Deficiency of Lymph Node-Resident Dendritic Cells (DCs) and Dysregulation of DC Chemoattractants in a Malnourished Mouse Model of Leishmania donovani Infection

ABSTRACTMalnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. Malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoanLeishmania donovani. We previously established a murine model of childhood malnutrition and found that malnutrition decreased the lymph node barrier function and increased the early dissemination ofL. donovani. In the present study, we found reduced numbers of resident dendritic cells (conventional and monocyte derived) but not migratory dermal dendritic cells in the skin-draining lymph nodes ofL. donovani-infected malnourished mice. Expression of chemokines and their receptors involved in trafficking of dendritic cells and their progenitors to the lymph nodes was dysregulated. C-C chemokine receptor type 2 (CCR2) and its ligands (CCL2 and CCL7) were reduced in the lymph nodes of infected malnourished mice, as were CCR2-bearing monocytes/macrophages and monocyte-derived dendritic cells. However, CCR7 and its ligands (CCL19 and CCL21) were increased in the lymph node and CCR7 was increased in lymph node macrophages and dendritic cells. CCR2-deficient mice recapitulated the profound reduction in the number of resident (but not migratory dermal) dendritic cells in the lymph node but showed no alteration in the expression of CCL19 and CCL21. Collectively, these results suggest that the malnutrition-related reduction in the lymph node barrier to dissemination ofL. donovaniis related to insufficient numbers of lymph node-resident but not migratory dermal dendritic cells. This is likely driven by the altered activity of the CCR2 and CCR7 chemoattractant pathways.

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Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection

Microorganisms ◽

10.3390/microorganisms9061211 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1211

Author(s):

Mahnaz Norouzi ◽

Shaghayegh Norouzi ◽

Alistaire Ruggiero ◽

Mohammad S. Khan ◽

Stephen Myers ◽

...

Keyword(s):

Type 2 Diabetes ◽

Risk Factor ◽

Inflammatory Responses ◽

Significant Risk ◽

Significant Risk Factor ◽

Diabetic Patients ◽

Angiotensin Converting Enzyme 2 ◽

Immune System Dysfunction ◽

Current Outbreak

The current outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19), has generated a notable challenge for diabetic patients. Overall, people with diabetes have a higher risk of developing different infectious diseases and demonstrate increased mortality. Type 2 diabetes mellitus (T2DM) is a significant risk factor for COVID-19 progression and its severity, poor prognosis, and increased mortality. How diabetes contributes to COVID-19 severity is unclear; however, it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Using the envelope spike glycoprotein SARS-CoV-2, COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) receptors, a key protein expressed in metabolic organs and tissues such as pancreatic islets. Therefore, it has been suggested that diabetic patients are more susceptible to severe SARS-CoV-2 infections, as glucose metabolism impairments complicate the pathophysiology of COVID-19 disease in these patients. In this review, we provide insight into the COVID-19 disease complications relevant to diabetes and try to focus on the present data and growing concepts surrounding SARS-CoV-2 infections in T2DM patients.

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Subcutaneous sacrococcygeal ependymoma with inguinal lymph node metastastis

Journal of Neurosurgery ◽

10.3171/jns.1988.68.3.0474 ◽

1988 ◽

Vol 68 (3) ◽

pp. 474-477 ◽

Cited By ~ 23

Author(s):

G. W. P. M. Kramer ◽

E. Rutten ◽

J. Sloof

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Inguinal Lymph Node ◽

Content Type ◽

Inguinal Lymph Nodes ◽

Fine Print

✓ A patient with a subcutaneous sacrococcygeal ependymoma and metastasis to the inguinal lymph nodes is presented and his treatment is described. Previous reports on sacrococcygeal ependymoma are reviewed.

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Abstract 2605: Hypoglycemia Does Not Increase Long-term Mortality Or Morbidity In Diabetic Patients With Myocardial Infarction. A Report From The Digami 2 Trial.

Circulation ◽

10.1161/circ.116.suppl_16.ii_577 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Linda G Mellbin ◽

Klas Malmberg ◽

Anders Waldenstrom ◽

Hans Wedel ◽

Lars Ryden

Keyword(s):

Myocardial Infarction ◽

Blood Glucose ◽

Negative Impact ◽

Significant Risk ◽

Significant Risk Factor ◽

Diabetic Patients ◽

Type 2 Dm ◽

Hazard Ratios

Aims Tight, insulin-based glucose control is recommended to diabetic patients (DM pat) with acute myocardial infarction (AMI). A potential draw-back would be if insulin induced hypoglycaemia (HG) had a negative impact of future prognosis. Methods 1253 pat (mean age 68 years; 67% males) with type 2 DM and suspect AMI were followed for a median of 2.1 years. 947 were randomised to insulin infusion during at least 24 hours while 306 were treated routinely. HG (blood glucose<3.0 mmol/L with or without symptoms) was recorded during hospitalisation. Unadjusted and adjusted (age, sex, smoking, previous MI and heart failure, renal function, duration of DM, coronary interventions, blood glucose at randomisation) Hazard Ratios (HR) and 95% Confidence Intervals (CI) for cardiovascular events (CVE = death, MI or stroke) during follow up were calculated. Results 153 pat (12.2%) experienced HG. During the first 24 hours 111 (11.7%) insulin-treated pat experienced HG (symptomatic 23.4%) compared with 3 (1.0%) pat on routine treatment (symptomatic 33.3%). As outlined in the figure HG was not an independent predictor of subsequent CVE. Conclusion Insulin induced HG was not a significant risk factor for subsequent CVE in AMI-pat with type 2 DM. Hypoglycaemic seem to identify patients at high risk for other reasons.

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Cervical Lymph Node Schwannoma—An Unexpected Diagnosis

Clinical Pathology ◽

10.1177/2632010x19829239 ◽

2019 ◽

Vol 12 ◽

pp. 2632010X1982923

Author(s):

Catarina Falcão Silvestre ◽

Joana Almeida Tavares ◽

Dolores López-Presa ◽

Vanessa Rebelo dos Santos ◽

José Rocha ◽

...

Keyword(s):

Differential Diagnosis ◽

Lymph Node ◽

Lymph Nodes ◽

Cervical Lymph Node ◽

Spindle Cell ◽

English Literature ◽

Abdominal Cavity ◽

Neurofibromatosis Type ◽

Benign Neoplasms

Introduction: Schwannomas—Schwann cells–originating tumors—may develop in many locations. However, primary schwannomas arising within lymph nodes are extremely rare, with only a few cases described to this date in the English literature. For the intranodal location, most of the cases are described in the abdominal cavity. In these cases, clinicians may consider and check for familial disorders, such as neurofibromatosis type 2 (NF2) and schwannomatosis also called neurofibromatosis type 3. Schwannomas are benign neoplasms. Histologically, differential diagnosis for spindle-cell lesions in lymph nodes is important and must be done carefully, mainly because they may be attributable to metastatic disease. We report a case of a primary schwannoma arising in a cervical lymph node. Background: Primary schwannomas arising within lymph nodes are extremely rare, with only a few cases reported. Since they are benign neoplasms, the differential diagnosis with other intranodal spindle cell lesions, mostly malignant, is important. Methods: An asymptomatic 69-year-old woman, previously submitted to left hemithyroidectomy for a benign folicular nodule, underwent thyroidectomy totalization following the identification of a large thyroid nodule in routine evaluation. Results: Gross and microscopic examination and ancillary studies were consistent with the diagnosis of intranodal schwannoma. The patient had acquired bilateral hypoacusia. Therefore, type 2 neurofibromatosis was considered and vestibular schwannomas ruled out. Conclusion: Herein, we present the second case of a primary schwannoma in a cervical lymph node reported so far. The relevance of the differential diagnosis is highlighted.

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Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes

Journal of Experimental Medicine ◽

10.1084/jem.20081430 ◽

2008 ◽

Vol 205 (12) ◽

pp. 2839-2850 ◽

Cited By ~ 160

Author(s):

Claudia Jakubzick ◽

Milena Bogunovic ◽

Anthony J. Bonito ◽

Emma L. Kuan ◽

Miriam Merad ◽

...

Keyword(s):

Dendritic Cells ◽

Lymph Node ◽

Steady State ◽

Lymph Nodes ◽

Lymphatic Vessels ◽

Inflammatory Stimulus ◽

Major Fraction ◽

Reporter Mouse ◽

Relationship Of ◽

The Relationship

Observations that dendritic cells (DCs) constitutively enter afferent lymphatic vessels in many organs and that DCs in some tissues, such as the lung, turnover rapidly in the steady state have led to the concept that a major fraction of lymph node DCs are derived from migratory DCs that enter the lymph node through upstream afferent lymphatic vessels. We used the lysozyme M–Cre reporter mouse strain to assess the relationship of lymph node and nonlymphoid organ DCs. Our findings challenge the idea that a substantial proportion of lymph node DCs derive from the upstream tissue during homeostasis. Instead, our analysis suggests that nonlymphoid organ DCs comprise a major population of DCs within lymph nodes only after introduction of an inflammatory stimulus.

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The Number of Metastatic Lymph Nodes is a Significant Risk Factor for Bone Metastasis and Poor Outcome After Surgery for Linitis Plastica-type Gastric Carcinoma

World Journal of Surgery ◽

10.1007/s00268-008-9672-z ◽

2008 ◽

Vol 32 (9) ◽

pp. 2015-2020 ◽

Cited By ~ 11

Author(s):

Yasuhiro Kodera ◽

Seiji Ito ◽

Yoshinari Mochizuki ◽

Yoshitaka Yamamura ◽

Kazunari Misawa ◽

...

Keyword(s):

Risk Factor ◽

Bone Metastasis ◽

Gastric Carcinoma ◽

Lymph Nodes ◽

Significant Risk ◽

Significant Risk Factor ◽

Linitis Plastica ◽

Metastatic Lymph Nodes ◽

Poor Outcome ◽

Metastatic Lymph

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Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture

Journal of Neurosurgery ◽

10.3171/jns.2000.93.3.0379 ◽

2000 ◽

Vol 93 (3) ◽

pp. 379-387 ◽

Cited By ~ 410

Author(s):

Seppo Juvela ◽

Matti Porras ◽

Kristiina Poussa

Keyword(s):

Risk Factors ◽

Smoking Status ◽

Significant Risk ◽

Significant Risk Factor ◽

Aneurysm Rupture ◽

Content Type ◽

Unruptured Aneurysms ◽

Unruptured Intracranial Aneurysms ◽

History Of ◽

Fine Print

Object. The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed.Methods. One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using life-table analyses and Cox's proportional hazards regression models including time-dependent covariates.The median follow-up time was 19.7 years (range 0.8–38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1–1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93–1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04–2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21–7.66, p = 0.02).Conclusions. Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.

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CDS and bank ownership structures: does the credit side show who advocates more risk?

The Journal of Risk Finance ◽

10.1108/jrf-09-2015-0085 ◽

2016 ◽

Vol 17 (2) ◽

pp. 169-193 ◽

Cited By ~ 1

Author(s):

Dennis Froneberg ◽

Florian Kiesel ◽

Dirk Schiereck

Keyword(s):

Credit Risk ◽

Ownership Structure ◽

Negative Impact ◽

Significant Risk ◽

Credit Default Swap ◽

Significant Risk Factor ◽

Risk Indicators ◽

Content Type ◽

Bank Ownership ◽

Regulatory Bodies

Purpose This study aims to investigate whether ownership compositions effect credit risk profiles of banks prior to and during the financial crisis. In detail, this study examines whether more powerful owners of a bank impact the credit risk profile. Design/methodology/approach The effects of the ownership structure on credit risk are estimated using credit default swap (CDS) spreads. Therefore, 86 global privately held and publicly listed banks from 23 countries are considered in a panel analysis for the period 2005-2008. Findings The results indicate that banks with a more concentrated ownership structure tend to be riskier, as they have larger CDS spreads. Furthermore, we observe that bank regulation has a negative impact on banks’ credit risk. Larger banks exhibit significantly lower risk than smaller banks. Originality/value These findings are of high relevance for the respective national regulative environment and for the respective financial institutions themselves. Regulatory bodies have to be aware of whether certain ownership compositions lead to a significant risk factor and which risk indicators exhibit the risk more precisely and in timely fashion.

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