Leptospiral Infection, Pathogenesis and Its Diagnosis—A Review

Leptospirosis is a perplexing conundrum for many. In the existing literature, the pathophysiological mechanisms pertaining to leptospirosis is still not understood in full. Considered as a neglected tropical zoonotic disease, leptospirosis is culminating as a serious problem worldwide, seemingly existing as co-infections with various other unrelated diseases, including dengue and malaria. Misdiagnosis is also common as non-specific symptoms are documented extensively in the literature. This can easily lead to death, as the severe form of leptospirosis (Weil’s disease) manifests as a complex of systemic complications, especially renal failure. The virulence of Leptospira sp. is usually attributed to the outer membrane proteins, including LipL32. With an armament of virulence factors at their disposal, their ability to easily adhere, invade and replicate within cells calls for a swift refinement in research progress to establish their exact pathophysiological framework. As an effort to reconstitute the current knowledge on leptospirosis, the basis of leptospiral infection, including its risk factors, classification, morphology, transmission, pathogenesis, co-infections and clinical manifestations are highlighted in this review. The various diagnostic techniques are also outlined with emphasis on their respective pros and cons.

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Adrenal suppression from glucocorticoids: preventing an iatrogenic cause of morbidity and mortality in children

BMJ Paediatrics Open ◽

10.1136/bmjpo-2019-000569 ◽

2019 ◽

Vol 3 (1) ◽

pp. e000569 ◽

Cited By ~ 1

Author(s):

Alexandra Ahmet ◽

Arati Mokashi ◽

Ellen B Goldbloom ◽

Celine Huot ◽

Roman Jurencak ◽

...

Keyword(s):

Risk Factors ◽

Side Effect ◽

Healthcare Professionals ◽

Inhaled Corticosteroids ◽

Physiological Stress ◽

Current Knowledge ◽

Adrenal Suppression ◽

Adrenal Crisis ◽

Children At Risk ◽

Specific Symptoms

Adrenal suppression (AS) is an important side effect of glucocorticoids (GCs) including inhaled corticosteroids (ICS). AS can often be asymptomatic or associated with non-specific symptoms until a physiological stress such as an illness precipitates an adrenal crisis. Morbidity and death associated with adrenal crisis is preventable but continues to be reported in children. There is a lack of consensus about the management of children at risk of AS. However, healthcare professionals need to develop an awareness and approach to keep these children safe. In this article, current knowledge of the risk factors, diagnosis and management of AS are reviewed while drawing attention to knowledge gaps and areas of controversy. Possible strategies to reduce the morbidity associated with this iatrogenic condition are provided for healthcare professionals.

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The Clinical Spectrum of Acute GVHD: Beyond Day 100.

Blood ◽

10.1182/blood.v106.11.5377.5377 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5377-5377

Author(s):

Daniel R. Couriel ◽

Rima Saliba ◽

Shubhra Gosh ◽

Marcos De Lima ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Acute Gvhd ◽

Current Knowledge ◽

Chronic Gvhd ◽

Clinical Manifestations ◽

Disease Status ◽

Response To Therapy ◽

Preparative Regimen ◽

Prognostic Implications ◽

The Difference

Abstract Objective: To assess the clinical and prognostic implications of the timing of acute GVHD (aGVHD). Introduction: Traditionally, the syndrome of acute GVHD has been chronologically defined as GVHD occurring before day 100. It has become increasingly clear that this syndrome can occur after day 100, which raises the question of historical misclassification of aGVHD occurring after day 100 (“late aGVHD”) as chronic GVHD. On the other hand, timing of GVHD could have prognostic implications and the case in hyperacute forms of GVHD are an example. In this study, we redifine aGVHD based on clinical manifestations and we evaluate risk factors as well as clinical and prognostic differences between late aGVHD and GVHD before day 100 (“classic aGVHD”). Methods: Retrospective evaluation of records and database on all matched sibling transplants (n= 128) performed at UT MDACC from 1/00 to 2/02. Results: A total of 47 patients (37%) had “classic” aGVHD and another 67 (52%) were classified as chronic GVHD (cGVHD) in our database. Upon review of medical records, 30/67 patients (45%) were found to have late aGVHD, and the remainder true cGVHD. Of these 30 patients, 9 had aGVHD progressing through day 100 and were reclassified as classic aGVHD. The remainder 21 had newly diagnosed late aGVHD. We evaluated risk factors for developing late aGVHD in patients who were alive at day 100. Only a later engraftment (ANC>500 beyond day 12) was associated with a higher incidence of late aGVHD, while age, gender, malignancy, disease status at transplant, type of preparative regimen (nonmyeloablative versus others), bone marrow vs peripheral blood or CD3,4 or 8 infused did not impact the incidence of late acute GVHD. Compared to classic aGVHD, the late group had a significantly higher proportion of grade 2–4 GVHD (85 vs 61%, p= 0.03) with similar grade 3–4 aGVHD (29 vs 27%, p= 0.5). Skin and GI involvement, as well as isolated elevation of the alkaline phosphatase were more common manifestations of late aGVHD. There was a trend to better response (CR/PR) to first line immunosuppression in patients with late aGVHD (81 vs 63%, p= 0.13), but this was not statistically significant. The overall survival (OS) and non-relapse mortality (NRM) since the diagnosis of GVHD were substantially better in patients with late aGVHD (OS 70 vs 29%, p= 0.01; NRM 16 vs 39%, p= 0.06). Finally, the NRM of patients with chronic GVHD prior to reclassifying patients with late aGVHD (n= 67) was 28% at 2 years. When patients with late aGVHD were excluded, the NRM at 2 years for the remainder 37 patients with chronic GVHD was 20% (p= 0.3). Conclusions: 1- The current chronological definition of acute GVHD may lead to misclassification of late aGVHD as chronic GVHD. This could have implications in interpreting the current knowledge and literature on GVHD, 2- There was a trend to higher NRM in the chronic GVHD group prior to reclassifying cases of late aGVHD, althought the difference was not statistically significant, 3-Patients with late aGVHD share similarities with those with classic aGVHD, although there seems to be a trend to better response to therapy and better survival in patients developing aGVHD beyond day 100. Thus, timing of aGVHD may affect its outcome.

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COVID-19: Our Current Knowledge of Epidemiology, Pathology, Therapeutic Approaches, and Diagnostic Methods

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210201101245 ◽

2021 ◽

Vol 21 ◽

Author(s):

Faroogh Marofi ◽

Ramyar Azizi ◽

Roza Motavalli ◽

Ghasem Vahedi ◽

Maryam Nasimi ◽

...

Keyword(s):

Epithelial Cells ◽

Skin Color ◽

Color Change ◽

Clinical Symptoms ◽

Current Knowledge ◽

Clinical Manifestations ◽

Diagnostic Techniques ◽

Diagnostic Methods ◽

World Health ◽

Therapeutic Approaches

: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) firstly emerged in Wuhan, China at the end of 2019. After going through the experimental process, the virus was named the novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in February 2020 which has created a global pandemic. The coronavirus disease 2019 (COVID-19) infection is challenging the people who are especially suffering from chronic health problems such as asthma, diabetes, and heart disease or immune system deteriorating disorders, including cancers, Alzheimer's, etc. Other predisposing/risk factors consist of smoking and age (elderly people are at higher risk). The 2019-nCoV attacks epithelial cells in all organs, particularly epithelial cells in the lungs, resulting in viral pneumonia. The 2019-nCoV starts its invasion with the attachment and entry into the respiratory tract epithelial cells via angiotensin-converting enzyme 2 (ACE2) receptors on the epithelial cells. The critical problem with 2019-nCoV is its ability in human to the human asymptomatic transmission which causes the rapid and hidden spread of the virus among the population. Also, there are several reports of highly variable and tightly case-dependent clinical manifestations caused by SARS-CoV2, which made the virus more enigmatic. The clinical symptoms are varied from common manifestations which occurred in flu and cold, such as cough, fever, body-ache, trembling, and runny nose to severe conditions, like the acute respiratory distress syndrome (ARDS) or even uncommon/unusual symptoms such as anosmia, skin color change, and stroke. In fact, besides serious injuries in the respiratory system, COVID-19 invades and damages various organs, including the kidney, liver, gastrointestinal, and nervous system. Accordingly, to cut the transmission chain of disease and control the infection spread. One of the major solutions seems to be early detection of the carriers, particularly the asymptomatic people with the help of sensitive and accurate diagnostic techniques. Moreover, developing novel and appropriate therapeutic approaches will contribute to the suitable management of the pandemic. Therefore, there is an urgent necessity to make comprehensive investigations and study reviews about COVID-19, offering the latest findings of novel therapies, drugs, epidemiology, and routes of virus transmission and pathogenesis. In this review, we discuss new therapeutic outcomes and cover and the most significant aspects of COVID-19, including the epidemiology, biological features, organs failure, and diagnostic techniques.

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A “Galactic” Chest X-ray

Diagnostics ◽

10.3390/diagnostics11050899 ◽

2021 ◽

Vol 11 (5) ◽

pp. 899

Author(s):

Cristiano Carbonelli ◽

Angela de Matthaeis ◽

Antonio Mirijello ◽

Concetta Di Micco ◽

Evaristo Maiello ◽

...

Keyword(s):

Clinical Manifestations ◽

Pulmonary Involvement ◽

Diagnostic Techniques ◽

Low Grade ◽

X Ray ◽

Endoscopic Techniques ◽

Metastatic Lesions ◽

Chest X Ray ◽

Radiological Pattern ◽

Specific Symptoms

Clinical manifestations accompanying respiratory failure with insidious and rapidly progressive onset are often non-specific. Symptoms such as a cough, dyspnea, and fever are common to a large number of inflammatory, infectious, or neoplastic diseases. During the COVID-19 pandemic it is essential to limit the use of hospital services and inappropriate diagnostic techniques. A particular radiological pattern can orient the clinical and laboratory scenario and guide the diagnostic workup. A 58-year-old woman was admitted to our COVID-19 unit for suspected coronavirus infection. She was complaining of worsening dyspnea, tachycardia, and low grade fever. A chest X-ray showed diffuse, alveolar, and interstitial lung involvement with micronodules tending to coalescence. This radiographic pattern known as “galaxy sign”, consistent with diffuse, coalescing nodular miliary pulmonary involvement, simulating a non-specific alveolar opacification of the lungs is typical of a few pneumological differential diagnoses, represented by sarcoidosis, tuberculosis, pneumoconiosis, and metastatic lesions, and virtually excludes an interstitial viral pneumonitis. The use of endoscopic techniques can, in such cases, confirm the clinical suspicion for initiating appropriate targeted therapies.

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HUMAN BARTONELLA INFECTION: A REVIEW OF LITERATURE

Journal of IMAB - Annual Proceeding (Scientific Papers) ◽

10.5272/jimab.2021272.3759 ◽

2021 ◽

Vol 27 (2) ◽

pp. 3759-3764

Author(s):

Bistra Blagova ◽

◽

Nikolay Yanev ◽

Keyword(s):

Current Knowledge ◽

Bartonella Henselae ◽

Clinical Manifestations ◽

Diagnostic Techniques ◽

Etiological Agent ◽

Cat Scratch Disease ◽

Review Of Literature ◽

Clinical Syndromes ◽

Wide Range

Cat scratch disease has been reported in the literature for more than half a century as a syndrome of regional lymphadenopathy and fever. However, only a quarter of a century has passed since Bartonella henselae was identified as an etiological agent. As diagnostic techniques have improved, Bartonella has been found to be responsible for a wide range of clinical syndromes. This review summarizes current knowledge about microbiology, clinical manifestations, diagnostic techniques and treatment of Bartonella henselae infection.

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The Current Status of Tardive Dyskinesia

Australian & New Zealand Journal of Psychiatry ◽

10.1080/j.1440-1614.2000.00737.x ◽

2000 ◽

Vol 34 (3) ◽

pp. 355-369 ◽

Cited By ~ 83

Author(s):

Perminder S. Sachdev

Keyword(s):

Risk Factors ◽

Tardive Dyskinesia ◽

Effective Treatment ◽

Current Knowledge ◽

Clinical Manifestations ◽

Current Status ◽

Neuroleptic Treatment ◽

Duration Of Treatment ◽

Schizophrenic Patients

Objective: This paper aims to provide an overview of the current knowledge on neuroleptic-induced tardive dyskinesia (TD) in relation to its clinical features, risk factors, pathophysiology and management. Method: The published literature was selectively reviewed and assessed. Results: Tardive diskinesia is a common neurological side-effect of neuroleptic medication, the cumulative incidence of which increases with increasing duration of treatment. Its clinical manifestations are diverse and subsyndromes have been described. Many risk factors for TD are now recognised, but increasing age remains pre-eminent as a risk factor. The pathophysiology of TD is not completely understood. Of the neurotransmitter hypotheses, the dopamine receptor supersensitivity hypothesis and the γ-aminobutyric acid insufficiency hypothesis are the main contenders. There is increasing recognition that TD may in fact be caused by neuroleptic-induced neuronal toxicity through free radical and excitotoxic mechanisms. The occurrence of spontaneous dyskinesias in schizophrenic patients and even healthy subjects suggests that neuroleptics act on a substratum of vulnerability to dyskinesia. As no effective treatment for TD is available, the primary emphasis is on prevention. Many drugs can be tried to reduce symptoms in established cases. The increasing use of atypical neuroleptics has raised the possibility of a lower incidence of TD in the future. Conclusions: After four decades of clinical recognition, the pathophysiology of TD is still not understood and no effective treatment is available. Its prevention with the optimal usage of currently available drugs and regular monitoring of patients on long-term neuroleptic treatment remain the best strategies to reduce its impact.

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Inhibitors in Hemophilia B

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0038-1660817 ◽

2018 ◽

Vol 44 (06) ◽

pp. 578-589 ◽

Cited By ~ 11

Author(s):

Gabriele Quintavalle ◽

Giancarlo Castaman ◽

Erminia Baldacci ◽

Antonietta Ferretti ◽

Federica Riccardi ◽

...

Keyword(s):

Risk Factors ◽

Viral Infections ◽

Current Knowledge ◽

Rare Event ◽

Bleeding Risk ◽

Severe Form ◽

Factor Ix ◽

Hemophilia B ◽

Clinical Aspects ◽

The Impact

AbstractHemophilia B (HB) is an X-linked bleeding disorder caused by deficiency of factor IX (FIX). Patients with the severe form (FIX <1%) account approximately for 30 to 45% of persons with HB and usually suffer from recurrent joint, soft-tissue, and muscle bleeds. The availability of safe plasma-derived and recombinant products has virtually abolished the risk of viral infections and the adoption of prophylactic regimens has attenuated the impact of hemophilic arthropathy. Therefore, the development of an inhibitor against FIX is currently the most serious complication that can still occur in the new generations of HB patients. The development of an inhibitor in HB is a rare event (1.5–3% of all patients) but is associated with a significant morbidity, related not only to the bleeding risk but also to the frequent occurrence of allergic/anaphylactic reactions and nephrotic syndrome. Due to the relative rarity of this event, few data exist about risk factors, pathophysiology, and clinical aspects of inhibitors in HB. The induction of immune tolerance is often unsuccessful and can be otherwise affected by many complications in patients with history of allergy or anaphylaxis. Therefore, alternative therapeutic strategies and new approaches are developing. The aim of this narrative review is to discuss current knowledge about risk factors, pathophysiology, and clinical aspects of this rare but serious complication.

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Chlamydia buteonis in birds of prey presented to California wildlife rehabilitation facilities

PLoS ONE ◽

10.1371/journal.pone.0258500 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258500

Author(s):

Brittany A. Seibert ◽

Michael K. Keel ◽

Terra R. Kelly ◽

Roger A. Nilsen ◽

Paula Ciembor ◽

...

Keyword(s):

Risk Factors ◽

Current Knowledge ◽

Winter Season ◽

Clinical Manifestations ◽

Birds Of Prey ◽

Factors Associated ◽

Rehabilitation Centers ◽

Wildlife Rehabilitation ◽

Potential Risk Factors ◽

Buteo Swainsoni

Chlamydial infections, caused by a group of obligate, intracellular, gram-negative bacteria, have health implications for animals and humans. Due to their highly infectious nature and zoonotic potential, staff at wildlife rehabilitation centers should be educated on the clinical manifestations, prevalence, and risk factors associated with Chlamydia spp. infections in raptors. The objectives of this study were to document the prevalence of chlamydial DNA shedding and anti-chlamydial antibodies in raptors admitted to five wildlife rehabilitation centers in California over a one-year period. Chlamydial prevalence was estimated in raptors for each center and potential risk factors associated with infection were evaluated, including location, species, season, and age class. Plasma samples and conjunctiva/choana/cloaca swabs were collected for serology and qPCR from a subset of 263 birds of prey, representing 18 species. Serologic assays identified both anti-C. buteonis IgM and anti-chlamydial IgY antibodies. Chlamydial DNA and anti-chlamydial antibodies were detected in 4.18% (11/263) and 3.14% (6/191) of patients, respectively. Chamydial DNA was identified in raptors from the families Accipitridae and Strigidae while anti-C.buteonis IgM was identified in birds identified in Accipitridae, Falconidae, Strigidae, and Cathartidae. Two of the chlamydial DNA positive birds (one Swainson’s hawk (Buteo swainsoni) and one red-tailed hawk (Buteo jamaicensis)) were necropsied, and tissues were collected for culture. Sequencing of the cultured elementary bodies revealed a chlamydial DNA sequence with 99.97% average nucleotide identity to the recently described Chlamydia buteonis. Spatial clusters of seropositive raptors and raptors positive for chlamydial DNA were detected in northern California. Infections were most prevalent during the winter season. Furthermore, while the proportion of raptors testing positive for chlamydial DNA was similar across age classes, seroprevalence was highest in adults. This study questions the current knowledge on C. buteonis host range and highlights the importance of further studies to evaluate the diversity and epidemiology of Chlamydia spp. infecting raptor populations.

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Sex differences and emerging new risk factors for atherosclerosis and its thrombotic complications

Current Pharmaceutical Design ◽

10.2174/1381612826666201118094209 ◽

2020 ◽

Vol 26 ◽

Author(s):

Teresa Padro ◽

Natalia Muñoz-Garcia ◽

Esther Peña ◽

Lina Badimon

Keyword(s):

Risk Factors ◽

Sex Differences ◽

Gene Expression Regulation ◽

Current Knowledge ◽

Clinical Manifestations ◽

Men And Women ◽

Thrombotic Complications ◽

Traditional Risk Factors ◽

Specific Disorders ◽

Female Specific

: Cardiovascular disease (CVD) stays as the world's leading cause of death and disability in both men and women, but with different prognostic and outcome between sexes. Although the burden of CVD is generally related to the conventional risk factors, the relevance of non-traditional risk factors is increasingly recognized to explain the so-called “residual risk”. Men and women share many similarities regarding classical cardiovascular risk factors, but have different disease pathophysiology, clinical presentations, prevalence and outcome of CVD. How sex-specificities regarding effects of nontraditional risk factors may contribute to the evolution of atherosclerosis and its clinical manifestations in male and female remain largely under-analyzed. The present review summarizes the current knowledge for sex differences in atherosclerotic plaque composition and clinical evolution in association to risk factors such as inflammation, lipoprotein(a), haemostasis, intraplaque calcification and depression. We further discuss the potential sex-differential impact of chronic infectious diseases, gut microbiome and, epigenetic gene expression regulation for atherosclerosis and the effect of female-specific disorders in CVD.

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Takayasu Arteritis – A Systematic Review

Acta Medica Bulgarica ◽

10.2478/amb-2019-0033 ◽

2019 ◽

Vol 46 (3) ◽

pp. 56-64

Author(s):

D. Hrisrova ◽

S. Marchev

Keyword(s):

Takayasu Arteritis ◽

Clinical Presentation ◽

Current Knowledge ◽

Pulmonary Arteries ◽

Clinical Manifestations ◽

Asian Women ◽

Close Monitoring ◽

Laboratory Markers ◽

Laboratory Biomarkers ◽

Specific Symptoms

Abstract Takayasu arteritis is a chronic, progressive, idiopathic, large-vessel vasculitis that affects the aorta, its main branches and the pulmonary arteries. It typically occurs in young Asian women but can be found in any ethnic group and in men. The disease is named after Mikito Takayasu, a Japanese ophthalmologist, who first described the arteriovenous anomalies in the retina of a patient with the disease in 1908. The etiopathogenesis is not known, but studies are being conducted regarding the immunological, infection and genetic aspects of the disease. Early during the course of the disease, inflammation of the involved arteries progresses, resulting in segmental stenosis, occlusion, dilatation and/or aneurysm. The clinical presentation of Takayasu arteritis varies depending on the blood vessels involved. Early symptoms are nonspecific, making the diagnosis difficult. Subsequently, arterial occlusions occur, producing more specific ischemic symptoms. Paucity of specific symptoms and laboratory biomarkers, as well as difficulties in assessing the disease activity and progression, make it often unrecognized at onset, and its activity is frequently underestimated. The diagnosis is usually confirmed by a combination of clinical manifestations, laboratory markers, diagnostic criteria and imaging methods. The purpose of this review is to address the current knowledge on pathogenesis, investigations, classification and management, and to emphasize the need for timely diagnosis, effective therapeutic intervention, and close monitoring of this disease.

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