Introduction Anti-platelet factor 4 (PF4) antibodies have been identified as the cause of vaccine-induced immune thrombotic thrombocytopenia following adenoviral vector-based COVID-19 vaccines. Previous studies have primarily focused on determining the frequency of anti-PF4 antibodies shortly after the first COVID-19 vaccination, leaving the rates of anti-PF4 antibody positivity after second vaccinations largely unknown.

Introduction Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare but life-threatening prothrombotic syndrome observed in individuals following vaccination with vector-based SARS-CoV-2 (ChAdOx1 CoV-19) vaccine. Laboratory findings indicate that VITT is caused by antibodies (Abs) that recognize specific heparin-independent epitopes on the endogenous chemokine platelet factor 4 (PF4) which results in the initiation of a multicellular driven prothrombotic condition and onset of thrombosis at unusual sites. Despite PF4 has been identified as the primary target of anti-PF4 VITT patient antibodies, a deeper understanding regarding the mechanisms of anti-PF4 VITT Ab-mediated prothrombotic conditions is missing. In this study we investigate the regulatory and mechanistic role of PF4 in anti-PF4 VITT Ab-induced procoagulant platelet (PLT) and thrombus formation ex vivo.

Aims:The objective of this study is to establish the frequency of Anti-Nuclear antibody (ANA) in our population and to evaluate its association with severity of clinical presentation, disease remission and its association with other auto immune diseases.Methods: This was a descriptive cross-sectional study that included 160 ITP patients from February 2021 to July 2022.Patients were screened for ANA antibodies and other causes of secondary ITP.ANA positive patients were compared with ANA negative patients in terms of bleeding manifestations and platelet counts at initial presentation, association with other auto immune diseases and response to first line treatment.Results: In our study 43 (26.9%)patients were ANA positive and 117 (73.1%) were negative for ANA.Median (range) platelet count at baseline in the ANA positive group was 20(94) while 18 (98) in the ANA negative group.No significant association ( p-value > 0.05) in the median platelet counts during the study follow-ups was observed between the two groups.Similarly, bleeding symptoms were not found to be significantly different among the two groups, table 1. 79.1% of the ANA positive patients reported presence of other auto immune markers compared to 20.9% ANA negative patients, showing a significant association ( p-value < 0.00).Response to treatment

Introduction Inherited thrombocytopenia related to distinctive and clinically relevant bleeding disorder are rare diseases. Special diagnostic tools and intensive medical care are needed for these patients. Chronic thrombocytopenia is a disorder defined by low platelet count (<150.000 platelets/µl) caused by autoimmune platelet destructions or reduced platelet production by megakaryocytes. Growth factor inhibitor 1B (GFI1B) mutations have been reported to be related to thrombocytopenia and distinctive bleeding tendencies of patients.1,2 In mice, impaired erythropoiesis and thrombopoiesis were associated with GFI1B deficiency.3 A syndrome named bleeding disorder Platelet-Type 17 (BDPLT17) is rare but already reported on the Online Mendelian Inheritance in Man OMIM database.

Introduction A subgroup of anti-platelet factor 4 (PF4) antibodies can activate platelets via Fcgamma RIIA and cause thrombotic and thrombocytopenic diseases such as heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia (VITT). Nonpathological anti-PF4 antibodies are detected in 1-7% of healthy blood donors and in 2-8% of SARS-CoV-2 vaccinated individuals. In this study, we investigated the long-term course of anti-PF4 antibodies detected after the first SARS-CoV-2 vaccination in healthy subjects and in patients with VITT.

Background: Accumulating evidence indicates an association between Sars-CoV-2 associated coagulopathy and increased platelet activation. The molecular mechanisms was investof thrombus formation in patients affected by COVID-19. Aims: To investigate the role of phosphoinositid-3-kinase/AKT (PI3K/AKT) signaling pathway in platelet activation in patients with COVID-19. Methods: The Activation status of platelets and PI3/AKT signaling in COVID-19 patients or after incubation of washed healthy platelets with patients' sera was analysed by flow cytometry and Western blot. The functionality was tested by platelets adhesion ability on fibrinogen with PI3K and AKT inhibitors was analysed in vitro. Results: Platelets from COVID-19 patients admitted to the intensive care unit (ICU) showed significantly higher expression of P-selectin (CD62). Western blot analysis showed that platelets from COVID-19 patients display increased phosphorylation of the PI3K as well as of the downstream target protein kinase B/AKT at Ser473 residue. More importantly, sera from these patients induced phosphorylation of PI3K and AKT in healthy donor platelets leading to enhanced activation, which was dependent on Fc-gamma-RIIA (FcγRIIA). The inhibition of AKT as well as PI3K prevented the enhanced activation, adhesion to fibrinogen as well as procoagulant platelet formation. Conclusions: Our study shows that pAKT/AKT signaling pathway is significantly associated with platelet activation in severe COVID-19 patients, which is mediated by FcγRIIA. The strong correlations between platelet activation and pAKT/AKT suggest that inhibiting PI3K/AKT phosphorylation might represent a promising strategy to prevent onset of thrombosis in patients with severe COVID-19.

The management of all wounds requires a holistic approach. After a holistic assessment, attention must be focused on the wound bed. One of the most important factors during wound bed preparation is the removal of necrotic tissue. Maggot debridement treatment (MDT) is one of debridement methods. Because of its advantages as well as disadvantages compared with other methods, patient selection is important. We evaluated the patients who received MDT for non-healing wounds between 2013 and 2015 in this study. It was planned as a prospective case series. Patients needing sharp debridement received this treatment. The diameter of the wounds was measured before and after treatment. A culture sample was collected from each patient before treatment. A post-treatment sample was collected when it was justified by clinical suspicion of infection. We used MDT in 12 patients with non-healing wounds. Microbiological samples taken before MDT application revealed bacterial pathogens in 7 patients and fungal pathogen in one patient. After MDT, only 2 patients had positive wound culture. The other patients were not subjected to wound culture because they did not have any sign of infection. After the MDT application, a decrease in necrotic tissue and increase in granulation tissue was observed. We showed that MDT decreases necrotic tissue in chronic wounds. Since MDT is an easy and cost-effective treatment, it can be considered in selected cases.

The causative pathogens in diabetic foot infections differ in studies of European compared with Asian populations. The purpose of this study was to determine the causative microorganisms and their antibiotic sensitivity patterns in diabetic patients with a foot infection in Turkey, a country at the crossroads of these two continents. We performed a comprehensive literature search to identify all published studies pertaining to DFIs in patients cared for in Turkey. To assess changes in causative organisms and their antibiotic sensitivity patterns over time, we compared the results of just the most recent 5 years (2007-2011) with those of the past 20-years (1989-2011). We identified 31 studies meeting our inclusion criteria. Overall, these studies reported 2,097 patients, from whom 1,974 microorganisms were isolated. The total percentage of gram-negative and gram-positive aerobic bacteria were similar in each of the assessed periods. The rate of isolation of Staphylococcus aureus during the entire period, compared with just the past 5 years, was 23.8% and 19.1%, respectively, while the rate of methicillin-resistant S. aureus was 7.8% and 5.7%, respectively. The isolation rate of Pseudomonas aeruginosa was 13.7% for the entire period and 14.9% for the past 5 years. While linezolid, vancomycin and teicoplanin were the most active agents against gram-positive microorganisms, imipenem and cefoperazone-sulbactam were the most active against gram-negative microorganisms. This systematic review demonstrated few substantial changes in diabetic foot microbiology over the past 20 years. The data may help develop and update local clinical guidelines regarding antibiotic therapy for diabetic foot infections in Turkey. Further studies, especially with optimal culture methods, would be useful to validate these findings.

We read with great interest the article by Kavakli et al. in which the total oxidant and the antioxidant status were investigated in patients with carbon monoxide (CO) poisoning. Although lipid peroxidation has been linked to CO-induced neuropathology for more than two decades, serum levels of oxidative stress markers have not been investigated before. In this study, they measured, in patients with CO poisoning (n 1⁄4 88) and control subjects (n 1⁄4 37), serum levels of total oxidant and antioxidant status and calculated oxidative stress index (1⁄4 total oxidant status/total antioxidant status). They found that total oxidant status and oxidative stress index, but not total antioxidant status significantly increased in patients with CO poisoning when compared with controls. Additionally, they found that carboxyhemoglobin (COHb), total oxidant status and oxidative stress index were significantly reduced after 6 h of treatment. We applaud their efforts to gain insight into the pathophysiology of CO poisoning, which is a frequent cause of morbidity and mortality in Turkey. In the discussion, they conclude that ‘ . . . oxidative stress index may be a useful guide in planning treatment of CO poisoned patients’ and ‘ . . . in decision of hyperbaric oxygen therapy application, oxidative stress index levels should be taken into consideration’. We think that the data presented in this article is not sufficient to support their conclusion that oxidative stress index is a marker of severity and can be used in the selection of patients for hyperbaric oxygen therapy. Oxygen is first-line therapy in CO poisoning. Severely poisoned patients are referred to hyperbaric oxygen therapy. In order to argue that oxidative stress index can discriminate severely poisoned patients, they should have compared oxidative stress index levels in mild, moderate and severely poisoned patients. They could also analyze whether there is a correlation between COHb and oxidative stress markers. If the data is available, the authors could also analyze the correlation between oxidative stress markers and the number of clinical manifestations. Interestingly, in a recent study Garrabou et al. measured serum levels of lipid peroxidation (oxidative stress) in patients with CO poisoning and analyzed its correlation with clinical findings. Although, serum levels of lipid peroxidation were similar in patients with moderate and severe CO poisoning, pretreatment lipid peroxidation level was strongly correlated with the total number of symptoms along the 3 months follow-up. In addition, pretreatment lipid peroxidation was significantly higher in patients who developed late neurological sequel (LNS) compared with those without LNS. Since COHb poorly correlates with severity of CO poisoning, new serum markers are needed to evaluate severity and outcome of patients with CO poisoning. Further studies are needed to elucidate the value of oxidative stress markers in the management of CO poisoning.

Corresponding Author: Günalp Uzun, MD; e-mail: gunalpuzun@gmail.com 707 Dear Editor, A 68-year-old male patient, with type 2 diabetes mellitus of 38 years’ duration was referred to our Department with a large chronic wound (7 × 5 cm) on his left leg (Figure 1). The wound occurred two months ago during hospitalization. On examination, bilateral pedal pulses were absent. A lower extremity Doppler ultrasonography detected arterial stenosis at mid crural level on the patient’s left leg suggestive of diabetic angiopathy. The 10-g-Semmes–Weinstein monofilament test revealed reduced sensation suggestive of diabetic peripheral neuropathy. Because of the wound’s localization, probable etiologic factors other than peripheral arterial disease or bed sores were suspected. The patient’s past medical history revealed a 10 days hospitalization at an intensive care unit (ICU) due to respiratory failure, two months ago. During his stay he was on mechanical ventilation and his blood pressure had been monitored continuously by an inflatable blood pressure cuff. Since he had IV ways on both arms, the cuff had been placed over his left leg. On reanimation the patient noticed pain on the site where the sphygmomanometer cuff was placed. When the cuff was removed, a large necrotic area was observed underneath. Although preventive measures are implemented, nosocomial injuries continue to be a constant threat in the hospital settings1. Diabetic patients are prone to injuries due to diabetic angiopathy and sensory neuropathy. Besides pressure ulcers, diabetic patients may also suffer injuries at several other locations resulting from different sources2. Our patient had several

A 62-year-old male with type 2 diabetes of 25 years’ duration presented with extensively dry and severely cracked feet. He reported to experience these lesions for almost one year, that he did not feel any pain on walking and that he did not use any moisturizers during this period. On examination he had heavy callus formation and extensive skin cracks over the plantar surface of the hind-feet (Figure 1), which were more significant over the medial and lateral aspects of the heel (Figure 2). Autonomous neuropathy was evident on inspection. Arterial doppler sonography indicated monophasic waveform on the trifurcation arteries and 10-g monofilament examination revealed sensory neuropathy on both feet. The patient was referred to the dermatology department.

The aim of our study was to evaluate the efficacy and timing of hyperbaric oxygen (HBO) treatment in sepsis. Forty male adult Wistar rats were divided into five groups: in group 1, 1 ml of 0.9% saline solution was injected intraperitoneally; in group 5, 1 ml of 0.5 Mc Farland E. coli solution was injected intraperitoneally; in groups 2, 3 and 4, 1 ml of 0.5 Mc Farland E. coli solutions were injected intraperitoneally and the rats were treated with HBO at 2.5 ATA with 6 hour intervals after the 2 nd , 6 th and 12 th hours of injection, respectively. At the end of the treatment, tissue levels of glutathione peroxidase (GP), superoxide dismutase (SOD), catalase (CAT) and lipid hydroperoxide (LPO) from liver, kidney and brain were studied. Mean GP levels of groups 2, 3 and 4 were higher than group 5 (all p values being <0.05). Mean GP level of group 2 was higher than those of groups 3 and 4 (p values <0.05) which were statistically indifferent. Mean kidney and liver CAT levels in groups 2, 3 and 4 were higher than group 5. Mean CAT level of group 2 was statistically higher when compared with those of groups 3 and 4 (p values <0.05). Brain and kidney LPO levels of groups 2 and 3 were lower than groups 4 and 5 (p values <0.05). Liver LPO levels of group 2 were lower than those of groups 3 and 4 (p<0.05). Overall, we imply that HBO treatment can be an adjunct to other well established treatment modalities and it seems likely that the early it is started the better will be the outcome. Further studies with larger samples are needed to confirm our preliminary results. (Anatol J Clin Investig 2009:3(1):44-47). Ozet

Inside attendants are medical staff who accompany patients during hyperbaric oxygen treatments. Dysbaric osteonecrosis (DON) is a well-known consequence of hyperbaric exposure. The aim of this study was to evaluate DON in inside attendants using magnetic resonance imaging (MRI). The bilateral shoulder, hip and knee joints of 12 inside attendants (four men, eight women; mean age 29 years; age range 22-36 years) were investigated. The mean +/- SD duration of employment as an inside attendant was 3.8 +/- 3.0 years (range 1-9 years) and the mean +/- SD number of hyperbaric exposures was 198 +/- 267 (median 96; range 30-950). None of the inside attendants had a history of decompression sickness. The MRIs of the attendants did not reveal bone lesions consistent with DON. This study failed to find an increased risk for DON in inside attendants. Additional multicentre epidemiological studies are warranted to investigate the occupational safety of inside attendants.