The role of pancreatic stone protein as a prognostic factor for COVID-19 patients.

OBJECTIVE: The outbreak of Severe Acute Respiratory Syndrome-CoronaVirus 2 (SARS-CoV-2) has rapidly spread throughout the world straining health care systems. Several biomarkers indicate the presence of hyper-inflammation and evaluate the severity of the disease. Our aim was to investigate the prognostic value of pancreatic stone protein plasma concentration in patients with SARS-CoV-2 pneumonia. PATIENTS AND METHODS: We prospectively studied 55 patients with acute SARS-CoV-2 pneumonia admitted to our tertiary hospital. Sepsis biomarkers, including pancreatic stone protein (PSP), were measured on admission. The role of these biomarkers in the prediction of in-hospital mortality (28 day) and length of hospital stay was investigated. RESULTS: Although Pancreatic stone protein did not have significant prognostic value for in-hospital mortality, there was a moderate accuracy for prolonged length of stay. The optimal cut-off value for prolonged hospital stay was 51 ng/dL (Sensitivity: 0.65, Specificity: 0.913). CONCLUSIONS: Pancreatic Stone Protein on admission could accurately identify patients requiring prolonged hospitalization. The results of this study can serve as a strong early basis for future validation studies of such an innovative approach.

CTPA imaging findings, beyond pulmonary embolism, in patients with Severe Acute Respiratory Syndrome Corona Virus-2 infection and their relation to clinical outcome - a single center experience.

OBJECTIVE: The aim of our study was to investigate a potential association between the severity of COVID-19 disease and related 28-day mortality, with the presence of mediastinal lymphadenopathy, the extension of lung parenchymal infiltrates, the presence of pulmonary embolism, the density and distribution of mediastinal and subcutaneous fat, the inflammatory markers and the direct and indirect radiological signs of right heart overload and strain. PATIENTS AND METHODS: We retrospectively included patients diagnosed with SARS-CoV-2 infection, who were admitted to the Departments of Internal and Respiratory Medicine of Patras University Hospital during the second pandemic wave (February 2021 up to July 2021) and underwent CTPA for routine diagnostic workup. Demographic characteristics, routine laboratory, radiological parameters and 28-day mortality were also recorded. RESULTS: Fifty-three consecutive patients were included. The mean age was 64.47±17.1 years and 64,1% (n=34) were males. Pulmonary embolism (PE) (p=0.019), Right Ventricle-to-Left Ventricle Diameter (RV/LV)  Ratio>1 (p<0.01), Reverse Flow in Hepatic Veins (RFHV) (p=0.019), higher density in subcutaneous fat (-99 HU vs. -104HU, p=0.016), increased Lactic Dehydrogenase (LDH), Polymorphonuclear cells (PMN), ferritin, and d-dimer levels (534 vs. 367 U/L, p=0.001, 9220 vs. 5660 Κ/µL, p=001, 956 vs. 360 ng/ml, p=0.005 and 2300 vs. 1040 µg/ml, p=0.003, respectively) were statistically significant related with worse 28-day mortality. Binomial multivariate regression analysis revealed that only RV/LV diameter>1, higher subcutaneous fat density and higher LDH values were independently associated with increased 28-day mortality (OR: 82.9, 95%CI: 1.334-5158, p=0.036, OR: 1.2, 95%CI: 1.016-1.426, p=0.032 and OR:1.016, 95% CI:1.004-1.029, p=0.011, respectively). Subgroup analysis revealed that mediastinal lymph node enlargement (EML) and PE were associated to increased Pulmonary Disease Severity Index (PDSI) score (p=0.042 and p=0.007, respectively), but not to mortality. CONCLUSIONS: Our study showed that right heart strain as depicted by a RV/LV diameter>1, higher subcutaneous fat density and higher LDH values are independently associated with an increased 28-day mortality in our SARS-COV2 patient group.

Pathophysiology and management of Akathisia 70 years after the introduction of the chlorpromazine, the first antipsychotic.

OBJECTIVE: Akathisia is among the most troubling effects of psychiatric drugs as it is associated with significant distress on behalf of the patients, and it limits treatment adherence. Though it most commonly presents during treatment with antipsychotic drugs which block dopamine D2 receptors, Akathisia has also been reported during treatment with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), stimulants, mirtazapine, tetrabenazine and other drugs. MATERIALS AND METHODS: This article was designed as a narrative review on akathisia with a focus on its clinical presentation, pathophysiology and management. A PubMed search for akathisia was conducted which returned 8481 articles. RESULTS: Akathisia is experienced as severe restlessness commonly accompanied by dysphoria and purposeless movement which relieves subjective tension. It has been attributed to an imbalance between dopaminergic and noradrenergic neurotransmission in the basal ganglia. Acute akathisia commonly resolves upon treatment discontinuation but tardive and chronic akathisia may persist after the causative agent is withdrawn and prove resistant to pharmacological treatment. Even drugs which induce no other extrapyramidal side effects (such as clozapine, quetiapine, aripiprazole and cariprazine) may induce akathisia. A high index of suspicion should be maintained in patients with motor disabilities, drug-induced parkinsonism and those under mechanical restraint. Propranolol and low-dose mirtazapine are the most thoroughly studied pharmacological interventions for akathisia, though benzodiazepines, voltage-gated calcium channel blockers (gabapentin, pregabalin) and opioids may be effective. CONCLUSIONS: Pharmacological management may pose a challenge in chronic akathisia. Rotation between different pharmacological management strategies may be optimal in resistant cases. Discontinuation of the causative drug and use of b-blockers, mirtazapine, benzodiazepines or gabapentinoids for symptomatic relief is the basis of management.

Converging dopaminergic neurotoxicity mechanisms of antipsychotics, methamphetamine and levodopa.

OBJECTIVE: Drugs affecting dopaminergic neurotransmission may exert toxic and beneficial effects that persist after discontinuation by modulating gene expression in key brain regions. Drug addiction, cravings and the tardive symptoms associated with chronic exposure to antipsychotics are among the most common processes attributed to long-term dopaminergic neurotoxicity. The purpose of this review was to investigate the mechanisms of dopaminergic neurotoxicity induced by neuroleptic drugs, dopamine agonists, levodopa, stimulants and known dopaminergic neurotoxins MATERIALS AND METHODS: A PubMed search for each of the dopaminergic compounds in question was carried out. The heterogenous nature of the relevant preclinical studies precluded a systematic review, so a narrative review was carried out. RESULTS: The dopaminergic neurotoxins 6-oxidopamine and 1-methyl-4-phenyl-tetrahydropyridine (MPTP) promote oxidative stress and inhibit mitochondrial function, while their affinity for the dopamine transporter ensures they are attain toxic intracellular concentrations exclusively in dopaminergic neurons. Stimulants which inhibit the vesicular monoamine transporter such as amphetamine and its derivatives promote oxidative stress by greatly increasing intracellular dopamine concentrations and enabling dopamine autooxidation. Antipsychotics increase dopamine release and turnover by blocking autoinhibitory D2 receptors and lead to upregulation of post-synaptic D2 receptors. Dopamine agonists may slow the progression of Parkinson's disease by reducing dopamine turnover, but downregulation of D2 receptors may underlie their behavioural toxicity. CONCLUSIONS: Though the mechanisms have not been completely elucidated yet, it seems drugs which affect dopaminergic neurotransmission may exert long-term effects which reverse slowly upon discontinuation, if at all. Until the nature of these changes is clear it would be best to utilize drugs which affect dopaminergic neurotransmission cautiously especially if prolonged treatment is required.

Procalcitonin and sepsis in the Emergency Department: an update.

OBJECTIVE: Due to significant mortality and morbidity which may be reduced by prompts treatment, there is great interest in determining an ideal biomarker for the diagnosis of sepsis upon presentation to the Emergency Department. The most specific test is a positive blood culture, but its sensitivity is very low, and the results are usually available 2 days after sampling. For this reason, research is conducted into serum biomarkers with greater sensitivity for which results can be available within hours of presentation. High initial procalcitonin levels are a sensitive marker of bacterial infection, and the degree of procalcitonin elevation may determine which patients are at greater risk for adverse outcomes (mortality or ICU admission). The purpose of this narrative review is to evaluate the utility of procalcitonin as a diagnostic marker of sepsis in the emergency department and the use of procalcitonin-guided management algorithms. MATERIALS AND METHODS: A PubMed search was conducted in June 2020 for procalcitonin, resulting in the retrieval of 371 articles which were screened for relevance. 48 articles were included in the review. CONCLUSIONS: Procalcitonin elevation may be used as an indication for initiation of antibiotic treatment, and antibiotics may be discontinued once procalcitonin normalizes. This approach leads to reduced antibiotic consumption, but it is not yet clear whether it ensures better outcomes for patients. Procalcitonin in centers where it is available could be a useful diagnostic and prognostic biomarker for patients presenting to the Emergency Department with symptoms suggestive of sepsis. Further research is however required to determine whether the use of procalcitonin measurements in management algorithms leads to improved patient outcomes.

Efavirenz as a psychotropic drug.

OBJECTIVE: Antiretroviral drugs are the mainstay of treatment for human immunodeficiency virus (HIV) infection. Lifelong highly active antiretroviral therapy (HAART) is indicated to prevent disease progression to acquired immunodeficiency syndrome (AIDS). Efavirenz was a first-line component of HAART across the world for many years. The purpose of this article is to review the psychotropic properties of efavirenz, which are the most important adverse events associated with the drug and commonly result in treatment discontinuation. MATERIALS AND METHODS: A PubMed search was conducted using efavirenz as a search term, which returned 4655 results. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included in the narrative review. RESULTS: Acute exposure to efavirenz may cause profound perceptual disturbances (delusions and hallucinations) whereas chronic exposure may be associated with abnormal dreams and other sleep disturbances, anxiety, depressed mood and suicidality. It may also be abused as a hallucinogen, especially in individuals with a history of poly-substance abuse. Recent research indicates that efavirenz directly affects monoaminergic neurotransmission and may partially substitute for psychedelic drugs, such as lysergic acid diethylamide (LSD). Efavirenz acts as a serotonin 5-HT2A receptor antagonist, a serotonin-dopamine reuptake inhibitor, an inhibitor of monoamine oxidase (MAO) and a vesicular monoamine transporter 2 (VMAT2) inhibitor, which are mechanisms common with many psychotropic drugs. Efavirenz interacts with many of the same molecular targets as the empathogen methylendioxymethamphetamine (MDMA), but the effects of the 2 drugs may differ. CONCLUSIONS: The exact mechanism of action of efavirenz as a psychotropic drug remains unclear and future studies should focus on evaluating whether prolonged exposure could lead to irreversible side effects.

Demographic and clinical features of critically ill patients with COVID-19 in Greece: The burden of diabetes and obesity.

AIMS: The aim of the study was to investigate the association between type-2 diabetes mellitus, other underlying diseases and obesity with the outcomes of critically ill Covid-19 patients in Greece. METHODS: In this retrospective observational multi-centre study, data and outcomes of 90 RNA 2109-nCoV confirmed critically ill patients from 8 hospitals throughout Greece, were analysed. All reported information stand through April 13th 2020. RESULTS: The median age of the patients was 65.5 (IQR 56-73), majority were male (80%) and obesity was present in 34.4% of patients most prevalent to younger than 55 years. Hypertension was the prevailing comorbidity (50%), followed by cardiovascular diseases (21.1%) and type-2 diabetes (18.9%). At admission, common symptoms duration had a median of 8 (IQR 5-11) days. A 13.3% of the patients were discharged, 53.4% were still in the ICUs and 28.9% deceased who were hospitalised for fewer days than the survivors [6 (IQR 3-9) vs. 9 (IQR 7-14.5) respectively]. Aging was not a risk factor but diabetes deteriorates the outcomes. Obesity poses a suggestive burden as it was more notable in deceased versus survivors. CONCLUSIONS: Type 2 diabetes and obesity may have contributed to disease severity and mortality in COVID-19 critically ill patients in Greece.

"Too many cooks spoil the broth": the more antigens present, the easier, the quicker, and the more severe the anaphylaxis

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Individualized significance of the -251 A/T single nucleotide polymorphism of interleukin-8 in severe infections.

Based on the concept of the individualized nature of sepsis, we investigated the significance of the -251 A/T (rs4073) single nucleotide polymorphism (SNP) of interleukin (IL)-8 in relation to the underlying infection. Genotyping was performed in 479 patients with severe acute pyelonephritis (UTI, n = 146), community-acquired pneumonia (CAP, n = 109), intra-abdominal infections (IAI, n = 119), and primary bacteremia (BSI, n = 105) by restriction fragment length polymorphism of the polymerase chain reaction (PCR) product and compared with 104 healthy volunteers. Circulating IL-8 was measured within the first 24 h of diagnosis by an immunosorbent assay. Carriage of the AA genotype was protective from the development of UTI (odds ratio 0.38, p: 0.007) and CAP (odds ratio 0.30, p: 0.004), but not from IAI and BSI. Protection from the development of severe sepsis/septic shock was provided for carriers of the AA genotype among patients with UTI (odds ratio 0.15, p: 0.015). This was accompanied by greater concentrations of circulating IL-8 among patients with the AA genotype. It is concluded that carriage of rs4073 modifies susceptibility for severe infection in an individualized way. This is associated with a modulation of circulating IL-8.

Surgical or interventional revascularization in diabetic patients with coronary artery disease?

The combination of diabetes mellitus and coronary artery disease (CAD) constitutes an aggressive disease characterized biologically by chronic inflammatory, proliferative and pro-thrombotic situation. In the "diabetic patient" the increased frequency and gravity of simultaneous myocardial infarction and the deterioration of congestive heart failure contribute to the inevitable unfavourable final result. Diabetes accelerates the natural course of atherosclerosis and involves a great number of coronary vessels with more diffuse atherosclerotic lesions. Moreover, the risks of plaque ulceration and thrombosis have been shown to be considerably higher in diabetic patients. The treatment should be also aggressive and be based on the combined treatment of CAD and the effective regulation of glucose levels. The decision of revascularization in the diabetic patient should be posed relatively earlier. The surgical choice of revascularization seems to be advantageous over the interventional, with better early and late results.

Fever with multiple organ failure: not always sepsis.

We present the case of a 52-year-old female admitted with fever and multiple organ failure, initially treated for presumed sepsis. However the combination of multiple organ failure, hyperthermia and vascular instability raised the suspicion of a phaeochromocytoma multisystem crisis. An emergency abdominal ultrasound in the intensive care unit disclosed a large tumour of the right adrenal. Despite specific medical treatment for the presumed adrenal emergency and multiple organ failure, the patient succumbed. Postmortem examination verified the diagnosis of phaeochromocytoma.

Thyroid storm presenting as intra-abdominal sepsis with multi-organ failure requiring intensive care.

Thyroid storm is a rare but life-threatening condition manifesting with several clinical presentations. Atypical thyroid storm should be part of the differential diagnosis in patients with multiple organ dysfunction of unknown aetiology. In this case report, delayed recognition of thyroid storm in a young female who presented with acute abdomen increased the risk of poor outcome. Prompt initiation of anti-thyroid therapy once the diagnosis of thyroid storm was established, combined with adequate vital organ support using a goal-directed therapy protocol in the intensive care unit resulted in a good outcome.

SAPHO Syndrome Diagnosis and Treatment: Report of Five Cases and Review of the Literature.

BACKGROUND: The term "SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) syndrome" includes a variety of musculoskeletal disorders associated with skin conditions; Osteitis is the most prominent skeletal lesion, whereas palmoplantar pustulosis and acne are the main skin lesions. Diagnosing SAPHO syndrome is difficult, because this syndrome is often confused with suppurative osteomyelitis, which has similar clinical and pathologic findings. SAPHO diagnosis is even more difficult when atypical sites are involved and there are no skin lesions. PATIENTS AND METHODS: This case series presents five patients (3 women, 2 men), ages 27 to 44 years, who came to the Orthopaedic Department outpatient clinic for evaluation of pain in the humerus, clavicle, sacroiliac joints, and/or distal radius, and were diagnosed with SAPHO syndrome. Clinical and radiologic findings, treatment and outcome data, with up to 4 years of follow-up are presented. An extensive discussion of the clinical presentation, published literature, treatment options and outcome of SAPHO syndrome is also included. RESULTS: Once the diagnosis of SAPHO syndrome was established, treatment with antibiotics (clindamycin) and non steroid anti-inflammatory drugs (lornoxicam) was remarkably effective. All patients did well and remained symptom free for up to four years, after a 3-8 month course of treatment. INTERPRETATION: SAPHO syndrome should be included in the differential diagnosis when evaluating patients with lytic, sclerotic, or hyperostotic bone lesions and pain. Prompt SAPHO syndrome recognition, followed by appropriate therapy with antibiotics and NSAIDs can produce rapid symptom resolution, while avoiding unnecessary procedures and longterm antibiotic therapy.

Favourable medium term outcome following hepatic vein recanalisation and/or transjugular intrahepatic portosystemic shunt for Budd Chiari syndrome.

BACKGROUND: We report our experience with management of patients with Budd Chiari syndrome over the past two decades. In 1996 we described a novel approach involving recanalisation of hepatic veins by combined percutaneous and transvenous approaches. This was incorporated into an algorithm published in 1999 in which our preferred treatment for all cases of Budd Chiari syndrome with short segment occlusion or stenosis of the hepatic veins involves recanalisation of the hepatic veins by transvenous or combined percutaneous-transvenous approaches. In symptomatic Budd Chiari syndrome where recanalisation is not possible, we perform transjugular intrahepatic portosystemic shunts (TIPS) because TIPS decompresses the portal circulation directly in an adjustable way. In this series of patients with Budd Chiari syndrome treated with radiological interventions alone, we assess their medium term outcome using two independent objective prognostic indices. METHODS: We retrospectively studied 61 patients with non-malignant Budd Chiari syndrome treated by radiological intervention alone in our centre. RESULTS: Actuarial survival for the entire cohort at one year and five years was 94% and 87%, respectively. Survival of our patients with mild disease (according to the Murad classification) was 100% at one year and at five years, with intermediate disease severity 94% at one year and 86% at five years, and with severe disease 85% at one year and 77% at five years. CONCLUSION: Management of Budd Chiari syndrome by interventional radiology resulted in excellent medium term survival for patients in all categories of disease severity.

Brain MRI findings in cirrhotic patients: correlation with Doppler US hepatic flow parameters.

BACKGROUND/AIMS: To determine the relationship of basal ganglia alterations demonstrated on brain MRI and clinical presentation, evaluated with Child-Pugh score, using Color Doppler Ultrasonography parameters of portal hemodynamics in cirrhotic patients with signs of portal hypertension. METHODOLOGY: Twenty randomly selected cirrhotic patients (16 males and 4 females with a mean age of 63.6+/-8.9 years) classified according to Child-Pugh score (grade A=16 patients, grade B=4), were submitted to Color Doppler US evaluation of hepatic flow and brain MRI. The obtained flow parameters were: PVD, PVCSA, MPVF, MPVFV, HAD, MHAF, hepatic artery RI, CI and MHI. The basal ganglia signal intensity, on T1-weighted images on brain MRI was evaluated both qualitatively (normal, mild, moderate and severe) and quantitatively with the ROI method. RESULTS: Among Color Doppler parameters, only the CI exhibited a modest correlation with the Child's clinical score (p for linear trend by ANOVA <0.05). Subjective MRI grading demonstrated an excellent correlation with the qualitative assessment of signal density (Spearman p=0.95, p<0.01). When signal intensity on T1-weighted images was analyzed as a continuous variable with normal distribution and ultrasonographic parameters as possible determinants, the portal vein diameter (PVD) and consequently the cross-sectional area (PVCSA) emerged as the sole predictor of MR signal intensity (Pearson's r=0.58, p=0.01). CONCLUSIONS: Although this is a preliminary study and further research should be performed including a larger number of patients, it suggests that Color Doppler US might play a prognostic role in predicting hepatocellular dysfunction and hepatic encephalopathy.

Quantitative evaluation of magnetic resonance imaging (MRI) abnormalities in subclinical hepatic encephalopathy.

BACKGROUND/AIMS: Cirrhotic patients often demonstrate high signal intensity on T1-weighted magnetic resonance (MRI) images in basal ganglia with accumulation of manganese being the predominant causing factor. In these patients, electrophysiological tests and especially electroencephalogram (EEG) are considered to be the most sensitive methods in detection of subclinical hepatic encephalopathy. The aim of this study is to correlate MRI findings with biochemical parameters and EEG alterations in cirrhotic patients without clinically overt encephalopathy. METHODOLOGY: Twenty-two cirrhotic patients (16 males and 6 females, mean age of 65.2 +/- 9.5 years), classified according to Child-Pugh score, were submitted to brain MRI, neurological assessment (including psychometric tests and EEG) and complete biochemical testing. None of them had any clinical signs of brain dysfunction. MRI findings were evaluated both qualitatively (normal, mild, moderate and severe) and quantitatively with the ROI method. EEG alterations were also classified as normal, mild, moderate and severe. RESULTS: Statistical analysis revealed a significant linear association between EEG grading and MRI signal intensity (r2=0.248, p=0.035). Among clinical and biochemical parameters, overall Child-Pugh score and albumin levels were identified as significant predictors of the MRI signal intensity (p=0.006 and p=0.021 respectively). CONCLUSIONS: Although further investigation must be performed to confirm the clinical impact of brain MRI in hepatic cirrhosis, our study strongly suggests that MRI alterations are good predictors of liver and brain dysfunction in cirrhotic patients.

HCV infection in the general population of a Greek island: prevalence and risk factors.

BACKGROUND/AIMS: Although HCV seroprevalence in blood donors in Greece is low (0.2-0.4%) epidemiologic characteristics of HCV infection in the general population have not been studied enough. The objective of this study was to examine the seroprevalence of HCV infection and associated risk factors in the general population of Zakinthos, a Greek island with a well-defined mixed (urban and rural) population. METHODOLOGY: A household health survey was carried out in a randomly selected sample of 718 adults. A questionnaire was completed and a blood sample was obtained from all participants. Serum samples were tested for anti-HCV antibodies by third generation enzyme-linked immunosorbent assay and supplemental test. The influence of sociodemographic characteristics and possible associated risk factors on the HCV seroprevalence was investigated by logistic regression analysis. RESULTS: The overall anti-HCV prevalence was 1.25%. A well-defined rural area with a significant higher prevalence (6.8% vs. 0.62%; P < 0.001) was identified. There was a trend of increasing prevalence with age, with a significant difference (P < 0.027) between the age groups 15-44 (0%) and over 45 (2.15%). The logistic regression analysis confirmed a significant association between anti- HCV positivity and: increasing age (P < 0.001), history of blood transfusion (0.0001), intramuscular injections (P < 0.04). CONCLUSIONS: The results of this field-survey in a well-defined general population, indicates that HCV seroprevalence (1.25%) is much higher than that of blood donors in the same area. The increasing prevalence with age and the association with parenteral exposure indicates that HCV infection can mainly be attributed to parenteral techniques in the past. The identification of a concrete rural area with particularly high seroprevalence needs further study of the whole population of the area.