from red blood cells has been documented previously. The present study was designed to evaluate whether the cotton-wool filters can effectively remove leukocytes from platelet concentrates. Sixty pools of random-donor platelets and single-donor plateletpheresis products were filtered through a cotton-wool filter. The efficacy of filtration was determined by measuring the absolute numbers of leukocytes and platelets and subpopulations of mononuclear cells. The average platelet loss was 8% per pool of random platelets and 10% per plateletpheresis product. The average leukocyte removal was 99% from a pool of random platelets and plateletpheresis concentrates collected by CS-3000 and 90% from plateletpheresis concentrates harvested by single-stage COBE/IBM-2997. The filtration removed 100% of granulocytes, 95% of monocytes, 90% of B-lymphocytes, and 85% of T-lymphocytes. We conclude that filtration through a cotton-wool filter is an efficient and cost-effective method for preparation of leukocyte-poor platelets.     

脂质过氧化物与大鼠烫伤后急性肺损伤的关系

本文从体内氧自由基引发的链产物——LPO为主要指标,观察大鼠烫伤后LPO变化与血清CH_(50),PMN,以及肺血管通透性间的关系。结果表明:烫伤后急性肺损伤的发生与补体活化、激活PMN,使其在肺内聚集释放氧自由基,引发血管内皮细胞膜脂过氧化反应有关。     

Genetics in multiple sclerosis: past and future perspectives

The enormous development in the field of molecular genetics during the last decades has lead to optimism concerning the possibilities for identifying the causes of multiple sclerosis (MS) through genetic studies. However, we have learned that dense mapping of large sample sets is needed, which only can be achieved through large collaborative studies. The contribution from each yet unidentified gene is probably weaker than that of the well established human leukocyte antigen association. The ultimate goal of the search for susceptibility genes in MS is to develop diagnostic tools and better treatments that can prevent or reduce the development of symptoms of this often devastating disease.