Acute Clinical Manifestations Research Articles

Characteristics and outcome‐related factors of seizure at the first onset of autoimmune encephalitis: A retrospective study

AimsSeizure outcome of autoimmune encephalitis (AE) varies from seizure‐free to refractory epilepsy, and the associated factors remain unclear. We aimed to describe seizure characteristics, identify seizure outcome‐related factors, and discuss the medication strategy of antiepileptic drugs (AEDs) at the first onset of AE.MethodsWe retrospectively studied the data of 86 patients with clinically diagnosed AE. The clinical characteristics were described using a chi‐square test. Seizure outcome‐related factors were assessed using multivariable logistic regression analysis.Results56 patients were finally enrolled, with antibodies to N‐methyl‐D‐aspartate receptor found in 29, to γ‐aminobutyric acid receptor B found in 13, and to leucine‐rich glioma‐inactivated protein 1 found in 14. Status epilepticus occurrence and onset with seizure lead to a poor seizure outcome, while administration of human gamma globulin and a low antibody titer contributed to a good seizure outcome.ConclusionsIn the acute phase, seizure characteristics may be considered in the utilization of AEDs. For patients with seizure‐free status in the acute phase, clinical manifestation (onset with seizure or not, whether status epilepticus occurs or not), therapy regimen (human gamma globulin administered or not), and antibody titer may be considered when formulating the strategy for withdrawal of AEDs post‐acute phase.

Risk factors for the delayed diagnosis of extrapulmonary TB.

BACKGROUND: Extrapulmonary TB (EPTB) is more difficult to diagnose than pulmonary TB. The delayed management of EPTB can lead to complications and increase the socio-economic burden.METHODS: Patients newly diagnosed with EPTB were retrospectively enrolled from 11 general hospitals in South Korea from January 2017 to December 2018. The basic characteristics of patients were described. Univariable and multivariable analyses were performed between early and delayed diagnosis groups to identify risk factors for delayed diagnosis and treatment in EPTB.RESULTS: In total, 594 patients were enrolled. Lymph node TB (28.3%) was the predominant form, followed by abdominal (18.4%) and disseminated TB (14.5%). Concurrent lung involvement was 17.8%. The positivity of diagnostic tests showed no significant difference between the two groups. Acute clinical manifestations in disseminated, pericardial and meningeal TB, and immunosuppression were associated with early diagnosis. Delayed diagnosis was associated with outpatient clinic visits, delayed sample acquisition and diagnostic departments other than infection or pulmonology.CONCLUSION: The delay in diagnosis and treatment of EPTB was not related to differences in microbiological characteristics of Mycobacterium tuberculosis itself; rather, it was due to the indolent clinical manifestations that cause referral to non-TB-specialised departments in the outpatient clinic and delay the suspicion of TB and diagnostic testing.

CXCR3 chemokine receptor ligands in sarcoidosis

Sarcoidosis is a polysystemic inflammatory disease of unknown etiology, morphologically related to the group of granulomatosis, with heterogeneous clinical manifestations and outcomes. Immune cells, in particular T helper cells, are attracted to lung tissue and/or other organs by chemokine gradients and play an important role in the granuloma formation. T helper cells migrate from peripheral blood to the tissues due to expression of CXCR3 chemokine receptor on their surface. It interacts, e.g., with CXCL9/MIG, CXCL10/IP- 10, and CXCL11/I-TAC. Our study was aimed for determining the levels of CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC chemokines in peripheral blood of the patients with sarcoidosis, depending on the features of their clinical course before administration of immunosuppressive therapy. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 52). In 37% (19/52), they exhibited acute clinical manifestations, and 63% (33/52) had chronic sarcoidosis. The control group included peripheral blood samples from healthy volunteers (n = 22). The chemokine concentrations (pg/ml) were determined by multiplex analysis using xMAP technology (Luminex), and Milliplex MAP test system (Millipore, USA). In the patients with sarcoidosis, significantly higher levels of chemokines were shown relative to healthy volunteers: CXCL9, 4013.00 pg/ml vs 1142.00 pg/ml (p < 0.001); CXCL10, 565.90 pg/ml vs 196.60 pg/ml (p < 0.001); CXCL11, 230.20 pg/ml vs 121.10 pg/ml (p = 0.018). Plasma concentrations of CXCL9 and CXCL10 were significantly increased both in blood samples from patients with acute and chronic sarcoidosis compared to healthy volunteers, p < 0.001. The level of CXCL11 chemokine was significantly increased only in the patients with chronic sarcoidosis, compared to the healthy volunteers: respectively, 251.50 pg/ml and 121.10 pg/ml (p = 0.044). The levels of this chemokine correlated with the activity of angiotensin-converting enzyme (ACE), with r = 0.374; p = 0.042. The ACE level in sarcoidosis is considered a clinical and laboratory index of the disease activity. In acute sarcoidosis, the level of CXCL11 chemokine was not significantly higher than in healthy individuals, whereas the CXCL9 chemokine content was significantly increased and correlated with ACE activity (r = 0.762; p = 0.037). The level of CXCL9 chemokine was significantly decreased in patients with signs of fibrosis as compared with fibrosis-free patients (1839.88 pg/ml vs 4375.52 pg/ml, p = 0.035). Significantly higher levels of CXCL9 were detected in cases of systemic sarcoidosis, i.e. 6036.84 pg/ml, as compared with 1927.44 pg/ml in the patients without these signs (p = 0.018). Evaluation of clinical and laboratory diagnostic characteristics for plasma chemokine levels in sarcoidosis patients allowed to assess their sensitivity and specificity. The respective values were as follows: in acute sarcoidosis: for CXCL9, 84% and 95%; for CXCL10, 84% and 95%; for CXCL11, 74% and 59%. In chronic sarcoidosis, the respective values for CXCL9 were 82% and 72%; for CXCL10, 91% and 77%; for CXCL11, 79% and 55%, respectively. Thus, the determination of plasma CXCL9, CXCL10, and CXCL11 chemokines in sarcoidosis allows of understanding their role in development of the disease, e.g., recruitment of T helper cells from peripheral blood to the lung tissue, and granuloma formation. Clinical and immunological comparisons of CXCL9 levels in the peripheral blood of patients and characteristics of the clinical course of sarcoidosis indicate to the role of this diagnostic parameter for assessing the disease activity, signs of lung fibrosis, and systemic manifestations in this disease.

Mast Cell Activation Disorders.

Background and Objectives: Mast cell disorders comprise a wide spectrum of syndromes caused by mast cells’ degranulation with acute or chronic clinical manifestations. Materials and Methods: In this review article we reviewed the latest findings in scientific papers about mast cell disorders with a particular focus on mast cell activation syndrome and mastocytosis in pediatric age. Results: Patients with mast cell activation syndrome have a normal number of mast cells that are hyperreactive upon stimulation of various triggers. We tried to emphasize the diagnostic criteria, differential diagnosis, and therapeutic strategies. Another primary mast cell disorder is mastocytosis, a condition with a long-known disease, in which patients have an increased number of mast cells that accumulate in different regions of the body with different clinical evolution in pediatric age. Conclusions: Mast cell activation syndrome overlaps with different clinical entities. No consensus was found on biomarkers and no clearly resolutive treatment is available. Therefore, a more detailed knowledge of this syndrome is of fundamental importance for a correct diagnosis and effective therapy.

Giardia spp. and the Gut Microbiota: Dangerous Liaisons.

Alteration of the intestinal microbiome by enteropathogens is commonly associated with gastrointestinal diseases and disorders and has far-reaching consequences for overall health. Significant advances have been made in understanding the role of microbial dysbiosis during intestinal infections, including infection with the protozoan parasite Giardia duodenalis, one of the most prevalent gut protozoa. Altered species composition and diversity, functional changes in the commensal microbiota, and changes to intestinal bacterial biofilm structure have all been demonstrated during the course of Giardia infection and have been implicated in Giardia pathogenesis. Conversely, the gut microbiota has been found to regulate parasite colonization and establishment and plays a critical role in immune modulation during mono and polymicrobial infections. These disruptions to the commensal microbiome may contribute to a number of acute, chronic, and post-infectious clinical manifestations of giardiasis and may account for variations in disease presentation within and between infected populations. This review discusses recent advances in characterizing Giardia-induced bacterial dysbiosis in the gut and the roles of dysbiosis in Giardia pathogenesis.

Aspects of health and environmental services using TES therapy

Considering the prevalence of coronary heart disease and myocardial infarction, the problem of improving the pharmacotherapy of coronary heart disease continues to be one of the most urgent problems in modern pharmacology. In recent years, the point of view has become generally accepted that the most real factor in both the initiation and progression of atherosclerosis and the development of its acute clinical manifestations is inflammation, and the destabilization of an atherosclerotic plaque is determined by the high activity of a chronic inflammatory process in it. The most promising theory of atherogenesis is that the accumulation and increased content of cytokines in the peripheral blood against the background of changes in the initial level of cholesterol (CS) may be the primary trigger of the atherosclerotic process.

Sickle Cell Disease.

Sickle cell disease is an umbrella term for a group of hemoglobinopathies characterized by the presence of 2 β-globin gene mutations or deletions, at least 1 of which is the point mutation that leads to the production of hemoglobin S. Sickle cell disease is associated with hemolytic anemia, significant chronic end-organ damage, and early death. In high-income countries, at least 95% of children with the disease survive into adulthood, resulting in a growing population of affected adults with significant comorbidities, complex medical issues, and not enough specialists to provide care. Hydroxyurea is the primary therapy, and recent advances in understanding disease pathophysiology have led to new therapies; progress in bone marrow transplant and gene editing has resulted in cure in some patients. The purpose of this review is to provide an overview of the diagnosis, common acute and chronic clinical manifestations, and best practices for management of sickle cell disease.

Clinical manifestations and diagnosis of acute myeloid leukemia in a patient with a medical history of pulmonary tuberculosis (a case report)

The aim is to familiarize practitioners with the initial clinical manifestations of acute myeloid leukemia and its diagnosis in a patient with a past medical history of pulmonary tuberculosis.Materials and methods. The article presents a clinical case of acute myeloid leukemia clinical manifestations based on our own clinical experience and its diagnosis in the patient with previous pulmonary tuberculosis. The patient was followed-up and diagnosed with acute myeloid leukemia in the Municipal Institution “Zaporizhzhia Regional Tuberculosis Clinical Dispensary”.Results. The patient presented in this study was diagnosed with pulmonary tuberculosis and received antimycobacterial treatment including isoniazid and rifampicin, which may have initially contributed to the hematopoietic mechanisms impairment. Perhaps the stressful situation triggered the development of acute myeloid leukemia due to underlying impaired mechanisms of hematopoiesis that had occurred. In this case, the initial clinical manifestations were weakness, loss of appetite and weight loss. A clinical blood analysis with leukogram and the bone marrow biopsy with aspirate examination became priority methods in diagnosing acute myeloid leukemia. The clinical case presented primarily demonstrates patient’s irresponsibility for their own health, who having symptoms such as weakness, loss of appetite, and weight loss for 5 months as well as past medical history of tuberculosis, did not seek medical advice timely.Conclusions. In a patient with a past medical history of pulmonary tuberculosis, priority task is to confirm or rule out reactivation tuberculosis. The initial clinical manifestations of acute myeloid leukemia are: unprovoked weakness for several months; increasing exertional dyspnea; anemia, leukopenia, neutropenia, ESR acceleration. The primary methods to diagnose acute myeloid leukemia are: clinical blood test with leukogram, biochemical blood tests to determine the levels of erythropoietin, ferritin and vitamin B12; bone marrow biopsy with aspirate examination (myelogram); cytochemical examination of bone marrow (myeloperoxidase); bone marrow immunophenotyping (expression of myeloid-associated antigens).

A Case of Dermatomyositis presenting with Fulminant Rhabdomyolysis without Myoglobinuric Acute Kidney Injury-A Rare Clinical Manifestation

Rhabdomyolysis and myoglobinuria are a rare complication of dermatomyositis. Rhabdomyolysis has a wide range of presentations, from asymptomatic to life-threatening. The most dramatic presentation can result in acute renal failure, electrolyte imbalances, and/or disseminated intravascular coagulation (DIC). Recognition of this fact has important therapeutic implications as patients require immunotherapy in addition to the symptomatic treatment for renal failure.

Acute and chronic graft versus host disease after hematopoietic stem cell transplant

Graft versus host disease is one of the main complications of Hematopoietic stem cell, in­volving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

Analysis of Providing Emergency Care to Patients with Myocardial Infarction without ST Segment Elevation

A high mortality rate due to acute myocardial infarction (AMI) stimulates the analysis of the quality of emergency medical care at the prehospital stage. Firstly, an analysis of the reasons for the treatment of patients with AMI to general practitioners is necessary. Secondly, the quality of the provision of medical services by general practitioners is one of the criteria for the effectiveness of the implementation of patient management protocols, which requires a systematic analysis and relevant studies.The objective: to analyze the provision of emergency medical care to patients with acute myocardial infarction without ST segment elevation (NSTEMI) when they seek medical care.Materials and methods. The referral routes for hospitalization of patients with acute coronary syndrome and clinical manifestations were analyzed among 280 patients with STEMI and 91 patients with NSTEMI. The assessment of treatment tactics in patients with NSTEMI was carried out in the following paragraphs of the emergency medical care protocol: determination of blood saturation, ensuring reliable venous access, administration of nitroglycerin in aerosol (1–2 doses or 0,4–0,8 mg), use of acetylsalicylic acid (ASA ) after chewing 160–325 mg, the use of clopidogrel 300 mg orally; the appointment of β-blocker; narcotic analgesic; anticoagulant. Statistical data processing was carried out using non-parametric criterion χ2.Results. Appeals to primary health care centers were significantly more frequent in patients with NSTEMI, due to the clinical course of the disease.Conclusion. At the stage of medical care by general practitioners, only the appointment of acetylsalicylic acid met the criteria for the implementation of the protocol for the provision of emergency medical care to patients with NSTEMI.

Аналіз надання екстреної медичної допомоги хворим на інфаркт міокарда без елевації сегмента ST при звернені по медичну допомогу

A high mortality rate due to acute myocardial infarction (AMI) stimulates the analysis of the quality of emergency medical care at the prehospital stage. Firstly, an analysis of the reasons for the treatment of patients with AMI to general practitioners is necessary. Secondly, the quality of the provision of medical services by general practitioners is one of the criteria for the effectiveness of the implementation of patient management protocols, which requires a systematic analysis and relevant studies.The objective: to analyze the provision of emergency medical care to patients with acute myocardial infarction without ST segment elevation (NSTEMI) when they seek medical care.Materials and methods. The referral routes for hospitalization of patients with acute coronary syndrome and clinical manifestations were analyzed among 280 patients with STEMI and 91 patients with NSTEMI. The assessment of treatment tactics in patients with NSTEMI was carried out in the following paragraphs of the emergency medical care protocol: determination of blood saturation, ensuring reliable venous access, administration of nitroglycerin in aerosol (1–2 doses or 0,4–0,8 mg), use of acetylsalicylic acid (ASA) after chewing 160–325 mg, the use of clopidogrel 300 mg orally; the appointment of β-blocker; narcotic analgesic; anticoagulant. Statistical data processing was carried out using non-parametric criterion χ2.Results. Appeals to primary health care centers were significantly more frequent in patients with NSTEMI, due to the clinical course of the disease.Conclusion. At the stage of medical care by general practitioners, only the appointment of acetylsalicylic acid met the criteria for the implementation of the protocol for the provision of emergency medical care to patients with NSTEMI.

Fatal acute Chagas disease by Trypanosoma cruzi DTU TcI, Ecuador

BackgroundChagas disease is caused by the haemoflagellate protozoan Trypanosoma cruzi. Currently, T. cruzi recognizes seven discrete typing units (DTUs): TcI to TcVI and Tcbat. The genetic diversity of T. cruzi is suspected to influence the clinical outcome. Acute clinical manifestations, which include myocarditis and meningoencephalitis, are sometimes fatal; occur most frequently in children and in immunocompromised individuals. Acute disease is often overlooked, leading to a poor prognosis.Case presentationA 38-year-old man from a subtropical area of the Andes mountains of Ecuador was hospitalized after 3 weeks of evolution with high fever, chills, an enlarged liver, spleen, and lymph nodes, as well as facial edema. ECG changes were also observed. T. cruzi was identified in blood smears, culture and amplification of DNA by PCR. Tests for anti-T. cruzi IgG and IgM and HIV were negative. Molecular typing by restriction fragment length polymorphism (PCR-RFLP) determined the parasite to DTU TcI. In the absence of a timely anti-T. cruzi medication, the patient died.ConclusionsThis is a case of severe pathogenicity and the virulence of a DTU TcI strain in an adult patient. The severe acute Chagas disease was probably overlooked due to limited awareness and its low incidence. Our findings suggest that T. cruzi DTU TcI strains circulating in Ecuador are capable of causing fatal acute disease. Early diagnosis and prompt treatment is of paramount importance to avoid fatalities in acute infections.

DYSFUNCTIONS OF NEUTROPHILIC GRANULOCYTES IN CHILDREN WITH CONGENITAL CLEFT LIP AND PALATE

The problem of rehabilitation of children with congenital cleft lip and palate (CCLP) is a difficult task and doesn’t lose its relevance. Children with CCLP often suffer from repeated acute viral and bacterial infections of the respiratory tract and upper respiratory tract, which leads to a forced delay in surgical, orthodontic treatment, adequate speech therapy and complications after staged surgical operations. The development of inflammatory processes in children with CCLP is associated with anatomical and topographic features that facilitate the penetration of pathogenic microflora in oral and nose mucosa and, consequently, negative changes in the immune system (IS). The key cells of IS in maintaining homeostasis and ensuring oral health are neutrophil granulocytes (NG). NG dysfunctions in CCLP interfere with the elimination of pathogens and support their persistence. This can occur against the background of previously existing defects in the functioning of the NG system and is aggravated by the significant pathogenicity and massiveness of the impact of various infectious agents. Full diagnostics of NG dysfunctions is necessary for the further implementation of their timely immune correction and prevention of the development of pathological chronic inflammation in response to the pathogenic microflora long-term on the mucous membrane of the mouth and nose. For this purpose study was conducted of the functional activity and phenotypic characteristics of NG in children with CCLP at different stages of complex rehabilitation. Blood samples of 56 children with CCLP 1-3 years (n = 20, group 1), 4-6 years (n = 20, group 2), and 7-12 years (n = 20, group 3) at different stages of complex rehabilitation and 30 conditionally healthy children (control groups) of the corresponding age was studied. A violation of the microbiocenosis of the mucous membranes of the oral and nasal cavities was revealed, which may be a cause or a consequence of a decrease in antibacterial immunity, first of all NG dysfunctions. Common for all age groups children with CCLP NG dysfunction was found: the appearance of NG expressing CD14 receptors that are absent in children of all three control groups, which indicates the presence of viral and bacterial load; defects of phagocytosis associated with a decrease in the number of actively phagocytic NG, impaired NG capture functions; impaired NADPH oxidase release with partial or complete blockade of the response to additional antigenic load, even in the absence of acute clinical manifestations. Comparative analysis of the studied indicators of the expression level of the receptors CD64, CD16, CD32, CD14 NG in children with CCLP demonstrates different equipment, which determines the inconsistency of the phagocytic and microbicidal function of NG in different age periods. Thus, an increase in the expression of these membrane markers, especially CD64 and CD14, in older age groups is accompanied by more significant defects in phagocytic and killing functions of NG, which is associated not only with recurrent viral respiratory infections, but also with a high frequency of associated bacterial infections of the respiratory system and ENT – organs. Revealed NG dysfunctions in children with CCLP of various age groups indicate their inability to implement adequate anti-infective protection, which can lead to atypically occurring viral – bacterial infections and the occurrence of various, including purulent complications in the postoperative period, which requires the development of targeted immunotherapy, included in the program of comprehensive rehabilitation in children with CCLP and aimed at restoring impaired NG functions.

Acute phase response and clinical manifestation in outbreaks of interdigital phlegmon in dairy herds

Several Finnish dairy herds have suffered from outbreaks of interdigital phlegmon (IP). In these new types of outbreaks, morbidity was high and clinical signs severe, resulting in substantial economic losses for affected farms. In our study, we visited 18 free stall dairy herds experiencing an outbreak of IP and 3 control herds without a similar outbreak. From a total of 203 sampled cows, 60 suffered from acute stage IP. We demonstrated that acute phase response of bovine IP was evident and therefore an appropriate analgesic should be administered in the treatment of affected animals. The response was most apparent in herds with high morbidity in IP and with a bacterial infection comprising Fusobacterium necrophorum and Dichelobacter nodosus, indicating that combination of these two bacterial species affect the severity of the disease.

Optogenetic Modulation for the Treatment of Traumatic Brain Injury.

Although research involving traumatic brain injury (TBI) has traditionally focused on the acute clinical manifestations, new studies provide evidence for chronic and progressive neurological sequelae associated with TBI, highlighting the risk of persistent, and sometimes life-long, consequences for affected patients. Several treatment modalities to date have demonstrated efficacy in experimental models. However, there is currently no effective treatment to improve neural structure repair and functional recovery of TBI patients. Optogenetics represents a potential molecular tool for neuromodulation and monitoring cellular activity with unprecedented spatial resolution and millisecond temporal precision. In this review, we discuss the conceptual background and preclinical evidence of optogenetics for neuromodulation, and translational applications for TBI treatment are considered.

Sequestered Disc Herniation in a Dog

Background: Dogs are frequently affected by intervertebral disc degeneration, a structural failure associated with changes accelerated by aging. Disc degeneration may occur in the presence or absence of clinical signs, which are variable and common to other spinal cord diseases and therefore early diagnosis is crucial to a successful outcome. Treatment may be conservative or surgical according to severity of the clinical signs and should be combined with a rehabilitation protocol. Prognosis depends on the location of the spinal cord compression, volume and velocity of the disc material herniation and time between initial clinical signs, definitive diagnosis and therapeutic approach. Case: A nonchondrodystrophic 14-year-old dog with acute clinical manifestation of paraparesis and proprioceptive deficit in hind limbs was submitted to myelography examination. There was contrast column deviation in the T13-L1 region, determining spinal compression, and spondyloses were also noted in several thoracolumbar vertebrae. Hemilaminectomy was performed with complete removal of the compressor fragment. Histological analysis confirmed the presence of fibrocartilaginous material that corresponds to the part of the annulus fibrosus. The kidnap of the fragment was characterized by loss of continuity with the remaining disk. In these cases, magnetic resonance imaging does provides the definitive diagnosis, since neoplasm, arachnoid cysts and abscesses may be remaining differential diagnosis. Therefore, surgical approach followed by histopathological analysis of the obtained material are necessary to confirm the diagnosis.Discussion: The present report differs from most cases of disc herniation because it is a thoracolumbar lesion with an acute manifestation of significant neurological deficit in an elderly dog of non-chondrodystophic breed. Also, material of the free fibrous annulus itself in the medullary canal is not a common histopathological presentation of disc extrusion usually composed by nucleus pulposus. After neurolocalization of the lesion by clinical neurological examination, the radiographic evaluation shall precedes the myelography, since this is contraindicated when there is suspicion of discoespondylitis, fracture, dislocation or vertebral subluxation, which had not yet been discarded. Even if the MRI is performed, in the cases of a sequestered fragment, it still remais differential diagnoses include arachnoid cysts, discoespondylitis, hematomas, abscesses and neoplasms, including metastases, so only surgical approach to obtain material for histopathological analysis may provide definitive diagnosis. According to the histopathological examination, the herniated material had a fibrocartilaginous characteristic: several concentric fibrous blades, composed of collagen and fibrocartilage, thus characterizing the herniated material as a fragment of the fibrous ring. When removed from the vertebral canal, the contents did not show resistance, being withdrawn completely and without continuity with its origin intervertebral disc. The patient's disc herniation could not be classified as a disc protrusion because this affection is described as a projection of the fibrous annulus towards the vertebral canal due to the partial rupture of fibers and mineralization of the nucleus pulposus, without discontinuity of some content. Disc protrusion shows mild and progressive signs, except if there is complete rupture of the fibrous ring as can be seen in the sequestered disc herniation. Although infrequent, elderly animals of non-chondrodisiotic races may show acute signs of neurological deficits. Sequestrated disc herniation may mimic other lesions, requiring a surgical approach to obtain material for histopathological analysis to confirm the diagnosis.

Sickle cell disease: a review for the internist.

Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide in terms of frequency and social impact, recently recognized as a global public health problem by the World Health Organization. It is a monogenic but multisystem disorder with high morbidity and mortality. Vaso-occlusion, hemolytic anemia and vasculopathy are the hallmarks of SCD pathophysiology. This review focuses both on "time-dependent" acute clinical manifestations of SCD and chronic complications commonly described in adults with SCD. The review covers a broad spectrum of topics concerning current management of SCD targeted at the internists and emergency specialists who are increasingly involved in the care of acute and chronic complications of SCD patients.

Adenovirus Entry: From Infection to Immunity.

More than 80 different adenovirus (AdV) types infect humans through the respiratory, ocular, or gastrointestinal tracts. They cause acute clinical mani-festations or persist under humoral and cell-based immunity. Immuno-suppressed individuals are at risk of death from an AdV infection. Concepts about cell entry of AdV build on strong foundations from molecular and cellular biology-and increasingly physical virology. Here, we discuss how virions enter and deliver their genome into the nucleus of epithelial cells. This process breaks open the virion at distinct sites because the particle has nonisometric mechanical strength and reacts to specific host factors along the entry pathway. We further describe how macrophages and dendritic cells resist AdV infection yet enhance productive entry into polarized epithelial cells. A deep understanding of the viral mechanisms and cell biological and biophysical principles will continue to unravel how epithelial and antigen-presenting cells respond to AdVs and control inflammation and persistence in pathology and therapy.

Atypical Presentation of Bacteremia in Older Patients Is a Risk Factor for Death

BackgroundThe absence of fever in bacteremia in patients who are older is known to delay diagnosis. Our objective was to determine whether atypical presentation was associated to mortality as a result of bacteremia in this patient cohort as well as possible factors associated with this atypical presentation. MethodsWe conducted an observational prospective study in 2 French university hospitals in 2016-2017 including patients ages ≥75 years with bacteremia. Atypical presentation was defined as the absence of a temperature ≥38.3°C or <36°C, chills, or hypotension. Mortality and dependence for activities of daily living (ADL) were recorded at 1 week (D7) and 3 months (D90). ResultsAmong the 151 patients (mean age 85.4±5.8 years) enrolled, atypical presentation prevalence was 21.2%. D7 and D90 mortality rates were 7.9% and 40.0%, respectively. Atypical presentation was independently associated with D7 (odds ratio (OR) 4.46, 95% confidence interval (CI) 1.04-19.24) and D90 mortality (OR 3.76, 95% CI 1.30-10.92) after controlling for other prognostic factors. Patients with diabetes and those infected with Staphylococcus aureus were more likely to have atypical signs of infection. ADL score decreased from 3.6±2.0 before bacteremia to 2.8±2.1 at D90 (P <0.001). ConclusionPatients who are older with bacteremia have poor vital and functional prognoses in the short and long terms. The absence of typical signs of infection is associated with mortality. Blood culture should be considered for patients who are older, especially with diabetes with acute unexplained clinical manifestations.