Fluid resuscitation with balanced electrolyte solutions results in faster resolution of diabetic ketoacidosis than with 0.9% saline in adults - A systematic review and meta-analysis.

Fluid resuscitation during diabetic ketoacidosis (DKA) is most frequently performed with 0.9% saline despite its high chloride and sodium concentration. Balanced Electrolyte Solutions (BES) may prove a more physiological alternative, but convincing evidence is missing. We aimed to compare the efficacy of 0.9% saline to BES in DKA management. MEDLINE, Cochrane Library, and Embase databases were searched for relevant studies using predefined keywords (from inception to 27 November 2021). Relevant studies were those in which 0.9% saline (Saline-group) was compared to BES (BES-group) in adults admitted with DKA. Two reviewers independently extracted data and assessed the risk of bias. The primary outcome was time to DKA resolution (defined by each study individually), while the main secondary outcomes were changes in laboratory values, duration of insulin infusion, and mortality. We included seven randomized controlled trials and three observational studies with 1006 participants. The primary outcome was reported for 316 patients, and we found that BES resolves DKA faster than 0.9% saline with a mean difference (MD) of -5.36 [95% CI: -10.46, -0.26] hours. Post-resuscitation chloride (MD: -4.26 [-6.97, -1.54] mmoL/L) and sodium (MD: -1.38 [-2.14, -0.62] mmoL/L) levels were significantly lower. In contrast, levels of post-resuscitation bicarbonate (MD: 1.82 [0.75, 2.89] mmoL/L) were significantly elevated in the BES-group compared to the Saline-group. There was no statistically significant difference between the groups regarding the duration of parenteral insulin administration (MD: 0.16 [-3.03, 3.35] hours) or mortality (OR: -0.67 [0.12, 3.68]). Studies showed some concern or a high risk of bias, and the level of evidence for most outcomes was low. This meta-analysis indicates that the use of BES resolves DKA faster than 0.9% saline. Therefore, DKA guidelines should consider BES instead of 0.9% saline as the first choice during fluid resuscitation.

Application of Near Infrared Spectroscopy to Monitor the Quality Change of Sour Cherry Stored under Modified Atmosphere Conditions.

Determining and applying 'good' postharvest and quality control practices for otherwise highly sensitive fruits, such as sour cherry, is critical, as they serve as excellent media for a wide variety of microbial contaminants. The objective of this research was to report two series of experiments on the modified atmosphere storage (MAP) of sour cherries (Prunus cerasus L. var. Kántorjánosi, Újfehértói fürtös). Firstly, the significant effect of different washing pre-treatments on various quality indices was examined (i.e., headspace gas composition, weight loss, decay rate, color, firmness, soluble solid content, total plate count) in MAP-packed fruits. Subsequently, the applicability of near infrared (NIR) spectroscopy combined with chemometrics was investigated to detect the effect of various storage conditions (packed as control or MAP, stored at 3 or 5 °C) on sour cherries of different perceived ripeness. Significant differences were found for oxygen concentration when two perforations were applied on the packages of 'Kántorjánosi' (p < 0.01); weight loss when 'Kánorjánosi' (p < 0.001) and 'Újfehértói fürtös' (p < 0.01) were packed in MAP; SSC when 'Újfehértói fürtös' samples were ozone-treated (p < 0.05); and total plate count when 'Kántorjánosi' samples were ozone-treated (p < 0.01). The difference spectra reflected the high variability in the samples, and the detectable effects of different packaging. Based on the investigations with the soft independent modelling of class analogies (SIMCA), different packaging and storage resulted in significant differences in most of the cases even on the first storage day, which in many cases increased by the end of storage. The soft independent modelling of class analogies proved to be suitable for classification with apparent error rates between 0 and 0.5 during prediction regardless of ripeness. The research findings suggest the further correlation of NIR spectroscopic and reference parameters to support postharvest handling and fast quality control.

Point-of-care ultrasound improves clinical outcomes in patients with acute onset dyspnea: a systematic review and meta-analysis.

The early, appropriate management of acute onset dyspnea is important but often challenging. The aim of this study was to investigate the effects of the use of Point-of-Care Ultrasound (PoCUS) versus conventional management on clinical outcomes in patients with acute onset dyspnea. The Cochrane Library, MEDLINE, EMBASE and reference lists were searched to identify eligible trials (inception to October 14, 2021). There were no language restrictions. Randomized controlled trials (RCTs), and prospective and retrospective cohort studies that compared PoCUS with conventional diagnostic modalities (controls) in patients with acute onset dyspnea were included. Two independent reviewers extracted data and assessed the risk of bias. Disagreements were resolved by consensus. The primary study outcomes were time to diagnosis, time to treatment, and length of stay (LOS). Secondary outcomes included rate of appropriate treatment, 30-day re-admission rate, and mortality. We included eight RCTs and six observational studies with a total of 5393 participants. Heterogeneity across studies was variable (from low to considerable), with overall low or moderate study quality and low or moderate risk of bias (except one article with serious risk of bias). Time to diagnosis (mean difference [MD], - 63 min; 95% CI, - 115 to - 11 min] and time to treatment (MD, - 27 min; 95% CI - 43 to - 11 min) were significantly shorter in the PoCUS group. In-hospital LOS showed no differences between the two groups, but LOS in the Intensive Care Unit (MD, - 1.27 days; - 1.94 to - 0.61 days) was significantly shorter in the PoCUS group. Patients in the PoCUS group showed significantly higher odds of receiving appropriate therapy compared to controls (odds ratio [OR], 2.31; 95% CI, 1.61-3.32), but there was no significant effect on 30-day re-admission rate and in-hospital or 30-day mortality. Our results indicate that PoCUS use contributes to early diagnosis and better outcomes compared to conventional methods in patients admitted with acute onset dyspnea.

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs.

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development. Here we aimed to characterize a closed-chest porcine model of post-MI HF in adult Göttingen minipigs with long-term follow-up including serial cardiac magnetic resonance imaging (CMRI) and to compare it with the commonly used Landrace pig model. MI was induced by intraluminal balloon occlusion of the left anterior descending coronary artery for 120 min in Göttingen minipigs and for 90 min in Landrace pigs, followed by reperfusion. CMRI was performed to assess cardiac morphology and function at baseline in both breeds and at 3 and 6 months in Göttingen minipigs and at 2 months in Landrace pigs, respectively. Scar sizes were comparable in the two breeds, but MI resulted in a significant decrease of left ventricular ejection fraction (LVEF) only in Göttingen minipigs, while Landrace pigs did not show a reduction of LVEF. Right ventricular (RV) ejection fraction increased in both breeds despite the negligible RV scar sizes. In contrast to the significant increase of left ventricular end-diastolic (LVED) mass in Landrace pigs at 2 months, Göttingen minipigs showed a slight increase in LVED mass only at 6 months. In summary, this is the first characterization of post-MI HF in Göttingen minipigs in comparison to Landrace pigs, showing that the Göttingen minipig model reflects post-MI HF parameters comparable to the human pathology. We conclude that the Göttingen minipig model is superior to the Landrace pig model to study the development of post-MI HF.

Basicity-Tuned Reactivity: diaza-[1,2]-Wittig versus diaza-[1,3]-Wittig Rearrangements of 3,4-Dihydro-2H-1,2,3-benzothiadiazine 1,1-Dioxides.

The base-induced (t-BuOK) rearrangement reactions of 3,4-dihydro-2H-1,2,3-benzothiadiazine 1,1-dioxides result in a ring opening along the N-N bond, followed by ring closure with the formation of new C-N bonds. The position of the newly formed C-N bond can selectively be tuned by the amount of the base, providing access to new, pharmacologically interesting ring systems with high yield. While with 2 equiv of t-BuOK 1,2-benzisothiazoles can be obtained in a diaza-[1,2]-Wittig reaction, with 6 equiv of the base 1,2-benzothiazine 1,1-dioxides can be prepared in most cases as the main product, in a diaza-[1,3]-Wittig reaction. DFT calculations and detailed NMR studies clarified the mechanism, with a mono- or dianionic key intermediate, depending on the amount of the reactant base. Also, the role of an enamide intermediate formed during the workup of the highly basic (6 equiv of base) reaction was clarified. The substrate scope of the reaction was also explored in detail.

Role of duties related to COVID-19 suspected, probable and confirmed fatality cases / [Elhunytakkal kapcsolatos teendok COVID­19-gyanús, valószínusített és megerosített esetekben]

The outbreak caused by SARS-CoV-2 beta-coronavirus, first identified in Wuhan, China, was declared a pandemic by the World Health Organization on 11th March, 2020. In Hungary, the first confirmed COVID-19 case was reported on 4th March, 2020, and on 15th March, the first fatality related to the infection was announced. At the moment of the latter event, there was no central, standardized guideline, which could explain the necessary precautions, and provide an unequivocal description on how to handle the dead body. The procedure of transportation, storage, occurent autopsy or final disposition of the deceased raise a lot of questions, especially on how to carry out these tasks. Legislation related to infectious diseases and decedent management in general do not provide enough information on how to perform duties in a COVID-19 fatality case. The chief medical officer suspended the execution of autopsies, except in cases of unnatural death, since 19th March, however, the transportation and storage of fatalities can still be a problem. The Department of Pathology of the Healthcare Professional College of the Ministry of Human capacities published a procedure on recommended post-mortem duties on 21st March, but the suggested protocols only represent a narrow spectrum of international recommendations. Therefore supplementation may be necessary. Sadly, post-mortem protocols, in spite of their importance, are also underrepresented in the international literature. A further problem, wich makes adoptability difficult, is that available foreign guidelines and algorithms are optimized for different legislation, and organisations, resources not available in our country. In this article, besides providing a summary of literature, we would also like to make practical recommendations which may increase the safety of healthcare providers participating in the treatment or pathological duties with COVID-19 suspected, probable and confirmed cases. Orv Hetil. 2020; 161(17): 713­722.

Corrigendum to "Oxidative Stress-Related Parthanatos of Circulating Mononuclear Leukocytes in Heart Failure".

[This corrects the article DOI: 10.1155/2017/1249614.].

Oncological Screening of Kidney Transplant Patients: The Role of Ultrasound Examination.

INTRODUCTION: Immunosuppressive therapy used after organ transplantation represents a considerable oncological risk. Abdominal ultrasound examinations play an essential role in the oncological screening of organ transplant patients. Our aim was to study the effectiveness of the ultrasound screening protocol currently used in our clinic. METHODS: Reports of screening abdominal ultrasound examinations of kidney transplant recipients were processed at the Department of Transplantation and Surgery of Semmelweis University from January 2012 to December 2015. RESULTS: In 1478 studies, 14 patients were diagnosed with a malignant tumor, 11 of which were formed in the native shrunken kidney. The mean age for tumor diagnosis was 55.6 ± 12.6 years, and 80% of the patients diagnosed with tumor were male. On average, 7.5 ± 4.6 years passed between the transplantation and recognition of the tumor. All of the kidney tumors were diagnosed at an early stage: histologic examination of removed kidneys showed 73% pT1a- and 17% pT1b-stage tumors. CONCLUSION: In our study, early stage shrunken kidney cancers were outstandingly the most common post-transplant malignancies found by ultrasound screening. Annual ultrasound examinations as part of our current screening protocol allowed the detection of tumors at an early stage in kidney transplant recipients.

Metal- and redox homeostasis in prostate cancer with vitamin D3 supplementation.

Vitamin D3 supplementation has a beneficial effect on cancerous patients, although it can influence the redox- and metal homeostasis. The aim of our investigation was to demonstrate the effect of vitamin D3 consumption on the redox- and metal homeostasis in prostate cancer, because of the recommended daily dose increased from 200 IU to 2000 IU in recent years in Hungary. Forty-three volunteers were involved in the study. The grouping was applied according to the clinical routine laboratory parameters (vitamin D3) and the tumor markers (PSA, fPFA). Patients were divided into 5 groups: (A) patient control (N = 8), (B) patient control with vitamin D3 treatment (N = 9), (C) high-risk prostate cancer group (N = 6), (D) high-risk prostate cancer group with vitamin D3 treatment (N = 8) and (E) vitamin D3 treated cancerous group with androgen deprivation therapy (N = 11). The element concentrations were determined with ICP-OES. Among the redox parameters, free radical scavenging capacity and H-donating ability were determined with luminometry and spectrometry. Vitamin D3 treatment caused differences in the metal- and redox homeostasis in either patient control and cancerous groups. The concentration of Fe, Cr, and Pb significantly increased in the erythrocytes of prostate cancer patients. According to the higher scavenging capacity by vitamin D3 treatment, it seems that vitamin D3 helps to equilibrate the redox homeostasis that could affect the outcome of cancer positively. However, the tendency in the metal element status does not give a clear explanation of cancer's outcome, but the accumulation of Pb by vitamin D3 supplementation needs to be taken into more serious consideration in set terms of occupational diseases.

Oxidative Stress-Related Parthanatos of Circulating Mononuclear Leukocytes in Heart Failure.

BACKGROUND: The present study aims to examine the oxidative stress-related activation of poly(ADP-ribose) polymerase (PARP), a cause of parthanatos in circulating mononuclear leukocytes of patients with chronic heart failure (CHF), that was rarely investigated in the human setting yet. METHODS: Patients with CHF (n = 20) and age- and body mass index-matched volunteers (n = 15) with a normal heart function were enrolled. C-reactive protein, N-terminal probrain-type natriuretic peptide (pro-BNP), plasma total peroxide level (PRX), plasma total antioxidant capacity (TAC), oxidative stress index (OSI), leukocyte lipid peroxidation (4-hydroxynonenal; HNE), protein tyrosine nitration (NT), poly(ADP-ribosyl)ation (PARylation), and apoptosis-inducing factor (AIF) translocation were measured in blood samples of fasting subjects. RESULTS: Plasma PRX, leukocyte HNE, NT, PARylation, and AIF translocation were significantly higher in the heart failure group. Pro-BNP levels in all study subjects showed a significant positive correlation to PRX, OSI, leukocyte HNE, NT, PARylation, and AIF translocation. Ejection fraction negatively correlated with the same parameters. Among HF patients, a positive correlation of pro-BNP with PRX, OSI, and PARylation was still present. CONCLUSIONS: Markers of oxidative-nitrative stress, PARP activation, and AIF translocation in blood components showed correlation to reduced cardiac function and the clinical appearance of CHF. These results may reinforce the consideration of PARP inhibition as a potential therapeutic target in CHF.

Cardioprotection with palm oil tocotrienols: comparision of different isomers.

A recent study from our laboratory indicated the cardioprotective ability of the tocotrienol-rich fraction (TRF) from red palm oil. The present study compared cardioprotective abilities of different isomers of tocotrienol against TRF as recently tocotrienol has been found to function as a potent neuroprotective agent against stroke. Rats were randomly assigned to one of the following groups: animals were given, by gavage, either 0.35%, 1%, or 3.5% TRF for two different periods of time (2 or 4 wk) or 0.03, 0.3, and 3 mg/kg body wt of one of the isomers of tocotrienol (alpha, gamma, or delta) for 4 wk; control animals were given, by gavage, vehicle only. After 2 or 4 wk, rats were killed, and their hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. Dose-response and time-response experiments revealed that the optimal concentration for TRF was 3.5% TRF and 0.3 mg/kg body wt of tocotrienol given for 4 wk. TRF as well as all the isomers of tocotrienol used in our study provided cardioprotection, as evidenced by their ability to improve postischemic ventricular function and reduce myocardial infarct size. The gamma-isoform of tocotrienol was the most cardioprotective of all the isomers followed by the alpha- and delta-isoforms. The molecular mechanisms of cardioprotection afforded by tocotrienol isoforms were probed by evaluating their respective abilities to stabilize the proteasome, allowing it to maintain a balance between prodeath and prosurvival signals. Our results demonstrated that tocotrienol isoforms reduced c-Src but increased the phosphorylation of Akt, thus generating a survival signal.

Protective mechanisms of resveratrol against ischemia-reperfusion-induced damage in hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin.

The resveratrol-induced cardiac protection was studied in Zucker obese rats. Rats were divided into five groups: group 1, lean control; group 2, obese control (OC); group 3, obese rats treated orally with 5 mg kg(-1) day(-1) of resveratrol (OR) for 2 wk; group 4, obese rats received 10% glucose solution ad libitum for 3 wk (OG); and group 5, obese rats received 10% glucose for 3 wk and resveratrol (OGR) during the 2nd and 3rd wk. Body weight, serum glucose, and insulin were measured, and then hearts were isolated and subjected to 30 min of ischemia followed by 120 min of reperfusion. Heart rate, coronary flow, aortic flow, developed pressure, the incidence of reperfusion-induced ventricular fibrillation, and infarct size were measured. Resveratrol reduced body weight and serum glucose in the OR compared with the OC values (414 +/- 10 g and 7.08 +/- 0.41 mmol/l, respectively, to 378 +/- 12 g and 6.11 +/- 0.44 mmol/l), but insulin levels were unchanged. The same results were obtained for the OG vs. OGR group. Resveratrol improved postischemic cardiac function in the presence or absence of glucose intake compared with the resveratrol-free group. The incidence of ventricular fibrillation and infarct size was reduced by 83 and 20% in the OR group, and 67 and 16% in the OGR group, compared with the OC and OG groups, respectively. Resveratrol increased GLUT-4 expression and reduced endothelin expression and cardiac apoptosis in ischemic-reperfused hearts in the presence or absence of glucose intake. Thus the protective effect of resveratrol could be related to its direct effects on the heart.

Influence of hyperthyroidism on the effect of adenosine transport blockade assessed by a novel method in guinea pig atria.

The aim of the present study was to investigate the effect of hyperthyroidism on the trans-sarcolemmal adenosine (Ado) flux via equilibrative and nitrobenzylthioinosine (NBTI)-sensitive nucleoside transporters (ENT1) in guinea pig atria, by assessing the change in the Ado concentration of the interstitial fluid ([Ado]ISF) under nucleoside transport blockade with NBTI. For the assessment, we applied our novel method, which estimates the change in [Ado]ISF utilizing the altered inotropic response to N6-cyclopentyladenosine (CPA), a relative stable selective agonist of A1 Ado receptors, by providing a relative index, the equivalent concentration of CPA. Our results show an interstitial Ado accumulation upon ENT1 blockade, which was more extensive in the hyperthyroid samples (CPA concentrations equieffective with the surplus [Ado]ISF were two to three times higher in hyperthyroid atria than in euthyroid ones, with regard to the negative inotropic effect of CPA and Ado). This suggests an enhanced Ado influx via ENT1 in hyperthyroid atria. It is concluded that hyperthyroidism does not alter the prevailing direction of the Ado transport, moreover intensifies the Ado influx in the guinea pig atrium.

Beneficial effects of carbon monoxide-releasing molecules on post-ischemic myocardial recovery.

There is increasing evidence corroborating a protective role of carbon monoxide releasing molecules (CORMs) in injured tissues. Carbon monoxide (CO) carriers have been recently developed as a pharmacological tool to simulate the effect of heme oxygenase-1-derived CO. The effects of CORM-3, a water-soluble CO releaser, on the incidence of reperfusion-induced ventricular fibrillation (VF) and tachycardia (VT) were studied in isolated rat hearts. Hearts were treated with different doses of CORM-3 before the induction of 30 min global ischemia followed by 120 min reperfusion. We found that at concentrations of 25 microM and 50 microM of CORM-3 promoted a significant reduction in the incidence of VF and VT. Thus, the incidence of VF was reduced by 67% (p<0.05) and 92% (p<0.05) with 25 microM and 50 microM of CORM-3, respectively. The protective effect of CORM-3 on the incidence of VT followed the same pattern. The antiarrhythmic protection was associated with a marked attenuation in infarct size, significant decreases in cellular Na(+) and Ca(2+) gains and K(+) loss. Consequently, the recovery of post-ischemic function was significantly improved. In conclusion, CORM-3 exerts beneficial effects against ischemia/reperfusion-induced injury through its abilities to release CO which mediates a cardioprotective action by regulating tissue Na(+), K(+), and Ca(2+) levels.

Cardioprotective mechanisms of Prunus cerasus (sour cherry) seed extract against ischemia-reperfusion-induced damage in isolated rat hearts.

The effects of kernel extract obtained from sour cherry (Prunus cerasus) seed on the postischemic cardiac recovery were studied in isolated working rat hearts. Rats were treated with various daily doses of the extract for 14 days, and hearts were then isolated and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The incidence of ventricular fibrillation (VF) and tachycardia (VT) fell from their control values of 92% and 100% to 50% (not significant) and 58% (not significant), 17% (P<0.05), and 25% (P<0.05) with the doses of 10 mg/kg and 30 mg/kg of the extract, respectively. Lower concentrations of the extract (1 and 5 mg/kg) failed to significantly reduce the incidence of VF and VT during reperfusion. Sour cherry seed kernel extract (10 and 30 mg/kg) significantly improved the postischemic recovery of cardiac function (coronary flow, aortic flow, and left ventricular developed pressure) during reperfusion. We have also demonstrated that the extract-induced protection in cardiac function significantly reflected in a reduction of infarct size. Immunohistochemistry indicates that a reduction in caspase-3 activity and apoptotic cells by the extract, beside other potential action mechanisms of proanthocyanidin, trans-resveratrol, and flavonoid components of the extract, could be responsible for the cardioprotection in ischemic-reperfused myocardium.