Publications by authors named "Igor Petrovic"

108 Publications

Case report: Urgent liver pathologies: All in one.

Front Surg 2022 20;9:940856. Epub 2022 Jul 20.

Department of Surgery, University Hospital Centre Zagreb, Zagreb, Croatia.

Ruptured hepatocellular carcinoma (HCC) is a well-known serious complication of this most common primary liver malignancy. However, when HCC rupture is associated with other focal liver lesions, the diagnosis and therapy may be very challenging. Correct differentiation of focal liver lesions is of paramount importance for successful treatment. The aim of this report is to present a unique case of HCC rupture complicated with liver abscess, hematoma and portal vein thrombosis. We discuss possible pathophysiological mechanisms and radiologic findings of such clinical scenarios and review literature related to the management of HCC rupture.
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http://dx.doi.org/10.3389/fsurg.2022.940856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346066PMC
July 2022

Gait alterations in Parkinson's disease at the stage of hemiparkinsonism-A longitudinal study.

PLoS One 2022 21;17(7):e0269886. Epub 2022 Jul 21.

Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Background: Progressive gait impairment in Parkinson's disease (PD) leads to significant disability. Quantitative gait parameters analysis provides valuable information about fine gait alterations.

Objectives: To analyse change of gait parameters in patients with early PD at the stage of hemiparkinsonism and after 1 year of follow up, taking into account clinical asymmetry.

Methods: Consecutive early PD outpatients with strictly unilateral motor features underwent clinical and neuropsychological assessment at the study entry and after 1 year of follow up. Gait was assessed with GAITRite walkway using dual-task methodology. Spatiotemporal gait parameters (step time and length, swing time and double support time) and their coefficients of variation (CV), gait velocity and heel-to-heel base support were evaluated.

Results: We included 42 PD patients with disease duration of 1.3 years (±1.13). Progression of motor and non-motor symptoms, without significant cognitive worsening, was observed after 1 year of follow up. Significant shortening of the swing time, prolongation of the double support and increase of their CVs were observed during all task conditions similarly for most parameters on symptomatic and asymptomatic bodysides, except for CV for the swing time under the combined task.

Conclusion: Alterations of the swing time and double support time are already present even at the asymptomatic body side, and progress similarly, or even at faster pace, at this side, despite dopaminergic treatment These parameters deserve further investigation in larger, prospective studies to address their potential to serve as markers of progression in interventional disease modifying trials with early PD patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269886PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302743PMC
July 2022

Case report: two cases of spontaneous intramural duodenal hematoma associated with pancreatitis.

Acta Biomed 2022 Jun 29;93(S1):e2022226. Epub 2022 Jun 29.

Department of Surgery, University Hospital Centre Zagreb, Zagreb, Croatia.

Intramural duodenal hematoma (IDH) is a rare entity and is generally associated with trauma. Spontaneous (nontraumatic) intramural duodenal hematoma is associated with bleeding disorders, anticoagulation therapy, alcoholism, pancreatitis, tumours  and duodenal ulcers. We report two cases of spontaneous intramural duodenal hematoma in middle-aged men who subsequently developed pancreatitis. The underlying pathophysiology is still unclear. In the cases described, it is not clear whether the intramural duodenal hematoma contributed to the development of pancreatitis or pancreatitis has contributed to the development of IDH.
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http://dx.doi.org/10.23750/abm.v93iS1.13041DOI Listing
June 2022

Therapy Effect of the Stable Gastric Pentadecapeptide BPC 157 on Acute Pancreatitis as Vascular Failure-Induced Severe Peripheral and Central Syndrome in Rats.

Biomedicines 2022 Jun 1;10(6). Epub 2022 Jun 1.

Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

We revealed the therapy effect of the stable gastric pentadecapeptide BPC 157 (10 μg/kg, 10 ng/kg ig or po) with specific activation of the collateral rescuing pathways, the azygos vein, on bile duct ligation in particular, and acute pancreatitis as local disturbances (i.e., improved gross and microscopy presentation, decreased amylase level). Additionally, we revealed the therapy's effect on the acute pancreatitis as vascular failure and multiorgan failure, both peripherally and centrally following "occlusion-like" syndrome, major intoxication (alcohol, lithium), maintained severe intra-abdominal hypertension, and myocardial infarction, or occlusion syndrome, and major vessel occlusion. The application-sacrifice periods were ligation times of 0-30 min, 0-5 h, 0-24 h (cured periods, early regimen) and 4.30 h-5 h, 5 h-24 h (cured periods, delayed regimen). Otherwise, bile duct-ligated rats commonly presented intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, gross brain swelling, hemorrhage and lesions, heart dysfunction, lung lesions, liver and kidney failure, gastrointestinal lesions, and severe arterial and venous thrombosis, peripherally and centrally. Unless antagonized with the key effect of BPC 157 regimens, reversal of the inferior caval and superior mesenteric vein congestion and reversal of the failed azygos vein activated azygos vein-recruited direct delivery to rescue the inferior-superior caval vein pathway; these were all antecedent to acute pancreatitis major lesions (i.e., acinar, fat necrosis, hemorrhage). These lesions appeared in the later period, but were markedly attenuated/eliminated (i.e., hemorrhage) in BPC 157-treated rats. To summarize, while the innate vicious cycle may be peripheral (bile duct ligation), or central (rapidly developed brain disturbances), or peripheral and central, BPC 157 resolved acute pancreatitis and its adjacent syndrome.
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http://dx.doi.org/10.3390/biomedicines10061299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220115PMC
June 2022

Adherence to Medication among Parkinson's Disease Patients Using the Adherence to Refills and Medications Scale.

Int J Clin Pract 2022 23;2022:6741280. Epub 2022 Feb 23.

Clinic of Neurology, School of Medicine, University of Belgrade, Belgrade, Serbia.

Objectives: Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients.

Methods: A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms.

Results: The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (=0.013, =0.017, =0.041, =0.043, and =0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence.

Conclusion: Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence.
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http://dx.doi.org/10.1155/2022/6741280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159199PMC
June 2022

The correlation between genetic factors and freezing of gait in patients with Parkinson's disease.

Parkinsonism Relat Disord 2022 05 5;98:7-12. Epub 2022 Apr 5.

Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia.

Background: Clinical-related risk factors to freezing of gait (FOG) in Parkinson's disease (PD) have been identified. Still, the influence of genetic variations on the FOG occurrence has been poorly studied thus far.

Aim: We aimed to evaluate the association of six selected polymorphisms of DRD2, ANKK1, and COMT genes with the FOG occurrence and explore the influence of ANNK1/DRD2 haplotypes on the onset of FOG in the group of PD patients.

Method: PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. FOG was evaluated by posing a direct question. In addition, a comprehensive set of clinical scales was applied to all patients.

Results: FOG occurred in 132 (56.4%) PD patients in our cohort. Freezers were younger at PD onset, had longer disease duration, used higher levodopa daily doses and dopaminergic agents, and had higher motor and non-motor scales scores than non-freezers. FOG was more frequent among AA rs4680 COMT carriers than AG and GG rs4680 COMT carriers. Independent predictors of FOG were: disease duration of more than ten years, levodopa daily dose higher than 500 mg/day, motor status, and COMT AA genotype. AGGAA and GGAAA haplotypes were revealed as protective and vulnerability factors for FOG occurrence.

Conclusion: In addition to previously identified disease- and therapy-related risk factors, our results suggested a possible contribution of dopamine-related genes to the FOG occurrence.
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http://dx.doi.org/10.1016/j.parkreldis.2022.03.018DOI Listing
May 2022

Association of Atraumatic Splenic Rupture and Acute Pancreatitis: Case Report with Literature Review.

Case Rep Surg 2022 14;2022:8743118. Epub 2022 Feb 14.

School of Medicine, University of Zagreb, Zagreb, Croatia.

Atraumatic splenic rupture is an uncommon complication of acute pancreatitis. This article presents a case of a 35-year-old patient presenting with acute pancreatitis who subsequently developed a splenic vein thrombosis and splenic rupture requiring a laparotomy and splenectomy. This rare but life-threatening complication requires prompt recognition and management in patients with pancreatitis who develop sudden hemodynamic instability.
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http://dx.doi.org/10.1155/2022/8743118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860542PMC
February 2022

Genetic and phenotypic variability in adult patients with Niemann Pick type C from Serbia: single-center experience.

J Neurol 2022 Jun 7;269(6):3167-3174. Epub 2022 Jan 7.

Neurology Clinic, University Clinical Center of Serbia, Dr Subotića Starijeg 6, 11000, Belgrade, Serbia.

Background: Niemann Pick type C is an autosomal recessive lysosomal storage disorder caused by mutations in NPC1 and NPC2 genes. It is a neuro-visceral disease with a heterogeneous phenotype. Clinical features depend on the age at onset. Visceral manifestations are more prominent in the early onset (infantile) form, while neuro-psychiatric symptoms are more prominent in the late disease onset (juvenile and adult forms).

Methods: A total number of 150 patients have been screened for changes in NPC1 and NPC2 gene at the Neurology Clinic, University Clinical Centre of Serbia in the period 2012-2020. Clinical data were extracted for patients with biallelic mutations.

Results: Fifteen patients carried biallelic mutations in the NPC1. Out of eight different reported NPC1 variants, four are novel (c.1204_1205TT>GC, p.F402A; c.2486T>G, p.L829R; c.2795+5 G>C; c.3722T>A, p.L1241*). The mean age at the disease onset was 20.3 ± 11.9 years with the average diagnostic delay of 7.7 ± 4.3 years. Movement disorders and psychiatric or cognitive disturbances were the most common initial symptoms (in 33% and 28% patients, respectively). The average age at the first neurological manifestation was 21 ± 12.0 years. At the last examination, eye movement abnormalities (vertical slow saccades or vertical supranuclear gaze palsy), and ataxia were present in all patients, while dystonia was common (in 78.6% of patients). Presence of c.2861C>T, p.S954L mutation in homozygous state was associated with older age at the neurological symptom onset.

Conclusions: Clinical findings were in line with the expected, but the diagnostic delay was common. We hypothesize that the presence of c.2861C>T, p.S954L mutation may contribute to the phenotype attenuation.
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http://dx.doi.org/10.1007/s00415-021-10918-7DOI Listing
June 2022

Longitudinal White Matter Damage Evolution in Parkinson's Disease.

Mov Disord 2022 02 22;37(2):315-324. Epub 2021 Nov 22.

Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: White matter hyperintensities (WMHs) have a role in cognitive impairment in normal brain aging, while the effect on Parkinson's disease (PD) progression is still controversial.

Objective: To investigate the longitudinal evolution of micro- and macrostructural damage of cerebral white matter (WM) and its relationship with the clinical picture in PD.

Methods: A total of 154 PD patients underwent clinical, cognitive, and magnetic resonance imaging (MRI) assessment once a year for up to 4 years. Sixty healthy controls underwent the same protocol at baseline. WMHs were identified and total WMH volume was measured. WMHs were also used as exclusion masks to define normal-appearing white matter (NAWM). Using tract-based spatial statistics, diffusion tensor (DT) MRI metrics of whole-brain WM and NAWM were obtained. Linear mixed-effects models defined the longitudinal evolution and association between variables. WM alterations were tested as risk factors of disease progression using linear regression and Cox proportional hazards models.

Results: At baseline, PD patients showed alterations of all DT MRI measures compared to controls. Longitudinally, DT MRI measures did not vary significantly and no association with clinical variables was found. WMH volume changed over time and was associated with impairment in global cognition, executive functions, and language. Baseline WMH volume was a moderate risk factor for progression to mild cognitive impairment.

Conclusions: Our study suggests an association between WMHs and cognitive deterioration in PD, whereas WM microstructural damage is a negligible contributor to clinical deterioration. WMHs assessed by MRI can provide an important tool for monitoring the development of cognitive impairment in PD patients. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28864DOI Listing
February 2022

Functional MRI connectivity of the primary motor cortex in functional dystonia patients.

J Neurol 2022 Jun 12;269(6):2961-2971. Epub 2021 Nov 12.

Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.

Background: Functional movement disorders include a wide spectrum of clinically documented movement disorders without an apparent organic substrate.

Objective: To explore the functional connectivity (FC) of the primary motor (M1) cortex in functional dystonia (FD) patients relative to healthy controls, with a focus on different clinical phenotypes.

Methods: Forty FD patients (12 fixed [FixFD]; 28 mobile [MobFD]) and 43 healthy controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]) underwent resting state fMRI. A seed-based FC analysis was performed using bilateral M1 as regions of interest.

Results: Compared to controls, FD patients showed reduced FC between left M1 and left dorsal anterior cingulate cortex, and between right M1 and left M1, premotor/supplementary motor area (SMA), dorsal posterior cingulate cortex (PCC), and bilateral precuneus. Relative to yHC, FixFD patients showed reduced FC between M1 and precuneus bilaterally. Compared to oHC, MobFD patients revealed reduced FC between right M1 and left M1, premotor/SMA, dorsal-PCC, bilateral primary sensory cortices and parieto-occipital areas, and increased FC of right M1 with right associative visual cortex and bilateral ventral-PCC. FixFD patients, relative to MobFD, showed lower FC between the right M1 and right associative visual area, and bilateral precuneus and ventral-PCC.

Conclusions: This study suggests an altered brain FC of the motor circuit with areas involved in emotional processes and sense of agency in FD. FixFD patients showed FC abnormalities mainly in areas related to sense of agency, while MobFD in regions involved in sensorimotor functions (reduced FC) and emotional processing (increased FC).
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http://dx.doi.org/10.1007/s00415-021-10879-xDOI Listing
June 2022

NBIA Syndromes: A Step Forward from the Previous Knowledge.

Neurol India 2021 Sep-Oct;69(5):1380-1388

Neurology Clinic, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

A disturbed iron metabolism may damage brain and trigger disorders known as neurodegeneration with brain iron accumulation (NBIA). NBIAs are rare, inherited disorders in which responsible mutations affect the function of proteins that participate in tissue iron homeostasis. Accumulated iron, which may be recognized as a low signal intensity on T2-weighted MRI images, oftentimes points to a diagnosis. Recent genetic discoveries confirm that NBIA is not a homogenous group of diseases. Fifteen different NBIAs have been described to date; among these, autosomal recessive inheritance was reported in 13, and autosmal dominant and X-linked dominant inheritance in one disease, respectively. Among NBIAs, the most common is pantothenate kinase-associated neurodegeneration (PKAN-NBIA 1) (30%-50% of all NBIA cases), that occurrs as a consequence of the autosomal recessive mutation in PANK2 gene, followed by phospholipase 2-associated neurodegeneration (PLAN, NBIA 2), due to mutation in PLA2G6 gene, and mitochondrial membrane protein-associated neurodegeneration (MPAN) with the underlying C19orf12 mutation [Table 1]. NBIAs are characterized by complex motor presentations from early-onset degeneration and premature fatality to adult-onset parkinsonism and dystonia. Epileptic seizures, pyramidal signs, visual disorders, and cognitive deterioration can develop. NBIAs are often refractory to therapeutical strategies, although certain interventions may provide significant symptomatic relief in selected patients. In this review, we discuss the expanding clinical spectrum of these complex and rare syndromes, their genetic and imaging features, and potential therapeutical targets and strategies.
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http://dx.doi.org/10.4103/0028-3886.329603DOI Listing
November 2021

A rare case of devastating Clostridium septicum endogenous endophthalmitis.

Graefes Arch Clin Exp Ophthalmol 2022 06 1;260(6):2061-2064. Epub 2021 Nov 1.

University of Zagreb School of Medicine, Zagreb, Croatia.

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http://dx.doi.org/10.1007/s00417-021-05476-7DOI Listing
June 2022

Psychological Effects of "Double Crisis" (COVID-19 Pandemic and Earthquakes) on Croatian Medical Students.

Psychiatr Danub 2021 Sep;33(Suppl 10):120-125

Department of Surgery, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia,

Introduction: In 2020. the COVID-19 pandemic presented an additional source of stress and anxiety not just to the general population but also to medical students who are, even under normal circumstances, constantly under pressure due to demanding student duties. In addition, they experienced a series of devastating earthquakes in and around the Zagreb region which altogether could have had compromised their psychological well-being. The aim of this review was to evaluate the psychological effects of these two natural disasters on the mental health of Croatian medical students.

Results: According to standardized questionnaires for depression and anxiety evaluation, 75.3% of students were anxious and 65.2% were depressive during the "double crisis". No significant difference of these two outcomes was observed regarding genders, but it was found that first year students had a significantly higher anxiety score than older ones.

Conclusion: In such stressful situations, we should emphasize the importance of mental health not just of healthcare workers, but also of medical students in order to prevent serious psychological consequences and to alleviate the negative effects on students' motivation and their educational process.
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September 2021

Longitudinal clinical, cognitive, and neuroanatomical changes over 5 years in GBA-positive Parkinson's disease patients.

J Neurol 2022 Mar 23;269(3):1485-1500. Epub 2021 Jul 23.

Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.

Objective: To study the longitudinal disease course of Parkinson's disease (PD) patients with glucocerebrosidase (GBA) mutation (GBA-positive) compared to PD non-carriers (GBA-negative) along a 5-year follow-up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and gray-matter (GM) volumes.

Methods: Ten GBA-positive and 20 GBA-negative PD patients underwent clinical, neuropsychological, and MRI assessments (cortical thickness and subcortical, hippocampal, and amygdala volumes) at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared with 22 age-matched healthy controls. Clinical, cognitive, and MRI features were compared between groups at baseline and over time.

Results: At baseline, GBA-positive and GBA-negative PD patients had similar clinical and cognitive profiles. Compared to GBA-negative and controls, GBA-positive patients showed cortical thinning of left temporal, parietal, and occipital gyri. Over time, compared to GBA-negative, GBA-positive PD patients progressed significantly in motor and cognitive symptoms, and showed a greater pattern of cortical thinning of posterior regions, and frontal and orbito-frontal cortices. After 5 years, compared to controls, GBA-negative PD patients showed a pattern of cortical thinning similar to that showed by GBA-positive cases at baseline. The two groups of patients showed similar patterns of subcortical, hippocampal, and amygdala volume loss over time.

Conclusions: Compared to GBA-negative PD, GBA-positive patients experienced a more rapid motor and cognitive decline together with a greater, earlier and faster cortical thinning. Cortical thickness measures may be a useful tool for monitoring and predicting PD progression in accordance with the genetic background.
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http://dx.doi.org/10.1007/s00415-021-10713-4DOI Listing
March 2022

Clinical and Genetic Analysis of Psychosis in Parkinson's Disease.

J Parkinsons Dis 2021;11(4):1973-1980

Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Background: Recent studies explored polymorphisms of multiple genes as contributing to genetic susceptibility to psychosis in Parkinson's disease (PDP).

Objective: We aimed to examine the association of seven selected polymorphisms of genes related to dopamine pathways with PDP development. At the same time, demographic and clinical correlates of PDP were assessed.

Methods: PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. Also, variable number of tandem repeats polymorphism in the DAT gene was examined. Each patient underwent comprehensive neurological examination, assessment of psychosis, as defined by the NINDS/NIMH criteria, as well as screening of depression, anxiety, and cognitive status.

Results: Diagnostic criteria for PDP were met by 101 (43.2%) patients. They had longer disease duration, were taking higher doses of dopaminergic agents, and had higher scores of the motor and non-motor scales than the non-PDP group. Multivariate regression analysis revealed LEDD≥900 mg, Unified Parkinson's Disease Rating Scale III part score, the Hamilton Depression Rating Scale score≥7, the Hamilton Anxiety Rating Scale score > 14,and GG homozygotes of rs2734849 ANKK1 as independent predictors of the onset of PDP.

Conclusion: Besides previous exposure to dopaminergic drugs, impairment of motor status, depression and anxiety, as well-established clinical risk factors for the development of PDP, GG rs2734849 ANKK1 could also be a contributing factor, which requires addressing by future longitudinal studies.
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http://dx.doi.org/10.3233/JPD-212716DOI Listing
January 2022

Concomitant Presence of Hydatid Cyst and Colorectal Liver Metastasis

Turkiye Parazitol Derg 2021 06;45(2):146-148

University Hospital Centre Zagreb Faculty of Medicine, Department of Surgery, Zagreb, Croatia

A 65-year-old man, with signs of acute colon obstruction, was diagnosed with rectal tumour and liver hydatid cyst. Additionally, a focal liver lesion in segment 1 was detected. Moreover, physical examination revealed hepatomegaly and abdominal distension. Thus, rectal resection and small liver lesion biopsy was performed. Serological and pathohistological analyses showed concomitant presence of hydatid cyst and colorectal metastasis in the liver. Hence, the cyst was treated with anthelmintic therapy, and patient lived another year after the diagnosis. To the best of our knowledge, cases of concomitant hydatid cyst and colorectal liver metastasis has never been reported; thus, this article addresses a unique case of coexistence between these two serious liver diseases.
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http://dx.doi.org/10.4274/tpd.galenos.2020.7001DOI Listing
June 2021

Rupture of suppurated liver hematoma into the anterior abdominal wall in a patient with Rendu-Osler-Weber syndrome.

Cir Cir 2020 ;88(Suppl 2):66-70

Department of Surgery. University Hospital Centre Zagreb, Zagreb, Croatia.

We report a case of ruptured liver hematoma as a result of suppurated arteriovenous malformation (AVM) in a patient with Rendu-Osler-Weber (ROW) syndrome. The patient presented with unexplained fever and upper right abdominal pain associated with microcytic anemia. A computed tomography scan revealed increasing subcapsular liver hematoma and features of liver abscess. Intraoperatively, a left liver hematoma mixed with pus was found that was attached to the anterior abdominal wall. Surgery included left lateral bisegmentectomy, while pathohistological analysis showed AVM and genetic tests confirmed ROW. This is the first such life-threatening surgical case of ROW complication reported in the scientific literature.
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http://dx.doi.org/10.24875/CIRU.20000342DOI Listing
September 2021

The Profile and Evolution of Neuropsychiatric Symptoms in Multiple System Atrophy: Self- and Caregiver Report.

J Neuropsychiatry Clin Neurosci 2021 2;33(2):124-131. Epub 2020 Dec 2.

Clinic of Neurology, School of Medicine, University of Belgrade, Serbia (Jecmenica-Lukic, Petrovic, Pekmezovic, Tomic, Stankovic, Svetel, Kostic); and Institute of Epidemiology, School of Medicine, University of Belgrade, Serbia (Pekmezovic).

Objective: Recent research shows that patients with multiple system atrophy (MSA) have significant cognitive and neuropsychiatric comorbidities that can color the clinical presentation of the disease and affect their quality of life. The aims of this study were to determine the neuropsychiatric profile in a cohort of patients with the parkinsonian type of MSA (MSA-P) and their dynamic changes over a 1-year follow-up period and to compare rates of neuropsychiatric symptoms (NPSs) reported by caregivers and the patients themselves.

Methods: Forty-seven patients were assessed at baseline; of these, 25 were assessed again after 1 year. NPS assessment tools included the Neuropsychiatric Inventory (NPI), the Beck Depression Inventory, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Apathy Evaluation Scale.

Results: The prevalence of NPSs in patients with MSA-P was very high, with depression, sleep disturbances, apathy, and anxiety being the most frequently occurring features. The evolution of NPSs was found to be independent of motor, autonomic, and cognitive symptoms. None of the scales measuring NPSs, including the NPI, were capable of detecting changes over the 1-year follow-up period. Although the overall prevalence of depression, apathy, and anxiety obtained from caregivers and the patients themselves was similar, reports from these two sources cannot be considered interchangeable.

Conclusions: The progression of neuropsychiatric symptoms was not a subject of rapid change in MSA-P, in contrast to the observed motor, autonomic, and cognitive deterioration. These findings suggest the need to investigate the utility of available instruments in capturing the evolution of NPSs in MSA over time.
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http://dx.doi.org/10.1176/appi.neuropsych.20030057DOI Listing
October 2021

Changes of Phenotypic Pattern in Functional Movement Disorders: A Prospective Cohort Study.

Front Neurol 2020 5;11:582215. Epub 2020 Nov 5.

Clinical Centre of Serbia, Faculty of Medicine, Clinic for Neurology, University of Belgrade, Belgrade, Serbia.

Functional movement disorders (FMD) refer to a group of movement disorders that present with clinical characteristics incongruent to those due to established pathophysiologic processes, as for example in the case of neurodegeneration or lesions. The aim of this study was to assess clinical features that contribute to the specific phenotypic presentations and disease course of FMD. The study consisted of 100 patients with FMD treated at Clinic for Neurology, Clinical Center of Serbia, who were longitudinally observed. Comprehensive clinical and psychiatric assessment was performed at the baseline, when initial FMD phenotype was defined. Follow-up assessment of phenotypic pattern over the time and clinical course was done after 3.2 ± 2.5 years at average. We showed that 48% of FMD patients were prone to changes of phenotypic pattern during the disease course. Dystonia had tendency to remains as single and unchanged phenotype over the time (68.2%), while patients initially presented with Tremor, Gait disorder, Parkinsonism and Mixed phenotype were more susceptible to developing additional symptoms (62.5, 50, and 100%, respectively). Higher levels of somatoform experiences ( = 0.033, Exp(B) = 1.082) and higher motor severity ( = 0.040, Exp(B) = 1.082) at baseline assessment were associated with an increased likelihood of further enriching of FMD phenotype with additional functional symptoms. Also, these patients more frequently reported pain, and had higher scores on majority of applied psychiatric scales, together with more frequent presence of major depressive disorder. Results from this prospective study suggested tendency for progression and enrichment of functional symptoms in FMD patients over time. Besides functional core symptoms, other key psychological and physical features (like pain or multiple somatisations) were quite relevant for chronicity and significant dysability of FMD patients.
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http://dx.doi.org/10.3389/fneur.2020.582215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674825PMC
November 2020

Impact of depression on gait variability in Parkinson's disease.

Clin Neurol Neurosurg 2021 01 21;200:106324. Epub 2020 Oct 21.

Innovation Center, School of Electrical Engineering in Belgrade, Bulevar kralja Aleksandra 73, Belgrade, Serbia.

Objective: The goal of this study was to analyze how depression associated with Parkinson's disease (PD) affected gait variability in these patients using a dual-task paradigm. Additionally, the dependency of the executive functions and the impact of depression on gait variability were analyzed.

Patients And Methods: Three subject groups were included: patients with PD, but no depression (PD-NonDep; 14 patients), patients with both PD and depression (PD-Dep; 16 patients) and healthy controls (HC; 15 subjects). Gait was recorded using the wireless sensors. The participants walked under four conditions: single-task, motor dual- task, cognitive dual-task, and combined dual-task. Variability of stride length, stride duration, and swing time was calculated and analyzed using the statistical methods.

Results: Variability of stride duration and stride length were not significantly different between PD-Dep and PD-NonDep patients. The linear mixed model showed that swing time variability was statistically significantly higher in PD-Dep patients compared to controls (p = 0.001). Hamilton Disease Rating Scale scores were significantly correlated with the swing time variability (p = 0.01). Variability of all three parameters of gait was significantly higher while performing combined or cognitive task and this effect was more pronounced in PD-Dep group of patients.

Conclusions: Depression in PD was associated with swing time variability, and this effect was more prominent while performing a dual-task.

Significance: Diagnosing and treating depression might be important for gait improvement and fall reduction in PD patients.
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http://dx.doi.org/10.1016/j.clineuro.2020.106324DOI Listing
January 2021

Brain Structural Changes in Focal Dystonia-What About Task Specificity? A Multimodal MRI Study.

Mov Disord 2021 01 26;36(1):196-205. Epub 2020 Sep 26.

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: The neural basis of task specificity in dystonia is still poorly understood. This study investigated gray and white matter (WM) brain alterations in patients with task-specific dystonia (TSD) and non-task-specific dystonia (NTSD).

Methods: Thirty-six patients with TSD (spasmodic dysphonia, writer's cramp), 61 patients with NTSD (blepharospasm, cervical dystonia), and 83 healthy controls underwent 3D T1-weighted and diffusion tensor magnetic resonance imaging (MRI). Whole brain cortical thickness and voxel-based morphometry; volumes of basal ganglia, thalamus, nucleus accumbens, amygdala, and hippocampus; and WM damage were assessed. Analysis of variance models were used to compare MRI measures between groups, adjusting for age and botulinum toxin (BoNT) treatment.

Results: The comparison between focal dystonia patients showed cortical thickness and gray matter (GM) volume differences (ie, decreased in NTSD, increased in TSD) in frontal, parietal, temporal, and occipital cortical regions; basal ganglia; thalamus; hippocampus; and amygdala. Cerebellar atrophy was found in NTSD patients relative to controls. WM damage was more severe and widespread in task-specific relative to NTSD patients. TSD patients receiving BoNT, relative to nontreated patients, had cortical thickening and increased GM volume in frontoparietal, temporal, and occipital regions. NTSD patients experiencing pain showed cortical thickening of areas involved in pain-inhibitory mechanisms.

Conclusions: TSD and NTSD are characterized by opposite alterations of the main cortical and subcortical sensorimotor and cognitive-controlling brain structures, suggesting the possible presence of different pathophysiological and/or compensatory mechanisms underlying the complexity of the two clinical phenotypes of focal dystonia. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28304DOI Listing
January 2021

Tracking Cortical Changes Throughout Cognitive Decline in Parkinson's Disease.

Mov Disord 2020 11 4;35(11):1987-1998. Epub 2020 Sep 4.

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: The objectives of this study were to investigate progressive cortical thinning and volume loss in Parkinson's disease (PD) patients with different longitudinal patterns of cognitive decline: with stable normal cognition, with stable mild cognitive impairment, with conversion to mild cognitive impairment, and with conversion to dementia.

Methods: We recruited 112 patients (37 Parkinson's disease with stable normal cognition, 20 Parkinson's disease with stable mild cognitive impairment, 36 Parkinson's disease with conversion to mild cognitive impairment, 19 Parkinson's disease with conversion to dementia) and 38 healthy controls. All patients underwent at least 2 visits within 4 years including clinical/cognitive assessments and structural MRI (total visits, 393). Baseline cortical thickness and gray matter volumetry were compared between groups. In PD, gray matter changes over time were investigated and compared between groups.

Results: At baseline, compared with Parkinson's disease with stable normal cognition cases, Parkinson's disease with conversion to mild cognitive impairment patients showed cortical atrophy of the parietal and occipital lobes, similar to Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia patients. The latter groups (ie, patients with cognitive impairment from the study entry) showed additional involvement of the frontotemporal cortices. No baseline volumetric differences among groups were detected. The longitudinal analysis (group-by-time interaction) showed that, versus the other patient groups, Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia cases accumulated the least cortical damage, with Parkinson's disease with conversion to dementia showing unique progression of right thalamic and hippocampal volume loss; Parkinson's disease with conversion to mild cognitive impairment patients showing specific cortical thinning accumulation in the medial and superior frontal gyri, inferior temporal, precuneus, posterior cingulum, and supramarginal gyri bilaterally; and Parkinson's disease with stable normal cognition patients showing cortical thinning progression, mainly in the occipital and parietal regions bilaterally.

Conclusions: Cortical thinning progression is more prominent in the initial stages of PD cognitive decline. The involvement of frontotemporoparietal regions, the hippocampus, and the thalamus is associated with conversion to a more severe stage of cognitive impairment. In PD, gray matter alterations of critical brain regions may be an MRI signature for the identification of patients at risk of developing dementia. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28228DOI Listing
November 2020

[61-year-old Patient with acute abdomen and blood vomit].

Dtsch Med Wochenschr 2020 08 24;145(17):1225-1226. Epub 2020 Aug 24.

Klinik für Chirurgie, Universitätsklinikum Zagreb.

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http://dx.doi.org/10.1055/a-1193-9641DOI Listing
August 2020

Breakdown of the affective-cognitive network in functional dystonia.

Hum Brain Mapp 2020 08 3;41(11):3059-3076. Epub 2020 Apr 3.

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Milan, Italy.

Previous studies suggested that brain regions subtending affective-cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective-cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS-fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]). FC of brain regions of interest, known to be involved in affective-cognitive processes, and independent component analysis of RS-fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective-cognitive seeds of interest and the fronto-subcortical and limbic circuits; enhanced FC between the right affective-cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective-cognitive seeds of interest and the sensorimotor and high-order function ("cognitive") areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective-cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.
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http://dx.doi.org/10.1002/hbm.24997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336141PMC
August 2020

Dynamical stability of the weakly nonharmonic propeller-shaped planar Brownian rotator.

Phys Rev E 2020 Jan;101(1-1):012105

University of Kragujevac, Faculty of Science, Radoja Domanovića 12, 34000 Kragujevac, Serbia.

Dynamical stability is a prerequisite for control and functioning of desired nanomachines. We utilize the Caldeira-Leggett master equation to investigate dynamical stability of molecular cogwheels modeled as a rigid, propeller-shaped planar rotator. To match certain expected realistic physical situations, we consider a weakly nonharmonic external potential for the rotator. Two methods for investigating stability are used. First, we employ a quantum-mechanical counterpart of the so-called "first passage time" method. Second, we investigate time dependence of the standard deviation of the rotator for both the angle and angular momentum quantum observables. A perturbationlike procedure is introduced and implemented to provide the closed set of differential equations for the moments. Extensive analysis is performed for different combinations of the values of system parameters. The two methods are, in a sense, mutually complementary. Appropriate for the short time behavior, the first passage time exhibits a numerically relevant dependence only on the damping factor as well as on the rotator size. However, the standard deviations for both the angle and angular momentum observables exhibit strong dependence on the parameter values for both short and long time intervals. Contrary to our expectations, the time decrease of the standard deviations is found for certain parameter regimes. In addition, for certain parameter regimes nonmonotonic dependence on the rotator size is observed for the standard deviations and for the damping of the oscillation amplitude. Hence, nonfulfillment of the classical expectation that the size of the rotator can be reduced to the inertia of the rotator. In effect, the task of designing the desired protocols for the proper control of the molecular rotations becomes an optimization problem that requires further technical elaboration.
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http://dx.doi.org/10.1103/PhysRevE.101.012105DOI Listing
January 2020

Dynamics of impulsive-compulsive behaviors in early Parkinson's disease: a prospective study.

J Neurol 2020 Apr 4;267(4):1127-1136. Epub 2020 Jan 4.

Clinic of Neurology, School of Medicine, University of Belgrade, Dr Subotica 6, 11000, Belgrade, Serbia.

Introduction: Impulsive compulsive behaviors (ICBs) in Parkinson's disease (PD) are debilitating disorders of repetitive, excessive, and compulsive nature affecting up to one third of PD patients. Objectives are to address clinical, psychiatric, and cognitive characteristics of ICBs and to define risk factors in PD patients in the initial motor stage, followed up for 5 years.

Methods: We analyzed 106 consecutive PD outpatients at Hoehn and Yahr disease stage 1 and 125 healthy controls. The participants were assessed for the presence of any ICB using the current clinical criteria and underwent comprehensive clinical, psychiatric, and neuropsychological evaluations. The patients completed the same protocol at Years 1, 2, 3, and 5.

Results: ICBs were present in 21 (19.8%) PD patients and 13 (10.4%) healthy controls at baseline. Prevalence of ICBs increased to 29.2% at Year 5, significantly after Year 2. Multiple ICBs were present in 4,7% and 61.9% of PD-ICBs at the baseline and Year 5, respectively. ICBs resolved in 30% of cases (most often compulsive eating). Dopamine agonist treatment at the baseline carried five times higher risk of having or developing ICB(s) anytime during follow-up. We identified risk factors for compulsive eating (dopamine agonist treatment at baseline), hypersexuality (males), compulsive buying (depression and younger age), and punding (younger age and higher levodopa dose at baseline). Significant interaction of rate of motor progression and ICB diagnosis was shown.

Conclusions: PD patients showed increasing frequency of most ICBs during the 5-year follow-up. Specific risk factors were identified for different types of ICBs.
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http://dx.doi.org/10.1007/s00415-019-09692-4DOI Listing
April 2020

Cognitive impairment and structural brain damage in multiple system atrophy-parkinsonian variant.

J Neurol 2020 Jan 26;267(1):87-94. Epub 2019 Sep 26.

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.

In this multiparametric, cross-sectional study, we aimed to investigate cognitive impairment and brain structural changes in patients with multiple system atrophy (MSA)-parkinsonian variant (MSA-p). Twenty-six MSA-p patients and 19 controls underwent clinical and neuropsychological evaluation and 1.5 T brain MRI scan. Cortical thickness measures and volumes of deep grey matter structures were obtained. A regression analysis correlated MRI metrics with clinical features in MSA-p patients. Almost 46% of MSA-p patients showed a mild cognitive impairment involving mainly attentive-executive and memory domains. Apathy and depression were found in half of MSA-p patients. MSA-p patients showed significant cortical thinning of fronto-temporal-parietal regions and atrophy of periaqueductal grey matter, left cerebellar hemisphere, left pallidum and bilateral putamen, compared to controls. Cortical thinning in temporal regions correlated with global cognitive status and memory impairment. Grey matter cerebellar atrophy correlated with motor deficits. MSA-p patients showed a multidomain cognitive impairment with a prominent cortical damage in anterior more than posterior brain regions and grey matter volume reduction in subcortical structures. Cortical and subcortical structural changes might lead to cognitive dysfunction in MSA-p.
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http://dx.doi.org/10.1007/s00415-019-09555-yDOI Listing
January 2020

Clinical course of patients with pantothenate kinase-associated neurodegeneration (PKAN) before and after DBS surgery.

J Neurol 2019 Dec 29;266(12):2962-2969. Epub 2019 Aug 29.

Clinic of Neurology, Clinical Center of Serbia, Dr. Subotica 6, Belgrade, Serbia.

Introduction: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with a progressive clinical course. In addition to symptomatic therapy, DBS has been increasingly recognized as a potential therapeutic strategy, especially in severe cases. Therefore, we wanted to report our experience regarding benefits of DBS in five PKAN cases in 3-year follow-up study.

Methods: Five genetically confirmed PKAN patients from Serbia underwent GPi-DBS. To assess clinical outcome, we reviewed medical charts and applied: Schwab and England Activities of Daily Living Scale (S&E), EQ-5D questionnaire for quality of life, Patient Global Impression of Improvement (GPI-I), Functional Independence Measure (FIM), Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Barry Albright Dystonia Scale (BAD). Patients were evaluated in five visits: at the disease onset, 5 years after the onset, before surgery, 6 months and 14-36 months after the surgery. Improvement of 20% was accepted as significant.

Results: Overall, dystonia significantly improved after GPi-DBS at 6 and 14-36 months postoperatively, when assessed by the BFMDRS and BAD. However, two patients failed to improve considerably. Four patients reported improvement on GPI-I, while one remained unchanged. Three patients reported significant improvement, when assessed with S&E and FIM. EQ-5D showed the most prominent improvement in the domains of mobility and pain/discomfort.

Conclusion: Three out of our five patients experienced beneficial effects of the GPi-DBS, in up to 36 months follow-up. Two patients who had not reached significant improvement had longer disease duration; therefore, it might be reasonable to recommend GPi-DBS as soon as dystonia became disabling.
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http://dx.doi.org/10.1007/s00415-019-09499-3DOI Listing
December 2019

Urgent Surgical Treatment of GIST of Esophago-Gastric Junction in a Patient with Giant Hiatal Hernia.

Klin Onkol 2019 ;32(4):306-309

Gastrointestinal stromal tumors (GISTs), being the most common mesenchymal tumors of the gastrointestinal tract, arise most commonly in stomach (60-70%) and small intestine (20-25%) while other sites of origin are rare. In most cases, they are diagnosed accidentally due to their indolent clinical course; however, 10-30% have malignant potential. Gastric and esophageal GISTs carry a better prognosis than small bowel GISTs of similar size and mitotic rate. Complete surgical resection is the only potentially curative procedure, but despite its success, at least 50% of patients develop recurrence or metastases. Tyrosine kinase inhibitor imatinib gave positive results in treatment of unresectable, metastatic or recurrent GISTs. We present the case of a 69-year-old woman with a large unresectable GIST of esophago-gastric junction with multiple bilobar liver metastases who underwent an emergent palliative surgery due to diffuse bleeding from the tumor. Twelve months after the surgery, patient is still alive and stable under imatinib therapy with no signs of local recurrence of the disease. This example suggests that patients with locally advanced GISTs with distant metastases may benefit from surgery in terms of prolonged survival and quality of life.
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http://dx.doi.org/10.14735/amko2019306DOI Listing
January 2020
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