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Exploring potential therapeutic combinations for castration-sensitive prostate cancer using supercomputers: a proof of concept study
No full textTo address the challenge of finding new combination therapies against castration-sensitive prostate cancer, we introduce Vini, a computational tool that predicts the efficacy of drug combinations at the intracellular level by integrating data from the KEGG, DrugBank, Pubchem, Protein Data Bank, Uniprot, NCI-60 and COSMIC databases. Vini is a computational tool that predicts the efficacy of drugs and their combinations at the intracellular level. It addresses the problem comprehensively by considering all known target genes, proteins and small molecules and their mutual interactions involved in the onset and development of cancer. The results obtained point to new, previously unexplored combination therapies that could theoretically be promising candidates for the treatment of castration-sensitive prostate cancer and could prevent the inevitable progression of the cancer to the incurable castration-resistant stage. Furthermore, after analyzing the obtained triple combinations of drugs and their targets, the most common targets became clear: ALK, BCL-2, mTOR, DNA and androgen axis. These results may help to define future therapies against castration-sensitive prostate cancer. The use of the Vini computer model to explore therapeutic combinations represents an innovative approach in the search for effective treatments for castration-sensitive prostate cancer, which, if clinically validated, could potentially lead to new breakthrough therapies
YKL-40 as a risk stratification marker in acute pancreatitis: A prospective study
No full textBackground/objectives: Increased systemic concentrations of YKL-40 are seen in various inflammatory conditions. We explored the relationship between the serum YKL-40 concentrations and subsequent disease severity in patients with acute pancreatitis (AP).
Methods: Consecutive adults with AP were prospectively enrolled, and classified as having mild, moderate or severe disease. On admission and 48 h later, C-reactive protein (CRP), YKL-40, interleukin-6 and 8 (IL-6, IL-8), and tumor necrosis factor alpha (TNF-a) concentrations were measured. Patients were also classified as those with low (<50 ng/mL, in the range seen in 30 age and sex-matched non-AP subjects), high (190 ng/mL, seen in most of the other inflammatory conditions), and intermediate YKL-40 (50 e189 ng/mL).
Results: Incidence of mild, moderate and severe AP among the 150 enrolled patients was 80 (53.3 %), 59 (39.3 %), and 11 (7.4 %), respectively. Both on admission and 48 h later, high YKL-40 (vs. intermediate or low) was strongly associated with higher odds of a more severe AP, independently of the concurrent IL-8 and TNF-a concentrations (OR around 3.5e4.0, or higher). On admission, the association was independent also of the concurrent CRP, whereas the association between the later concentrations and the outcome was conditional on CRP e uncertain at low, strong at high CRP. The high YKL-40 e outcome association at both time-points was conditional on concurrent IL-6: uncertain if IL-6 was low, strong if IL- 6 was high.
Conclusions: Serum YKL-40 is a plausible candidate for further evaluation as an early biochemical indicator of subsequent AP severity, particularly if considered jointly with CRP and/or IL-6
Principi liječenja mekotkivnih ozljeda mišićno-koštanoga sustava prema rehabilitacijskim akronimima
No full textUvod: Kako bi se optimiziralo rehabilitacijsko liječenje mekotkivnih ozljeda mišićno-koštanoga sustava, došlo je do promjena u rehabilitacijskim akronimima koji opisuju sastavnice principa liječenja utemeljenih na znanstvenim dokazima.
Cilj: Ovaj rad usmjeren je edukaciji i širenju osviještenosti o značaju i učinkovitosti suvremenijih pristupa u optimizaciji rehabilitacijskoga liječenja, respektirajući razvojne faze mekotkivnih ozljeda.
Pregled: Pretraživali smo literaturu koristeći baze Web of Science i Google Scholar - pregledne radove, meta-analize, randomizirane kontrolirane studije, pisma uredniku od 1985. do 2021.g. temeljem ključnih riječi soft tissue injuries; rehabilitation acronyms; cryotherapy. Inicijalno je etabliran protokol koji uključuje primjenu krioterapije u obliku leda, kompresiju i elevaciju ozlijeđenog ekstremiteta. Potom je nadograđen principima, u obliku rehabilitacijskih akronima koji se odnose na odmor, poštedu, stabilizaciju i postupno opterećivanje ozlijeđenog ekstremiteta. Svemu navedenome zajedničko je obilježje potreba za provođenjem krioterapije, nasuprot suvremenom principu predstavljenom u obliku akronima koji mijenja
dosadašnju paradigmu. Ovaj princip u sebi obuhvaća hodograme za neposrednim zbrinjavanjem blaže do umjerene mekotkivne ozljede mišićno-koštanoga sustava, kao i za nastavno rehabilitacijsko liječenje upućivanjem na potrebu edukacije bolesnika, te uzimajući u obzir psihosocijalne čimbenike u smislu doprinosa k optimalnom rehabilitacijskom ishodu. Temeljem ovoga protokola primjena protuupalnih lijekova i krioterapija nisu uključene u rehabilitaciju nakon ozljeda mekih tkiva zbog njihovih potencijalno nepovoljnih učinaka na biološke mehanizme cijeljenja tkiva. No, kod rehabilitacijskoga liječenja umjereno teških i teških mekotkivnih ozljeda u akutnoj fazi potrebno je pribjegavati principu koji uključuje krioterapiju s kompresijom, izbjegavanje većeg opterećenja, rehabilitaciju i edukaciju.
Zaključak: Izostavljanjem primjene protuupalnih lijekova i krioterapije u okviru rehabilitacijskog liječenja manjih do umjerenih mekotkivnih ozljeda došlo je do svojevrsne promjene paradigme, no krioterapija i dalje neizostavno zauzima svoje mjesto prilikom liječenja umjereno teških i teških mekotkivnih ozljeda u akutnoj fazi
The role of the NY-ESO-1 in the prognosis of gastric cancer
No full textGastric cancer (GC) is one of the most common malignancies worldwide and the fourth leading cause of cancer-related deaths. GC is a multifactorial disease influenced by both environmental and genetic factors. Its most critical features include invasiveness and high metastatic potential. Metastasis is a complex process, and our understanding of the mechanisms involved remains incomplete. Growing evidence suggests that cancer-testis antigens (CTAs) play a crucial role in the metastatic potential of various tumors. Several studies have linked CTA expression with lower tumor differentiation, higher metastatic potential, and poor chemotherapy response. New York esophageal squamous cell carcinoma-1 (NY-ESO-1) antigen, part of the CTA group, is expressed in tumor tissues, while its expression in normal tissues is restricted to spermatogonia. This study aimed to determine the expression of NY-ESO-1 in primary adenocarcinoma of the stomach, both with and without metastasis in regional lymph nodes, and to compare it with TNM stage, age, gender, and survival. We analyzed GC tissue from 53 node-negative and 55 node-positive primary gastric carcinoma patients for NY-ESO-1 expression using immunohistochemical assay. The results were correlated with clinicopathological parameters and survival. Patients with positive NY-ESO-1 expression in primary tumors had a median survival of 19.0 months (range 14.1–24.0), in contrast to those with negative expression, who had a median survival of 52.0 months (range 0.0–133.3) (chi-square 7.99, P = 0.005). T status, N status, and NY-ESO-1 expression were all independently associated with shorter survival. No significant difference in NY-ESO-1 expression in primary tumors was observed concerning lymph node metastasis status. In summary, our findings suggest that increased expression of NY-ESO-1 could potentially serve as a prognostic biomarker for GC
Physical component of SF-36 is associated with measures of disease activity in patients with psoriatic arthritis: a real-life study from a tertiary referral centre
No full textPsoriatic arthritis (PsA) can lead to chronic disability. The aim of this study was to explore the association between disease activity and quality of life (QoL) in patients with PsA from the usual clinical practice. The study involved 143 consecutive adult patients with PsA (49.6% women and 50.4% males), with mean age of 57.75 ± 10.91 years, and duration of disease 11.6 ± 9 years. Tender (TJC) and swollen joints count (SJC), Disease activity score (DAS) 28, patient’s global assessment (PtGA), physician’s global assessment (PhGA), enthesitis score, number of fingers with dactylitis, sedimentation rate (ESR) and C-reactive protein (CRP) were evaluated. The functional assessment of chronic illness therapy - fatigue scale (FACIT-F) questionnaire was used in fatigue assessment and physical health domains of Short Form (SF)-36 questionnaire were chosen to assess subjective QoL: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP) and general health (GH). Significant correlations (p < 0.001) were found between FACIT-F and all SF-36 domains. DAS28, PtGA and PhGA were significantly correlated to two or three SF-36 domains, while ESR and CRP were not significantly correlated to any of SF-36 domains. Regression analysis showed, when controlling for age, that FACITF, dactylitis and DAS28 were the most significant predictors of SF-36 physical health domains. Regression and factor analyses confirmed that FACIT-F was most consistently associated with SF-36 physical health domains. In our real-life study most of the analyzed clinical measures of PsA were significantly associated with physical health domains of SF-36 questionnaire. Considering the strength of those associations, we conclude that PsA activity has mild to moderate impact on health-related Qol
Comparative Targeted Metabolomics of Ischemic Stroke: Thrombi and Serum Profiling for the Identification of Stroke-Related Metabolites
No full textIschemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Therefore, identifying reliable biomarkers for early detection, prognostics, and therapy can facilitate the early prediction and prevention of stroke. Metabolomics has been shown as a promising tool for biomarker discovery since many post-ischemic metabolites can be found in the plasma or serum of the patient. In this research, we performed a comparative targeted metabolomic analysis of stroke thrombi, stroke patient serums, and healthy control serums in order to determine the alteration in the patients’ metabolomes, which might serve as biomarkers for early prediction or stroke prevention. The most statistically altered metabolites characterized in the patient serums compared with the control serums were glutamate and serotonin, followed by phospholipids and triacylglycerols. In stroke thrombi compared with the patients’ serums, the most significantly altered metabolites were classified as lipids, with choline-containing phospholipids and sphingomyelins having the highest discriminatory score. The results of this preliminary study could help in understanding the roles of different metabolic changes that occur during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers for ischemic stroke
Resistance to KRAS inhibition in advanced non-small cell lung cancer
No full textLung cancer remains the leading cause of cancer death globally. More than 50% of new cases are diagnosed in an advanced or metastatic stage, thus contributing to the poor survival of such patients. Mutations in the KRAS (Kirsten rat sarcoma virus) gene occur in nearly a third of lung adenocarcinoma and have for decades been deemed an ‘undruggable’ target. Yet, in recent years, a growing number of small molecules, such as the GTPase inhibitors, has been investigated in clinical trials of lung cancer patients harboring KRAS mutations, yielding promising results with improved outcomes. Currently, there are only two approved targeted therapies (adagrasib and sotorasib) for advanced or metastatic KRAS - mutated NSCLC from the second-line setting onwards. In this narrative review, we will focus on KRAS, its molecular basis, the role of its co-mutations, clinical evidence for its inhibition, putative mutation to resistance, and future strategies to overcome resistance to KRAS inhibition
lontophoresis-assisted corneal cross-linking method: potential therapy for keratoconus
No full textTo present procedure of iontophoresis-assisted corneal cross-linking
Paradigm shift in cancer rehabilitation – new principles in kinesiotherapy and extracorporeal shock-wave therapy
No full textOnkološka rehabilitacija primarno je fokusirana na individualne funkcionalne deficite i njihov učinak na onesposobljenost i kvalitetu života povezanu sa zdravljem. Potrebno je što ranije integrirati onkološku rehabilitaciju u kontinuum skrbi o onkološkim bolesnicima. Najvrjedniji dio onkološke rehabilitacije predstavlja individualna kinezioterapija, s ciljem poboljšanja funkcionalnog zdravlja bolesnika. Iz razumljivih razloga mnogi onkološki bolesnici su smanjenih tjelesnih mogućnosti, snage i izdržljivosti. Prednosti kinezioterapije su prepoznate u smislu poboljšanja tjelesnih kapaciteta, mentalnog zdravlja i kvalitete u različitim aspektima života. U nekim tipovima malignih bolesti kontinuirana bi kinezioterapija mogla utjecati na preživljavanje. Sve se češće daje prednost treningu visokog intenziteta nasuprot etabliranim kontinuiranim vježbama umjerenog intenziteta. Pokazalo se da je vrijeme provedeno u zoni maksimalnoga aerobnog napora, povećavajući maksimalni aerobni kapacitet, superiorno u odnosu na standardne umjerene vježbe ili bez vježbi. Osnovana je Međunarodna radna skupina za provođenje vježbi (skr. IBMEWG) u bolesnika s koštanim metastazama, budući da bi isti mogli imati koristi od vježbanja. U cilju prevladavanja potencijalnih funkcionalnih deficita u nadolazećem razdoblju onkološkog liječenja važno mjesto zauzima prehabilitacija. U Hrvatskoj jedinica za onkološku rehabilitaciju djeluje od 1979. godine. Unutar brojnih zdravstvenih institucija diljem svijeta implementiran je koncept pod nazivom Sveobuhvatni centar za rak (engl. Comprehension Cancer Center, CCC) koji u sebi integrira različite jedinice, platforme i skupine. U Austriji je primjerice Tim za rehabilitaciju onkoloških bolesnika (engl. Tumor Board for Cancer Rehabilitation) integriran unutar CCC Platforme za upravljanje nuspojavama, potpornu skrb i rehabilitaciju (engl. CCC Platform for Side Effects- Management, Supportive Care & Rehabilitation), kao klinički relevantan pristup u svrhu podrške u kreiranju rehabilitacijskih strategija kod onkoloških bolesnika. Kao odgovor na potrebu za učinkovitim, brzim i neinvazivnim liječenjem muskuloskeletnih bolesti unazad nekoliko godina razvio se interes za terapijom izvantjelesnim udarnim valom u kontekstu onkološke rehabilitacije. Nedavno se promijenila tradicionalna paradigma u vezi kliničkih indikacija i kontraindikacija za propisivanje liječenja udarnim valom u onkoloških bolesnika.Cancer rehabilitation is primarily focused on individual functional deficits and their impact on disability and health-related quality of life. It is necessary to integrate cancer rehabilitation into the care continuum for these patients as soon as possible. The crown of cancer rehabilitation is individual kinesiotherapy to improve the patient’s functional health. For understandable reasons, many cancer patients have reduced physical capabilities, strength, and endurance. The advantages of kinesiotherapy are widely known for improving physical capacities, mental health, and quality in various aspects of life. In some types of malignant diseases, continuous kinesiotherapy might have a favorable effect on survival. Moreover, some cancer patients prefer high-intensity training over established continuous moderate-intensity exercises. Time spent in the zone of maximum aerobic exertion, increasing maximum aerobic capacity, was shown to be superior to standard moderate exercise or without exercise. An International Bone Metastasis Exercise Working Group (IBMEWG) has been established to conduct exercises in patients with bone metastases since they could benefit from exercise. In order to overcome potential functional deficits in the upcoming period of oncologic treatment prehabilitation takes an important place. In Croatia, the cancer rehabilitation unit has been operating since 1979. Within numerous health institutions worldwide, a concept Comprehension Cancer Center (CCC) has been implemented which integrates different platforms, units, and groups. For example in Austria, the Tumor Board for Cancer Rehabilitation has been integrated within the CCC Platform for Side Effects-Management, Supportive Care & Rehabilitation as a clinically relevant approach to support the creation of cancer rehabilitation strategies. In response to the need for effective, rapid, and non-invasive treatment of musculoskeletal diseases an interest in extracorporeal shock wave therapy (ESWL) has developed in the context of cancer rehabilitation over the past few years. Recently, the traditional paradigm regarding clinical indications and contraindications for prescribing ESWL in cancer patients has changed
How will lung cancer screening and lung nodule management change the diagnostic and surgical lung cancer landscape?
No full textIntroduction: Implementation of lung cancer screening, with its subsequent findings, is anticipated to change the current diagnostic and surgical lung cancer landscape. This review aimed to identify and present the most updated expert opinion and discuss relevant evidence regarding the impact of lung cancer screening and lung nodule management on the diagnostic and surgical landscape of lung cancer, as well as summarise points for clinical practice.
Methods: This article is based on relevant lectures and talks delivered during the European Society of Thoracic Surgeons–European Respiratory Society Collaborative Course on Thoracic Oncology (February 2023). Original lectures and talks and their relevant references were included. An additional literature search was conducted and peer-reviewed studies in English (December 2022 to June 2023) from the PubMed/Medline databases were evaluated with regards to immediate affinity of the published papers to the original talks presented at the course. An updated literature search was conducted ( June 2023 to December 2023) to ensure that updated literature is included within this article.
Results: Lung cancer screening suspicious findings are expected to increase the number of diagnostic investigations required therefore impacting on current capacity and resources. Healthcare systems already face a shortage of imaging and diagnostic slots and they are also challenged by the shortage of interventional radiologists. Thoracic surgery will be impacted by the wider lung cancer screening implementation with increased volume and earlier stages of lung cancer. Nonsuspicious findings reported
at lung cancer screening will need attention and subsequent referrals where required to ensure participants are appropriately diagnosed and managed and that they are not lost within healthcare systems.
Conclusions: Implementation of lung cancer screening requires appropriate mapping of existing resources and infrastructure to ensure a tailored restructuring strategy to ensure that healthcare systems can meet the new needs