Arterial hypertension in patients with diabetic nephropathy

Šećerna bolest najčešći je uzrok kroničnog bubrežnog zatajenja u svijetu. Dijabetička nefropatija je bolest koju karakteriziraju perzistentna proteinurija, pad glomerularne filtracije (GF), povišenje krvnog tlaka i progresija u završnoj fazi zatajenja bubrega. Hipertenzija je česta kod bolesnika s kroničnom bolesti bubrega (KBB) i šećerne bolesti. U ovoj populaciji hipertenzija povećava rizik za nastanak bolesti bubrega i napredovanja i kardiovaskularnog (KV) morbiditeta i mortaliteta. Dijabetička nefropatija (DN) je najčešći uzrok KBB u onih s dijabetesom. Mehanizam hipertenzije dijabetičke nefropatije je složen, nedovoljno razjašnjen, a uključuje višak zadržavanja natrija, simpatički živčani sustav (SNS) i aktivaciju renin-angiotenzin-aldosteron (RAAS) sistema, disfunkciju endotelnih stanica. Ti mehanizmi su odgovorni za nastanak i pogoršanje hipertenzije u ovoj populaciji i doprinijeli su povećanom riziku za nepovoljni KV ishod. Trenutno upravljanje hipertenzije kod dijabetičke nefropatije treba uključivati terapije koje blokiraju proizvodnju angiotenzina ili akciju i ciljeva liječenja krvnog tlaka s tim lijekova trebaju biti usmjereni na krvni tlak < 130/80 mmHg. Važno postizanje tog cilja će biti potrebno korištenje obje nefarmakološke intervencije u kombinaciji s više antihipertenzivnih lijekova. Nedavne studije istražuju korištenje kombiniranih terapija koje koriste više od jednog RAAS lijeka, te formalne preporuke čekaju svoje rezultate.Diabetes mellitus is the most common cause of chronic renal failure in the world. Diabetic nephropathy is a disease characterized by persistent proteinuria, decreased glomerular filtration rate (GF), blood pressure and progression to the final stage of kidney failure. Hypertension is common in patients with chronic kidney disease (CKD) and diabetes. In this population, hypertension increases the risk of kidney disease and progression of cardiovascular (CV) morbidity and mortality. Diabetic nephropathy (DN) is the most common cause of CKD in patients with diabetes. The mechanism of hypertension, diabetic nephropathy is complex and insufficiently understood, and includes the excess sodium retention, sympathetic nervous system (SNS) and the activation of Irene - angiotensin - aldosterone system (RAAS) system, dysfunction of the endothelium - muscle cells. These mechanisms are responsible for the development and aggravation of hypertension in this population and have contributed to the increased risk of adverse CV outcome. Current management of hypertension in diabetic nephropathy should include therapies that block the production or action of angiotensin and blood pressure treatment goals with these drugs should be focused on blood pressure < 130/80 mmHg. Important to the achievement of this goal will be necessary to use both non - pharmacological intervention in combination with more antihypertensive drugs. Recent studies investigating the use of combination therapy using more than one drug RAAS, and formal recommendations await their results

Arterial hypertension in patients with diabetic nephropathy

Šećerna bolest najčešći je uzrok kroničnog bubrežnog zatajenja u svijetu. Dijabetička nefropatija je bolest koju karakteriziraju perzistentna proteinurija, pad glomerularne filtracije (GF), povišenje krvnog tlaka i progresija u završnoj fazi zatajenja bubrega. Hipertenzija je česta kod bolesnika s kroničnom bolesti bubrega (KBB) i šećerne bolesti. U ovoj populaciji hipertenzija povećava rizik za nastanak bolesti bubrega i napredovanja i kardiovaskularnog (KV) morbiditeta i mortaliteta. Dijabetička nefropatija (DN) je najčešći uzrok KBB u onih s dijabetesom. Mehanizam hipertenzije dijabetičke nefropatije je složen, nedovoljno razjašnjen, a uključuje višak zadržavanja natrija, simpatički živčani sustav (SNS) i aktivaciju renin-angiotenzin-aldosteron (RAAS) sistema, disfunkciju endotelnih stanica. Ti mehanizmi su odgovorni za nastanak i pogoršanje hipertenzije u ovoj populaciji i doprinijeli su povećanom riziku za nepovoljni KV ishod. Trenutno upravljanje hipertenzije kod dijabetičke nefropatije treba uključivati terapije koje blokiraju proizvodnju angiotenzina ili akciju i ciljeva liječenja krvnog tlaka s tim lijekova trebaju biti usmjereni na krvni tlak < 130/80 mmHg. Važno postizanje tog cilja će biti potrebno korištenje obje nefarmakološke intervencije u kombinaciji s više antihipertenzivnih lijekova. Nedavne studije istražuju korištenje kombiniranih terapija koje koriste više od jednog RAAS lijeka, te formalne preporuke čekaju svoje rezultate.Diabetes mellitus is the most common cause of chronic renal failure in the world. Diabetic nephropathy is a disease characterized by persistent proteinuria, decreased glomerular filtration rate (GF), blood pressure and progression to the final stage of kidney failure. Hypertension is common in patients with chronic kidney disease (CKD) and diabetes. In this population, hypertension increases the risk of kidney disease and progression of cardiovascular (CV) morbidity and mortality. Diabetic nephropathy (DN) is the most common cause of CKD in patients with diabetes. The mechanism of hypertension, diabetic nephropathy is complex and insufficiently understood, and includes the excess sodium retention, sympathetic nervous system (SNS) and the activation of Irene - angiotensin - aldosterone system (RAAS) system, dysfunction of the endothelium - muscle cells. These mechanisms are responsible for the development and aggravation of hypertension in this population and have contributed to the increased risk of adverse CV outcome. Current management of hypertension in diabetic nephropathy should include therapies that block the production or action of angiotensin and blood pressure treatment goals with these drugs should be focused on blood pressure < 130/80 mmHg. Important to the achievement of this goal will be necessary to use both non - pharmacological intervention in combination with more antihypertensive drugs. Recent studies investigating the use of combination therapy using more than one drug RAAS, and formal recommendations await their results

SMJERNICE ZA OBRADU TRAUMATSKIH OZLJEDA GLAVE U ODRASLOJ POPULACIJI U HITNOJ SLUŽBI U KLINIČKOJ BOLNICI DUBRAVA

Head trauma is a common presentation in the Emergency Department (ED), ranging from skull fractures, minor traumatic brain injuries (TBIs) to severe TBIs in polytraumas. In moderate traumatic brain injuries, patient assessment and diagnostic work-ups can be ameliorated with the application of Clinical Decision Rules (CDRs) such as the Canadian CT Head Rule (CCHR) and the National Institute for Care and Excellence (NICE) guidelines. Optimal adherence to these CDRs greatly benefi ts patients, reduces waiting times, ED overcrowding, mortality and ED clinician pitfalls. The aim of this report is to provide the reader with a brief review of the CCHR and NICE guidelines, which are implemented in Dubrava University Hospital, with an overview as to how our ED collaborates with its neurosurgical team and other surgical specialists in situations of polytrauma and TBI patients, mainly focusing on TBI. In addition, we will introduce the Dubrava Model, one of the neurotrauma models implemented in fast treatment of TBIs in rural hospitals devoid of resident neurosurgeon.Trauma glave, sežući od prijeloma lubanje i manje traumatske ozljede mozga do teške traumatske ozljede mozga u politraumama, česta je prezentacija u hitnoj službi. Kod umjerenih/srednje teških traumatskih ozljeda mozga pristup bolesniku i dijagnostička obrada mogu se poboljšati primjenom kliničkih smjernica kao što su Canadian CT Head Rule (CCHR) i smjernice National Institute for Care and Excellence (NICE). Optimalno pridržavanje navedenih smjernica uvelike koristi bolesnicima, smanjuje vrijeme čekanja, prenapučenost hitne službe, smrtnost i pogreške liječnika u hitnoj službi. Cilj ovoga rada je pružiti čitatelju kratak pregled smjernica CCHR i NICE koje se primjenjuju u Kliničkoj bolnici Dubrava, s osvrtom na suradnju naše hitne službe i neurokirurškog tima te liječnika drugih kirurških grana u obradi politraumatiziranih bolesnika i bolesnika s traumatskim ozljedama mozga. Uz to, prikazujemo Model “Dubrava”, jedinstveni model pristupu neurotraumi koji se primjenjuje u brzom liječenju traumatskih ozljeda mozga u ruralnim bolnicama lišenim službujućeg neurokirurga

Long term tracking of pallidal deep brain stimulation used in generalized dystonia – case report

Cilj: Generalizirana distonija karakterizirana je nevoljnim kontrakcijama mišića koje dovode do pojave abnormalnog držanja i ponavljajućih pokreta. Duboka stimulacija mozga (engl. Deep Brain Stimulation, DBS) učinkovita je u distoniji otpornoj na lijekove, međutim, postoji manjak radova o dugoročnom učinku. Cilj rada je prezentirati dugoročni učinak primjene DBS-a kod pacijenata s generaliziranom distonijom. Prikaz slučaja: Pacijent je 29-godišnji muškarac s generaliziranom distonijom. Nakon rođenja primijećena je faciopareza po perifernom tipu, što je bilo pripisano cerebralnoj paralizi. Prvi simptomi, problemi s pisanjem zbog grčenja ruke, primijećeni su sa sedam godina. S petnaest godina primijećeni su problemi u govoru i pogoršanje distonije ruke. Distonične kretnje i držanje postupno se pogoršavalo, uzrokujući probleme s hodanjem i narušavajući kvalitetu života pacijenta. Simptomi se nisu popravljali unatoč primjeni farmakoterapije i kada je pacijent imao dvadeset i jednu godinu implantirane su mu elektrode u bazalne ganglije, što je drastično poboljšalo distonične kretnje, držanje i hod. Nakon operacije, unatrag osam godina, pacijent je redovito praćen, elektrode su reprogramirane uz kontinuiranu fizikalnu i terapiju govora. U dva navrata nastupio je povratak kliničke slike radi ispražnjene baterije neurostimulatora koja je prvi put zamijenjena nepunjivom, a drugi put punjivom baterijom, što je dovelo do potpunog oporavka. Zaključak: Idiopatska distonija često je neprepoznata. Iako je DBS sigurna i učinkovita metoda, nije dovoljno korištena za liječenje distonije otporne na lijekove. Ovaj slučaj pokazao je perzistentan i izvrstan učinak DBS-a na generaliziranu distoniju i pacijentovu kvalitetu života kroz duži vremenski period.Aim: Generalized dystonia is characterized by involuntary muscle contractions leading to abnormal postures and repetitive movements. Deep brain stimulation (DBS) is effective in medication-refractory dystonia, but there is a lack of studies about long-term effect. The goal of this case report is to show long-term effect in a patient with generalized dystonia treated with DBS. Case report: We present a case of a 29-years-old patient with isolated generalized dystonia. At birth, peripheral facial palsy was noticed which was attributed to cerebral paralysis. First symptoms noticed at 7-years-old were problems with handwriting due to hand spasms. At 15, speech problems started and dystonia of his hand worsened. Then, dystonic movements and postures gradually expanded causing walking problems and poor quality of life. Symptoms did not improve with available medications and at the age of 21 electrodes were implanted into basal ganglia which extremely improved his dystonic movements, posture and gait. After the surgery, during these eight years, the patient was regularly controlled, electrodes were reprogramed with continuous physical and speech therapy. Twice he presented with returned complete clinical presentation due to the empty battery of the neurostimulator that was replaced first with a non-rechargeable and then with a rechargeable battery leading to complete improvement. Conclusion: Idiopathic dystonia is often unrecognized. Although, DBS is a safe and effective method, it is not used enough for treating medication-refractory dystonia. Our case has shown persistent and excellent effect of DBS on generalized dystonia and patients’ quality of life over a long period of time

Microvascular decompression in supinated position for trigeminal neuralgija treatment

Cilj: Prikazati operacijsku tehniku i učinkovitost mikrovaskularne dekompresije trigeminusa provedene u supinacijskom položaju bolesnika. Bolesnici i metode: Tijekom 2009., 2010. i 2011. godine na Zavodu za neurokirurgiju KB “Dubrava” operirano je 48 bolesnika s neuralgijom trigeminusa; učinjena im je mikrovaskularna dekompresija živca trigeminusa. Operirana su 22 muškarca i 26 žena, prosječne starosti od 56 godina i prosječnog trajanja bolesti 7 godina; kod 16 bolesnika bol je bio lokaliziran u području inervacije jedne grane trigeminusa, kod 25 bolesnika u području inervacije dviju grana, a kod 7 bolesnika u području inervacije svih triju grana trigeminusa. Rezultati: Kod 43 bolesnika nađen je jasan neurovaskularni konflikt. Početni uspjeh operacijskog liječenja (potpuni nestanak bolova ili prisutni značajno blaži bolovi) zabilježen je kod 42 bolesnika. Rasprava i zaključak: Mikrovaskularna dekompresija koja predstavlja jedino uzročno liječenje neuralgije trigeminusa dobra je i učinkovita metoda liječenja te bolesti te se uspješno može provesti u supinacijskom položaju bolesnika.Aim: To describe the operating technique and efficacy of microvascular decompression of trigeminus done in patients in supinated position. Patients and methods: During 2009, 2010 and 2011 in Department of neurosurgery University hospital Dubrava microvascular decompression was performed on 48 patients with trigeminal neuralgia. There were 22 male and 26 female patients with average age 56 years and average duration of pain 7 years. A total of 16 patients had pain distribution in only one trigeminal branch, 25 had pain in two branches and 7 in three branches. Results: A total of 43 patients had a clear neurovascular conflict intraoperatively and 42 patients had initial pain improvement. Discussion and conslusion: Microvascular decompression is the only treatment of trigeminal neuralgia that affects the cause of the illnes and is a good and effective method performed in the supinated position

Epidemiological characteristics, baseline clinical features, and outcomes of critically ill patients treated in a coronavirus disease 2019 tertiary center in continental Croatia

Aim To describe epidemiological characteristics and base - line clinical features, laboratory findings at intensive care unit (ICU) admission, and survival rates of critically ill coro - navirus disease 2019 (COVID-19) patients treated at a ter - tiary institution specialized for COVID-19 patients. Methods This retrospective study recruited 692 patients (67.1% men). Baseline demographic data, major comorbid - ities, anthropometric measurements, clinical features, and laboratory findings at admission were compared between survivors and non-survivors. Results The median age was 72 (64-78) years. The median body mass index was 29.1 kg/m 2 . The most relevant comor - bidities were diabetes mellitus (32.6%), arterial hyperten - sion (71.2%), congestive heart failure (19.1%), chronic kid - ney disease (12.6%), and hematological disorders (10.3%). The median number of comorbidities was 3 and median Charlson Comorbidity Index (CCI) was 5. A total of 61.8% patients received high-flow nasal oxygen therapy (HFNO) and 80.5% received mechanical ventilation (MV). Median duration of HFNO was 3, and that of MV was 7 days. ICU mortality rate was 72.7%. Survivors had significantly lower age, number of comorbidities, CCI, sequential organ failure assessment score, serum ferritin, C-reactive protein, D-dim - er, and procalcitonin, interleukin-6, lactate, white blood cell, and neutrophil counts. They also had higher lymphocyte counts, Pa O 2 /FiO 2 ratio, and glomerular filtration rate at ad - mission. Length of ICU stay was 9 days. The median surviv - al was 11 days for mechanically ventilated patients, and 24 days for patients who were not mechanically ventilated. Conclusion The parameters that differentiate survivors from non-survivors are in agreement with published data. Further multivariate analyses are warranted to identify in - dividual mortality risk factor

Identification of a Novel, Small Molecule Partial Agonist for the Cyclic AMP Sensor, EPAC1

Screening of a carefully selected library of 5,195 small molecules identified 34 hit compounds that interact with the regulatory cyclic nucleotide-binding domain (CNB) of the cAMP sensor, EPAC1. Two of these hits (I942 and I178) were selected for their robust and reproducible inhibitory effects within the primary screening assay. Follow-up characterisation by ligand observed nuclear magnetic resonance (NMR) revealed direct interaction of I942 and I178 with EPAC1 and EPAC2-CNBs in vitro. Moreover, in vitro guanine nucleotide exchange factor (GEF) assays revealed that I942 and, to a lesser extent, I178 had partial agonist properties towards EPAC1, leading to activation of EPAC1, in the absence of cAMP, and inhibition of GEF activity in the presence of cAMP. In contrast, there was very little agonist action of I942 towards EPAC2 or protein kinase A (PKA). To our knowledge, this is the first observation of non-cyclic-nucleotide small molecules with agonist properties towards EPAC1. Furthermore, the isoform selective agonist nature of these compounds highlights the potential for the development of small molecule tools that selectively up-regulate EPAC1 activity

Primary dural lymphoma mimicking meningioma: a clinical and surgical case report

INTRODUCTION: Primary central nervous system lymphoma and its subtype, primary dural lymphoma, are types of non-Hodgkin's lymphoma that only occur in the central nervous system without any dissemination. They are extremely rare cases of extra nodal lymphomas accounting for 1--5% of intracranial tumors. ----- CASE REPORT: We present a patient diagnosed with primary dural lymphoma in right frontal brain region who underwent surgical resection. Histopathological analysis revealed diffuse B-type large cell non-Hodgkin lymphoma. Patient underwent four cycles of R-CHOP and intrathecal methotrexate protocol. Six months postoperative, no signs of newly onset infiltration were present. ----- DISCUSSION: Primary dural lymphoma most likely presents with unusual radiological signs, which can easily be mistaken for meningioma, the main differential diagnosis. A thorough immunological, histopathological and clinical patients profile should be conducted in order to establish the certainty of diagnosis. Although there are few treatment options: surgery, radiotherapy or chemotherapy, there is no established treatment protocol

Functional and cardioprotective effects of simultaneous and individual activation of protein kinase A and Epac

BACKGROUND AND PURPOSE: Myocardial cAMP elevation confers cardioprotection against ischaemia/reperfusion (I/R) injury. cAMP activates two independent signalling pathways, PKA and Epac. This study investigated the cardiac effects of activating PKA and/or Epac and their involvement in cardioprotection against I/R. EXPERIMENTAL APPROACH: Hearts from male rats were used either for determination of PKA and PKC activation or perfused in the Langendorff mode for either cardiomyocyte isolation or used to monitor functional activity at basal levels and after 30 min global ischaemia and 2 h reperfusion. Functional recovery and myocardial injury during reperfusion (LDH release and infarct size) were evaluated. Activation of PKA and/or Epac in perfused hearts was induced using cell permeable cAMP analogues in the presence or absence of inhibitors of PKA, Epac and PKC. H9C2 cells and cardiomyocytes were used to assess activation of Epac and effect on Ca(2+) transients. KEY RESULTS: Selective activation of either PKA or Epac was found to trigger a positive inotropic effect, which was considerably enhanced when both pathways were simultaneously activated. Only combined activation of PKA and Epac induced marked cardioprotection against I/R injury. This was accompanied by PKCε activation and repressed by inhibitors of PKA, Epac or PKC. CONCLUSION AND IMPLICATIONS: Simultaneous activation of both PKA and Epac induces an additive inotropic effect and confers optimal and marked cardioprotection against I/R injury. The latter effect is mediated by PKCε activation. This work has introduced a new therapeutic approach and targets to protect the heart against cardiac insults