Permanent and Persistent Atrial Fibrillations Are Independent Risk Factors of Mortality after Severe COVID-19.

Background: The new coronavirus disease (COVID-19), a pandemic infection caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), had a deep global influence on morbidity and mortality profiles. Comorbidities, especially cardiovascular diseases, were identified to strongly modify the clinical course of COVID-19. However, the prognostic role of incident or prevalent atrial fibrillation has not been fully explained. The aim of this study was to evaluate the association between atrial fibrillation and outcomes following hospitalization in patients with severe COVID-19. Methods: We analyzed 199 patients (72 female, median age 70 years) with severe COVID-19 hospitalized between November 2020 and February 2021, due to SARS-CoV-2 infection. The study cohort included 68 patients with a history of AF (34 patients with paroxysmal AF, 19 with permanent AF, 15 patients with persistent AF), and 51 patients presented with AF during hospitalization. Results: Overall mortality during 90 days from the admission to hospital was 41% (n = 82). Non-survivors were older, had significantly elevated inflammation markers (CRP, WBC, procalcitonin, IL-6), NT-proBNP and D-dimer on the first day of hospitalization, lower left ventricular ejection fraction and worse kidney function, as compared to those who stayed alive during the follow-up. Among the hospitalized patients with COVID-19, a history of AF and the presence of AF during hospitalization contributed to higher mortality. Patients with permanent and persistent AF were at the highest risk of death. Different presentations of AF (any history of AF, the subtypes of AF-paroxysmal, permanent, persistent-and the presence of AF during hospitalization) were included in multivariate analysis, aiming to identify independent risk factors of death in the study period. We found that AF was related to worse prognosis, and persistent or permanent forms represented an independent predictor of mortality. Conclusions: Different clinical presentations of AF have varying impacts on survival in severe COVID-19. Mortality in hospitalized patients with severe COVID-19 was higher among patients with a history of AF, especially with persistent and permanent types of AF, and with AF present during hospitalization.

An unusual non­metastatic, mismatch repair­deficient primary gastric squamous cell carcinoma presenting as a large, exophytic, bleeding tumor: A case report.

Primary gastric squamous cell carcinoma (GSCC) is an extremely rare malignancy with a poor prognosis. Despite the improved knowledge regarding its pathogenesis and biology, the treatment options remain limited. The present study reported on the unique case of a mismatch repair-deficient (dMMR) primary GSCC in a 79-year-old woman reporting fatigue and symptoms of upper gastrointestinal tract bleeding. Physical examination revealed abdominal pain at palpation. Gastroscopy revealed a large, exophytic, bleeding tumor. Medical imaging confirmed a mushroom-like polyp in the lumen of the stomach, with no signs of disease spread. Total gastrectomy and D2 lymphadenectomy were performed. Pathological examination of the post-operational material confirmed a well-differentiated SCC invading the mucosa, submucosa and muscle layer. There were no signs of dissemination observed in any of the 32 excised lymph nodes. Notably, according to the last follow-up, the patient remains well, supporting the 5-year GSCC survival rate statistics. To the best of our knowledge, this is the first such GSCC case reported in the Surgical Oncology Outpatient Clinic (Copernicus Memorial Hospital, Lodz, Poland) and these findings add to the limited data on GSCC. Although this is a very rare condition, it should always be considered during the process of diagnosis of gastric tumors.

Early Effects of Nivolumab and Ipilimumab Combined Immunotherapy in the Treatment of Metastatic Melanoma in Poland: A Multicenter Experience.

Nivolumab and ipilimumab combination became the first-line standard in advanced melanoma. We assessed its efficacy in a real-life study in Poland. In a one-year follow-up, we evaluated the medical records of 50 melanoma patients treated with that modality in five oncology centers. We recorded therapy outcomes and adverse events (AEs) after 3 and 12 months of therapy. At the first checkpoint, the disease control rate (DCR) was recorded in 58% (n = 29) of patients, but the same number of patients (n = 29, 58%) stopped immunotherapy due to disease progression (PD, n = 14, 48.3%), toxicity (n = 11, 37.9%) or death (n = 4, 13.8%). Among patients with DCR after the induction phase, 8 (27.6%) terminated due to toxicity, and 21 (72.4%) continued. However, at the 12-month checkpoint, only 14 patients (27% of all) were still receiving immunotherapy. In 7 (33.3%) it was discontinued due to PD (n = 2), toxicity (n = 2, 28.6% each), or death (n = 3, 42.9%). AEs occurred in 66.7% (n = 34) of patients; severe (grade 3 or 4) in half of them. Interestingly, those with AEs had an 80% lower risk of death (hazard ratio [HR] 0.2, 95% confidence interval [CI] 0.07−0.57, p = 0.001) and PD (HR 0.2, 95%CI 0.09−0.47, p < 0.0001). In the entire group of patients, after a 12-month follow-up, the median overall survival was not reached (NR, range: 6.8 months-NR) and progression-free survival was 6.3 (range: 3-NR) months. Our results demonstrate that combined immunotherapy is less effective in real-life than in pivotal trials. However, early responders will likely continue the therapy after a one-year follow-up. AEs occurrence might be a predictor of clinical effectiveness.

The effect of l-arginine supplementation and surgical trauma on the frequency of myeloid-derived suppressor cells and T lymphocytes in tumour and blood of colorectal cancer patients.

PURPOSE: l-arginine (L-arg) deficiency causes immunosuppression, but it is unknown if L-arg supplementation in colorectal cancer (CRC) patients restores immune system activity. Our objective was to investigate the effect of L-arg supplementation on the frequency of monocytic (M) and polymorphonuclear (PNM) myeloid-derived suppressor cells (M-MDSCs and PMN-MDSCs, respectively). METHODS: We enrolled 65 CRC patients (34 males, 31 females) aged 69 â€‹± â€‹10 years into a prospective, randomised, double-blind study. Twenty-eight patients received L-arg and 37 received placebo for 9 days at a dose of 10 â€‹g/day. The frequency changes in MDSC, CD4+ cells and the concentration of C-reactive protein (CRP) were assessed before supplementation with L-arg (test 1), after 9 days of supplementation (test 2), and after surgery on day 11 (test 3). RESULTS: The frequency of M-MDSC in the tumours of patients receiving L-arg supplementation was higher than in placebo-treated patients, as was the frequency of PMN-MDSC and M-MDSC in the mucosa. CRP concentration in the serum of placebo-treated patients in test 2 was higher than in test 1, and the concentration in the serum of patients with L-arg supplementation in test 2 was lower than in test 1. Moreover, the expression pattern of the argininosuccinate synthase 1 (ASS1) suggests that CRC is not auxotrophic for L-arg. CONCLUSIONS: The results of this study do not support the hypothesis that L-arg supplementation in CRC patients can reduce immunosuppression by decreasing the frequency of suppressor cells and increasing the frequency of effector CD4+ T cells.

Lipid profile in Polish women following lacto-ovo-vegetarian and vegan diets - preliminary study.

The European Atherosclerosis Society and American College of Cardiology and American Heart Association guidelines have introduced several new recommendations, according to which vegetarian diets are concerned as beneficial for the cardiovascular system. This study was aimed to investigate the lipid profile in 56 healthy Polish young women - 13 vegans, 18 lacto-ovo-vegetarians and 25 omnivores. HDL cholesterol concentrations were higher in the vegans and vegetarians than in the omnivores. LDL cholesterol levels were lower in the vegans than in both other diet groups. The use of a vegetarian - especially vegan - diet in Polish conditions is associated with a favorable lipid profile and may have cardioprotective effects.

CAR-NK Cells in the Treatment of Solid Tumors.

CAR-T (chimeric antigen receptor T) cells have emerged as a milestone in the treatment of patients with refractory B-cell neoplasms. However, despite having unprecedented efficacy against hematological malignancies, the treatment is far from flawless. Its greatest drawbacks arise from a challenging and expensive production process, strict patient eligibility criteria and serious toxicity profile. One possible solution, supported by robust research, is the replacement of T lymphocytes with NK cells for CAR expression. NK cells seem to be an attractive vehicle for CAR expression as they can be derived from multiple sources and safely infused regardless of donor-patient matching, which greatly reduces the cost of the treatment. CAR-NK cells are known to be effective against hematological malignancies, and a growing number of preclinical findings indicate that they have activity against non-hematological neoplasms. Here, we present a thorough overview of the current state of knowledge regarding the use of CAR-NK cells in treating various solid tumors.

Remission of Thymoma on Steroid Therapy in a Patient With Atypical Thymoma-Associated Multiorgan Autoimmunity: A Case Report and Literature Review.

In up to 34% of cases, thymoma, itself a rare neoplasm, is accompanied by autoimmune disorders, two of which are thymoma-associated multiorgan autoimmunity (TAMA) and paraneoplastic autoimmune multiorgan syndrome (PAMS). Unfortunately, differential diagnosis between these two entities can be challenging since no strict PAMS definition exists and PAMS can overlap with a subgroup of TAMA patients with skin lesions as leading presentation. We present a case of a 68-year-old woman with a diagnosis of thymoma accompanied by myasthenia gravis, hypothyroidism and GvHD-like mucocutaneous lesions that initially could account to both TAMA and PAMS diagnosis. However, following the exclusion of humoral autoimmunity against components of epithelial cells junction, TAMA was finally established. Interestingly, the introduction of corticosteroid therapy for TAMA symptom management resulted in unexpected partial remission of thymoma with no impact on mucocutaneous lesions. Our case study is an example of two extremely rare phenomena accompanying thymomas: unprecedented TAMA presentation with GvHD-like mucositis, which as we postulate should be placed in the spectrum of TAMA, and tumor remission on steroids.

Leukemia Inhibitory Factor: A Potential Biomarker and Therapeutic Target in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, treatment-resistant cancer. Five-year survival rate is about 9%, one of the lowest among all solid tumors. Such a poor outcome is partly due to the limited knowledge of tumor biology, and the resulting lack of effective treatment options and robust predictive biomarkers. The leukemia inhibitory factor (LIF) has recently emerged as a potential biomarker and therapeutic target for PDAC. Accumulating evidence has suggested that LIF plays a role in supporting cancer evolution as a regulator of cell differentiation, renewal and survival. Interestingly, it can be detected in the serum of PDAC patients at higher concentrations than healthy individuals, this supporting its potential value as diagnostic biomarker. Furthermore, preliminary data indicate that testing for LIF serum concentration or tissue expression may help with treatment response monitoring and prognostication. Finally, studies in PDAC mouse models have also shown that LIF may be a valuable therapeutic target, and first-in-human clinical trial is currently ongoing. This article aims to review the available data on the role of LIF in PDAC promotion, and to discuss the evidence supporting its potential role as a biomarker and target of effective anti-cancer therapy in this setting.

Impact of diet and synbiotics on selected gut bacteria and intestinal permeability in individuals with excess body weight - A Prospective, Randomized Study.

Overweight and obese individuals may have leaky intestinal barrier and microbiome dysbiosis. The aim of this study was to determine whether body mass reduction with diet and synbiotics in an adult person with excess body mass has an influence on the gut microbiota and zonulin concentration. The study was a single blinded trial. 60 persons with excess body mass were examined. Based on randomization, patients were qualified either to the intervention group (Synbiotic group) or to the control group (Placebo group). Anthropometric measurements, microbiological assessment of faecal samples and zonulin concentration in the stool were performed before and after observation. After 3-months, an increase in the variety of intestinal bacteria (increase in the Shannon-Weaver index and the Simpson index) and a decrease in concentration of zonulin in faecal samples were observed in the Synbiotic group. Also, statistically significant correlation between zonulin and Bifidobacterium spp. (Spearman test, R=-0.51; p=0.0040) was noticed. There were no significant relationships between the body mass, BMI and changes in the intestinal microbiota or zonulin concentrations. The use of diet and synbiotics improved the condition of the microbiota and intestinal barrier in patients in the Synbiotic group.

Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP-ALL with PAX5 deletion.

Resistance to L-asparaginase (L-asp) is a major contributor to poor treatment outcomes of several subtypes of childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL). Asparagine synthetase (ASNS), legumain (LGMN) and cathepsin B (CTSB) serve a key role in L-asp resistance. The association between genetic subtypes of BCP-ALL and the expression of ASNS, LGMN and CTSB may elucidate the mechanisms of treatment failure. Bone marrow samples of 52 children newly diagnosed with BCP-ALL were screened for major genetic abnormalities and ASNS, LGMN and CTSB gene expression levels. The cohort was further divided into groups corresponding to the key genetic aberrations occurring in BCP-ALL: Breakpoint cluster region and Abelson murine leukemia viral oncogene homolog 1 fusion; hyperdiploidy, hypodiploidy, ETS variant 6 and runt-related transcription factor 1 fusion and other BCP-ALL with no primary genetic aberration identified. A subgroup analysis based on the differences in copy number variations demonstrated a significant increase of ASNS, LGMN and CTSB median expression in other BCP-ALL cases with paired box 5 (PAX5) deletion (P=0.0117; P=0.0036; P<0.0001, respectively) compared with those with wild-type PAX5. Patients with high ASNS expression exhibited longer relapse-free survival (RFS) compared with those with low ASNS levels (P=0.0315; HR, 0.19; 95% CI, 0.04-0.86); the 5-year RFS for patients in the high ASNS expression group was 90.15% (95% CI, 87.90-92.40%). Despite the impact on ASNS, LGMN and CTSB expression, PAX5 deletion did not influence RFS in the other BCP-ALL group (P=0.6839). Therefore, the results of the present study revealed high levels of ASNS, LGMN and CTSB expression in the other BCP-ALL group with concomitant PAX5 deletion and no subsequent deterioration in 5-year RFS. High ASNS expression level, as a single factor, was strongly associated with an improved outcome.

MLPA as a complementary tool for diagnosis of chromosome 21 aberrations in childhood BCP-ALL.

Chromosome 21 abnormalities are the most frequent genetic findings in childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL) cases. Majority of patients are effectively diagnosed with fluorescence in situ hybridization (FISH) and karyotyping; however, some cases may require additional tools to be used. Bone marrow samples of 373 childhood BCP-ALL patients were tested for chromosome 21 copy number variations (CNVs) with Multiplex Ligation-dependent Probe Amplification (MLPA) P327 array. Results from MLPA and cytogenetics were compared between groups according to the type of abnormality found on chromosome 21. Out the group of 235 patients, chromosome 21 multiplication was found by FISH assay in 56 cases (23.81%), ETV6-RUNX1 fusion in 34 (14.47%) and iAMP21 in 3 (1.28%) children, remaining 142 (60.43%) patients had no known chromosome 21 aberration. Median peak ratios of all tested probes in MLPA in aforementioned groups were 1.47 (IQR 1.28-1.77) vs. 1.00 (IQR 1.00-1.09) vs. 2.79 (IQR 1.97-2.83) vs. 1.00 (1.00-1.11), respectively. Aforementioned peak ratio of ETV6-RUNX1 fusion group was similar with patients of no known chromosome 21 aberration (p = 0.71). Interestingly, both groups differed from patients with chromosome 21 multiplication (p < 10-5) and with iAMP21 (p < 10-5). All cases of iAMP21 were correctly recognized by MLPA. MLPA seems to be good additional tool in the diagnostic process of chromosome 21 CNVs, especially in cases with iAMP21.

Association between different types of plant-based diets and leptin levels in healthy volunteers.

Leptin is an important factor regulating appetite and energety metabolism; disturbances in its signaling are related to adiposity and contribute to the excessive body fat. About a third of the human population is overweight or suffers from obesity, as well as from associated medical conditions. It is well established that vegetarian, especially vegan, diet is very effective in lowering BMI and body fat, thus, plant-based diets are associated with a lower risk of obesity. The aim of this study was to evaluate the plasma levels of leptin in lacto-ovo-vegetarian and vegan volunteers with normal BMI. The intake of energy and selected diet components such as polyunsaturated fatty acids (PUFA) and carbohydrates was also investigated. The study involved healthy women - 14 omnivores, 17 lacto-ovo-vegetarians, and 11 vegans. All women had a normal BMI (18.5-24.99). The plasma leptin levels were examined with immunoenzymatic test (ELISA). All participants were interviewed to estimate their nutrient intake by performing a 24-hour dietary recall. Both lacto-ovo-vegetarians and vegans had lower plasma leptin concentrations than their meat-consuming counterparts. Every analyzed diet group had a different body fat content, with the highest level in omnivores and the lowest in vegans. All participants had similar calorie, total fat, and total carbohydrates intake. Total PUFA and specifically omega-3 fatty acids consumption was lower in omnivores when compared to both types of plant diet; the same was found for fiber intake. Our results suggest that adopting a plant-based diet may be beneficial for energetic metabolism, as it significantly lowers the body fat storage and circulating leptin levels.

Protein-energy wasting and asymmetric dimethylarginine in peritoneal dialysis patients.

Cardiovascular (CVS) morbidity and mortality in the peritoneal dialysis patients (PD) is 10-30-fold higher than in the general population. A relatively low level of adiponectin and a higher level of leptin are important predictors of vascular complications as well as CVS events in PD patients. The asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is an important risk factor of CVS morbidity and mortality. It is very important to establish all CVS risk factors in the PD patients to prevent CVS morbidity and mortality in this population. The aim of the study was to determine the plasma concentration of ADMA and adipokines in relation to the protein-energy wasting (PEW) in PD patients. The study was performed in 30 PD patients and in the control group which consisted of 23 healthy volunteers. Plasma levels of hsC-reactive protein, TNF, IL-6, leptin, adiponectin, oxyLDL and ADMA were measured by ELISA method in both groups. The nutritional status was determined by measuring the albumin, body mass index (BMI), the percentage of body fat (%F), lean body mass (LBM) and Subjective Global Assessment Score (SGA). The adequacy of dialysis was estimated by weekly Kt/V. In all PD patients, significantly higher levels of ADMA, leptin, oxyLDL, hsCRP and TNF in comparison to controls were observed. In contrast to well-nourished subjects, patients with PEW, in addition to increased hsCRP, showed significantly higher ADMA. PEW was associated with high levels of ADMA and hsCRP and this could probably be responsible for increased CVS risk in PD patients.

Fasting and postprandial acyl and desacyl ghrelin and the acyl/desacyl ratio in obese patients before and after different types of bariatric surgery.

INTRODUCTION: The mechanism underlying beneficial outcomes of bariatric surgery still remains unclear. Especially little is known about hormonal and metabolic changes induced by the novel bariatric procedure mini gastric bypass (MGB). AIM: To evaluate pre- and post-prandial changes in both ghrelin isoforms in obese patients without diabetes and cardiovascular complications treated with MGB, sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) surgery. MATERIAL AND METHODS: From 45 patients initially enrolled in the study, 23 persons completed a one-year follow-up period. Venous blood for acyl and desacyl ghrelin (AG and DAG) as well as other metabolic assays was collected 3 months before and 6 and 12 months after bariatric surgery (MGB, RYGB, SG) - in the fasting state and 2 h after the consumption of a standard 300 kcal-mixed meal (Nutridrink standard, Nutricia). RESULTS: AG and DAG levels (both fasting and prandial) as well as AG/DAG ratio did not change after 6 and 12 months in MGB and RYGB groups. In the SG group we observed a significant decrease in fasting and postprandial DAG levels and consecutively an increase in the fasting AG/DAG ratio after 6 and 12 months. Six months after surgery we observed some differences between carbohydrate metabolism measures in the MGB group (lower HbA1c, HOMA-IR and fasting insulinaemia) in comparison to the rest of the participants, but 12 months after each type of surgery body mass index and indices of carbohydrate and lipid metabolism did not differ. CONCLUSIONS: The results of our study demonstrate that all studied bariatric procedures can successfully reduce overall body weight and suggest also that the mechanisms of weight loss and improvement in carbohydrate and lipid metabolism after all three types of surgery are independent of ghrelin and the acyl/desacyl ghrelin ratio.

Iron status and dietary iron intake in vegetarians.

BACKGROUND: Iron is one of the nutrients that require special consideration in a plant-based diet. The widespread belief is that meat is the best source of iron and a vegetarian diet increases the risk of its deficiency. This conviction has been the subject of analysis in a growing number of scientific reports. OBJECTIVES: The aim of this study was to assess the iron intake and iron metabolism in vegetarians and vegans compared to a control group. MATERIAL AND METHODS: A total of 55 vegetarians and 36 healthy volunteers were studied. The following parameters were measured in serum: iron, ferritin, transferrin, transferrin receptor, and hepcidin-25, using the enzyme-linked immunosorbent assay (ELISA) method. The dietary iron intake was assessed by a 24-h dietary recall. RESULTS: The mean daily intake (DI) of iron was significantly higher in the female vegan group compared to the control group. Iron, hepcidin-25, ferritin and transferrin receptor in serum remained within their normal ranges. The ferritin concentration was significantly decreased and that of transferrin significantly higher in both female groups and in the male vegan group. CONCLUSIONS: The obtained results show that the studied parameters, excluding transferrin, remained within normal ranges. However, the ferritin concentration was significantly decreased in the female vegetarian group and also in both vegan groups. This may indicate low iron storage.

Analysis of Outcomes of the Nutritional Status in Patients Qualified for Aortic Valve Replacement in Comparison to Healthy Elderly.

Severe aortic stenosis (AS) is associated with the reduction of muscle mass and may be associated with deterioration of nutritional status. Furthermore, malnourished cardiac patients are characterized by a higher risk of postoperative complications and mortality. The aim of this study was the evaluation and comparison of nutritional status, appetite and body composition in older people with severe aortic stenosis before aortic valve replacement and healthy elderly volunteers. One hundred and one patients, aged >65 years old with severe AS were included in the study. Nutritional status was assessed. Body composition was estimated using bioelectrical impedance analysis. Concentrations of albumin, prealbumin, triglycerides, total cholesterol and C-reactive protein were measured, and a complete blood count was done. About 40% of AS patients were at risk of malnutrition. They had decreased hand grip strength and they lost more body mass than the control group. Malnourished AS patients were older, had lower body mass indexes (BMIs) and lower aortic valve areas in comparison to well-nourished patients. Older AS patients, like their peers, show excessive body mass and, at the same time, the features of malnutrition. They have additional factors such as unintentional weight lost and decreased muscle strength which may be associated with worse outcomes.

Fasting and post-prandial peptide YY levels in obese patients before and after mini versus Roux-en-Y gastric bypass.

BACKGROUNDː The mechanisms underlying the metabolic effect of surgical treatment for morbid obesity are still unclear. Furthermore, the hormonal and metabolic response to the promising and less-invasive version of Roux-en-Y gastric bypass (RYGB), i.e. mini gastric bypass (MGB), is poorly known. The aim of this study was to evaluate pre- and postprandial changes in peptide YY (PYY) and metabolic parameters in obese patients without diabetes and cardiovascular complications treated by both versions of gastric bypass. METHODSː Venous blood for PYY and other assays was collected three months before and six months after bariatric operation (MGB and RYGB), in the fasting state and two hours after the consumption of a standard 300-kcal mixed meal (Nutridrink Standard, Nutricia Advanced Medical Nutrition, part of the Danone company, Schiphol, The Netherlands). RESULTSː In the MGB group, elevated concentrations of the PYY has been detected both fasting and postprandially. The effect of the MGB on the PYY levels did not differ from the RYGB group outcomes. CONCLUSIONSː The results of our study suggest similar endocrine and metabolic effects of MGB and RYGB procedures. Long-term efficacy and metabolic benefits of MGB require further research.

Born-Oppenheimer Molecular Dynamics Study on Proton Dynamics of Strong Hydrogen Bonds in Aspirin Crystals, with Emphasis on Differences between Two Crystal Forms.

In this study, the proton dynamics of hydrogen bonds for two forms of crystalline aspirin was investigated by the Born-Oppenheimer molecular dynamics (BOMD) method. Analysis of the geometrical parameters of hydrogen bonds using BOMD reveals significant differences in hydrogen bonding between the two crystalline forms of aspirin, Form I and Form II. Analysis of the trajectory for Form I shows spontaneous proton transfer in cyclic dimers, which is absent in Form II. Quantization of the O-H stretching modes allows a detailed discussion on the strength of hydrogen-bonding interactions. The focal point of our study is examination of the hydrogen bond characteristics in the crystal structure and clarification of the influence of hydrogen bonding on the presence of the two crystalline forms of aspirin. In the BOMD method, thermal motions were taken into account. Solving the Schrödinger equation for the snapshots of 2D proton potentials, extracted from MD, gives the best agreement with IR spectra. The character of medium-strong hydrogen bonds in Form I of aspirin was compared with that of weaker hydrogen bonds in aspirin Form II. Two proton minima are present in the potential function for the hydrogen bonds in Form I. The band contours, calculated by using one- and two-dimensional O-H quantization, reflect the differences in the hydrogen bond strengths between the two crystalline forms of aspirin, as well as the strong hydrogen bonding in the cyclic dimers of Form I and the medium-strong hydrogen bonding in Form II.

The Stricter the Better? The Relationship between Targeted HbA1c Values and Metabolic Control of Pediatric Type 1 Diabetes Mellitus.

INTRODUCTION: It remains unclear how HbA1c recommendations influence metabolic control of paediatric patients with type 1 diabetes mellitus. To evaluate this we compared reported HbA1c with guideline thresholds. MATERIALS AND METHODS: We searched systematically MEDLINE and EMBASE for studies reporting on HbA1c in children with T1DM and grouped them according to targeted HbA1c obtained from regional guidelines. We assessed the discrepancies in the metabolic control between these groups by comparing mean HbA1c extracted from each study and the differences between actual and targeted HbA1c. RESULTS: We included 105 from 1365 searched studies. The median (IQR) HbA1c for the study population was 8.30% (8.00%-8.70%) and was lower in "6.5%" than in "7.5%" as targeted HbA1c level (8.20% (7.85%-8.57%) versus 8.40% (8.20%-8.80%); p = 0.028). Median difference between actual and targeted HbA1c was 1.20% (0.80%-1.70%) and was higher in "6.5%" than in "7.5%" (1.70% (1.30%-2.07%) versus 0.90% (0.70%-1.30%), resp.; p < 0.001). CONCLUSIONS: Our study indicates that the 7.5% threshold results in HbA1c levels being closer to the therapeutic goal, but the actual values are still higher than those observed in the "6.5%" group. A meta-analysis of raw data from national registries or a prospective study comparing both approaches is warranted as the next step to examine this subject further.

Aliskiren attenuates oxidative stress and improves tubular status in non-diabetic patients with chronic kidney disease-Placebo controlled, randomized, cross-over study.

PURPOSE: Pharmacological inhibition of the renin-angiotensin-aldosteron system (RAAS) may have a beneficial impact on proteinuria and chronic kidney diseases (CKD) progression. Despite recent progress by means of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), there is still no optimal therapy which can stop progression of the nephropathy. Recently introduced aliskiren is the first orally bioavailable direct renin inhibitor approved for the treatment of hypertension. The purpose was to evaluate the extent of oxidative stress and tubular injury after the direct renin inhibitor, aliskiren compared with placebo and perindopril in patients with non-diabetic chronic kidney disease (NDCKD). MATERIAL/METHODS: A randomized, double-blind, cross-over trial was performed in 14 patients receiving 300mg aliskiren, 10mg perindopril and placebo in random order. The end point was a change in the urinary excretion of N-acetyl-ß-D-glucosaminidase (NAG) and α1-microglobulin (α1m) and 15-F(2α)-isoprostane. RESULTS: Aliskiren reduced excretion of 15-F(2α)-isoprostane (p=0.03) and α1m (p=0.01) as compared to placebo. There were no differences between aliskiren and perindopril in this regard. NAG urine excretion did not change after aliskiren and perindopril. CONCLUSIONS: Aliskiren attenuates oxidative stress and may improve functional status of tubules in patients with NDCKD.