Primary pulmonary and mediastinal synovial sarcoma: a clinicopathologic study of 60 cases and comparison with five prior series.

Primary pulmonary and mediastinal synovial sarcoma is rare and poses a diagnostic challenge particularly when unusual histological features are present. We present 60 cases of primary pulmonary and mediastinal synovial sarcoma (29 male and 27 female subjects; mean age, 42 years) and compare our results with five prior series to better define unusual histological features. Clinically, patients with mediastinal synovial sarcoma were younger with a male gender bias. Radiologically, tumors were well delineated with distinctive magnetic resonance imaging features and little vascular enhancement. In all, 21/46 patients died of disease within 5 years. Histologically, all tumors had dense cellularity, interlacing fascicles, hyalinized stroma, and mast cell influx. Hemangiopericytoma-like vasculature (48/60), focal myxoid change (30/60), and entrapped pneumocytes (23/60) were seen. Calcification was not prevalent (10/60). Unusual histological features included Verocay body-like formations (7/60), vague rosettes (6/60), well-formed papillary structures (3/60), adenomatoid change (3/60), and rhabdoid morphology (2/60). Immunohistochemistry demonstrated expression of pancytokeratin (39/58), epithelial membrane antigen (29/53), cytokeratin 7 (26/40), cytokeratin 5/6 (5/7), calretinin (15/23), CD99 (19/23), bcl-2 (24/24), CD56 (11/11), S-100 (9/51), and smooth muscle actin (8/32). In total, 92% (36/39) of primary pulmonary and mediastinal synovial sarcomas studied were positive for t(x;18). In conclusion, our study confirms the clinical, histological, immunohistochemical, and molecular data from previous large series of primary pulmonary and mediastinal synovial sarcoma. Compared with soft tissue synovial sarcoma, primary pulmonary and mediastinal synovial sarcoma has less calcification, less obvious mast cell influx, and less radiologic vascularity, but similar magnetic resonance imaging features, percentage of poorly differentiated tumors, and number of t(x;18)-positive tumors. Awareness of focal unusual histology can prevent misdiagnosis particularly in t(x;18)-negative tumors.     

Vital Signs During the COVID-19 Outbreak: A Retrospective Analysis of 19,960 Participants in Wuhan and Four Nearby Capital Cities in China

Background:The implications of city lockdown on vital signs during the COVID-19 outbreak are unknown.Objective:We longitudinally tracked vital signs using data from wearable sensors and determined associations with anxiety and depression.Methods:We selected all participants in the HUAWEI Heart Study from Wuhan and four nearby large provincial capital cities (Guangzhou, Chongqing, Hangzhou, Zhengzhou) and extracted all data from 26 December 2019 (one month before city lockdown) to 21 February 2020. Sleep duration and quality, daily steps, oxygen saturation and heart rate were collected on a daily basis. We compared the vital signs before and after the lockdown using segmented regression analysis of the interrupted time series. The depression and anxiety cases were defined as scores ≥8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A] in 727 participants who finished the survey.Results:We included 19,960 participants (mean age 36 yrs, 90% men). Compared with pre-lockdown, resting heart rate dropped immediately by 1.1 bpm after city lockdown (95% confidence interval [CI]: –1.8, –0.4). Sleep duration increased by 0.5 hour (95% CI: 0.3, 0.8) but deep sleep ratio decreased by 0.9% (95% CI: –1.2, –0.6). Daily steps decreased by 3352 steps (95% CI: –4333, –2370). Anxiety and depression existed in 26% and 17% among 727 available participants, respectively, and associated with longer sleep duration (0.2 and 0.1 hour, both p < 0.001).Conclusions:Lockdown of Wuhan in China was associated with an adverse vital signs profile (reduced physical activity, heart rate, and sleep quality, but increased sleep duration). Wearable devices in combination with mobile-based apps may be useful to monitor both physical and mental health.Clinical trial registration:The trial is registered at Chinese Clinical Trial Registry (ChiCTR) website (ChiCTR-OOC-17014138).     

N-acetylated Proline-Glycine-Proline induced G-protein dependent chemotaxis of neutrophils is independent of CXCL8 release

Chronic inflammation in lung diseases contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline–Glycine–Proline (N-ac-PGP). In this study, we investigated in more detail the mechanism of action of N-ac-PGP in neutrophilic inflammation. N-ac-PGP was chemotactic for human neutrophils via pertussis toxin sensitive G protein-coupled receptors in vitro and directly activated this cell type, which led to cytosolic calcium mobilization and release of CXCL8. Furthermore, using a selective CXCR2 antagonist confirmed that N-ac-PGP-induced neutrophil chemotaxis is mediated through CXCR2 activation. To determine whether N-ac-PGP was solely responsible for the migration and activation of human neutrophils in vitro and not the released CXCL8 upon stimulation with N-ac-PGP, an antibody directed against CXCL8 was used. Performing chemotaxis and calcium influx assays in the presence of this antibody did not alter the effects of N-ac-PGP whereas effects of CXCL8 were attenuated. These experiments indicate that N-ac-PGP, in addition to the direct induction of chemotaxis, also directly activates neutrophils to release CXCL8. In vivo, this may lead in the long term to a self-maintaining situation enhanced by both N-ac-PGP and CXCL8, leading to a further increase in neutrophil infiltration and chronic inflammation.     

Trimetrexate in advanced carcinoma of the esophagus

Summary Twenty-four patients with advanced epidermoid carcinoma of the esophagus were treated with trimetrexate (TMTX), a lipid soluble non-classical antifol. Patients were given TMTX 8 mg/m² intravenously day 1–5 every 28 days. In nine of these patients the dose was escalated to 12 mg/m² day 1–5 every 28 days. Three patients had a partial response (95% confidence limit 3–32%) with a median response duration of 14 weeks. No hematologic toxicity was documented. Two patients developed moderate stomatitis and only 3 patients experienced any nausea or vomiting. The median survival of all patients is 12 weeks. It is concluded that a higher dose of TMTX should be studied in patients with esophageal cancer in order to assess the true therapeutic value of the agent at a dose closer to the median tolerated dose. A phase II ECOG study using TMTX 12 mg/m² intravenously day 1–5 every 21 days is currently being conducted.     

Growth cone configuration and advance: a time-lapse study using video-enhanced differential interference contrast microscopy

We have analyzed the dynamics of growth cone configuration using video-enhanced contrast differential interference contrast microscopy. Regenerating neurites from NGF-treated PC12 cells and sympathetic neurons were observed in real time during their elongation and reviewed by time-lapse video recordings. This technique provided a high-resolution view of motile growth cone elements including filopodia, microspikes, lamellipodia and ruffles. On the basis of our observations, a multistage model for growth cone advance is proposed. Elongation commences with lamellipodial spreading. If the newly extended lamellipodium does not retract or lift off the substrate in the form of a ruffle, a second phase--consolidation--occurs, in which the lamellipodium thickens as it fills with cytoplasm and organelles. The consolidated area then undergoes further transformation into an area of neuritic shaft as new lamellipodia form at the leading and peripheral zones of the distal process. We never observed filopodia or microspikes contracting to propel the growth cone forward. We also noted that elongating tips generally had large varicosities within 20 micron of their leading edges. These may play a role in neurite outgrowth and in the formation of smaller, synaptic vesicle-containing varicosities. The dynamic behavior of the growth cone was under the control of NGF. Withdrawal of NGF resulted in the disappearance of motile structures and cessation of growth, while readdition of NGF triggered the rapid reappearance of these structures and the resumption of growth. The high-resolution video microscopy of living growth cones provides necessary baseline information, as well as a bioassay paradigm, for future studies on the molecular mechanisms of nerve growth.     

Antifungal susceptibility testing with dermatophytes

The determination of the in vitro activity of antimycotics against dermatophytes has for long been considered as irrelevant from a practical point of view. Recently, however, this approach has been questioned. Various different tests such as agar diffusion test, agar dilution test and broth dilution test can be used for the determination of minimum inhibitory concentrations with dermatophytes. A close correlation between in vitro data and clinical outcome could especially be demonstrated for the micro dilution test. In future, the antimycogram of a dermatophyte isolated from an individual patient should gain more and more importance for the selection of the drug to be used and its dosage.     

A phase II trial of CI-921 in advanced malignancies

CI-921, (9-[[2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino]-N,5-dimethyl-4-acridinecarboxamide 2-hydroxyethanesulfonate (11)), an anilinoacridine derivative with activity in experimental solid tumors was studied in a multicenter phase II trial in patients with solid tumors. Eligible tumor types included cancers of the breast, stomach, pancreas, nonsmall cell lung, small cell lung, colon, head and neck area, and melanoma. Prestudy requirements included an ECOG performance status of 2, no CNS metastases, and measurable disease. CI-921 was administered intravenously over 1–2 hours on days 1,8, and 15 of a 35-day course at an initial dose of 270 mg/M², with modification in subsequent courses based upon tolerance. Principal toxicities included leukopenia, marked phlebitis, and mild nausea and vomiting. One hundred fifty patients were entered of whom 132 were evaluable for response. There was one complete and one partial response among 19 patients with breast cancer, and two partial responses, one each among 14 head and neck and 36 nonsmall cell lung cancer patients.     

New endogenous CXC chemokine ligands as potential targets in lung emphysema

Chronic respiratory inflammation is caused by a sustained influx of macrophages and neutrophils, which leads to tissue remodeling and collagen breakdown. Recently, we have identified collagen-breakdown products that can activate and attract inflammatory cells via the CXC (two cysteines with an inverting amino acid)1 and CXC2 receptors (CXCR1 and CXCR2). By using a technique called 'inverted hydropathy', small peptides were synthesized that interact specifically with the responsible collagen-breakdown products and inactivate them. After inactivation, the collagen-breakdown products are no longer able to bind to their receptors. These neutralizing peptides inhibited neutrophil influx, heart hypertrophy and lung emphysema in animal models, and they are likely to be useful in other diseases that are characterized by a chronic inflammation, such as rheumatoid arthritis and inflammatory bowel diseases, where neutrophils are potential target cells. In this opinion article we will present a new hypothesis through which the chronicity and remodeling of tissue of several inflammatory diseases could be explained.