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Tissue engineering and future directions in regenerative medicine for knee cartilage repair: a comprehensive review
This review evaluates the current landscape and future directions of regenerative medicine for knee cartilage repair, with a particular focus on tissue engineering strategies. In this context, scaffold-based approaches have emerged as promising solutions for cartilage regeneration. Synthetic scaffolds, while offering superior mechanical properties, often lack the biological cues necessary for effective tissue integration. Natural scaffolds, though biocompatible and biodegradable, frequently suffer from inadequate mechanical strength. Hybrid scaffolds, combining elements of both synthetic and natural materials, present a balanced approach, enhancing both mechanical support and biological functionality. Advances in decellularized extracellular matrix scaffolds have shown potential in promoting cell infiltration and integration with native tissues. Additionally, bioprinting technologies have enabled the creation of complex, bioactive scaffolds that closely mimic the zonal organization of native cartilage, providing an optimal environment for cell growth and differentiation. The review also explores the potential of gene therapy and gene editing techniques, including CRISPR-Cas9, to enhance cartilage repair by targeting specific genetic pathways involved in tissue regeneration. The integration of these advanced therapies with tissue engineering approaches holds promise for developing personalized and durable treatments for knee cartilage injuries and osteoarthritis. In conclusion, this review underscores the importance of continued multidisciplinary collaboration to advance these innovative therapies from bench to bedside and improve outcomes for patients with knee cartilage damage
Recommendation for Management of Deep Vein Thrombosis in the Emergency Medicine
Duboka venska tromboza je multifaktorska bolest u koje dolazi do nastanka tromba u dubokim venama. Važno je njezino rano prepoznavanje i liječenje jer može uzrokovati plućnu emboliju te najopasniju komplikaciju, smrtni ishod. Cilj je ovih smjernica standardiziran pristup bolesniku u hitnoj medicinskoj službi, koji će omogućiti brzo i točno postavljanje dijagnoze i pravovremeno liječenje u bolničkim ili kućnim uvjetima. U dijagnostičkom smislu, najprije je važno procijeniti kliničku vjerojatnost pomoću Wellsova skora, potom odrediti D-dimere i, ako je potrebno, prema postupniku učiniti kolor-dopler. Osnovu liječenja duboke venske tromboze predstavlja antikoagulantna terapija, čime sprječavamo progresiju tromba i potencijalnu embolizaciju, a samim time i ozbiljne životno ugrožavajuće komplikacije.Deep vein thrombosis is a multifactorial disease in which thrombus formation occurs in deep veins. Its early recognition and treatment are important, because it can cause pulmonary embolism and its most dangerous complication, death. The goal of these guidelines is a standardized approach to the patient in the emergency medical service, which will enable quick and accurate diagnosis and timely treatment in hospital or home conditions. In the diagnostic sense, it is first important to assess the clinical probability using the Wells score, then to determine D-dimers and, if necessary, to perform a Collor Doppler ultrasound according to the procedure. Anticoagulant therapy is the basis of deep vein thrombosis treatment, which prevents thrombus progression and potential embolization, and thus serious life-threatening complications
Utjecaj COVID pandemije na dijagnozu i liječenje raka prostate: rezultati iz hrvatskog tercijarnog referentnog centra
The COVID-19 pandemic had a negative impact on the treatment of diseases
other than COVID. The aim of our study was to demonstrate the impact it had on the diagnosis and
treatment of patients with prostate cancer. By reviewing the work performed at the Clinic of Urology
of the Clinical Hospital Centre Rijeka, we compared the following data for the period before the
pandemic (2018) and the period during the pandemic (2021): number of prostate biopsies performed,
number of newly-diagnosed cancers, PSA levels at biopsy, waiting time from the diagnosis to start of
the treatment, stage of disease at biopsy and stage after prostatectomy, and finally the treatment options
used. The results confirm the hypothesis that the pandemic had a negative impact on both diagnosis
and treatment. The number of newly-diagnosed patients decreased by 37.24%, which correlates
with a lower number of all prostate biopsies. We also noted a longer time to the start of the treatment
for patients and an increase in poorer pathohistological outcomes after radical prostatectomy. Due to
the higher disease stages, radiotherapy and chemotherapy were used more frequently.COVID-19 pandemija negativno je utjecala na liječenje ne-COVID bolesti. Cilj našeg istraživanja je pokazati utjecaj
iste na dijagnostiku i liječenje bolesnika oboljelih od karcinoma prostate. Pretražujući arhivu Klinike za urologiju Kliničkog
bolničkog centra Rijeka usporedili smo sljedeće podatke za prepandemijsku 2018. i pandemijsku 2021. godinu: broj biopsija
prostate, broj novodijagnosticiranih karcinoma, vrijednosti PSA pri upućivanju na biopsiju, vrijeme čekanja od postavljanja
dijagnoze do početka liječenja, stadij bolesti na temelju bioptata i stadij na temelju uzorka nakon prostatektomije te korištene
oblike liječenja. Rezultati potvrđuju hipotezu negativnog utjecaja pandemije na dijagnostiku i liječenje. Postotak novodijagnosticiranih bolesnika smanjio se za 37.24% što korelira s manjim brojem biopsija prostate. Također primijetili smo produljeni vremenski period do početka liječenja bolesnika te porast lošijih patohistoloških rezultata nakon radikalne prostatektomije.
Sukladno lošijem stadiju bolesti, nešto učestalije se primjenjivala radioterapija i kemoterapija u nastavku njihova liječenja
Otrovanje kofeinom sa smrtnim ishodom – je li češće samoubojstvo ili slučajno predoziranje?
Caffeine is a natural stimulant of plant origin found in many products such as coffee, tea, chocolate, and energy drinks. It is also often used as an active substance in over-the-counter drugs such as painkillers and preparations for the treatment of colds and allergies. While caffeine is generally considered safe when moderately consumed, excessive intake in a single dose or through repeated small doses over time can lead to caffeine intoxication. Symptoms of caffeine intoxication can vary depending on the amount of caffeine consumed and can include restlessness, rapid heart rate, muscle tremors, nausea, vomiting, and confusion. In severe cases, caffeine intoxication can lead to convulsions, coma, and even death. This mini-review presents an overview of caffeine’s characteristics and intoxication including symptoms, causes, diagnosis, and treatment. It addresses risk factors associated with caffeine intoxication and presents current recommendations for safe caffeine consumption. The studies we have reviewed suggest that in cases of fatal caffeine intoxications, intentional intoxication is more common than unintentional.Kofein je prirodni stimulans biljnog podrijetla koji se nalazi u mnogim prehrambenim proizvodima poput kave, čaja, čokolade i energetskih napitaka. Također, često se koristi kao jedna od aktivnih tvari u bezreceptnim lijekovima poput lijekova protiv bolova i pripravaka za liječenje prehlade i alergija. Dok se kofein općenito smatra sigurnim ako se umjereno konzumira, pretjerani unos u jednoj dozi ili ponavljanim malim dozama tijekom vremena može dovesti do otrovanja kofeinom. Simptomi otrovanja kofeinom ovise o količini konzumiranog kofeina i mogu uključivati nemir, ubrzan rad srca, drhtanje, mučninu, povraćanje i zbunjenost. Teški slučajevi otrovanja kofeinom moge dovesti do konvulzija, kome, pa čak i smrti. U ovom su preglednom radu prikazane karakteristike otrovanja kofeinom uključujući uzroke, simptome, dijagnozu i liječenje. Opisani su čimbenici rizika povezani s otrovanjem kofeinom te navedene trenutne preporuke za sigurnu konzumaciju kofeina. Iz rezultata objavljenih istraživanja prikazanih u ovome preglednom radu može se zaključiti da je u slučajevima smrtonosnih otrovanja kofeinom, namjerno otrovanje češće nego slučajno
Učinkovitost pokrova polietilena visoke gustoće (HDPE) u sprječavanju emisija odlagališnih plinova: smanjenje atmosferskih koncentracija H2S, NH3 i PM10
We investigated the effectiveness of high-density polyethylene (HDPE) covers in reducing landfill emissions of hydrogen sulphide (H2S), ammonia (NH3), and inhalable particulate matter smaller than 10 μm in diameter (PM10) at the Waste Management Centre Marišćina (Croatia) by comparing air quality data from 2018, prior to the installation of the HDPE cover, with data from 2021, post-installation. The results demonstrate a significant reduction in H2S and PM10 concentrations (36.76 % and 24.18 %, respectively). However, NH3 levels unexpectedly increased by 20.48 %, suggesting the presence of additional sources of ammonia in the vicinity of the centre or changes in landfill microenvironment. Our findings highlight the effectiveness of HDPE covers in controlling specific landfill emissions and the need for a comprehensive environmental management strategy to address all pollutants. Future research should also investigate the long-term effects of HDPE cover on landfill emissions and how they could contribute to broader environmental goals, such as reducing greenhouse gas emissions and improving air quality.U ovom radu analizirali smo učinkovitost primjene pokrova polietilena visoke gustoće (HDPE) u smanjenju emisija sumporovodika (H2S), amonijaka (NH3) i lebdećih čestica promjera manjeg od 10 μm (PM10) s odlagališta na području Centra za gospodarenje otpadom Marišćina. U istraživanju smo usporedili podatke o kakvoći zraka prikupljene na mjernoj postaji smještenoj u blizini Centra tijekom 2018. godine, kada HDPE pokrov nije bio instaliran, s podacima iz 2021. godine, nakon ugradnje pokrova. Rezultati pokazuju značajno smanjenje koncentracija H2S (36,76 %) i PM10 (24,18 %), što potvrđuje učinkovitost HDPE pokrova u smanjenju tih specifičnih emisija. Međutim, razine NH3 neočekivano su porasle 20,48 %, što upućuje na moguće postojanje dodatnih izvora amonijaka u blizini Centra ili na promjene u mikrookolišu samog odlagališta otpada. U radu se ističe važnost primjene HDPE pokrova kao mjere za kontrolu emisija s odlagališta otpada, ali se istodobno upućuje i na potrebu za sveobuhvatnim pristupom upravljanju okolišem kako bi se smanjile emisije svih onečišćujućih tvari u okoliš. Buduća istraživanja trebala bi biti usmjerena na procjenu dugoročnih učinaka HDPE pokrova na emisije s odlagališta, s naglaskom na smanjenje emisija stakleničkih plinova i poboljšanje ukupne kakvoće zraka
GALAD, or des-gamma-carboxy prothrombin compared with alpha-foetoprotein for the diagnosis of hepatocellular carcinoma in people with chronic liver disease
Objectives: This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:. To estimate the diagnostic accuracy of des-gamma-carboxy prothrombin, GALAD (Gender, Age, Lens culinaris agglutinin-reactive AFP, AFP and DCP), and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma of any size, and at any stage, in adults with chronic liver disease, in either a surveillance programme or a clinical setting. We acknowledge the possibility that theoretically, the accuracy of the tests in a surveillance programme may differ from that in a clinical setting due to variation in inclusion criteria and the prevalence of the target condition. However, we do not plan a separate analysis for surveillance and clinical settings, as they are not clearly distinct in current clinical practice (Forner 2018; Poustchi 2011). In routine evaluation of people with chronic liver disease, index tests, as well as ultrasound, are already part of standard procedure. Given that HCC typically presents with no symptoms and is often asymptomatic, suspicion of the disease is typically based solely on the presence of advanced chronic liver disease. However, we do plan to consider the study setting as a potential source of heterogeneity. To compare the diagnostic accuracy of des-gamma-carboxy prothrombin (DCP) alone or GALAD alone versus alpha-foetoprotein (AFP), for the diagnosis of hepatocellular carcinoma (HCC) of any size, at any stage; in adults with chronic liver disease, either in a surveillance programme or a clinical setting. Secondary objectives To estimate the diagnostic accuracy of DCP or GALAD versus AFP, for resectable HCC in people with chronic liver disease, in a surveillance programme and a clinical setting. To investigate the following predefined sources of heterogeneity for each of the index tests: study design (case-control studies compared to cross-sectional studies); inclusion of participants without cirrhosis (studies including more than 10% of participants without cirrhosis compared to studies including less than 10% of participants without cirrhosis); study location (population differences): studies conducted in North and South America and Europe compared to Asia and Africa; prevalence of the target condition (studies with hepatocellular carcinoma prevalence more than 10% compared to studies with hepatocellular carcinoma prevalence less than 10%); participant selection (participants recruited from planned surveillance programmes compared to clinical cohorts); different reference standards (histology of the explanted liver compared to liver biopsy compared to another reference standard); different aetiology: studies including at least 90% of participants with chronic viral hepatitis compared to studies including less than 90% of participants with chronic viral hepatitis
CD44 Immunohistochemical Expression in Central and Peripheral Parts of Prostatic Adenocarcinoma: An Institutional Study
Background and Objectives: Prostate cancer is one of the most commonly diagnosed cancers in the male population and the fifth leading cause of cancer death worldwide in men as of 2022. One of the potential biomarkers that can predict the progression of the disease is the transmembrane adhesion molecule CD44s. The aims of this study were to determine the expression of CD44s in prostate cancer in the central tumor mass and in the tumor periphery of the disease and to compare it with the clinicopathological parameters (PSA, Gleason score, surgical margins, and biochemical recurrence of the disease) in patients treated with radical prostatectomy. Materials and Methods: The research was randomized retrospectively during the period from 2001 to 2006. Tissue microarrays of 121 archival acinar prostate carcinoma samples were immunohistochemically evaluated for CD44s expression. The immunoexpression was determined semiquantitatively, taking into account the percentage (0 (0–5%), 1 (6–24%), 2 (26–75%), and 3 (76–100%) and intensity of the membranous staining of the tumor cells (0 absent; 1 weak at 400×; 2 intermediates at 100×; 3 strong at 40×) and calculated to obtain a final score (0–3 were regarded as negative; 4–6 were regarded as positive). Results: For statistical purposes, we divided the tumors into two categories: Gleason grade group 1 makes up 80.7% and grade group 2, which includes all the remaining Gleason grade groups (out of 2–5), accounts for 19.3% of the tumors. Grade group 1 had the highest incidence of score 4 (positive expression). There were statistically significantly more positive expressions in those tumors with negative prostatectomy margins (chi square: p = 0.001; Cramer V: 0.319). There was no correlation between CD44s expression and biochemical recurrence (p = 0.218), nor with the preoperative PSA values (p = 0.165). In the grade group 1 tumors, the CD44s immunoexpression and status of prostatectomy margin were statistically significantly related with negative margins (p = 0.028). An analysis of the expression of CD44s according to the localization in the central part of the tumor mass and on the periphery of the cancer in the group of tumors with a positive margin did not show a significant correlation because the sample was too small. Descriptively, it can be noted that the expression on the periphery was higher, and the central/peripheral expression ratio was higher in favor of the periphery. Conclusions: Our results provide insight into the possible value of CD44s expression for predicting the behavior of prostate tumors and the justification of therapy after a prostatectomy. Also hypothetically, they indicate a protective role of CD44s in a group of well-differentiated tumors at the periphery of the tumor mass. Therefore, it is useful to study the CD44s molecule further in this sense
Profilaktička mastektomija i nasljednji karcinom dojke
In the female population, breast cancer is the most common malignant disease. Breast cancers caused by mutations in the BRCA 1 and BRCA 2 genes are responsible for up to 10% of all cases. With advances in genetics, there is the possibility of identifying women at high risk of developing breast cancer. These women receive assistance in the form of genetic counseling, psychological support, and surgical treatments to reduce their risk of developing breast cancer. Prophylactic mastectomy can be performed as a skin-sparing mastectomy, a skin and nipples sparing mastectomy, and a simple mastectomy, which involves the complete removal of the parenchyma, skin, and nipples of both breasts. In the same act as the prophylactic mastectomy, breast reconstruction can be performed as either a primary reconstruction within the same surgical act or as a separate surgical procedure, in which case it is referred to as secondary reconstruction. Artificial material implants are predominantly used today due to their superior aesthetic results, faster healing, and smaller scars. Such surgeries can lead to various postoperative issues, including infection, hematoma, and seroma formation, while capsular contracture, implant rupture, and anaplastic large cell lymphoma have all been linked to the use of artificial implants.Karcinom dojke najčešća je maligna bolest u populaciji žena. Mutacije gena BRCA1 i BRCA2 odgovorne su za 10% svih nastalih karcinoma dojke. Napretkom genetike postoji mogućnost identifikacije žena s visokim rizikom obolijevanja. Takvim ženama pruža se pomoć u vidu genetičkog savjetovanja, psihološke pomoći i smanjenje rizika od nastanka karcinoma dojke kirurškim metodama. Profilaktičku mastektomiju danas je moguće napraviti s poštedom kože, s poštedom kože i bradavice te jednostavnu mastektomiju koja podrazumijeva potpuno odstranjivanje parenhima, kože i bradavice obiju dojki. U istom aktu s profilaktičkom mastektomijom moguće je učiniti i rekonstrukciju dojke, tada se to naziva primarnom rekonstukcijom. Kada se izvodi kao zaseban kirurški zahvat naziva se sekundarnom rekonstrukcijom. Danas se gotovo isključivo koriste implantati
izrađeni od umjetnih materijala koji pružaju vrhunske estetske rezultate, osiguravaju brži oporavak, a ožiljak je manji. Postoperativne komplikacije ovakvih zahvata mogu biti razne; infekcija, stvaranje hematoma i seroma, dok upotrebom umjetnih
implantata može nastati kapsularna kontraktura, ruptura implantata i anaplastični limfom velikih stanica
Nediferencirani pleomorfni sarkom dojke u muškarca
Objective: The objective of this case report is to present a rare case of inflammatory undifferentiated pleomorphic sarcoma in a male breast. Case report: a 64-year-old man palpated a painless nodule on the left breast. Core needle biopsy did not reveal the final diagnosis as it was classified as B3 so an excisional biopsy of the tissue was performed, which revealed an undifferentiated pleomorphic sarcoma with a diameter of 4.5 cm, infiltrated with inflammatory cells. After we confirmed the sarcoma operation therapy was indicated. Stewart incision was performed and mastectomy was done. Pathohistological analysis confirmed negative surgical resection margins. After one month PET CT scan revealed lungs metastases and the patient underwent 6 chemotherapy cycles of doxorubicin with good response and contribution of lungs metastases remission. Three years later, the tumor recurred and infiltrated the thoracic wall. The patient underwent again to surgical procedure. We did the extirpation of tumor, resection of thoracic wall with large pectoral muscle and within fifth, sixth and seventh ribs resection and thoracoplasty with core matrix and bio-net was performed for reconstruction of the defect. On pathohistology findings distal resection margin was infiltrated by tumor cells so radiotherapy was performed. Larger thoracic resection was not possible as it would affect breathing mechanics. The postoperative course was normal, without paradoxical breathing. The patient has been in remission according to PET-CT examination for four years after them treatment. Conclusion: We have presented a rare case of undifferentiated pleomorphic sarcoma in the breast, its potential for recurrence and distant metastases, the possibilities of treatment, the importance and limitations of operative treatment as well as benefit of oncological procedures and unpredictable clinical course of disease.Cilj: Cilj je ovog rada prikazati rijedak slučaj inflamatornog nediferenciranog pleomorfnog sarkoma u muškoj dojci.
Prikaz slučaja: 64-godišnji muškarac napipao je bezbolni čvor u lijevoj dojci. Širokoiglena biopsija nije razjasnila završnu dijagnozu te je klasificirana sa B3. Stoga se pristupilo operacijskom postupku. Učinjena je ekstirpacija tumora, a patohistološki nalaz potvrdio je nediferencirani pleomorfni sarkom promjera 4,5 cm, infiltriran upalnim stanicama. Nakon potvrde sarcoma indicirana je bila operacijska terapija. Pristupilo se inciziji po Stewartu te se učinila mastektomija. Patohistološkom analizom potvrđeni su negativni kirurški resekcijski rubovi. Mjesec dana kasnije PET CT pregledom otkrivene su plućne metastaze, zbog čega je pacijent prošao kroz 6 kemoterapijskih ciklusa doksorubicina sa dobrim odgovorom na terapiju te je postignuta kompletna remisija plućnih metastaza. Tri godine kasnije CT nalaz pokazao je recidiv tumora sa infiltracijom cijele debljine torakalne stijenke. Indicirano je bilo kirurško liječenje. Operacijom je uklonjen tumor i veliki pektoralni mišić u bloku sa šestim, sedmim i osmim rebrom te je učinjena torakoplastika core matrixom i biološkom mrežicom u svrhu rekonstrukcije defekta. U patohistološkom nalazu distalni resekcijski rub bio je pozitivan, infiltriran tumorskim stanicama, te je stoga bolesnik bio podvrgnut radioterapiji. Širi opseg operacije nije bio moguć zbog opasnosti utjecaja na mehaniku disanja. Postoperativni tijek je bio uredan, bez paradoksalnog disanja. Bolesnik je sljedeće četri godine praćen jednom godišnje PET CT- om te do sada nije imao znakove ponovnog recidiva bolesti kao niti metastaza.
Zaključak: Prikazali smo rijedak slučaj nediferenciranog pleomorfnog sarkoma u dojci, njegov potencijal za lokalnu invaziju i sklonost recidiviranju kao i metastaziranju, te važnost, ali i ograničenja operativnog liječenja kao i značaj sveobuhvatne onkološke terapije i nepredvidiv klinički tijek bolesti
Kako su europske zemlje koje graniče s Mediteranom utjecale na bioetiku; s posebnim naglaskom na Hrvatsku, Grčku, Italiju i Španjolsku
One of the promising ways of constructing bioethics outside the global mainstream – characterized by a perspective narrowed down to issues related to medical ethics and research – is undoubtedly the Mediterranean bioethics, based on the rich intellectual heritage of the basin between European, Asian, and African continents. This bioethics, addressing the entire bios and thus far closer to the original ideas of Fritz Jahr and Van Rensselaer Potter, has particularly been nourished in Spain, Italy, Croatia, and Greece, producing an extensive corpus of publications. Following an international project devoted to investigating those cultural traditions and their bioethical roots, the present paper offers a tentative overview of the most influential individuals and their ideas and the most active institutions in the area.Jedan od obećavajućih načina konstruiranja bioetike izvan globalnog mainstreama – karakteriziranog perspektivom suženom na pitanja vezana uz medicinsku etiku i istraživanje – nedvojbeno je mediteranska bioetika, utemeljena na bogatom intelektualnom nasljeđu bazena između europskog, azijskog i afričkog kontinenta. Ta se bioetika, koja se bavi cijelim biosom i time daleko bliža izvornim idejama Fritza Jahra i Van Rensselaera Pottera, posebno njegovala u Španjolskoj, Italiji, Hrvatskoj i Grčkoj, proizvevši opsežan korpus publikacija. Nakon međunarodnog projekta posvećenog istraživanju tih kulturnih tradicija i njihovih bioetičkih korijena, ovaj rad nudi okvirni pregled najutjecajnijih pojedinaca i njihovih ideja te najaktivnijih institucija na tom području