Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus.

An abnormal neutrophil subset has been identified in the PBMC fractions from lupus patients. We have proposed that these low-density granulocytes (LDGs) play an important role in lupus pathogenesis by damaging endothelial cells and synthesizing increased levels of proinflammatory cytokines and type I IFNs. To directly establish LDGs as a distinct neutrophil subset, their gene array profiles were compared with those of autologous normal-density neutrophils and control neutrophils. LDGs significantly overexpress mRNA of various immunostimulatory bactericidal proteins and alarmins, relative to lupus and control neutrophils. In contrast, gene profiles of lupus normal-density neutrophils do not differ from those of controls. LDGs have heightened capacity to synthesize neutrophils extracellular traps (NETs), which display increased externalization of bactericidal, immunostimulatory proteins, and autoantigens, including LL-37, IL-17, and dsDNA. Through NETosis, LDGs have increased capacity to kill endothelial cells and to stimulate IFN-α synthesis by plasmacytoid dendritic cells. Affected skin and kidneys from lupus patients are infiltrated by netting neutrophils, which expose LL-37 and dsDNA. Tissue NETosis is associated with increased anti-dsDNA in sera. These results expand the potential pathogenic roles of aberrant lupus neutrophils and suggest that dysregulation of NET formation and its subsequent responses may play a prominent deleterious role.

Diagnosis of metaplastic synovial cysts in clinical dermatology.

Metaplastic synovial cysts are a rare clinical finding, with less than 70 cases diagnosed to date. These cysts are painful and can greatly impact patients' quality of life. The goal of this case report is to describe the manifestations of these cysts to aid in clinical diagnosis and management. We herein report a case of a 58-year-old male who presented with a bump on the lateral left knee. He experienced pain upon walking. Notably, he had a past medical history of left knee replacement 15 years prior to presentation. Upon physical exam, the bump resembled a firm subcutaneous nodule. It was subsequently biopsied via eight-mm punch excision, revealing a metal portion of the patient's knee replacement; biopsy resulted in the removal of the entire bump. Biopsy results showed a cystic space in the deep dermis containing papillary villous projections consisting of fibrous cores, partially surfaced by a synovial-like lining. Based on these results, a metaplastic synovial cyst was diagnosed. The patient was referred to orthopaedic surgery for replacement to prevent recurrence, as the metal in the knee replacement was presumed the source of the cyst. The patient was then reassessed 3 months later, and he described resolution of his knee pain. Physical exam showed a well-healed linear scar. This patient's history and exam findings, along with the dermatopathology results, reflect the characteristic pattern in patients suffering from metaplastic synovial cysts. Prompt identification and subsequent removal can significantly improve patient's pain and ability to carry out daily activities.

An induced annual modulation signature in COSINE-100 data by DAMA/LIBRA's analysis method.

The DAMA/LIBRA collaboration has reported the observation of an annual modulation in the event rate that has been attributed to dark matter interactions over the last two decades. However, even though tremendous efforts to detect similar dark matter interactions were pursued, no definitive evidence has been observed to corroborate the DAMA/LIBRA signal. Many studies assuming various dark matter models have attempted to reconcile DAMA/LIBRA's modulation signals and null results from other experiments, however no clear conclusion can be drawn. Apart from the dark matter hypothesis, several studies have examined the possibility that the modulation is induced by variations in detector's environment or their specific analysis methods. In particular, a recent study presents a possible cause of the annual modulation from an analysis method adopted by the DAMA/LIBRA experiment in which the observed annual modulation could be reproduced by a slowly varying time-dependent background. Here, we study the COSINE-100 data using an analysis method similar to the one adopted by the DAMA/LIBRA experiment and observe a significant annual modulation, however the modulation phase is almost opposite to that of the DAMA/LIBRA data. Assuming the same background composition for COSINE-100 and DAMA/LIBRA, simulated experiments for the DAMA/LIBRA without dark matter signals also provide significant annual modulation with an amplitude similar to DAMA/LIBRA with opposite phase. Even though this observation does not directly explain the DAMA/LIBRA results directly, this interesting phenomenon motivates more profound studies of the time-dependent DAMA/LIBRA background data.

New physics searches at the BESIII experiment.

The standard model (SM) of particle physics, comprised of the unified electroweak and quantum chromodynamic theories, accurately explains almost all experimental results related to the micro-world, and has made a number of predictions for previously unseen particles, most notably the Higgs scalar boson, that were subsequently discovered. As a result, the SM is currently universally accepted as the theory of the fundamental particles and their interactions. However, in spite of its numerous successes, the SM has a number of apparent shortcomings, including: many free parameters that must be supplied by experimental measurements; no mechanism to produce the dominance of matter over antimatter in the universe; and no explanations for gravity, the dark matter in the universe, neutrino masses, the number of particle generations, etc. Because of these shortcomings, there is considerable incentive to search for evidence for new, non-SM physics phenomena that might provide important clues about what a new, beyond the SM theory (BSM) might look like. Although the center-of-mass energies that BESIII can access are far below the energy frontier, searches for new, BSM physics are an important component of its research program. This report reviews some of the highlights from BESIII's searches for signs of new, BSM physics by: measuring rates for processes that the SM predicts to be forbidden or very rare; searching for non-SM particles such as dark photons; performing precision tests of SM predictions; and looking for violations of the discrete symmetries C and CP in processes for which the SM expectations are immeasurably small.

Strong constraints from COSINE-100 on the DAMA dark matter results using the same sodium iodide target.

We present new constraints on dark matter interactions using 1.7 years of COSINE-100 data. The COSINE-100 experiment, consisting of 106 kg of tallium-doped sodium iodide [NaI(Tl)] target material, is aimed to test DAMA's claim of dark matter observation using the same NaI(Tl) detectors. Improved event selection requirements, a more precise understanding of the detector background, and the use of a larger dataset considerably enhance the COSINE-100 sensitivity for dark matter detection. No signal consistent with the dark matter interaction is identified and rules out model-dependent dark matter interpretations of the DAMA signals in the specific context of standard halo model with the same NaI(Tl) target for various interaction hypotheses.

Clusterin expression in cutaneous CD30-positive lymphoproliferative disorders and their histologic simulants.

BACKGROUND: Clusterin is a ubiquitous 80 kDa heterodimeric glycoprotein previously shown to be expressed on tumor cells of systemic and, to a lesser extent, primary cutaneous anaplastic large cell lymphoma (PC-ALCL). Lymphomatoid papulosis (LyP), an important differential diagnosis of ALCL, has been studied for clusterin expression in only a small number of cases. The aim of this study was to compare clusterin immunostaining patterns in LyP and other cutaneous histologic simulants with those of PC-ALCL. METHODS: Formalin-fixed, paraffin-embedded sections of PC-ALCL (6), LyP (20), mycosis fungoides with large cell transformation (MF-LCT, 12), pityriasis lichenoides et varioliformis acuta (PLEVA, 12), arthropod bite reaction (ABR, 12) and lymphomatoid reactions (LR, 9) were immunostained for clusterin and evaluated for staining pattern and distribution. All diagnoses were made with clinicopathologic correlation. RESULTS: Characteristic dot-like Golgi staining was identified in 10/20 LyP (50%), 4/6 PC-ALCL (67%) and 9/12 MF-LCT (75%). Two of 12 PLEVA (17%), 1 of 12 ABR (8%) and 2 of 8 LR (25%) had lymphocytes (< 25%) with diffuse cytoplasmic staining. Dermal dendritic cells stained strongly for clusterin. High background staining occurred in some cases. CONCLUSION: Clusterin immunostaining does not reliably distinguish between LyP, PC-ALCL or MF-LCT, but could distinguish LyP from its reactive histologic simulants.

Diagnostic value of CD163 in cutaneous spindle cell lesions.

BACKGROUND: The histologic diagnosis of atypical fibroxanthoma (AFX) can sometimes be challenging. No specific marker exists to confirm the diagnosis other than excluding other entities. CD163 has been shown to have great specificity for tumors of monocyte/histiocyte lineage. In this study, we evaluated the diagnostic utility of CD163 in diagnosing AFX and in identifying skin lesions with histiocytic/dendritic derivation. METHODS: A total of 157 cases, including 14 AFXs, 5 spindle cell squamous cell carcinomas (SCCs), and 7 spindle cell/desmoplastic melanomas, along with other cutaneous spindle cell and histiocytic/fibrohistiocytic lesions, were stained with CD163. RESULTS: CD163 was expressed in 11 of 14 (79%) AFXs, with moderate to strong intensity. No staining was observed in cases of spindle cell SCC (0/5) and dermatofibrosarcoma protuberans (0/10). Rare spindle cell/desmoplastic melanomas (2/7) and cutaneous leiomyosarcomas (1/5) demonstrated positive staining. CD163 reactivity was seen in 24 of 29 of benign fibrous histiocytomas (BFHs), including 8 of 8 cellular fibrous histiocytomas and 6 of 9 epithelioid cell histiocytomas. The majority of cutaneous histiocytic lesions, including juvenile xanthogranuloma, Langerhans cell histiocytosis and Rosai-Dorfman disease, were positive for CD163. CONCLUSION: CD163 is a useful adjunct in distinguishing AFX from other malignant cutaneous spindle cell tumors and offers improved specificity in identifying cutaneous histiocytic/dendritic lesions.

Tumor budding in intestinal-type gastric adenocarcinoma is associated with nodal metastasis and recurrence.

Gastric adenocarcinoma (GAC) is a common cause of cancer-related death worldwide. GAC can be classified as intestinal or diffuse. Intestinal-type cancers are common and reported to have a better prognosis compared to diffuse cancers. Studies have shown the presence and amount of tumor budding in intestinal carcinomas of the colon and esophagus to predict nodal metastasis and recurrence. Our aim is to determine if tumor budding in intestinal-type GAC correlates with prognostic features. One hundred four patients treated with primary surgical excision between 1999 and 2013 were identified. Histologic type (intestinal, diffuse, or mixed), tumor grade, T-stage, and lymph node status were evaluated. Tumor bud scores were assigned to all intestinal-type cancers using methods previously described for colorectal adenocarcinoma. Scores of <1 were designated as low and ≥1 as high. Tumor characteristics were as follows: 52 intestinal (50%), 36 diffuse (35%), and 16 mixed (15%). Of the 52 cases with intestinal histology, 4 were well (8%), 28 were moderately (54%), and 20 were poorly differentiated (38%). Thirty-three (63%) of the intestinal tumors had high tumor bud scores. Cases with high scores were associated with higher T-stage, N-stage, and grade (P<.001, P<.001, and P=.002). These also had a higher likelihood of recurrence (P=.007). In our cohort, high tumor bud scores in intestinal-type GAC have higher T-stage, N-stage, grade, and likelihood of recurrence. Assessment of tumor budding may guide clinical management in a subset of patients.

Results of Carotid Endarterectomy Using Bovine Pericardium Patch Closure, with a Review of Pertinent Literature.

Patch closure after carotid endarterectomy lowers risk of recurrent stenosis and perioperative neurologic events. Although vein patches have theoretic benefits, few differences between vein and nonautologous patches have been noted. Bovine pericardium has been increasingly used in carotid surgery over the last 15 years, with favorable reports. This study reviews a large carotid surgery series using this patch. Data were gathered on 464 consecutive carotid operations using the bovine pericardium patch; all complications were analyzed and pertinent literature review was performed. Of 464 procedures, 218 (47%) were performed for symptomatic disease. Total perioperative ipsilateral stroke rate was 0.65 per cent. A low rate of postoperative bleeding was noted. Recurrence of >70 per cent stenosis was 1.6 per cent at follow-up of 26 months in 410 patients. Handling was subjectively described as excellent. Literature review comprising 3239 carotid operations revealed low risks of stroke, bleeding requiring intervention, or high rates of recurrent stenosis. Bovine pericardium patch angioplasty has low perioperative and late complications and good handling characteristics, making it an acceptable choice for use in carotid surgery.

Rebuilding after the tsunami: getting it right.

The practice of integrated coastal management (ICM) has matured sufficiently since its beginnings in the early 1980s to suggest a set of principles that could be used to guide the massive investments that will be made over the next several years to rehabilitate and reconstruct the thousands of kilometers of coastlines devastated by the 26 December 2004 tsunami. We offer six principles to guide what can be done to make coastal communities less vulnerable, to improve the conditions of the poor, and to avoid repeating the mistaken judgements that have been made in the past about how shorelines are allocated and developed. We then offer a set of five principles to guide how action plans are formulated and implemented. These stress the critical importance of tailoring principles to the unique conditions and needs of each place. The roles of national government in setting policies to guide a decentralized planning and decision-making process are distinguished from a negotiation process that engages the people of the place in a bottom-up application of ICM good practices.

Carotid endarterectomy remains the gold standard.

BACKGROUND: To compare the safety and efficacy of carotid endarterectomy (CEA) as performed in a community medical center with the Asymptomatic Carotid Atherosclerosis Study (ACAS) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) standards and with representative published results regarding carotid angioplasty and stenting (CAS). METHODS: Between 1 January 1994 and 31 July 2000, 267 CEA procedures were performed on 236 patients at Madigan Army Medical Center (MAMC). Prospectively acquired patient demographics, operative indications, and surgical outcomes were reviewed using clinical records, carotid duplex evaluations, and follow-up examinations. The resultant data were compared with ACAS, NASCET, and published results of CAS. RESULTS: The perioperative stroke rate was 2.2% (6 of 267) overall, 0.7% (1 of 139) among asymptomatic patients, and 3.9% (5 of 128) among symptomatic patients. There were no perioperative deaths from any cause in the entire series. The respective ACAS and NASCET early stroke-death rates were 2.3% (19 of 825) and 5.8% (19 of 328). The largest published series of CAS reported stroke-death rates of 5.7% (299 of 5,210) overall, and 3.4% (46 of 1,361) and 5.8% (93 of 1,614) for asymptomatic and symptomatic patients, respectively. CONCLUSIONS: CEA remains the standard of care. It is a safe, effective, and durable procedure that can be performed in a facility such as MAMC with outcomes that compare favorably with ACAS and NASCET. Results of CEA at MAMC are superior to similar data regarding CAS. Widespread use of CAS should be deferred pending completion of on-going prospective trials versus CEA.

Intraoperative duplex ultrasonography as an adjunct to technical excellence in 100 consecutive carotid endarterectomies.

PURPOSE: To evaluate the relationship of intraoperative duplex ultrasonography (duplex) results to neurologic outcomes and restenosis among patients undergoing carotid endarterectomy (CEA). METHODS: One hundred consecutive CEAs were performed at a military medical center over 28 months. Prospectively acquired demographics, duplex results, revisions, and surgical outcomes were reviewed. RESULTS: Thirty-four percent (34 of 100) of sites were abnormal by completion duplex. Of these, 70% (24 of 34) were B-mode flap type defects located in the common carotid artery (CCA), internal carotid artery (ICA), or external carotid artery (ECA). Twenty-one percent of the defects (7 of 34) were technically unacceptable and immediately revised. Subsequently, 3 perioperative neurologic events occurred, 2 strokes and 1 transient ischemic attack (TIA), all among patients with an identified but unrepaired defect involving the ICA or CCA. This association of unrepaired defect with early stroke or TIA was significant (P = 0.02). No significant association (P >0.05) between unrepaired defects and late ipsilateral stroke or TIA or restenosis was identified. CONCLUSIONS: Intraoperative duplex scanning is a useful adjunct to CEA that can identify correctable mechanical problems. Residual elevated velocities or B-mode flaps 2 mm or greater in the ICA warrant consideration for immediate repair. Findings not requiring revision include flaps <2 mm, as well as isolated ECA defects. Prospectively validated duplex criteria are needed to further define which defects require immediate repair.

Intraoperative use of isosulfan blue in the treatment of persistent lymphatic leaks.

BACKGROUND: Lymphatic leaks are a major source of morbidity after lower extremity vascular surgery. We determined the ability of isosulfan blue (Lymphazurin) use to identify and help ligate offending lymphatics, and compared postoperative complication rates and length of stay versus nonoperative therapy alone. METHODS: From January 1993 through March 2002, we identified 15 patients with lymphatic leaks. The first group consisted of 5 patients treated nonoperatively. The second group was 10 patients (11 explorations) treated operatively aided by isosulfan blue, after a trial of nonoperative therapy. RESULTS: Isosulfan blue identified the leak in 10 of 11 cases. Mean drainage time for the nonoperative group was 47.6 days versus 1.8 days for the operative group (P = 0.036). Within the operative group, the mean drainage time during their initial conservative treatment phase was 15 days versus 1.8 days after surgery (P < 0.01). Complications were significantly less in the operative group (P < 0.05). Postoperative length of stay was a mean of 4.7 days versus 8.1 days for nonoperative patients (P = not significant). CONCLUSIONS: Intraoperative isosulfan blue use accurately identifies disrupted lymphatic channels and helps ensure definitive ligation. This simple procedure is associated with fewer complications, and a trend toward shorter hospital stay.

Mucosal melanoma of the head and neck: predictors of prognosis.

OBJECTIVES: To identify significant clinical and pathological predictors of survival in mucosal melanoma of the head and neck. DESIGN: Retrospective case series. We reviewed cases of mucosal melanoma of the head and neck from a prospectively collected database after institutional review board approval. SETTING: A single academic institution. PATIENTS: Fifty-two patients with mucosal melanoma of the head and neck. RESULTS: With a median follow-up of 97 months, the median overall survival was 52 months, with a 5-year overall survival of 38%. The median disease-free survival was 15 months, with a 5-year disease-free survival of 22%. Younger age (P = .02), lower T status (P = .003), and lower American Joint Committee on Cancer stage (P < .001) were associated with better overall survival. Positive surgical margins predicted poorer overall survival (P = .01), but patients who required reexcision to achieve negative margins had outcomes that were not significantly different from those with initially negative surgical margins (P = .71). Sex, smoking history, and primary site did not affect disease-free or overall survival. Adjuvant radiotherapy and/or chemotherapy did not predict improved outcomes. Fewer mitoses (P = .02) and the absence of ulceration (P = .01) predicted improved overall survival. CONCLUSIONS: Our experience confirms the utility of current staging systems in predicting outcomes of mucosal melanoma of the head and neck and stresses the importance of achieving negative surgical margins. Pathologically, fewer mitoses and the absence of ulceration predict better outcomes and should be reported as part of routine histological profiles of mucosal melanoma. Further studies are necessary to change the paradigm of care for this rare and deadly disease.