Investigation on the relationship between serum periostin, MMP-7, TGF-ß, and IL-18 levels and the clinical course and prognosis of COVID-19.

OBJECTIVE: Cytokines are involved in the inflammatory/anti-inflammatory balance and have been shown to play an important role in the course of COVID-19. This study aimed to evaluate the relationship of periostin, transforming growth factor-beta (TGF-ß), interleukin-18 (IL-18), and matrix metalloproteinase 7 (MMP-7) levels with clinical course and mortality in patients with early COVID-19 pneumonia. PATIENTS AND METHODS: A total of 150 hospitalized patients were diagnosed with COVID-19 between June and October 2021, and a control group of 30 healthy individuals were included in our study. The COVID-19 patients were divided into those who developed macrophage activation syndrome (MAS) in Group 1 and those who did not in Group 2. Serum periostin, MMP-7, TGF-ß, and IL-18 levels were measured from blood samples obtained at admission using enzyme-linked immunosorbent assay (ELISA). RESULTS: Periostin, MMP-7, and IL-18 levels were significantly higher in COVID-19 patients compared to the control group (p<0.001 for all). Periostin and MMP-7 levels were also significantly higher in Group 1 than in Group 2 (p<0.001 for both). Periostin, MMP-7, IL-18, and TGF-ß levels were significantly higher in non-surviving patients compared to survivors (p=0.04, p<0.001, p<0.001, and p<0.001, respectively). In the receiver operating characteristic (ROC) curve analysis, MMP-7 was found to have high sensitivity (90%) at a predictive value of 2.66 ng/mL. CONCLUSIONS: It is still not possible to predict which patients with early COVID-19 pneumonia will go on to develop MAS despite receiving standard treatment. The results of our study suggest that elevation of periostin and MMP-7 levels in the early period may predict the development of macrophage activation syndrome.

Is Immune Thrombocytopenia and its Treatment Associated with Sarcopenia?

BACKGROUND: Immune thrombocytopenia (ITP) is defined as an isolated platelet count less than 100 × 109/L in the absence of other causes of thrombocytopenia. Sarcopenia is a body-wide muscular disorder with a progressive nature that leads to reduced mobility, physical disability, falls, and poor quality of life. We aimed to evaluate the frequency of objectively diagnosed sarcopenia in patients with ITP and to determine whether ITP therapies have sarcopenic effects. METHODS: This prospective study included patients who were followed up with ITP in the hematology outpatient clinic. Patients who had received corticosteroids within 3 months were excluded. The handgrip strength test, appendicular skeletal muscle mass (ASMM), ASMM/height2 value, soft lean mass (SLM), trunk soft lean mass (SLMT), and the 6-min walking speed test were applied for muscular evaluations and physical performance assessment. RESULTS: We included 53 patients (female/male: 73.58%/26.42%). While sarcopenia was not observed in 77.36% of ITP patients, possible sarcopenia was diagnosed in 9.43% and confirmed sarcopenia in 13.21%. Severe sarcopenia was not seen in any of the patients. Loss of muscle strength was observed in 22.64% of patients. SLM was found to be low in 92.45%. CONCLUSION: Sarcopenia may be more frequent among patients with ITP compared to the population, and it is important to note that 92.45% of patients had low SLM and 54.72% had low SLMT. Eltrombopag therapy might be beneficial as demonstrated by higher SLM, ASMM, and ASMM/height2 values.

Bilateral peroneal nerve paralysis in agricultural workers: three case reports.

The peroneal nerve can be injured due to direct trauma or non-traumatic causes, with the injury mostly occurring between the fibular head and neck and mostly unilateral. This injury mostly results from prolonged squatting, cross-legged sitting or sitting with one foot tucked under the other leg. In this report, we present three agricultural workers with a history of prolonged squatting who developed bilateral foot drop due to bilateral peroneal nerve injury, two of whom recovered almost completely after physical therapy, and one remained disabled. Agricultural workers should be advised to avoid prolonged squatting for more than 2 h, to extend the knee and to strengthen the muscles around the knee in order to prevent neuropathy.

Time trends, frequency, characteristics and prognosis of short-duration transient global amnesia.

BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia lasting up to 24 h. One major differential for TGA is transient epileptic amnesia, which typically lasts < 1 h. However, TGA can also be short in duration and little is known about the time trends, characteristics and prognosis of TGA cases lasting < 1 h. METHODS: We compared the clinical features of TGA ascertained in two independent cohort studies in Oxfordshire, UK [Oxford cohort 1977-1987 versus Oxford Vascular Study (OXVASC) 2002-2018] to determine the time trends of clinical features of TGA. Results were validated in another independent contemporary TGA cohort in Italy [Northern Umbria TGA registry (NU) 2002-2018]. We compared the risk factors, clinical features and long-term prognosis (major cardiovascular events, recurrent TGA and seizure/epilepsy) of patients presenting with episodes lasting < 1 h versus those lasting ≥ 1 h. RESULTS: Overall, 639 patients with TGA were included (114 Oxford cohort, 100 OXVASC, 425 NU). Compared with the original Oxford cohort, there were more cases with TGA lasting < 1 h in OXVASC [32 (32.0%) vs. 9 (8.8%)] and NU (11.8% vs. 8.8% in Oxford cohort). In both OXVASC and NU, patient age, vascular risk factors and clinical features were largely similar between those with TGA lasting < 1 h versus those lasting ≥ 1 h. Moreover, there was no difference in the long-term risk of seizure/epilepsy or major cardiovascular events between TGA lasting < 1 h versus TGA lasting ≥ 1 h. CONCLUSIONS: Short-duration TGA episodes (<1 h) were not uncommon and were more frequent than in earlier studies. The clinical features and long-term prognosis of short-duration TGA did not differ from more typical episodes lasting ≥ 1 h.

Inhibition of midkine by metformin can contribute to its anticancer effects in malignancies: A proposal mechanism of action of metformin in context of endometrial cancer prevention and therapy.

Metformin, a drug widely used in the treatment of type II diabetes mellitus (T2DM), has been the focus of interest as a potential therapeutic agent for certain types of malignancies, including gynaecological cancers [i.e. endometrial cancer (EC)]. Although the exact mechanism behind the potential anticancer activity of metformin is still not completely understood, certain studies have suggested that different effects on cell functions, such as inhibition of cell migration, apoptosis and tumor cell proliferation, are involved in its preventive and therapeutic effects in certain types of malignancies, including EC. In contrast, midkine (MK), a heparin-binding growth factor and cytokine, which induces carcinogenesis and chemoresistance, promotes the development and progression of many malignant tumours by increasing diverse cell functions such as cell proliferation, cell survival and antiapoptotic activities via mainly the activation of phosphatidyl inositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. The same pathways are also subject to certain therapeutic effects of metformin, although this cytokine and this drug have some different mechanism of action pathways as well. Taken together, MK and metformin appear to have opposite effects in various biological processes such as apoptosis, cell proliferation, cell survival, cell migration, and angiogenesis. On the other hand, MK activates PI3K and MAPK cell signal pathways, whereas metformin inhibits these two pathways. It seems likely that almost all the pathways and cell functions, which play important roles in malignancies, are inhibited by metformin and activated by MK. Given the opposite relationship between the actions of metformin and MK, we hypothesize that metformin may act like a novel MK inhibitor in some malignancies. We also discuss the possible relationship between metformin and MK in the context of EC, the most common gynecological cancer worldwide, which incidence is rising rapidly, in parallel with the increase in obesity, T2DM and insulin resistance. In this respect, the therapeutic use of metformin may improve the survival of EC or other cancers, via inhibiting or overcoming the unwanted effects of MK in carcinogenesis.

A population-based comparison of joint survival of hemiarthroplasty versus total shoulder arthroplasty in osteoarthritis and rheumatoid arthritis.

AIMS: Few studies have compared survivorship of total shoulder arthroplasty (TSA) with hemiarthroplasty (HA). This observational study compared survivorship of TSA with HA while controlling for important covariables and accounting for death as a competing risk. PATIENTS AND METHODS: All patients who underwent shoulder arthroplasty in Ontario, Canada between April 2002 and March 2012 were identified using population-based health administrative data. We used the Fine-Gray sub-distribution hazard model to measure the association of arthroplasty type with time to revision surgery (accounting for death as a competing risk) controlling for age, gender, Charlson Comorbidity Index, income quintile, diagnosis, and surgeon factors. RESULTS: During the study period, 5777 patients underwent shoulder arthroplasty (4079 TSA, 70.6%; 1698 HA, 29.4%), 321 (5.6%) underwent revision, and 1090 (18.9%) died. TSA patients were older (TSA mean age 68.4 years (sd 10.2) vs HA mean age 66.5 years (sd 12.7); p = 0.001). The proportion of female patients was slightly lower in the TSA group (58.0% vs 58.4%). The adjusted association between surgery type and time to shoulder revision interacted significantly with patient age. Compared with TSA patients, revision was more common in the HA group (adjusted-health ratio (HR) 1.214, 95% confidence interval (CI) 0.96 to 1.53) but this did not reach statistical significance. CONCLUSION: Although there was a trend towards higher revision risk in patients undergoing HA, we found no statistically significant difference in survivorship between patients undergoing TSA or HA. Cite this article: Bone Joint J 2019;101-B:454-460.

CYTOGENETIC AND MOLECULAR RESPONSES OF AMMONIUM SULPHATE APPLICATION FOR TOLERANCE TO EXTREME TEMPERATURES IN VICIA FABA L.

Effects of ammonium sulphate [(NH4)2SO4] on mitosis, cell cycle and chromosomes in Vicia faba L. seeds exposed to extreme temperatures were investigated using flowcytometric and cytogenetic analysis. Seeds germinated at high and low temperatures showed a signiicant decrease in mitotic index as compared to those of optimum temperature conditions. Application of 50 and 1000 µM (NH4)2SO4 were successful in alleviating the negative effects of low and high temperature on mitotic activity, respectively. 50 µM (NH4)2SO4 showed the most positive effect on cell cycle at the extreme temperatures. This concentration increased the cell division removing or decreasing the negative effects of temperature stress. Namely, the highest G2/M and S phase percentages under stress conditions were obtained with application of 50 µM (NH4)2SO4. Chromosomal aberrations were not observed in cells of seeds germinated in distilled water and also at any temperatures. However, the frequency of chromosomal aberrations increased significantly by increasing (NH4)2SO4 concentration. The highest aberration frequency in all temperature degree tested was found at 1000 µM (NH4)2SO4 concentration.

Biomechanical comparison of dynamic hip screw, proximal femoral nail, cannulated screw, and monoaxial external fixation in the treatment of basicervical femoral neck fractures.

PURPOSE OF THE STUDY The objective of this study was to establish relative fixation strengths of proximal femoral nail (PFN), dynamic hip screw (DHS), monolateral external fixator (EF), and cannulated screw (CS) in basicervical hip fracture model. MATERIAL AND METHODS The study involved four groups of implanted composite proximal femoral synthetic bones of eight specimens per group; nailing with PFN, DHS, fixation with three cannulated screws, and EF. 70˚ osteotomy was performed to simulate a Pauwels Type 3 basicervical fracture. Minimum preload of 100 N was applied before loading to failure. The constructs were subjected to cyclic loading with 16˚ to midline from 100 N to 1,000 N for 10,000 cycles at 3Hz. Axial loading was applied at 10 mm/min until failure. Failure load, failure mode, and displacement were documented. RESULTS Mean failure load was 2182.5 ± 377.9 N in PFN group, 2008.75 ± 278.4 N in DHS group, 1941.25 ± 171.6 N in EF group, and 1551.6 ± 236.2 N in CS group. Average displacement was 15.6 ± 4.5 mm, 15.5 ± 6.7 mm, 11.7 ± 1.9 mm, and 15 ± 1.7 mm, respectively. No significant difference was noted among groups for fixation strength except CS group. All CS constructs failed during cyclic loading. CONCLUSION Our findings suggest that PFN, DHS and EF achieved higher fixation strengths than CS in basicervical fracture. PFN has higher failure loads and possesses biomechanical benefits for fixation of unstable basicervical fractures compared with DHS and EF. Key words: basicervical fracture, internal fixation, biomechanics.

Increased Risk of Unfavorable Metabolic Outcome in Patients with Clinically Nonfunctioning Pituitary Adenomas.

The aim of this study was to investigate atherosclerotic risk markers in women with clinically nonfunctioning pituitary adenomas (CNFAs). Records of 47 women with CNFAs and 73 healthy women who were treated as outpatients between January 2010 and March 2014 were evaluated retrospectively. All study data were obtained from file records. Lipid parameters, mean platelet volume (MPV), total testosterone (TT), androstenedione (AS), and dehydroepiandrostenedione sulfate (DHEAS) were recorded. Insulin resistance (IR) was calculated with homeostatic model assessment-insulin resistance (HOMA-IR). Among the atherosclerotic risk markers, the HOMA-IR and AS levels were higher in patients with CNFAs than in healthy subjects (p=0.003, p=0.021, respectively). A positive correlation between AS and insulin/HOMA-IR levels was found among the metabolic parameters in the patients with CNFAs (p=0.001, r=0.550, p=0.004, r=0.498, respectively). The data showed that patients with CNFAs had high atherosclerotic risk markers such as insulin resistance and hyperandrogenemia. Insulin resistance may also cause hyperandrogenemia in patients with CNFAs.

Characterization of V804M-mutated RET proto-oncogene associated with familial medullary thyroid cancer, report of the largest Turkish family.

PURPOSE: Analysis of the RET proto-oncogen is very important for diagnosis and prognosis of medullary thyroid cancer (MTC). Genotype-phenotype correlation is also well known. Here we report features of the largest known family in Turkey with the V804M-mutated RET proto-oncogene. METHODS: Thirty members from three generations were evaluated. A RET proto-oncogen mutation, calcitonin (Ct) measurement and thyroid ultrasound were performed on all individuals. Seventeen members had V804M mutation. Fourteen of these patients underwent total thyroidectomy and additional central lymph node dissection for five subjects. RESULTS: The mean age of patients with MTC was 46.5 (30-61) years. The mean calcitonin level of RET positive members was 13.27 pg/mL (1-49.8 pg/mL). Three had a basal Ct level above normal limits. Seven of the 14 patients were diagnosed with MTC, and two were diagnosed with papillary thyroid cancer without MTC. One patient had central neck metastasis. Hyperparathyroidism or pheochromocytoma was not detected in any case. Patients who were RET negative, had normal Ct levels and no suspected nodule on ultrasound examination. CONCLUSIONS: Our study revealed a relatively good prognosis in patients with V804M mutation. Despite the surgery was performed in older age no advance disease was observed.

Optimum air-demand ratio for maximum aeration efficiency in high-head gated circular conduits.

Oxygen is an important component of water quality and its ability to sustain life. Water aeration is the process of introducing air into a body of water to increase its oxygen saturation. Water aeration can be accomplished in a variety of ways, for instance, closed-conduit aeration. High-speed flow in a closed conduit involves air-water mixture flow. The air flow results from the subatmospheric pressure downstream of the gate. The air entrained by the high-speed flow is supplied by the air vent. The air entrained into the flow in the form of a large number of bubbles accelerates oxygen transfer and hence also increases aeration efficiency. In the present work, the optimum air-demand ratio for maximum aeration efficiency in high-head gated circular conduits was studied experimentally. Results showed that aeration efficiency increased with the air-demand ratio to a certain point and then aeration efficiency did not change with a further increase of the air-demand ratio. Thus, there was an optimum value for the air-demand ratio, depending on the Froude number, which provides maximum aeration efficiency. Furthermore, a design formula for aeration efficiency was presented relating aeration efficiency to the air-demand ratio and Froude number.

Experimental investigations of aeration efficiency in high-head gated circular conduits.

The primary purpose of water aeration is to increase the oxygen saturation of the water. This can be achieved by using hydraulic structures because of substantial air bubble entrainment at these structures. Closed conduit aeration is a particular instance of this. While there has been a great deal of research on air-demand ratio within closed conduit, very little research has specifically addressed aeration efficiency of closed conduit. In the present work an experimental study was conducted to investigate the aeration efficiency of high-head gated circular conduits. Results showed that high-head gated circular conduits were effective for oxygen transfer. The effects of Froude number and ratio of the water cross-sectional flow area to the conduit cross-sectional area on aeration efficiency were particularly significant, whereas the effect of conduit length was only moderate. Further, a design formula for the aeration efficiency was presented relating the aeration efficiency to ratio of water cross-sectional flow area to conduit cross-sectional area and Froude number. The obtained results will be useful in future modeling processes and aid the practicing engineer in predicting aeration efficiency for design purposes.

Clinical presentation of Von Hippel Lindau syndrome type 2B associated with VHL p.A149S mutation in a large Turkish family.

Von Hippel Lindau (VHL) syndrome is an autosomal dominant disorder characterized by benign and malignant tumors. This study presents the clinical and genetic features of VHL syndrome in a Turkish family. For the diagnosis of pheochromocytoma-related diseases, 49 family members from three generations were evaluated between March 2008 and January 2013. Family members were examined to identify components of pheochromocytoma-related genetic syndromes through physical examination, laboratory tests, and imaging methods. For the causative mutation, sequence analysis of VHL gene was performed. Nine patients were diagnosed with pheochromocytoma. Lumbal spinal hemangioblastoma and pancreatic neuroendocrine tumor without pheochromocytoma were detected in one patient. In patients with pheochromocytoma, additional tumors, such as retinal angioma, renal cell carcinoma, pancreatic serous cystadenoma, and pancreatic neuroendocrine tumors were detected. All patients were diagnosed as VHL syndrome type 2B. Sequence analysis of VHL gene revealed heterozygous p.A149S mutation in all symptomatic patients and in seven of the asymptomatic family members. This is the first study that identified VHL p.A149S mutation in a Turkish family with VHL syndrome. However, VHL p.A149S mutation was identified in an American family by Atuk et al. (J Clin Endocrinol Metab, 83:117-120, 14) and the family was defined as VHL type 2A. In our study, the family was identified as VHL type 2B. This variability in the phenotypic features suggests that further studies are required to beter assess the genotype-phenotype correlation in such cases.

Gastrointestinal tract access for enteral nutrition in critically ill and trauma patients: indications, techniques, and complications.

BACKGROUND: Enteral nutrition (EN) is a widely used, standard-of-care technique for nutrition support in critically ill and trauma patients. OBJECTIVE: To review the current techniques of gastrointestinal tract access for EN. METHODS: For this traditional narrative review, we accessed English-language articles and abstracts published from January 1988 through October 2012, using three research engines (MEDLINE, Scopus, and EMBASE) and the following key terms: "enteral nutrition," "critically ill," and "gut access." We excluded outdated abstracts. RESULTS: For our nearly 25-year search period, 44 articles matched all three terms. The most common gut access techniques included nasoenteric tube placement (nasogastric, nasoduodenal, or nasojejunal), as well as a percutaneous endoscopic gastrostomy (PEG). Other open or laparoscopic techniques, such as a jejunostomy or a gastrojejunostomy, were also used. Early EN continues to be preferred whenever feasible. In addition, evidence is mounting that EN during the early phase of critical illness or trauma trophic feeding has an outcome comparable to that of full-strength formulas. Most patients tolerate EN through the stomach, so postpyloric tube feeding is not needed initially. CONCLUSION: In critically ill and trauma patients, early EN through the stomach should be instituted whenever feasible. Other approaches can be used according to patient needs, available expertise, and institutional guidelines. More research is needed in order to ensure the safe use of surgical tubes in the open abdomen.

[Bicuspid aortic valve--ethiopathogenesis and natural history]. / Bikuspidální aortální chlopen--etiopatogeneze a prirozený vývoj.

Bicuspid aortic valve is a disease with autosomal dominant inheritance with small penetration. The population of patients with bicuspid aortic valve is heterogenous. In the absence of dilatation of ascending aorta, valvular lesion or degenerative changes of valve leaflets patients are considered to belong to the low risk population. On the other hand patients with the above mentioned characteristics compose a high risk group. Dilatation of the ascending aorta in patients with bicuspid aortic valve has a progressive feature and continues even after replacement of the aortic valve. With progression of aortic dilatation the risk of aortic dissection and rupture increases. The main reasons for aortic dilatation are changes in quality of aortic wall and possibly mechanical stress of aortic wall during asymmetrical and turbulent flow. The progression of aortic dilatation or aortic valve disease is not essentially influenced by farmacologic treatment. Surgery is the treatment of choice. Physiology and pathophysiology of bicuspid and tricuspid aortic valves, prevalence of bicuspid aortic valve in general population and in the group of patients operated on for aortic valve disease, phenotypes of bicuspid aortic valve and follow-up of asymptomatic patients with normal bicuspid valve are reviewed in this article. Indications for operation of dilated ascending aorta according to american, european and czech guidelines are discussed.

Molecular, morphological, and cytological analysis of diverse Brachypodium distachyon inbred lines.

Brachypodium distachyon (brachypodium) is a small grass with the biological and genomic attributes necessary to serve as a model system for all grasses including small grains and grasses being developed as energy crops (e.g., switchgrass and Miscanthus). To add natural variation to the toolkit available to plant biologists using brachypodium as a model system, it is imperative to establish extensive, well-characterized germplasm collections. The objectives of this study were to collect brachypodium accessions from throughout Turkey and then characterize the molecular (nuclear and organelle genome), morphological, and cytological variation within the collection. We collected 164 lines from 45 diverse geographic regions of Turkey and created 146 inbred lines. The majority of this material (116 of 146 inbred lines) was diploid. The similarity matrix for the diploid lines based on AFLP analysis indicated extensive diversity, with genetic distances ranging from 0.05 to 0.78. Organelle genome diversity, on the other hand, was low both among and within the lines used in this study. The geographic distribution of genotypes was not significantly correlated with either nuclear or organelle genome variation for the genotypes studied. Phenotypic characterization of the lines showed extensive variation in flowering time (7-22 weeks), seed production (4-193 seeds/plant), and biomass (15-77 g). Chromosome morphology of the collected brachypodium accessions varied from submetacentric to metacentric, except for chromosome 5, which was acrocentric. The diverse brachypodium lines developed in this study will allow experimental approaches dependent upon natural variation to be applied to this new model grass. These results will also help efforts to have a better understanding of complex large genomes (i.e., wheat, barley, and switchgrass).

[Aortic valve sparing operations and reconstruction--from anatomy to the long-term results]. / Záchovné operate a plastiky aortální chlopne--od anatomie chlopne az k dlouhodobým výsledkum.

The implantation of an artificial heart valve (a mechanical valve or a xenograft valve) involves the risk of serious and life-threatening complications for the patient, such as hemorrhagic complications, thromboembolic complications, the risk of endocarditis, the risk of premature degeneration of the xenograft valve, etc. Preserving the patient's own aortic valve eliminates or at least significantly reduces the above complications. On the other hand, it brings about the disadvantage of a technically more demanding surgery and the possible risk of reoperation due to failure of the spared aortic valve. The authors present a comprehensive and up-to-date view ofthe issue of aortic valve sparing surgeries and plastic corrections, beginning with the basics of aortic root anatomy and ending with the indications and principles of cardiosurgical techniques, and long-term results.

An unusual cause of mismanagement in an acute myocardial infarction case: pseudothrombocytopenia.

Thrombocytopenia determined by an automated counter may represent a benign, incidental finding in an asymptomatic patient or a potentially life-threatening disorder. Even if the low platelet count actually is a benign condition itself, in some conditions, any delay resulting from this condition consequently may be seriously hazardous. Low platelet count may alter the decision of heparin administration, which is an essential part of management during acute coronary syndromes. EDTA-dependent pseudothrombocytopenia (PTCP) is reported to have a prevalence of 0.1% in a general hospital; however, it is also reported that around 15% of the patients referred for a specialized center for isolated thrombocytopenia are actually cases of PTCP. In this report, we describe a patient with PTCP who could not receive reperfusion therapy during acute myocardial infarction because of the low platelet counts reported by an automated counter.