Early Clinical Signs Research Articles

Educating caregivers to recognise the clinical signs of pneumonia in children younger than 6 months

Background. Pneumonia remains the foremost cause of death in young children in sub-Saharan Africa. This phenomenon is largely driven by poor access to healthcare and delay in seeking medical care for childhood pneumonia. Objective. To assess the effectiveness of training caregivers to recognise the early clinical signs of pneumonia. Methods. The study involved a cohort of women presenting to the Child Welfare Clinic at the Komfo Anokye Teaching Hospital in Kumasi, Ghana, between 7 July and 8 September 2016. A total of 90 women with children younger than 10 weeks were recruited. Participants were trained on identifying early signs of pneumonia using low-cost equipment. Follow-up training and assessment sessions formed part of the programme. Results. At pre-training assessment, the majority of the participants ( n =83/90; 92.2%) recognised lower chest indrawing as a sign of respiratory disease requiring immediate hospital intervention. Participants’ performance in determining rhythms of 50 breaths per minute (bpm) and 60 bpm improved significantly across sessions ( p =0.011 and p ≤0.001, respectively). After training, 87 participants (96.7%) were able to determine rapid breathing accurately compared with 73 participants (81.1%) before training ( p =0.001). Conclusion. The results suggest that caregivers can be effectively trained to identify clinical signs of pneumonia in young children, even in low-resource settings. A training initiative as described in this study could be an effective public health intervention to help address the burden of pneumonia in low-resource settings.

Elevated Intraocular Pressure in Burn Patients Undergoing Fluid Resuscitation: An Opportunity to Avoid Orbital Compartment Syndrome

Abstract Objective This study aims to discuss clinical characteristics of burn patients who developed elevated intraocular pressure (IOP). We propose management strategies to prevent orbital compartment syndrome before invasive treatment is required. Methods A retrospective review of 47 burn patients at the University of California San Diego (UCSD), Burn Intensive Care Unit (ICU; major regional burn center for San Diego county), was analyzed for demographics, fluid resuscitation volumes, and physical exam findings. Patients requiring topical treatment for high-IOP, defined as ≥30 mm Hg in either or both eyes, were compared with those who did not require treatment, using the t-test and Fisher's exact test. Linear regression tested for an association between peak IOP and fluid volume. Logistic regression evaluated the association between total fluid and treatment of high IOP, while adjusting for other characteristics. Results Six of 47 patients required IOP-lowering treatment. Of the patients requiring treatment, one drop of dorzolamide/timolol in both eyes twice daily was the most common treatment recommendation. Presence of periocular burns was a significant risk factor in patients who required treatment for high IOP. No patients developed orbital compartment syndrome or required surgical intervention to lower IOP. The mean total fluid volume delivered in the first 24 hours was 0.8 times the level prescribed by fluid resuscitation guidelines. Conclusion By treating early clinical signs and properly managing fluid resuscitation, development of orbital compartment syndrome in burn patients can be avoided.

Patients with Lately Diagnosed Cerebrotendinous Xanthomatosis

Objectives: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive inborn lipid storage disorder due to various pathogenic mutations in the CYP27A1 gene. Although the symptoms begin commonly in infancy, CTX diagnosis is often delayed. In this study, we report 7 Turkish CTX patients who had a delayed diagnosis despite early clinical signs and belonged to 6 unrelated families. Methods: We have retrospectively evaluated clinical, laboratory, imaging, and genetic findings of CTX patients, which were collected from 2 centers specialized in movement disorders: the Department of Neurology, Faculty of Medicine, Istanbul University, and the Department of Neurology, Faculty of Medicine, Mersin University. Results: All patients were diagnosed with CTX after neurological symptom development, and their mean age at diagnosis was 38.7 ± 9.6 years, despite a mean onset age of 12.4 ± 10.6 years. The mean follow-up period was 28 months (range: 3–60 months). The most common initial clinical abnormalities in our cohort were unexplained chronic diarrhea (42%), febrile convulsion (42%), juvenile cataract (85%), childhood depression and autism (14%), parkinsonism (14%), and intellectual disability (100%). The most prominent neurological findings were the pyramidal-cerebellar syndrome (85%) and extrapyramidal signs (42%). All patients were genetically confirmed. Serum cholestanol levels were elevated in all patients and decreased after chenodeoxycholic acid (CDCA) treatment in 6 patients. Conclusion: This cohort is the largest CTX case series in Turkey. All cases showed improvement in gastrointestinal symptoms as a response to CDCA treatment and stabilization on neurological symptoms, i.e., no further progression of neurological abnormalities were noted during this treatment. Therefore, early diagnosis and treatment is crucial in preventing clinical deterioration.

Tongue Fasciculations Presenting as an Early Clinical Sign of Cobalamin Deficiency (5164)

Tongue Fasciculations Presenting as an Early Clinical Sign of Cobalamin Deficiency (5164)

Detecting SARS-CoV-2 at Point of Care: Preliminary Data Comparing Loop-Mediated Isothermal Amplification (LAMP) to PCR

Background: The need for a fast and reliable test for COVID-19 is paramount in managing the current pandemic. A cost effective and efficient diagnostic tool as near to the point of care (PoC) as possible would be a game changer in current testing. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 minutes, alongside standard methods in a real-life clinical setting. Methods: This service improvement project piloted a research RT-LAMP method on nasal and pharyngeal swabs on 21 residents in an NHS Category 1 care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We calculated the sensitivity, specificity, positive and negative predictive values of a single RT-LAMP swab compared to RT-PCR, as per STARD guidelines. We also recorded vital signs of patients to correlate clinical and laboratory information. Findings: The novel method accurately detected 8/10 PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a “gold standard”, the sensitivity and specificity of the novel test were 80% and 73% respectively. Positive predictive value (PPV) was 73% and negative predictive value (NPV) was 83%. We also observed hypothermia to be a significant early clinical sign in a number of COVID-19 patients in this setting. Interpretation: RT-LAMP testing for SARS-CoV-2 was found to be promising, fast, easy to use and to work equivalently to RT-PCR methods. Definitive studies to evaluate this method in larger cohorts are underway. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the point of care. This method could be deployed in mobile testing units in the community, care homes and hospitals to detect disease early and prevent spread.

Human Thrombomodulin Transgene Expression Prevents Intracardiac Thrombus in Life Supporting Pig-to-Baboon Cardiac Xenotransplantation

Transplantation of organs from animals to humans (xenotransplantation) has been proposed to address the critical shortage of organs for transplantation. The use of genetically engineered organ xenografts, including knock-out (KO) of alpha 1-3 galactosyltransferase (GTKO) along with insertion of a human complement regulator genes (hCD46, hDAF) and other cell surface carbohydrate KOs, has been helpful in circumventing acute and subacute rejection. However, thrombotic complications still remain. Xenografts with additional human transgenes, including hTBM, have been generated to address this barrier. Here, we studied the importance of hTBM in preventing coagulation by comparing two transplanted groups utilizing GE donors with or without hTBM. Specific pathogen-free baboons of either sex weighing 15-30 kg (2-3 years of age) were used as recipients. 6 to 8-week-old genetically modified pigs with hTBM (GTKO.hCD46.hTBM) or without hTBM (triple knock out-GTKO.B4KO.CMAHKO, with or without hCD46 and hDAF) were used as donors, provided by Revivicor. Expression of transgenes were consistent and high level across all pigs. All animals were used in compliance with guidelines provided by the Institutional Animal Care and Use Committee (IACUC). GTKO.hCD46.hTBM donors (n=3) were found to have no intracardiac thrombus with survival up to 30 days post-transplant. However, all non-hTBM donors (n=3) were found to have a large intracardiac thrombus burden with propagation into major vascular structures such as the aorta, pulmonary artery and coronary sinus. Gross examination of thrombi indicated acute and subacute components, suggesting early formation of the thrombus postoperatively. Additionally, early clinical signs of thrombus formation included profound hypocalcemia requiring continuous calcium infusions in the first 48-72 hours postoperatively. These phenomena were not prevented by continuous heparin infusion. Histologic examination revealed no signs of rejection. hTBM prevents intracardiac thrombus in this model. While immunologic rejection has been circumvented with novel immunosuppression regimens and GTKO, it is likely that hTBM or other transgenes involved in regulation of coagulation may be needed for prevention of thrombotic complications.

Role of Serum Amyloid A Protein in the Early Detection of Late Onset Sepsis in Neonate

Background: Late onset sepsis (LOS) is an important cause of serious illness and deaths among neonates. Diagnosis of neonatal sepsis remains a challenge owing to nonspecific early clinical signs and the non-availability of a reliable biomarker. Serum amyloid A (SAA), the precursor protein in inflammation-associated reactive amyloidosis, whose level in the blood increases up to 1000 fold in response to inflammation and it is also an acute phase reactant like PCT and CRP. Objectives: assessing the accuracy and rapidity of SAA in detection of LOS in neonates. Method: This is a case-control study which was carried out on neonates admitted in (NICU) of Benha University Hospital and Benha Teaching Hospital during the period (from June 2018 to November 2019). Group 1 (patients group): 45 neonates with neonatal sepsis, group 2 (control group): 40 healthy neonates age and sex matched. SAA was measured. Results: mean value of SAA in septic group was 38.8 µg/ml compared to 1.26 µg/ml in control group , with statistically significant increase in patients than controls (p 2.8 µg/ml, SAA had a sensitivity 86.7%, specificity 85%, PPV 86.7%, and NPV 85% for early diagnosis of LOS. At a cut-off value of SAA>45.2 µg/ml, SAA had a sensitivity 83.3%, specificity 69.7%, PPV 50%, and NPV 92% for the prediction of mortality among LOS patients. Conclusion: The high sensitivity, specificity, positive predictive value and negative predictive value of SAA protein could help the clinicians for early diagnosis of LOS.

Treatable Inherited Movement Disorders in Children: Spotlight on Clinical and Biochemical Features.

About 80% of monogenic metabolic diseases causing movement disorders (MDs) emerges during the first 2 decades of life, and a number of these conditions offers the opportunity of a disease-modifying treatment. The implementation of enlarged neonatal screening programs and the impressive rapid increase of the identification of new conditions are enhancing our potential to recognize and treat several diseases causing MDs, changing their outcome and phenotypic spectrum. A literature review of monogenic disorders causing MDs amenable to treatment was conducted focusing on early clinical signs and diagnostic biomarkers. A classification in 3 broad categories based on the therapeutic approach has been proposed. Some disorders result in irreversible neurotoxic lesions that can only be prevented if treated in a presymptomatic stage, and others present with a progressive neurological impairment that a timely diagnosis and treatment may reverse or improve. Some MDs are the result of the failure of intracellular energy supply or altered glucose transport. The treatment in these conditions includes vitamins or a metabolic shift from a carbohydrate to a fatty acid catabolism, respectively. Finally, a group of highly treatable MDs are the result of defects of neurotransmitter metabolism. In these disorders, the supplementation of precursors or mimetics of neurotransmitters can deeply change the disease natural history. To prevent serious and irreversible neurological impairment, the diagnostic work-up of MDs in children should consider a number of clinical red flags and biomarkers denoting specifically treatable diseases.

Maraviroc attenuates the pathogenesis of experimental autoimmune encephalitis

It has been shown that the blockade of chemokine receptor type 5 can dampen inflammatory reaction within the central nervous system (CNS). In the present study, we utilized maraviroc, a potent antagonist o CCR5, to examine whether this drug can mitigate neuroinflammation in the spinal cord of mice induced by experimental autoimmune encephalitis (EAE), considered a murine model of multiple sclerosis (MS). For this aim, mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55), followed by pertussis toxin to induce paralysis in EAE mice. The animals intraperitoneally received various doses of maraviroc (5, 25, and 50 mg/kg body weight) when the early clinical signs of EAE appeared. The results demonstrated that the administration of maraviroc led to a marked decrease in the clinical score and improvement in behavioral motor functions. Moreover, our finding indicated that the administration of maraviroc significantly attenuates the infiltration of inflammatory cells to the spinal cord, microgliosis, astrogliosis, pro-inflammatory cytokines, and cell death in EAE mice. The flow cytometry data indicated that a decreased number of CD4+ and CD8+ T cells in the peripheral blood of mice with EAE without affecting the number of T regulatory cells (CD4 + CD25+ forkhead box protein 3+). Finally, it seems that maraviroc is well-tolerated, and targeting CCR5 could open up a new horizon in the treatment of MS.

Widespread outbreaks of the emerging mandarinfish ranavirus (MRV) both in natural and ISKNV-FKC vaccinated mandarinfish Siniperca chuatsi in Guangdong, South China, 2017

Widespread outbreaks of mandarinfish (Siniperca chuatsi) ranavirus (MRV) have emerged in many mandarinfish farms in Guangdong, the most important region of the mandarinfish industry in China. Unlike the early typical clinical signs of abnormally swollen abdomens due to extremely severe ascites, diseased fish from the reemerging natural outbreaks of MRVs had little ascites but showed lethargy, anorexia and a typical sleepy syndrome. The disease duration of the natural outbreak of MRV could last for 1 to 5 months. Additionally, the majority of the surviving fish showed persistent anorexia and body emaciation and deformity, which is also very different from the symptoms of mandarinfish infectious spleen and kidney necrosis virus (ISKNV)—the notorious and well-known iridoviral agent in the mandarinfish industry. Mandarinfish vaccinated with the ISKNV-inactivated vaccine showed no protective effect against the natural outbreak of MRV, whereas the ISKNV vaccine seamed to induce a stronger outbreak of the MRV disease in MRV carrier fish. By real-time quantitative PCR, the liver, spleen, kidney as well as intestine are shown to be the major viral reservoirs, both under artificial infection and natural outbreak. Additionally, histopathology, immuno-histochemistry, immunofluorescence assay and transmission electron microscopy also confirmed the pathogenicity of MRV to mandarinfish. Collectively, the emerging MRV disease remained a severe and actual threat to the mandarinfish industry. As two different genera members in the family Iridoviridae, the ISKNV vaccine provided no cross-protection against MRV. A combination vaccine, containing both ISKNV and MRV, is urgently needed.

Role of microRNAs as Clinical Cancer Biomarkers for Ovarian Cancer: A Short Overview.

Ovarian cancer has the highest mortality rate among gynecological cancers. Early clinical signs are missing and there is an urgent need to establish early diagnosis biomarkers. MicroRNAs are promising biomarkers in this respect. In this paper, we review the most recent advances regarding the alterations of microRNAs in ovarian cancer. We have briefly described the contribution of miRNAs in the mechanisms of ovarian cancer invasion, metastasis, and chemotherapy sensitivity. We have also summarized the alterations underwent by microRNAs in solid ovarian tumors, in animal models for ovarian cancer, and in various ovarian cancer cell lines as compared to previous reviews that were only focused the circulating microRNAs as biomarkers. In this context, we consider that the biomarker screening should not be limited to circulating microRNAs per se, but rather to the simultaneous detection of the same microRNA alteration in solid tumors, in order to understand the differences between the detection of nucleic acids in early vs. late stages of cancer. Moreover, in vitro and in vivo models should also validate these microRNAs, which could be very helpful as preclinical testing platforms for pharmacological and/or molecular genetic approaches targeting microRNAs. The enormous quantity of data produced by preclinical and clinical studies regarding the role of microRNAs that act synergistically in tumorigenesis mechanisms that are associated with ovarian cancer subtypes, should be gathered, integrated, and compared by adequate methods, including molecular clustering. In this respect, molecular clustering analysis should contribute to the discovery of best biomarkers-based microRNAs assays that will enable rapid, efficient, and cost-effective detection of ovarian cancer in early stages. In conclusion, identifying the appropriate microRNAs as clinical biomarkers in ovarian cancer might improve the life quality of patients.

Risk Factors for Early-Onset Colorectal Cancer

Colorectal cancer (CRC) incidence and mortality are increasing among persons younger than 50 years old in the United States, but risk factors associated with early-onset CRC (EOCRC) have not been widely studied. We conducted a case-control study of US veterans 18 to 49 years old who underwent colonoscopy examinations from 1999 through 2014. EOCRC cases were identified from a national cancer registry; veterans who were free of CRC at their baseline colonoscopy through 3 years of follow-up were identified as controls. We collected data on age, sex, race/ethnicity, body weight, body mass index (BMI), diabetes, smoking status, and aspirin use. Multivariate-adjusted EOCRC odds were estimated for each factor, with corresponding 95% confidence interval (CI) values. Our final analysis included 651 EOCRC cases and 67,416 controls. Median age was 45.3 years, and 82.3% were male. Higher proportions of cases were older, male, current smokers, nonaspirin users, and had lower BMIs, compared with controls (P < .05). In adjusted analyses, increasing age and male sex were significantly associated with increased risk of EOCRC, whereas aspirin use and being overweight or obese (relative to normal BMI) were significantly associated with decreased odds of EOCRC. In post hoc analyses, weight loss of 5 kg or more within the 5-year period preceding colonoscopy was associated with higher odds of EOCRC (odds ratio 2.23; 95% CI 1.76-2.83). In a case-control study of veterans, we found increasing age and male sex to be significantly associated with increased risk of EOCRC, and aspirin use to be significantly associated with decreased risk; these factors also affect risk for CRC onset after age 50. Weight loss may be an early clinical sign of EOCRC. More intense efforts are required to identify the factors that cause EOCRC and signs that can be used to identify individuals at highest risk.

Oral manifestations as an early clinical sign of acute myeloid leukemia: A report of two cases

Oral manifestations as an early clinical sign of acute myeloid leukemia: A report of two cases

Pulmonary insufficiency in acute stroke: risk factors and mechanisms of development

Various degrees of pulmonary insufficiency (PI) (PaO2 ≤60 mm Hg, SaO2 ≤90%) are diagnosed in most of patients with severe acute stroke (AS). Frequency and severity of PI positively correlates with the severity of AS. PI worsens patient's condition, prolongs the hospitalization period, and increases the probability of fatal outcome. Early clinical signs of PI may be undiagnosed due to the severity of stroke and thus not treated. The initiating pathogenic mechanism of PI is stress-related activation of sympathetic nervous system (SNS) and systemic immunosuppression. In severe stroke with mass effect, the rapid and significant increase in intracranial pressure may additionally activate the SNS. Risk factors of PI include older age, previous pulmonary disease, prolonged supine position, respiratory muscle dysfunction, apnea, and concomitant somatic diseases. Decompensation of somatic diseases leads to multiple stage reactions with facilitation of functional and morphologic changes in the pulmonary system, hypoxemia and hypoxia, promotes infectious complications and multiple organ failure and worsens neurological outcome. Diagnosis and treatment of PI in AS decreases mortality and improves rehabilitation prognosis.

Relationship between ACR and other determinants of microalbuminuria in T2DM patients

Introduction: The occurrence of microalbuminuria in type 2 diabetes mellitus (T2DM) patients is regarded as an early clinical sign of incipient kidney damage. Microalbuminuria is often evaluated as urinary albumin to urinary creatinine ratio (ACR). Aim: To assess determinants of microalbuminuria in T2DM patients without prior diagnosis of nephropathy using ACR cut-off values. Materials and Methods: ACR was measured in a total of 90 T2DM patients, during two months in three non-consecutive days, and routine biochemical analyses were performed, including glycated hemoglobin (HbA1c), serum uric acid (SUA), and atherogenic index of plasma (AIP). The cut-off values of ACR were ≤ 2.5 mg/mmol in males, and ≤ 3.5 mg/mmol in females. Duration of T2DM, history of hypertension, HbA1c, estimated glomerular filtration rate (eGFR), AIP, and SUA were investigated for association with microalbuminuria. Results: According to ACR patients were considered as non-albuminuric (n= 57) and microalbuminuric (n = 33). Compared to non-albuminuric group, microalbuminuric group had increased urinary creatinine, urinary albumin, HbA1c, triglycerides and SUA, whilst decreased HDL-cholesterol levels. Although eGFR was generally reduced, the correlation between LogACR and eGFR was not significant (p &gt; 0.05). However, the correlation between LogACR and LogHbA1c was significant. The multiple logistic regression analysis revealed HbA1c (t = 3.42; p = 0.012) and SUA (t = 2.44; p = 0.040) as independent predictors of microalbuminuria in T2DM patients. Conclusion: At ACR cut-off values, concentrations of HbA1c and SUA were independent predictors of microalbuminuria in T2DM patients not yet diagnosed with nephropathy.

Neonatal bacterial colonization of the intestine—Implications for the practitioner

Background: Neonatal intestinal bacterial colony balance has correlations with positive and negative health situations. The understanding of how neonate colonization occurs is therefore extremely important in providing life-extending and holistic care for infants. Certain medical interventions can impede optimal intestinal colonization. However, with proper screening and identification, side effects can be limited and compensated for, and complications can be minimized in an already compromised population. This study aims to identify influences on neonate microbiomes to create best practices for increased health outcomes. Develop mitigations for factors leading to intestinal microbiome conditions linked to negative neonate outcomes and increase opportunities for healthy colonization.&#x0D; Methods: The research team conducted a literature review via PubMed, Cumulative Index of Nursing and Allied Health Literature, and Academic Search Ultimate to collect data regarding neonatal bacterial colonization of the intestine. &#x0D; Results: Normal colonization is affected by birth age, birthing method, time spent in direct skin to skin contact with mother and feeding type. Iatrogenic influences include the use of oral and topical antibiotics, proton blockers, and practices that limit direct contact.&#x0D; Conclusion: The nursing process and policy adaptations can have a positive effect on developing a protective neonate intestinal microbiome. Awareness of risks and early clinical signs can improve positive interventions that may prevent life-threatening complications in susceptible neonates.&#x0D;

Evaluating the Use of a Modified Early Warning Score in Predicting Serious Adverse Events in Iranian Hospitalized Patients: A Prognostic Study

IntroductionAssessment of early clinical warning signs and appropriate response can prevent serious adverse events in hospitalized patients. The Modified Early Warning Score (MEWS) is an applicable early warning sign system that can be used to predict serious adverse events. This study aimed to evaluate the predictive capacity of the MEWS to identify patients in an Iranian hospital who are at risk of developing serious adverse events. MethodsIn this prognostic study, 381 adult patients from the emergency department who were admitted to an inpatient hospital unit of an Iranian hospital from May 2018 to October 2018 were included. The MEWS tool was completed for each patient at the time of admission and then daily for a period of up to 30 continuous days after admission or until the development of a serious adverse event. Receiver operating characteristic, specificity, sensitivity, positive predictive values, and negative predictive values were calculated. ResultsIn this study, a MEWS of ≥3 on admission was associated with an increased likelihood of developing serious adverse events within 30 days of admission with the area under the curve of 0.82 (95% confidence interval [CI]: 0.77–0.85), sensitivity of 82.81% (95% CI: 71.3–91.1), specificity of 75.39% (95% CI: 70.3–80), positive predictive value of 40.5% (95% CI: 35.2–45.9), and negative predictive value of 95.6% (95% CI: 92.7–97.4). DiscussionA MEWS ≥3 on admission can predict the occurrence of serious averse events in patients admitted to an Iranian hospital for 30 continuous days.

Genotype‐phenotype correlation in a French cohort of aniridia

AbstractCongenital aniridia consists in a complex malformation of the eye with congenital absence of iris. Aniridia is a rare panocular disorder affecting, beyond iris, cornea, angle structures, lens and fovea, and possibly associated with other anomalies.This genetic rare disease can cause severe visual impairment occurring from various mechanisms as glaucoma, limbal insufficiency and foveal hypoplasia. PAX6 gene is mainly involved in the disease. We aim to understand the features of patients with congenital aniridia, identifying the characteristics phenotypes of the disease and its associated anomalies. We analyse our patient cohort who underwent a complete ocular examination with ophthalmic exploration and who had genetic molecular analysis. Specific analysis of each ocular feature (as aniridia‐related keratopathy, glaucoma, cataract, foveal hypoplasia, optic nerve hypoplasia and other features) is detailed with early clinical signs that can be observed. An evaluation of risk factors is required for the follow‐up of aniridia patients in order to get a better therapeutic orientation.

Pulsatile arterial blood pressure mimicking aortic valve opening during continuous-flow LVAD support: a case report

BackgroundLeft ventricular assist devices (LVAD) have become a common treatment option in advanced heart failure. Lack of aortic valve opening during left ventricular unloading is a common complication and associated with a worse outcome. Maintaining a minimum pulse pressure is an important goal during the early postoperative period after LVAD implantation since it is commonly seen as secure sign of aortic valve opening.Aims/objectiveWe report a case of an LVAD-supported patient with early permanent closure of the aortic valve despite a pulse pressure > 15 mmHg at all times following LVAD implantation. We demonstrate how careful assessment of the invasive arterial blood pressure curve can indicate aortic valve closure irrespective of pulsatile blood flow.MethodA 69-year old male patient with terminal ischemic cardiomyopathy was referred for long-term mechanical circulatory support. Due to mild aortic regurgitation both an aortic bioprosthesis and a continuous-flow left ventricular assist device were implanted. Postoperative echocardiography documented a patent aortic bioprosthesis and an acceptable residual systolic left ventricular contractility. During invasive arterial blood pressure monitoring repetitive transient slight blood pressure decreases followed by slight blood pressure increases coincided with programmed LVAD flushing cycles. Permanent pulsatile flow with a pulse pressure of ≥15 mmHg conveyed systolic opening of the aortic valve. Echocardiography, however, proved early permanent aortic valve closure. In retrospect, transformation of the automated LVAD flushing cycles into visible changes of the arterial blood pressure curve during invasive blood pressure monitoring is indicative of ejection of the complete cardiac output through LVAD itself, and therefore an early clinical sign of aortic valve closure.Discussion/conclusionWe present this interesting didactic case to highlight caveats during the early postoperative period after LVAD implantation. Moreover, this case demonstrates that careful and differentiated observation of the arterial blood pressure waveform provides crucial information in this unique and growing patient population of continuous-flow LVAD support.

Early stages of Parkinson’s disease: aspects of the diagnosis and therapy

Parkinson’s disease (PD) is the second most common neurodegenerative disease that is characterized by steady progression and results into persistent disability. It has been known that more than 10 years may elapse between the onset of cell death in certain structures of the nervous system and the onset of clinical symptoms of the disease, and most of the dopaminergic neurons are lost during this period. The identification of patients in the period between the expected onset of dopaminergic cell loss and the onset of clinical parkinsonism may be crucial for the development of effective neuroprotective treatment strategies. The scientists around the world are currently paying special attention to the search for reliable clinical, neuroimaging and molecular markers that could help diagnose PD in the early stages, distinguish it from other pathological conditions, track progression, and detect a positive response to therapy. The article provides an overview of the status update on the problem of early diagnosis and search for early clinical signs, preclinical biochemical, genetic and neuroimaging markers of PD, the main modern directions of PD therapy. Symptomatic pharmacotherapy, which compensates for dopaminergic deficiency and is able to alleviate motor and some nonmotor symptoms of parkinsonism, as well as some neuroprotective treatment options, have been analysed. Among other factors, the role of amantidines is described in detail. The foreign and domestic experience of their use as monotherapy and complex treatment of PD is presented. The author provides an analysis of the clinical case of PK-Merz therapy of the initial stage of PD.