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Are treatment options used for adult-onset type 2 diabetes mellitus(equally)available and effective for children and adolescents?

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World Journal of Diabetes 2024年第4期15卷 623-628页

作者： Nevena Krnic Vibor Sesa Anna Mrzljak Maja Cigrovski Berkovic Clinics for Pediatrics University Hospital Center ZagrebZagreb 10000Croatia Department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia university of zagreb school of medicine Zagreb 10000Croatia Department for Sport and Exercise medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

Youth-onset type 2 diabetes mellitus(T2DM),influenced by an increase in obesity,is a rising problem *** mechanisms of this early-onset T2DM include both peripheral and hepatic insulin resistance,along with increa-sed hepatic fasting glucose production accompanied by inadequate first and second-phase insulin ***,the incretin effect is *** initial presentation of type 2 diabetes can be dramatic and symptoms may overlap with those of type 1 diabetes ***,immediate therapy should address hyperglycemia and associated metabolic derangements irrespective of ultimate diabetes type,while further therapy adjustments are prone to patients’*** agents with proven glycemic and beyond glycemia benefits,such as Glucagon-like polypeptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors,used in the adult population of T2DM patients,might become increasingly important in the treatment ***,metabolic surgery is an option for markedly obese(body mass index>35 kg/m^(2))children and adolescents suffering from T2DM who have uncontrolled glycemia and/or serious comorbidities when lifestyle and pharmacologic interventions *** this mini-review,we will discuss the potential of treatment options considering new data available from randomized control trials,including individuals with adult-onset type diabetes mellitus.

关键词： Youth-onset type 2 diabetes mellitus Treatment Complications Glucose lowering agents Extra-glycemic benefit

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Biological characteristics and clinical management of uveal and conjunctival melanoma

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Oncology Research 2024年第8期32卷 1265-1285页

作者： SNJEŽANA KAŠTELAN ANA DIDOVIĆPAVIČIĆ DARIA PAŠALIĆ TAMARA NIKUŠEVA-MARTIĆ SAMIRČANOVIĆ PETRA KOVAČEVIĆ SUZANA KONJEVODA school of medicine University of ZagrebZagreb10000Croatia Department of Ophthalmology Clinical Hospital DubravaZagreb10000Croatia Department of Ophthalmology Zadar General HospitalZadar23000Croatia Department of Medical Chemistry Biochemistry and Clinical ChemistrySchool of MedicineUniversity of ZagrebZagreb10000Croatia Department of Biology and Genetics School of MedicineUniversity of ZagrebZagreb10000Croatia school of medicine University of SplitSplit21000Croatia Department of Health Studies University of ZadarZadar23000Croatia

Uveal and conjunctival melanomas are relatively rare tumors;nonetheless,they pose a signiﬁcant risk of mortality for a large number of affected *** pathogenesis of melanoma at different sites is very similar,however,the prognosis for patients with ocular melanoma remains unfavourable,primarily due to its distinctive genetic proﬁle and tumor *** of considerable advances in understanding the genetic characteristics and biological behaviour,the treatment of uveal and conjunctival melanoma remains a formidable *** enhance the prospect of success,collaborative efforts involving medical professionals and researchers in theﬁelds of ocular biology and oncology are *** data show a lack of well-designed randomized clinical trials and limited beneﬁts in current forms of treatment for these *** advancements in the development of effective melanoma therapeutic strategies,all current treatments for uveal melanoma(UM)and conjunctival melanoma(CoM)remain unsatisfactory,resulting in a poor long-term *** trials offer hope for positive outcomes in advanced and metastatic tumors.A more comprehensive understanding of the genetic and molecular abnormalities involved in the development and progression of ocular melanomas opens the way for the development of personalized therapy,with various potential therapeutic targets currently under *** comprehension of the molecular pathogenesis of UM and CoM and their speciﬁcities may aid in the development of new and more effective systemic therapeutic agents,with the hope of improving the prognosis for patients with metastatic disease.

关键词： Uveal melanoma Conjunctival melanoma Genetic characteristics Immune checkpoint inhibitors Target molecular inhibitors

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Primary hyperparathyroidism-induced acute pancreatitis in pregnancy:A systematic review with a diagnostic-treatment algorithm

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World Journal of Gastroenterology 2024年第32期30卷 3755-3765页

作者： Goran Augustin Quirino Lai Maja Cigrovski Berkovic Department of Surgery University Hospital Centre Zagreb and School of Medicine University of ZagrebZagreb 10000Croatia General Surgery and Organ Transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy Department for Sport and Exercise medicine Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia

BACKGROUND Primary hyperparathyroidism(PHPT)-induced acute pancreatitis(AP)during pregnancy has rarely been *** to this rarity,there are no diagnostic or treatment algorithms for pregnant *** To determine appropriate diagnostic methods,therapeutic options,and factors related to maternal and fetal outcomes for PHPT-induced AP in *** A literature search of articles in English,Japanese,German,Spanish,and Italian was performed using PubMed(1946-2023),PubMed Central(1900-2023),and Google *** Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA)protocol was *** search terms included“pancreatite acuta,”“iperparatiroidismo primario,”“gravidanza,”“travaglio,”“puerperio,”“postpartum,”“akute pankreatitis,”“primärer hyperparathyreoidismus,”“Schwangerschaft,”“Wehen,”“Wochenbett,”“pancreatitis aguda,”“hiperparatiroidismo primario,”“embarazo,”“parto,”“puerperio,”“posparto,”“acute pancreatitis,”“primary hyperparathyroidism,”“pregnancy,”“labor,”“puerperium,”and“postpartum.”Additional studies were identified by reviewing the reference lists of retrieved ***,imaging,surgical,obstetric,and outcome data were *** Fifty-four cases were collected from the 51 *** median maternal age was 29 ***-induced AP starts at the 20th gestational week;higher gestational weeks were seen in mothers who died(mean gestational week 28).Median values of amylase(1399,Q1-Q3=519-2072),lipase(2072,Q1-Q3=893-2804),serum calcium(3.5,Q1-Q3=3.1-3.9),and parathormone(PTH)(384,Q1-Q3=123-910)were *** 46 cases,adenoma was the cause of PHPT,followed by 2 cases of carcinoma and 1 case of *** the remaining 5 cases,the diagnosis was not *** ultrasound was positive in 34 cases,whereas sestamibi was performed in 3 cases,and neck computed tomography or magnetic resonance imaging was performed in 9 cases(the enlarged parathyroid gland was not localized in 3 cases).Surgery was the prefer

关键词： Primary hyperparathyroidism Acute pancreatitis Pregnancy Diagnosis Maternal mortality Fetal mortality Algorithm

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Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients

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World Journal of Clinical Cases 2024年第6期12卷 1104-1110页

作者： Nikolina Basic-Jukic Ivana Juric Lea Katalinic Vesna Furic-Cunko Vibor Sesa Anna Mrzljak Department of Nephrology Arterial HypertensionDialysis and TransplantationUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of medicine School of MedicineZagreb 10000Croatia Department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia

BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains *** To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute *** A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute *** were obtained from hospital electronic medical *** acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal *** Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 *** analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the *** hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical *** included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive *** the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic *** survived without complications with a stable kidney allograft *** Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant *** mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

关键词： Acute pancreatitis COVID-19 Kidney transplant Angiotensin-converting enzyme-2 receptor Immunosuppressive agents

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Immunology demystified: A guide for transplant hepatologists

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World Journal of Transplantation 2024年第1期14卷 48-61页

作者： Iva Kosuta Tomislav Kelava Ana Ostojic Vibor Sesa Anna Mrzljak Hrvoje Lalic Department of Intensive Care medicine University Hospital Centre ZagrebZagreb 10000Croatia Department of Physiology School of MedicineUniveristy of ZagrebZagreb 10000Croatia Laboratory for Molecular Immunology Croatian Institute for Brain ResearchZagreb 10000Croatia Department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of medicine School of MedicineUniversity of ZagrebZagreb 10000Croatia Department of Physiology University of Zagreb School of MedicineZagreb 10000Croatia Laboratory for Cell Biology Croatian Institute for Brain ResearchUniversity of Zagreb School of MedicineZagreb 10000Croatia Department of Laboratory Immunology Clinical Department of Laboratory DiagnosticsUniversity Hospital Center ZagrebZagreb 10000Croatia

Liver transplantation has become standard practice for treating end-stage liver *** success of the procedure relies on effective immunosuppressive medications to control the host's immune *** the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune *** ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic ***,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased *** that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive *** knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

关键词： Liver transplantation Allograft rejection Operational immune tolerance Immune reaction Immunosuppression

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Challenges and pitfalls of youth-onset type 2 diabetes

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World Journal of Diabetes 2024年第5期15卷 876-885页

作者： Lavinia La Grasta Sabolic Sanda Marusic Maja Cigrovski Berkovic Department of Pediatric Endocrinology and Diabetology University Hospital Centre Sestre MilosrdniceZagreb 10000Croatia school of medicine Catholic University of CroatiaZagreb 10000Croatia Department for Sport and Exercise medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are *** rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes ***,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell ***,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in *** to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment *** this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

关键词： Youth-onset type 2 diabetes mellitus Insulin resistance Beta cell failure Risk factors Therapy Complications

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Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

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World Journal of Gastroenterology 2024年第7期30卷 759-769页

作者： Maja Cigrovski Berkovic Alessandro Coppola Vibor Sesa Anna Mrzljak Quirino Lai Department for Sport and Exercise medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Surgery Sapienza University of RomeRome 00185Italy Department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of medicine School of MedicineZagreb 10000Croatia General Surgery and Organ Transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor ***,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is *** this perspective,metformin is emerging as a molecule of *** studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR *** systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with *** To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of *** A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free *** A total of 13 studies(5674 patients)were included in this *** of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of *** T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS

关键词： Pancreatic neuroendocrine tumors Type 2 diabetes mellitus Prognosis Treatment Metformin

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Portal hypertension in patients with nonalcoholic fatty liver disease:Current knowledge and challenges

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World Journal of Gastroenterology 2024年第4期30卷 290-307页

作者： Anita Madir Ivica Grgurevic Emmanuel A Tsochatzis Massimo Pinzani Department of Gastroenterology Hepatology and Clinical NutritionUniversity Hospital DubravaZagreb 10000Croatia school of medicine University of ZagrebZagreb 10000Croatia Faculty of Pharmacy and Biochemistry University of ZagrebZagreb 10000Croatia UCL Institute for Liver and Digestive Health Royal Free Hospital and University College LondonLondon NW32PFUnited Kingdom

Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver *** early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver *** compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of *** spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with ***,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of *** theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this *** and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing *** change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the comp

关键词： Non-alcoholic fatty liver disease Portal hypertension Mechanotransduction Endothelial dysfunction Hepatic venous pressure gradient

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Managing end-stage carcinoid heart disease:A case report and literature review

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 1076-1083页

作者： Nikola Bulj Vedran Tomasic Maja Cigrovski Berkovic Department of Cardiology University Hospital Centre“Sestre Milosrdnice“Zagreb 10000Croatia Division of Gastroenterology Department of Internal MedicineUniversity Hospital Centre“Sestre Milosrdnice”Zagreb 10000Croatia Department for Sport and Exercise medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of *** complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic *** SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver *** the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to *** 10 years,he presented to the emergency room with signs and symptoms of right-sided heart *** markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic *** tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and ***,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart *** patient was not a candidate for valve *** started octreotide acetate treatment,and the dose escalated to 80 mg IM *** biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart *** heart disease and tumor burden are major prognostic factors of poor surviva

关键词： Gastroenteropancreatic neuroendocrine neoplasms Carcinoid syndrome Carcinoid heart disease Diagnosis Treatment Case report

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Expect the unexpected:Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism

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World Journal of Clinical Cases 2024年第7期12卷 1200-1204页

作者： Ana Majic Tengg Maja Cigrovski Berkovic Ivan Zajc Ivan Salaric Danko Müller Iva Markota Department of Endocrinology DiabetesMetabolic Diseases and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia Department for Sport and Exercise medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Oral Surgery Clinical Hospital DubravaZagreb 10000Croatia university of zagreb school of Dental medicine Zagreb 10000Croatia Clinical Department of Pathology and Cytology Clinical Hospital DubravaZagreb 10000Croatia

Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium *** commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and *** tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical *** tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic ***,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone *** diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and *** when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic *** of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical ***,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.

关键词： Brown tumor Hyperparathyroidism Lytic bone lesions Giant cell tumor

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