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Decreased brain volume may be associated with the occurrence of peri-lead edema in Parkinson's disease patients with deep brain stimulation
No full textBackground: Peri-lead edema (PLE) is a poorly understood complication of deep brain stimulation (DBS), which has been described in patients presenting occasionally with profound and often delayed symptoms with an incidence ranging from 0.4% up to even 100%. Therefore, our study aims to investigate the association of brain and brain compartment volumes on magnetic resonance imaging (MRI) with the occurrence of PLE in Parkinson's disease (PD) patients after DBS implantation in subthalamic nuclei (STN).
Methods: This retrospective study included 125 consecutive PD patients who underwent STN DBS at the Department of Neurosurgery, Dubrava University Hospital from 2010 to 2022. Qualitative analysis was done on postoperative MRI T2-weighted sequence by two independent observers, marking PLE on midbrain, thalamus, and subcortical levels as mild, moderate, or severe. Quantitative volumetric analysis of brain and brain compartment volumes was conducted using an automated CIVET processing pipeline on preoperative MRI T1 MPRAGE sequences. In addition, observed PLE on individual hemispheres was delineated manually and measured using Analyze 14.0 software.
Results: In our cohort, PLE was observed in 32.17%, mostly bilaterally. Mild PLE was observed in the majority of patients, regardless of the level observed. Age, sex, diabetes, hypertension, vascular disease, and the use of anticoagulant/antiplatelet therapy showed no significant association with the occurrence of PLE. Total grey matter volume showed a significant association with the PLE occurrence (r = -0.22, p = 0.04), as well as cortex volume (r = -0.32, p = 0.0005). Cortical volumes of hemispheres, overall hemisphere volumes, as well as hemisphere/total intracranial volume ratio showed significant association with the PLE occurrence. Furthermore, the volume of the cortex and total grey volume represent moderate indicators, while hemisphere volumes, cortical volumes of hemispheres, and hemisphere/total intracranial volume ratio represent mild to moderate indicators of possible PLE occurrence.
Conclusion: The results of our study suggest that the morphometric MRI measurements, as a useful tool, can provide relevant information about the structural status of the brain in patients with PD and represent moderate indicators of possible PLE occurrence. Identifying patients with greater brain atrophy, especially regarding grey matter before DBS implantation, will allow us to estimate the possible postoperative symptoms and intervene in a timely manner. Further studies are needed to confirm our findings and to investigate other potential predictors and risk factors of PLE occurrence
A virtual consultation system for very rare tumors in children and adolescents – an initiative of the European Cooperative Study Group in Rare Tumors in Children (EXPeRT)
No full textBackground: Very rare tumors (VRTs) in children and adolescents are orphan diseases defined by an annual incidence of <2/1000,000. For a long time, VRTs have been outside of clinical and research groups in the field of pediatric oncology. As a result, exchange of experience and development of therapeutic standards have not been promoted. After the foundation of several national VRT working groups and the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT), a virtual consultation system (VCS) has been established, which specifically aimed at facilitating access to clinical consultation in complicated cases of VRTs. Methods: The VCS has been open to physicians. After initial registration, they can present VRT patients free of charge. Patient consent and data pseudonymization were mandatory. Within the VCS, disease specific interdisciplinary panel discussions with at least three experts from the EXPeRT group and partners have been opened, and at the end of the discussion, a written summary and recommendation was provided. Results: Between Mai 2017 and March 2023, 160 cases from 27 countries (20 European, 7 non-European) have been discussed in the VCS. The most common diagnoses were adrenocortical carcinoma, malignant skin tumors and malignant ovarian tumors. In a survey three months after panel discussion, more than 90% of requesting physicians evaluated the VCS to be easy to use, helpful and to have a significant impact on patient management. Conclusion: A VCS may provide significant assistance in the management of children and adolescents with VRTs. Furthermore, it may help to overcome inequalities in access to adequate treatment in countries with lower health care system resources or without established VRT study groups. Therefore, EXPeRT will continue to support the VCS. For this purpose, the VRT panels have been integrated into the Clinical Patient Management System (CPMS) within the European Reference Network Initiative (ERN PAedCan
Associations between PIK3CA Mutations and Disease Free Survival in Patients with HR+, HER2− Tumors Treated with Adjuvant Hormonal Therapy: A Real‐World Study in Croatia
No full text. Disease recurrence in patients with the early hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2−) breast tumor subtype is particularly challenging to manage due to its complex and very heterogeneous biological nature. Namely, due to primary and secondary resistance, one‐quarter of patients with early‐stage disease will experience disease recurrence. This variability in the timing of recurrence highlights the need to better identify key biomarkers that could predict therapeutic outcomes and guide personalized treatment strategies for these patients. Mutations in the phosphatidylinositol 4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) gene are highly prevalent (30–40%) in HR+/HER2− advanced breast cancer. They lead to activation of the PI3K/AKT/mTOR pathway, promoting cell growth, and proliferation, and are associated with poor prognosis in advanced breast cancer. Our aim was to examine the association between and impact of PIK3CA mutation status on disease‐free survival (DFS) in HR+/HER2− early breast cancer patients.
. This cohort study was multicentric and retrospective in nature and was conducted at five Croatian institutions from July 2020 to December 2021. The study included initially early and locally advanced operable HR+/HER2− breast cancer patients who were diagnosed with disease recurrence during adjuvant hormonal treatment or within the first six years of follow‐up.
. A total of 186 patients were included, 40.9% of whom tested positive for the PIK3CA mutation. Primary and adjuvant treatment, particularly adjuvant endocrine treatment, were similar between the two groups. After adjustment for 14 relevant covariates, we found that patients with a positive PIK3CA status and the H1047 PIK3CA mutation had a significantly lower hazard of disease recurrence than patients with no PIK3CA mutation (HR 0.65; 95% CI 0.45; 0.95;
= 0.024; false discovery rate, FD
Surgical options in treating muscle-invasive carcinoma of the bladder
No full textOvaj rad detaljno analizira različite kirurške pristupe u liječenju mišićno-invazivnog karcinoma mokraćnog mjehura (MIKMM), koji predstavlja značajan zdravstveni izazov s obzirom na njegovu prevalenciju i potencijalno ozbiljne posljedice. Karcinom mokraćnog mjehura je drugi najčešći karcinom urinarnog trakta, a preko 90% karcinoma je urotelnog porijekla. Njegovi glavni uzroci uključuju faktore poput pušenja, izloženosti kemikalijama, kroničnih upala mjehura, teških metala i ionizirajućeg zračenja.
Karcinomi mokraćnog mjehura mogu biti klasificirati kao mišićno-neinvazivni ili mišićno-invazivni, pri čemu potonji čine oko 20% svih dijagnosticiranih slučajeva. Dijagnostički postupci uključuju analizu urina, uključujući i i citološku analizu urina, cistoskopiju kao i uporabu različitih slikovnih metoda poput ultrazvuka, CT i MR. Definitivna dijagnoza se postavlja transuretralnom resekcijom tumora (TURBT) ili biopsijom.
Kirurško liječenje MIKMM-a obuhvaća TURBT i radikalnu cistektomiju (RC). TURBT se koristi kao inicijalna metoda, dok je RC definitivna kirurška metoda. RC može biti otvorena ili laparoskopska, a uključuje uklanjanje mjehura, okolnog tkiva i limfnih čvorova. Važno je naglasiti da nakon RC treba učiniti jedan od oblika urinarne derivacije. Mokraćni sustav treba rekonstruirati kako bi se omogućilo normalno izlučivanje mokraće.
Odabir kirurške metode liječenja ovisi o stadiju bolesti, općem stanju pacijenta i željama pacijenta. Kirurško liječenje i dalje ostaje zlatni standard u terapiji MIKMM-a, ali zahtjeva pažljivu procjenu i prilagodbu za svakog pacijenta.This paper analyzes in detail different surgical approaches in the treatment of muscle invasive bladder cancer (MIBC), which represents a significant health challenge given its prevalence and potentially serious consequences. Bladder cancer is the second most common cancer of the urinary tract, and over 90% of cases are of urothelial origin. Its main causes include factors such as smoking, chemical exposure, chronic cystitis, heavy metals and ionizing radiation.
It is important to note that bladder cancers can be classified as non-muscle invasive or muscle invasive, with the latter accounting for about 20% of all diagnosed cases. Diagnostic procedures include various urine analyses, such as biochemical, microbiological and cytological analyses, as well as the use of various imaging methods such as cystoscopy, ultrasound, CT and MR imaging. Definitive diagnosis is established by transurethral resection (TUR) or biopsy.
Surgical treatment of MIBC includes transurethral resection of the urinary bladder (TUR) and radical cystectomy (RC). TUR is used in the early stages of the disease, while RC is reserved for advanced cancer that does not respond to other therapies. RC can be open or laparoscopic, and involves removing the bladder, surrounding tissue and lymph nodes.
It is important to emphasize that after RC the urinary system should be reconstructed in order to enable normal urine excretion. Laparoscopic RC is a minimally invasive method that is performed with the help of special instruments.
Although laparoscopic RC offers certain advantages such as less bleeding and faster recovery, it is important to note that it requires an experienced surgeon. The choice of treatment method depends on the stage of the disease, the patient's general condition and the patient's preferences. Surgical treatment remains the gold standard in the treatment of MIBC, but requires careful evaluation and tailoring for each patient
The role of exosomes in the pathophysiology of diabetes and their potential clinical implications : graduation thesis
No full textT2DM stands as one of the most prevalent chronic diseases globally, with an increasing incidence,
notably associated with obesity. While its pathophysiology remains incompletely understood, it is
primarily linked to insulin resistance, resulting in reduced glucose uptake by the liver, muscles, and
adipose tissue, consequently leading to elevated blood glucose levels. Classical clinical features of
T2DM include polydipsia, polyuria, and polyphagia, yet many patients are asymptomatic, underscoring
the importance of screening, particularly in obese individuals with a positive family history. Diagnosis
of T2DM currently relies on assessing levels of FPG, OGTT, and HbA1c. A myriad of glucose-lowering
medications are available in the market today. Poorly controlled T2DM is associated with numerous
complications, such as diabetic retinopathy, neuropathy, nephropathy, cardiomyopathy, and impaired
wound healing.
EVs are released by various cells and categorized into three types based on size: apoptotic bodies,
microvesicles, and exosomes, in ascending order. Recent research has underscored the pivotal role of
extracellular vesicles, particularly exosomes, in the physiology and pathophysiology of various
diseases, including T2DM. Exosomes, small vesicles facilitating intercellular communication, have
been shown to contribute to the pathophysiology of T2DM and its complications. Despite ongoing
investigations, much remains to be elucidated regarding exosomes. However, they hold immense
promise in the realm of theranostics—integrated therapeutic and diagnostic approaches—particularly
concerning T2DM complications. Continued research into exosomes has the potential to unveil novel
diagnostic tools and therapeutic strategies, revolutionizing the management and treatment of T2DM
and enhancing patient outcomes
The Effect of Severe Coronary Calcification on Diagnostic Performance of Computed Tomography-Derived Fractional Flow Reserve Analyses in People with Coronary Artery Disease
No full textBackground: Negative CCTA can effectively exclude significant CAD, eliminating the need for further noninvasive or invasive testing. However, in the presence of severe CAD, the accuracy declines, thus necessitating additional testing. The aim of our study was to evaluate the diagnostic performance of noninvasive cFFR derived from CCTA, compared to ICA in detecting hemodynamically significant stenoses in participants with high CAC scores (>400). Methods: This study included 37 participants suspected of having CAD who underwent CCTA and ICA. CAC was calculated and cFFR analyses were performed using an on-site machine learning-based algorithm. Diagnostic accuracy parameters of CCTA and cFFR were calculated on a per-vessel level. Results: The median total CAC score was 870, with an IQR of 642–1370. Regarding CCTA, sensitivity and specificity for RCA were 60% and 67% with an AUC of 0.639; a LAD of 87% and 50% with an AUC of 0.688; an LCX of 33% and 90% with an AUC of 0.617, respectively. Regarding cFFR, sensitivity and specificity for RCA were 60% and 61% with an AUC of 0.606; a LAD of 75% and 54% with an AUC of 0.647; an LCX of 50% and 77% with an AUC of 0.647. No significant differences between AUCs of coronary CTA and cFFR for each vessel were found. Conclusions: Our results showed poor diagnostic accuracy of CCTA and cFFR in determining significant ischemia-related lesions in participants with high CAC scores when compared to ICA. Based on our results and study limitations we cannot exclude cFFR as a method for determining significant stenoses in people with high CAC. A key issue is accurate and detailed lumen segmentation based on good-quality CCTA images
Analysis of granulysin expression in vitiligo and halo-nevus
No full textAbstract Vitiligo and halo nevus are immune-mediated skin diseases that have a similar pathogenesis and involve cellular cytotoxicity mechanisms that are not yet fully understood. In this study, we investigated the expression patterns of the cytolytic molecule granulysin (GNLY) in different cytotoxic cells in skin samples of vitiligo and halo nevus. Skin biopsies were taken from perilesional and lesional skin of ten vitiligo patients, eight patients with halo nevus and ten healthy controls. We analysed the expression of GNLY by immunohistochemistry in CD8+ and CD56+ NK cells. A significantly higher accumulation of GNLY+, CD8+ GNLY+ and fewer CD56+ GNLY+ cells was found in the lesional skin of vitiligo and halo nevus than in the healthy skin. These cells were localised in the basal epidermis and papillary dermis, suggesting that GNLY may be involved in the immune response against melanocytes. Similarly, but to a lesser extent, upregulation of GNLY+ and CD8+ GNLY+ cells was observed in the perilesional skin of vitiligo and halo nevus compared to healthy controls. In this study, we demonstrated for the first time an increased expression of CD8+ GNLY+ T lymphocytes and CD56+ GNLY+ NK cells in lesions of vitiligo and halo nevus, indicating the role of GNLY in the pathogenesis of both diseases
The Surviving, Not Thriving, Photoreceptors in Patients with ABCA4 Stargardt Disease
No full textStargardt disease (STGD1), associated with biallelic variants in the ABCA4 gene, is the most common heritable macular dystrophy and is currently untreatable. To identify potential treatment targets, we characterized surviving STGD1 photoreceptors. We used clinical data to identify macular regions with surviving STGD1 photoreceptors. We compared the hyperreflective bands in the optical coherence tomographic (OCT) images that correspond to structures in the STGD1 photoreceptor inner segments to those in controls. We used adaptive optics scanning light ophthalmoscopy (AO-SLO) to study the distribution of cones and AO-OCT to evaluate the interface of photoreceptors and retinal pigment epithelium (RPE). We found that the profile of the hyperreflective bands differed dramatically between patients with STGD1 and controls. AO-SLOs showed patches in which cone densities were similar to those in healthy retinas and others in which the cone population was sparse. In regions replete with cones, there was no debris at the photoreceptor-RPE interface. In regions with sparse cones, there was abundant debris. Our results raise the possibility that pharmaceutical means may protect surviving photoreceptors and so mitigate vision loss in patients with STGD1
Hormonal and neurohumoral changes as a stress response to surgery
No full textStres u medicini je zapravo poremećaj homeostaze. Tijekom operacije organizam je izložen velikom stresu, zbog toga se aktiviraju fiziološki mehanizmi kako bi se tijelo prilagodilo, održalo homeostazu i kako bi oporavak bio što brži i uspješniji. Endokrini odgovor aktivira se u osjetnim živčanim završecima koji šalju podražaje s mjesta kirurške ozljede prema CNS-u, točnije, u paraventrikularne jezgre hipotalamusa, talamus i u postcentralnu vijugu parijetalnog režnja. Vrlo bitne sastavnice odgovora na stres su hormonske i neurohumoralne promjene, a one uključuju aktivaciju hipotalamus-hipofiza-adrenalne (HPA) osovine, simpatikus-adrenergičkog sustava, aktivaciju renin-angiotenzin-aldosteron sustava (RAAS), otpuštanje antidiuretskog hormona (ADH) iz stražnjeg režnja hipofize, izlučivanje ACTH i hormona rasta iz adenohipofize. Bitnu ulogu u regulaciji imunološkog sustava imaju i citokini, medijatori koje luče imunološke stanice, oni se sintetiziraju kao odgovor na upalne procese u tijelu. Zajedničkim djelovanjem živčanog sustava i endokrinih žlijezda ostvaruju se neurohumoralne promjene. Primjer za to je aktivacija simpatoadrenalnog sustava koji uzrokuje otpuštanje katekolamina, noradrenalina i adrenalina. Katekolamini imaju ulogu održavanja hemodinamske stabilnosti i osiguravanje dovoljno izvora energije tijekom stresa.
Na intezitet kirurškog stresnog odgovora može se utjecati korištenjem kirurških metoda koje manje oštećuju tkivo i stvaraju manje ožiljke, isto tako, primjenom adekvatnih anestezioloških protokola, budući da je dokazano da je stresni odgovor manjeg inteziteta ako anestezija blokira neke od prije navedenih hormonskih i neurohumoralnih sustava.Stress in medicine is actually a disturbance of homeostasis. During surgery, the body is exposed to significant stress, which is why physiological mechanisms are activated in order for the body to adapt, maintain homeostasis, and to make recovery as quick and successful as possible. The endocrine response is activated in sensory nerve endings, which send stimuli from the site of surgical injury to the CNS, more specifically, to the paraventricular nuclei of the hypothalamus, the thalamus and the postcentral gyrus of the parietal lobe. Very important components of the stress response are hormonal and neurohumoral changes, which include the activation of the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic-adrenergic system, the activation of the renin-angiotensin-aldosterone system (RAAS), the release of antidiuretic hormone (ADH) from the posterior lobe of the pituitary gland, and the release of ACTH and growth hormone from the adenohypophysis. An essential role in the regulation of the immune system is played by cytokines, mediators secreted by immune cells, they are synthesized in response to inflammatory processes in the body. The joint action of the nervous system and endocrine glands results in neurohumoral changes. An example of this is the activation of the sympathoadrenal system, which causes the release of catecholamine, noradrenaline and adrenaline. Catecholamines have the role of maintaining hemodynamic stability and providing a sufficient source of energy during stress.
The intensity of the surgical stress response can be influenced by using surgical methods that damage less tissue and create smaller scars, as well as by applying adequate anesthesia protocols, since it has been proven that the stress response is less intense if anesthesia blocks some of the aforementioned hormonal and neurohumoral systems