Background Diabetes and its complications constitute a rising medical challenge. Special attention should be given to diabetic foot syndrome (DFS) due to its high rate of associated amputation and mortality. Negative pressure wound therapy (NPWT) is a frequently used supportive modality in a diabetic foot with ulcerations (DFUs). Design Here, we reviewed the current knowledge concerning the tissue and molecular mechanisms of NPWT action with an emphasis on diabetes research followed by a summary of clinical DFU studies and practice guidelines. Results Negative pressure wound therapy action results in two types of tissue deformations—macrodeformation, such as wound contraction, and microdeformation occurring at microscopic level. Both of them stimulate a wound healing cascade including tissue granulation promotion, vessel proliferation, neoangiogenesis, epithelialization and excess extracellular fluid removal. On the molecular level, NPWT results in an alteration towards more pro‐angiogenic and anti‐inflammatory conditions. It increases expression of several key growth factors, including vascular endothelial growth factor and fibroblast growth factor 2, while expression of inflammatory cytokinesis reduced. The NPWT application also alters the presence and function of matrix metalloproteinases. Clinical studies in DFU patients showed a superiority of NPWT over standard therapy in terms of efficacy outcomes, primarily wound healing and amputation rate, without a rise in adverse events. International guidelines point to NPWT as an important adjuvant therapy in DFU whose use is expected to increase. Conclusions This current knowledge improves our understanding of NPWT action and its tailoring for application in diabetic patients. It may inform the development of new treatments for DFU.

Background Type 2 diabetes mellitus (T2DM) is associated with a hypercoagulable state and increased neutrophil extracellular traps formation (NETosis). We investigated predictors of NETosis and cell death markers in circulating blood and their association with a prothrombotic state in T2DM. Methods In a cross-sectional study involving 113 T2DM patients aged 63.7 ± 8.2 years, we investigated citrullinated histone H3 (H3Cit), cell-free deoxyribonucleic acid (cfDNA), myeloperoxidase, neutrophil elastase, and inflammation markers, along with thrombin generation (TG), plasma clot lysis time (CLT), clot permeability (K s ) and fibrinolysis inhibitors. Results On multivariate logistic regression analysis adjusted for age and gender, predictors of high H3Cit (≥ 7.36 ng/mL, upper quartile) were: glycated hemoglobin (HbA1c) ≥ 7.0% and interleukin-6. Interleukin-6 was also found to be a predictor of high cfDNA (≥ 2.84 µg/mL, upper quartile) along with glucose. Citrullinated histone H3 and cfDNA correlated positively with CLT and inversely with K s , while TG associated solely with cfDNA. These associations were not seen with myeloperoxidase and neutrophil elastase. Patients with previous myocardial infarction (n = 21, 18.6%) had higher H3Cit (+108%, p < 0.001) and cfDNA (+45%, p = 0.022). On multivariable analysis adjusted for potential confounders, H3Cit and cfDNA, along with plasminogen activator inhibitor-1 and concomitant cardiovascular disease, were predictors of CLT. Citrullinated histone H3 alone was a predictor of K s and only cfDNA was a predictor of peak thrombin generated. Conclusions In T2DM, NETosis detectable in circulating blood is associated with inflammatory state and a prothrombotic state, especially hypofibrinolysis.

In this brief report, we describe the feat of four men with type 1 diabetes mellitus (T1DM) who decided to take part in a mountain ultramarathon in Bieszczady, Poland on May 27, 2016. Before participating in the competition, they asked two diabetologists for a consultation and to assist in diabetic control during the marathon. The aim of the study was to assess the metabolic safety in people with T1DM during extreme physical exertion in a mountain ultramarathon. All subjects were treated with continuous subcutaneous insulin infusion. The marathon route was 82 km, and the sum of the climbs and descents was 3235 and 3055 m, respectively. Diabetologists controlled glucose levels using a glucometer, plasma lactate levels, and ketones in the capillary blood. In addition, they monitored the intake of carbohydrates and fluids. Clinical tests were performed at the three checkpoints (at 32, 49, and 66 km) during the race and after completing the race (at 82 km). This study shows that extreme physical exertion by a person with type 1 diabetes is possible. All subjects avoided severe hypoglycemia by significantly reducing their insulin dose and consuming additional carbohydrates. Such actions, despite the occurrence of hyperglycemia >250 mg/dL did not result in ketoacidosis. Safe participation in mountain ultramarathons by people with type 1 diabetes can be achieved if they undertake appropriate physical and diabetologic preparation.

PurposeNegative pressure wound therapy (NPWT) is an adjunct method used in the treatment of diabetic foot ulceration (DFU). Real world data on its effectiveness and safety is scarce. In this prospective observational study, we assessed the short-term efficacy, safety, and long-term outcomes of NPWT in patients with type 2 diabetes (T2DM) and neuropathic, noninfected DFUs.MethodsBased on wound characteristics, mainly area (>1 vs. ≤1 cm2), 75 patients with DFUs treated in an outpatient clinic were assigned to NPWT (n = 53) or standard therapy (n = 22). Wound area reduction was evaluated after 8 ± 1 days. Long-term outcomes assessed included complete ulceration closure and recurrence rate.ResultsPatients assigned to NPWT were characterized by greater wound area (15.7 vs. 2.9 cm2). Reduction in wound area was found in both the NPWT (−1.1 cm2, −10.2%, p = 0.0001) and comparator group (−0.3 cm2, −18.0%, p = 0.0038). No serious adverse events related to NPWT were noted. Within 1 year, 55.1% (27/49) of DFUs were closed in the NPWT group and 73.7% (14/19) in the comparator group (p = 0.15). In the logistic regression, wound duration and smaller initial area, but not treatment mode, were associated with closure. One-year follow-up after DFU resolution revealed an ~30.0% recurrence rate in both groups (p = 0.88).ConclusionsNPWT is a safe treatment for neuropathic, nonischemic, and noninfected DFU in patients with T2DM, although this observational study did not prove its effectiveness over standard therapy. Additionally, we report a high rate of both closure and recurrence of ulcers, the latter irrespective of initial ulcer area.

Objectives. To evaluate the spectrum of neurological symptoms in patients with COVID-19 during the first 14 days of hospitalisation and its association with in-hospital mortality. Material and methods.We included 200 patients with RT-PCR-confirmed COVID-19 admitted to University Hospital in Krakow, Poland. In 164 patients, a detailed questionnaire concerning neurological symptoms and signs was performed prospectively within 14 days of hospitalisation. In the remaining 36 patients, such questionnaires were completed retrospectively based on daily observations in the Department of Neurology.Results. During hospitalisation, 169 patients (84.5%) experienced neurological symptoms; the most common were: fatigue (62.5%), decreased mood (45.5%), myalgia (43.5%), and muscle weakness (42.5%). Patients who died during hospitalisation compared to the remainder were older (79 [70.5-88.5] vs. 63.5 [51-77] years, p = 0.001), and more often had decreased level of consciousness (50.0% vs. 9.3%, p < 0.001), delirium (33.3% vs. 4.4%, p < 0.001), arterial hypotension (50.0% vs. 19.6%, p = 0.005) or stroke during (18.8% vs. 3.3%, p = 0.026) or before hospitalisation (50.0% vs. 7.1, p < 0.001), whereas those who survived more often suffered from headache (42.1% vs. 0%, p = 0.012) or decreased mood (51.7% vs. 0%, p = 0.003). www.journals.viamedica.pl/neurologia_neurochirurgia_polska Marcin Wnuk et al., Neurological symptoms in COVID-19 Conclusions. Most hospitalised patients with COVID-19 experience neurological symptoms. Decreased level of consciousness, delirium, arterial hypotension, and stroke during or before hospitalisation increase the risk of in-hospital mortality.

Background: Randomized trials and observational studies have shown that the use of FreeStyle Libre Ò intermittently scanned continuous glucose monitoring system (isCGMS) is associated with improved glycemic indices and quality of life. Materials and Methods: In this retrospective, real-world data analysis, we described country-specific glucometrics among isCGMS users from Poland and compared them with international data. The analyzed time period for the Polish data ranged between August 2016 and August 2020, and the analyzed time period for the international data ranged from September 2014 to August 2020. Results: Data from the Polish population were collected from 10,679 readers and 92,627 sensors with 113 million automatically recorded glucose readings. The worldwide database included information from 981,876 readers and 11,179,229 sensors with 13.1 billion glucose readings. On average, the users of isCGMS from Poland performed substantially more scans/day (21.2 -14.2 vs. 13.2 -10.7), achieved lower eHbA1c (7.0% -1.2% vs. 7.5% -1.5%), and spent more time-in-range (TIR) (64.2% -17.3% vs. 58.1% -20.3%) and less time-above-range (TAR) (29.7% -18.0% vs. 36.6% -21.3%) (P < 0.0001 for all comparisons). Moreover, they were more likely to achieve TIR >70% (36.3% vs. 28.8%), but spent more time-below-range (TBR) (4.7% vs. 3.6%). Our results confirmed that analyzed glucometrics improve as the scan rate frequency increases. However, at a similar scanning frequency to the comparative group, users from Poland achieved lower eHbA1c, higher TIR, and lower TAR, but higher TBR. Conclusions: We report more scanning and better glycemic control in isCGMS users in Poland than worldwide. The cause of this observation remains unknown. Our data also show that in real-life practice, a large number of patients may be willing to perform scanning more frequently than it is usually assumed.

Ghrelin is a hormone that regulates appetite. It is likely to be involved in the pathophysiology of varying forms of diabetes. In animal studies, the ghrelin expression was regulated by the hepatocyte nuclear factor 1 alpha (HNF1A). Mutations of the HNF1A gene cause maturity onset diabetes of the young (MODY). We aimed to assess the circulating ghrelin levels in HNF1A–MODY and in other types of diabetes and to evaluate its association with HNF1A mutation status. Our cohort included 46 diabetic HNF1A gene mutation carriers, 55 type 2 diabetes (T2DM) subjects, 42 type 1 diabetes (T1DM) patients, and 31 glucokinase (GCK) gene mutation carriers with diabetes as well as 51 healthy controls. Plasma ghrelin concentration was measured using the immunoenzymatic assay with polyclonal antibody against the C-terminal fragment of its acylated and desacylated forms. Ghrelin concentrations were 0.75 ± 0.32, 0.70 ± 0.21, 0.50 ± 0.20, and 0.40 ± 0.16 ng/ml in patients with HNF1A–MODY, GCK–MODY, T1DM, and T2DM, respectively. The ghrelin levels were higher in HNF1A–MODY and GCK–MODY than in T1DM and T2DM (p < 0.001 for all comparisons) but lower than in non-diabetic controls (1.02 ± 0.29 ng/ml, p < 0.001 for both comparisons). In the multivariate linear model, the differences between both MODY groups and common diabetes types remained significant. Analysis by a HNF1A mutation type indicated that ghrelin concentration is similar in patients with different types of sequence differences. Plasma ghrelin level is higher in HNF1A–MODY and GCK–MODY than in the common polygenic forms of diabetes.

AimsSGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes.MethodsWe examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level.ResultsThere were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was −6.57 ± 7.34 mg/ml (p = 0.04).ConclusionsA single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.