Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as evidence strengthens the clinical relevance of this immunological biomarker. TILs in the ...post-neoadjuvant residual disease setting are acquiring increasing importance as a stratifying marker in clinical trials, considering the raising interest on immunotherapeutic strategies after neoadjuvant chemotherapy. TILs in ductal carcinoma in situ, with or without invasive carcinoma, represent an emerging area of clinical breast cancer research. The aim of this report is to update pathologists, clinicians and researchers on TIL assessment in both the post-neoadjuvant residual disease and the ductal carcinoma in situ settings. The International Immuno-Oncology Working Group proposes a method for assessing TILs in these settings, based on the previously published International Guidelines on TIL Assessment in Breast Cancer. In this regard, these recommendations represent a consensus guidance for pathologists, aimed to achieve the highest possible consistency among future studies.
Transradial access (TRA) has received considerable attention in the field of neurointervention owing to its advantages over transfemoral access. However, the difficulty of left internal carotid ...artery (ICA) navigation under certain anatomical conditions of the aortic arch and its branches is a limitation of right TRA. In this study the authors aimed to investigate the anatomical predictors that impede navigation of the left ICA in right TRA.
From January to October 2020, 640 patients underwent transradial angiography at a single institute. Among them, 263 consecutive patients who were evaluated by contrast-enhanced MRA before transradial angiography were included in the study and assigned to success or failure groups according to whether left ICA navigation was possible or not. Several anatomical predictors were investigated to evaluate the correlation of the success of left ICA navigation in right TRA.
A higher grade of the aortic arch type (type I vs type III: OR 6.323, p = 0.0171), higher height of the right subclavian artery (OR 1.071, p = 0.0068), narrower turnoff angle of the left common carotid artery (CCA) (OR 0.953, p = 0.0017), wider distance between the innominate artery and the left CCA (OR 1.784, p < 0.0001), steeper angulation of the right subclavian artery (tortuous vs kinking: OR 6.323, p = 0.0066), and steeper angulation of the left CCA (normal vs tortuous: OR 7.453, p = 0.0087; normal vs kinking: OR 51.65, p < 0.0001) were significantly associated with successful navigation of the left ICA. The cutoff value of the height of the right subclavian artery, distance between the innominate artery and the left CCA, turnoff angle of the left CCA, and diameter of the left CCA were 54.83 mm, 4.25 mm, 17°, and 6.05 mm, respectively.
Successful left ICA navigation in right TRA was related to the specific vascular geometry of the aortic arch and its branches. Preprocedural evaluation of the anatomical predictors identified in this study may enhance the success rate of left ICA navigation in right TRA.
Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by ...platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage. Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.
Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma ...are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O
) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O
) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H
O
-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H
O
- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12-17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9-4.5 × 10
exosomes in 10 μL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 μg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.
Considerable molecular heterogeneity exists among human epidermal growth factor receptor 2 (HER2) -positive breast cancer regarding gene expression and mutation profiling. Evidence from preclinical, ...clinical neoadjuvant, and metastatic clinical trials suggested that PIK3CA mutational status and PAM50 intrinsic subtype of a tumor were markers of response to anti-HER2 therapies. We evaluated the predictive value of these two biomarkers in the adjuvant setting using archived tumor blocks from National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31.
Expression data for 49 genes using the nCounter platform were used to generate PAM50 intrinsic subtypes for 1,578 archived tumor blocks from patients in the B-31 trial. Six PIK3CA hotspot mutations were examined by mass spectrometry of the primer extension products in a randomly selected subset (n = 671). We examined the heterogeneity of trastuzumab treatment effect across different subsets defined by each marker using Cox regression and disease-free survival as the end point.
Seven hundred forty-one (47.0%) of 1,578 tumors were classified as HER2-enriched (HER2E) subtype, and 166 (24.7%) of 671 tumors had PIK3CA mutations. Hazard ratios (HRs) for trastuzumab in HER2E and other subtypes were 0.44 (95% CI, 0.34 to 0.58; P < .001) and 0.47 (95% CI, 0.35 to 0.62; P < .001), respectively (interaction P = .67). HRs for trastuzumab in PIK3CA wild-type and mutated tumors were 0.51 (95% CI, 0.37 to 0.71; P < .001) and 0.44 (95% CI, 0.24 to 0.82; P = .009), respectively (interaction P = .64).
Unlike results seen in the metastatic and neoadjuvant clinical trials, PIK3CA and PAM50 intrinsic subtypes were not predictive biomarkers for adjuvant trastuzumab in NSABP B-31. These data suggest that results from the metastatic and neoadjuvant setting may not be always applicable to the adjuvant setting.
Background
The predictors of graft infection after cranioplasty (GIC) following decompressive craniectomy are not well established. Knowledge of the risk factors for GIC will allow development of ...preventive measures designed to reduce infection rates. Therefore, the objective of this study was to identify risk factors for the development of GIC.
Methods
A total of 85 patients underwent reconstructive cranioplasty after decompressive craniectomy between January 2009 and July 2011 and had a follow-up period of > 1 year; charts were reviewed retrospectively. Although autograft was used whenever possible, artificial bone was used for cranioplasty. GIC was defined as infection requiring removal of the bone graft.
Results
GIC occurred in six patients (7.05 %). GIC was not related to the indications for craniectomy, the interval of cranioplasty, graft material, or the size of the bone defect (p = 0.433, p = 0.206, p = 0.665, and p = 0.999, respectively). The GIC rate was significantly related to previous temporalis muscle resection, preoperative subgaleal fluid collection, operative times > 120 min, and postoperative wound disruptions (p = 0.001, p < 0.001, p = 0.035, and p = 0.016, respectively). Multiple logistic regression showed that the presence of a subgaleal fluid collection before cranioplasty significantly increased the risk of GIC (OR: 38.53; 95 % CI: 2.77–535.6; p = 0.006).
Conclusions
The results of this study suggest that long operative times (> 120 min), craniectomy with temporalis muscle resection, the presence of preoperative subgaleal fluid collection, and postoperative wound disruption may be risk factors for graft infection after cranioplasty. Surgical techniques should be developed to reduce operative time and to avoid temporalis muscle resection when possible. In addition, meticulous dural closure aimed at reducing the formation of subgaleal fluid collection is important for the prevention of graft infections after cranioplasty.
Oxidative stress and inflammation are basic pathogenic factors involved in tissue injury and pain, as well as acute and chronic diseases. Since long-term uses of synthetic steroids and non-steroidal ...anti-inflammatory drugs (NSAIDs) cause severe adverse effects, novel effective materials with minimal side effects are required. In this study, polyphenol content and antioxidative activity of rosebud extracts from 24 newly crossbred Korean roses were analyzed. Among them, Pretty Velvet rosebud extract (PVRE) was found to contain high polyphenols and to show in vitro antioxidative and anti-inflammatory activities. In RAW 264.7 cells stimulated with lipopolysaccharide (LPS), PVRE down-regulated mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and thereby decreased nitric oxide (NO) and prostaglandin E
(PGE
) production. In a subcutaneous air-pouch inflammation model, treatment with PVRE decreased λ-carrageenan-induced tissue exudation, infiltration of inflammatory cells, and inflammatory cytokines such as tumor necrosis factor-α and interleukin-1β concentrations, as achieved with dexamethasone (a representative steroid). Notably, PVRE also inhibited PGE
, similar to dexamethasone and indomethacin (a representative NSAID). The anti-inflammatory effects of PVRE were confirmed by microscopic findings, attenuating tissue erythema, edema, and inflammatory cell infiltration. These results indicate that PVRE exhibits dual (steroid- and NSAID-like) anti-inflammatory activities by blocking both the iNOS-NO and COX-2-PG pathways, and that PVRE could be a potential candidate as an anti-inflammatory material for diverse tissue injuries.
Digital subtraction angiography is the gold standard to confirm complete removal of an arteriovenous malformation (AVM) nidus. However, the transfemoral approach requires specialized instrumentation ...and is cumbersome and difficult to perform with the patient in the prone or decubitus position. We report the use of intraoperative digital subtraction angiography (iDSA) with the transradial approach and examine its usefulness and safety.
We retrospectively reviewed clinical features, radiologic images, surgical findings, and iDSA findings of patients with AVM who underwent surgery for nidus removal. Transradial iDSA was performed within 30 minutes for patients who required angiographic confirmation after AVM resection. This procedure was simple with the radial arterial line for blood pressure monitoring used as digital subtraction angiography catheter access route.
Transradial iDSA was performed in 23 patients. Twelve patients were not in the general supine position during neurosurgery; 7 patients were operated on in prone position, and 5 patients were operated on in the park bench position. Remnant nidus was identified by iDSA in 2 patients, and additional measures were required.
Intraoperative cerebral angiography during surgery for cerebral AVM could be performed safely via the transradial approach. This approach showed several merits in terms of easy access; no extra requirements, such as preoperative sheath implantation, anticoagulation during the surgery, or a radiolucent table; and usefulness in any surgical position. Further studies using this approach and comparison with the transfemoral approach are necessary.
•Intraoperative angiography is a useful tool for completeness of AVM surgery.•We report the use of iDSA with the transradial approach and examine its usefulness and safety.•This approach demonstrated easy access, no extra requirements, and usefulness in prone or lateral surgical position.
Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or ...intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.
To record diaphragm excursion via M-mode ultrasonography in stroke patients with dysphagia and determine whether they present reduced diaphragm excursion during voluntary cough compared with stroke ...patients without dysphagia and healthy subjects.
Prospective cross-sectional study.
University rehabilitation hospital.
Acute stroke patients with dysphagia (n=23), acute stroke patients without dysphagia (n=24), and healthy control participants (n=27) (N=74).
Not applicable.
Diaphragm motions during quiet breathing, deep breathing, and voluntary coughing were recorded via ultrasonography using M-mode tracing (mm). Maximum inspiratory and expiratory pressures (cmH2O) and peak cough flow (L/min) during voluntary coughing were measured.
The mean diaphragm movement (mm) of the hemiplegic side for all groups during quiet breathing, deep breathing, and voluntary coughing was 14.8±4.3, 17.6±4.8, and 20.9±3.7 (P<.001); 23.8±7.1, 32.7±10.6, and 44.7±10.3 (P<.001); and 16.8±4.8, 28.5±4.9, and 36.0±8.2 (P<.001), respectively. The differences were statistically significant. Differences were observed in the maximum inspiratory (P<.001) and expiratory (P<.001) pressures and peak cough flow (P=.027) among the 3 groups. Forward selection stepwise regression analysis, which was performed to determine variables that help predict diaphragm excursion during voluntary coughing, showed that the presence of dysphagia explained up to 60% (P<.001) of the hemiplegic diaphragm movement during voluntary coughing in patients with stroke.
M-mode ultrasonography showed that stroke patients with dysphagia have decreased diaphragm excursion and compromised respiratory function during voluntary coughing.
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