Decision-making and duration to accept device-aided therapy in advanced Parkinson's disease / Döntési szempontok és az eszközös terápia elfogadásához szükséges ido elorehaladott Parkinson-kórban.

Összefoglaló. Bevezetés: Az elorehaladott Parkinson-kór bizonyos fázisában a motoros komplikációk már nem befolyásolhatók hatékonyan a hagyományos orális, illetve transdermalis gyógyszerekkel. Ilyenkor meg kell fontolni, komplex felmérési és döntési folyamatot követoen, az invazív eszközös terápiák bevezetését. Célkituzés: A döntéshozatal és a fontosabb klinikai paraméterek elemzése levodopa-karbidopa intestinalis géllel kezelt betegeinknél az elfogadás idotartamának függvényében. Módszer: Retrospektíven vizsgáltuk azon betegeink adatait, akiknél a marosvásárhelyi 2. Sz. Ideggyógyászati Klinikán 2011. június 1. és 2019. december 31. között vezettük be a levodopa-karbidopa intestinalis géllel történo terápiát. A kezelés elfogadásához szükséges idointervallum szerint két csoportot alkottunk: egy hónap vagy annál rövidebb, illetve egy hónapnál több ido az elso, célzott kivizsgálás és a tesztelés megkezdése között. Eredmények: A vizsgált idoszakban 163 betegnél teszteltük orrszondán a kezelés hatékonyságát, közülük 127 esetben történt meg a terápia véglegesítése. A döntéshozatal 56 betegnél egy hónap vagy annál rövidebb idot, míg 71 betegnél egy hónapnál több idot igényelt. A dyskinesisek átlagos idotartamának szempontjából szignifikáns különbséget találtunk a két csoport között (3,1 ± 0,7 vs. 2,8 ± 0,8 óra, p = 0,02). Az eszközös terápia bevezetése elotti levodopa-átlagadag 821,5 ± 246,6 mg volt, naponta átlagosan 5-ször adagolva. A kiegészíto terápiák alkalmazási arányai: a dopaminagonisták 80,3%-ban, a katechol-O-metiltranszferáz-gátlók 62,2%-ban, illetve a monoaminoxidáz-B-gátlók 68,5%-ban. Az átlagos off idotartam 4,7 ± 1,1 óra volt, és 85 betegünknél tapasztaltunk 2,9 ± 0,8 óra átlag-idotartamú dyskinesist. Következtetés: Hamarabb fogadják el az eszközös terápiát azok az elorehaladott Parkinson-kóros betegek, akiknek hosszabb idotartamú a napi dyskinesisük, illetve régebbi a betegségük. A terápiás irányelvek gyakorlatba ültetésekor figyelembe kell venni a helyi sajátosságokat: a kiegészíto gyógyszerekhez, illetve az eszközös terápiákhoz való hozzáférést. Orv Hetil. 2021; 162(21): 839-847. INTRODUCTION: In advanced stages of Parkinson's disease, motor complications cannot be effectively controlled with conventional therapies. In such cases, the complex assessment and decision-making process that leads to device-aided therapies should be considered. OBJECTIVE: To analyze the decision-making and key clinical parameters, as a function of duration of acceptance, patients treated with levodopa-carbidopa intestinal gel. METHOD: We retrospectively examined the data of patients who started levodopa-carbidopa intestinal gel therapy at the 2nd Department of Neurology Târgu Mures, between 1 June 2011 and 31 December 2019. Two groups were formed: less than one month and more than one month between the first targeted examination and the start of testing. RESULTS: Therapeutic efficiency was tested with nasal tube on 163 patients, out of whom 127 patients remained on treatment. Decision-making took one month or less for 56 patients and more than a month for 71 patients. Duration of dyskinesias was significantly different between the two groups (3.1 ± 0.7 vs 2.8 ± 0.8 hours, p = 0.02). Mean dose of levodopa prior to the introduction of device-aided therapy was 821.5 ± 246.6 mg, administered 5 times daily. Dopamine agonists were used in 80.3%, catechol-O-methyltransferase inhibitors in 62.2%, and monoamine oxidase-B inhibitors in 68.5% of cases. The mean off-time was 4.7±1.1 hours and data from 85 patients showed 2.9 ± 0.8 hours of dyskinesia. CONCLUSION: Device-aided therapy is adopted sooner by patients with advanced Parkinson's disease with longer disease duration and more dyskinesias. Local specificities, such as access to add-on medication and device-aided therapies, must be taken into account when implementing therapeutic guidelines. Orv Hetil. 2021; 162(21): 839-847.

The Diagnostic and Prognostic Role of Vascular Endothelial Growth Factor C in Sepsis and Septic Shock.

INTRODUCTION: Variations in the expression of vascular endothelial growth factor (VEGF) could be used as a biomarker in critically ill patients with sepsis and septic shock. Inflammation potently upregulates VEGF-C expression via macrophages with an unpredictable response. This study aimed to assess one of the newer biomarkers (VEGF-C) in patients with sepsis or septic shock and its clinical value as a diagnostic and prognostic tool. MATERIAL AND METHODS: The study involved 142 persons divided into three groups. Group A consisted of fifty-eight patients with sepsis; Group B consisted of forty-nine patients diagnosed as having septic shock according to the Sepsis -3 criteria. A control group of thirty-five healthy volunteers comprised Group C. Severity scores, prognostic score and organ dysfunction score, were recorded at the time of enrolment in the study. The analysis included specificity and sensitivity of plasma VEGF-C for diagnosis of septic shock. Circulating plasma VEGF-C levels were correlated with the APACHE II, MODS and severity scores and mortality. RESULTS: The mean (SD) plasma VEGF-C levels in septic shock patients (1374(789) pg./m), on vasopressors at the time of admission to the ICU, were significantly higher 1374(789)pg./mL, compared the mean (SD) plasma VEGF-C levels in sepsis patients (934(468) pg./mL); (p = 0.0005, Student's t-test.) Plasma VEGF-C levels in groups A and B were shown to be significantly correlated with the APACHE II (r = 0.21, p = 0.02; r = 0.45, p = 0.0009) and MODS score (r = 0.29, p = 0.03; r = 0.4, p = 0.003). There was no association between plasma VEGF-C levels and mortality [p = 0.1]. The cut-off value for septic shock was 1010 pg./ml. CONCLUSIONS: VEGF-C may be used as a prognostic marker in sepsis and septic shock due to its correlation with APACHE II values and as an early marker to determine the likelihood of developing MODS. It could be used as an early biomarker for diagnosing patients with septic shock.

The role of interleukin-6 as an early predictor of sepsis in a murine sepsis model.

AIM: Evaluating the role of interleukin-6 (IL-6) as an early predictor of sepsis in a murine model. MATERIALS AND METHODS: The study divided 26 Wistar rats into two experimental groups in which sepsis was induced through the intraperitoneal injection of different Escherichia coli cultures [Group 1: Extended-spectrum beta-lactamase (ESBL)-producing culture and Group 2: Standardized ATCC35218 culture] and a control group. IL-6 levels were determined at 5 and 24 hours post-inoculation and immunohistochemistry (IHC) was performed on tissue samples from the sacrificed animals. RESULTS: Mean plasma IL-6 levels in Group 1 peaked at 5 hours [37.4 pg∕mL; standard deviation (SD) = 2.4 pg∕mL] and decreased at 24 hours (34 pg∕mL; SD=3.2 pg∕mL) after inoculation. IL-6 levels in Group 1 were elevated compared to Group 2, at 5 hours (33.7 pg∕mL; SD=3.3 pg∕mL; p=0.019) and non-significantly so at 24 hours (32.5 pg∕mL; SD=2.4 pg∕mL; p=0.233). The results did not show an increase over control levels at either 5 hours (37.6 pg∕mL; SD=3.4 pg∕mL) or 24 hours (40.8 pg∕mL; SD=2.9 pg∕mL) after inoculation. The IHC shows a varying degree of IL-6 expression across all organ types studied. No statistically significant correlations were found between the tissue level quantification of IL-6 and serum values at 24 hours in either group. CONCLUSIONS: For an early stage of infection/inflammation, serum levels of IL-6 are not correlated with tissue-level inflammation disproving a potential role of IL-6 as a very precocious diagnostic and predictor test. Accumulation of IL-6 in lung, kidney and spleen tissue can be observed from the beginning of inflammation.

Factors Favouring the Development of Clostridium Difficile Infection in Critically Ill Patients.

Clostridium difficile, an anaerobic, spore-forming, toxin-forming, gram-positive bacillus present in the bacterial flora of the colon is the principal cause of nosocomial diarrhoea in adults. AIM: Assessment of favouring factors of Clostridium difficile infections as well as the interactions between them, in critically ill hospitalized patients undergoing complex medical and surgical treatments. MATERIAL AND METHODS: A retrospective case-control study involving eighty patients admitted in the Intensive Care Unit (ICU) of the County Clinical Emergency Hospital Tîrgu-Mures was conducted between January and October 2014. Patients aged eighteen years and over, who had undergone complex medical and surgical treatment, were divided into two subgroups. Group 1 included patients who developed diarrhoea but were not diagnosed as having a Clostridium difficile infection (CDI). Group 2 included patients who developed diarrhoea due to CDI as indicated by a positive culture and the expression of exotoxin. The assessed parameters were age, length of stay (LOS), antibiotic spectrum, association with proton pump inhibitors (PPI) or H2-receptor antagonists, immunological status, the presence or lack of gastrointestinal tract surgery. RESULTS: The mean age was 64.6 years with an average LOS of 10 days. Fifty-six percent of patients came to the ICU from internal medicine wards and forty-three percent from surgical wards. 20.5% of them were immunosuppressed. Co-association of ceftriaxone and pantoprazole significantly increased the risk of CDI compared to co-administration of any other antibiotic or pantoprazole (p=0.01). The odds ratio for Pantoprazole together with any antibiotic versus antibiotic therapy alone was significantly higher (p=0.018) with a sevenfold increase in the risk of positive exotoxin increase. CONCLUSIONS: Antibiotic use is associated with "no risk to develop CDI" in the first five days of administration. PPIs associated therapy increased the risk of CDI in first seventy-two hours regardless of the antibiotic type, and contributes to an active expression of CD exotoxin.

Influence of Ventilation Parameters on Intraabdominal Pressure.

INTRODUCTION: Intraabdominal pressure monitoring is not routinely performed because the procedure assumes some invasiveness and, like other invasive procedures, it needs to have a clear indication to be performed. The causes of IAH are various. Mechanically ventilated patients have numerous parameters set in order to be optimally ventilated and it is important to identify the ones with the biggest interference in abdominal pressure. Although it was stated that mechanical ventilation is a potential factor of high intraabdominal pressure the set parameters which may lead to this diagnostic are not clearly named. OBJECTIVES: To evaluate the relation between intraabdominal pressure and ventilator parameters in patients with mechanical ventilation and to determine the correlation between intraabdominal pressure and body mass index. MATERIAL AND METHOD: This is an observational study which enrolled 16 invasive ventilated patients from which we obtained 61 record sheets. The following parameters were recorded twice daily: ventilator parameters, intraabdominal pressure, SpO2, Partial Oxygen pressure of arterial blood. We calculated the Body Mass Index (BMI) for each patient and the volume tidal/body weight ratio for every recorded data point. RESULTS: We observed a significant correlation between intraabdominal pressure (IAP) and the value of PEEP (p=0.0006). A significant statistical correlation was noted regarding the tidal volumes used for patient ventilation. The mean tidal volume was 5.18 ml/kg. Another significant correlation was noted between IAP and tidal volume per kilogram (p=0.0022). A positive correlation was found between BMI and IAP (p=0.0049), and another one related to the age of the enrolled patients. (p=0.0045). CONCLUSIONS: The use of positive end-expiratory pressures and high tidal volumes during mechanical ventilation may lead to the elevation of intraabdominal pressure, a possible way of reducing this risk would be using low values of PEEP and also low volumes for the setting of ventilation parameters. There is a close positive correlation between the intraabdominal pressure levels and body mass index.

A Fatal Case of Community Acquired Cupriavidus Pauculus Pneumonia.

INTRODUCTION: Cupriavidus pauculus is a rarely isolated non-fermentative, aerobic bacillus, which occasionally causes severe human infections, especially in immunocompromised patients. Strains have been isolated from various clinical and environmental sources. CASE PRESENTATION: A 67-year-old man was admitted to the Intensive Care Unit with acute respiratory failure. The patient was diagnosed with bilateral pneumonia, pulmonary sepsis and underwent invasive mechanical ventilation. Examination revealed diminished bilateral vesicular breath sounds, fever, intense yellow tracheal secretions, a respiratory rate of 24/minute, a heart rate of 123/minute, and blood pressure of 75/55 mmHg. Vasoactive treatment was initiated. Investigations revealed elevated lactate and C-reactive protein levels. A chest X-ray showed bilateral infiltration. Parenteral ciprofloxacin and ceftriaxone were administered. Tracheal aspirate culture and blood culture showed bacterial growth of Cupriavidus pauculus. Colistin was added to the treatment. There was a poor clinical response despite repeated blood culture showing negative results. The diagnosis of multiple organ dysfunction syndrome (MODS) caused by C. pauculus was made. The patient died eleven days after admission. CONCLUSIONS: Clinical improvement cannot always be expected in spite of targeted antibiotic therapy. This pathogen should be considered responsible for infections that usually develop in immunocompromised patients.

The Role of Angiopoietine-2 in the Diagnosis and Prognosis of Sepsis.

INTRODUCTION: Angiopoietin-2 (ANG-2) is a new biomarker whose blood-serum values increase in sepsis and its expression is elevated in line with the severity of the degree of inflammation. The aim of this study was to identify the diagnostic role of ANG-2 in patients with non-surgical sepsis addmitted to an intensive care unit. MATERIAL AND METHODS: This was a prospective randomized study including 74 patients admitted in the Clinic of Intensive Care of the County Clinical Emergency Hospital Tirgu Mureș, divided into two groups: Group S: patients with sepsis (n=40, 54%) and Group C:control, without sepsis (n=34, 46%). ANG-2 levels were determined in both groups. RESULTS: From the Group S, 14 patients (35%) had positive haemocultures. ANG-2 values varied between 1 and 43 ng/mL, with an average of 6.0 ng/mL in patients without sepsis and 10.38 ng/mL in patients with sepsis (p=0.021). A positive correlation between ANG-2 and SAPS II, SOFA and APACHE II severity scores was demonstrated, as was a positive correlation between serum levels of ANG-2 and procalcitonine. ANG-2 had a 5.71% specificity and 74.36% sensitivity for diagnosis of sepsis. CONCLUSIONS: ANG-2 serum levels were elevated in sepsis, being well correlated with PCT values and prognostic scores. ANG-2 should be considered as a useful biomarker for the diagnosis and the prognosis of this pathology.

An Evaluation of Serum Procalcitonin and C-Reactive Protein Levels as Diagnostic and Prognostic Biomarkers of Severe Sepsis.

BACKGROUND: Recommendations have been made, following the multicenter Surviving Sepsis Campaign study, to standardize the definition of severe sepsis with reference to several parameters such as haemodynamic stability, acid-base balance, bilirubin, creatinine, International Normalized Ratio (INR), urine output and pulmonary functional value of the ratio between arterial oxigen partial pressure and inspiratory oxigen concentration. Procalcitonin (PCT) is considered to be a gold standard biomarker for the inflammatory response, and recent studies have shown that it may help to discover whether a seriously ill person is developing sepsis. C-reactive protein (CRP) is also used as a marker of inflammation in the body, as its blood levels increase if there is any inflammation in the body. The aim of this study was to evaluate serum procalcitonin and C-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis. MATERIAL AND METHOD: Sixty patients, diagnosed as being "septic", were admitted to the intensive care unit (ICU). Based on laboratory results and clinical findings a diagnosis of "severe sepsis" was made, and correlated with PCT and CRP values. The APACHE II, SAPS II and SOFA severity scores were calculated, analyzed and correlated with PCT and CRP. RESULTS: Fifty two patients (86.67%) presented with criteria for severe sepsis. Multivariate correlation analysis indicated a significant positive association between procalcitonin and all severity scores (APACHEII p<0.0001, SOFA p<0.0001, SAPS II p<0.0001). CRP proved to be significantly correlated only with the SAPS II score (p=0.0145). Mortality rate was high, with 48 patients (80%) dying. There was no significant correlation between the levels of the PCT and CRP biomarkers and severe sepsis (p=0.2059 for PCT, p=0.6059 for CRP). CONCLUSIONS: The procalcitonin levels are highly correlated with the severity scores (APACHE II, SAPS II, SOFA) regularly used in ICUs and therefore can be used for determining the severity of the septic process. Quantitive procalcitonin and C-reactive protein analysis was not shown to be useful in diagnosing severe sepsis. However, PCT and CRP can be used to predict the fatal progression of the septic patient.