The role of oxidized phospholipids in COVID-19-associated hypercoagulopathy.

OBJECTIVE: There is more pronounced hypercoagulation in COVID-19 infection than in other viral lung infections. Oxidized phospholipids (OxPLs) appear in COVID-19-infected lungs due to oxidative stress, after which they promote the induction of tissue factor (TF) expression and inflammatory programmers in monocytes, as well as activate endothelial cells to recruit and bind to monocytes. Therefore, we aimed to demonstrate the role of OxPLs in inflammatory and procoagulant responses in COVID-19 infection. PATIENTS AND METHODS: Patients with a positive SARS-CoV-2 polymerase chain reaction test and ten healthy donors were included in the study. Peripheral blood was drawn at inclusion for OxPAPC, IFN-γ, and CCL2 serum level measurements. Clinical data were collected from electronic patient medical files. The serum levels of OxPAPC, IFNγ, and CCL2 were measured by immune assays. RESULTS: Seventy-two patients were included in the study. OxPAPC and CCL2 were higher in the patients than in the controls (<0.003 and 0.011, respectively). INF-γ did not significantly differ between groups. There was no difference between the patients with lung involvement and those without CCL2, INF-γ, and OxPAPC. D-dimer, CRP, and ferritin were higher in the patients with lung involvement. Serum levels of INF-γ and CCL2 were positively correlated with each other (r:0.757, p<0.0001), but no correlation was detected between OxPAPC and INF-γ or CCL2. There was no correlation between OxPAPC and hematologic or biochemical parameters. CONCLUSIONS: OxPAPC, which is thought to contribute to hypercoagulability, was found to be high in the patients with Covid-19 infection. The role of OxPLs in COVID-19-associated hypercoagulopathy should be investigated further in experimental models and in larger patient groups.

A 3D finite element analysis of stress distribution on different thicknesses of mineral trioxide aggregate applied on various sizes of pulp perforation.

OBJECTIVES: The aim of this study was to evaluate the stress distribution on different thicknesses of mineral trioxide aggregate (MTA) placed on various widths of pulp perforations during the condensation of the composite resin material. MATERIALS AND METHODS: The mandibular molar tooth was modeled by COSMOSWorks program (SolidWorks, Waltham, MA). Three finite elemental analysis models representing 3 different dimensions of pulp perforations, 1, 2, and 3 mm in diameter, were created. The perforation area was assumed as filled with MTA with different thicknesses, 1, 2, and 3 mm for each pulp perforation width, creating a total of 9 different models. Then, a composite resin material was layered on MTA for each model. A 66.7 N load was applied and an engineering simulation program (ANSYS, Canonsburg, US) was used for the analysis. Results were presented considering von Mises stress criteria. RESULTS: As MTA thickness increased, the stress values recorded within the area between pulp and MTA decreased. Strain was decreased when the thickness of MTA increased. CONCLUSIONS: Stresses at MTA-pulp interface and strain on MTA decreased with the increase in MTA thickness. CLINICAL RELEVANCE: In clinical practice, when MTA is required for pulp capping, using a thick layer of the material seems to be a better option in order to reduce the stress under forces of hand condensation of overlying restorative materials.

Serum soluble Fas ligand levels and peripheral blood lymphocyte subsets in patients with drug-induced maculopapular rashes, dress, and viral exanthemas.

BACKGROUND: Fatty acid synthetase (Fas)/Fas ligand (FasL)-dependent apoptotic pathways have been reported as being involved in the pathogenesis of drug-induced maculopapular rashes. OBJECTIVE: We investigated serum soluble FasL (sFasL) levels and peripheral blood lymphocyte subtypes to discriminate maculopapular drug eruptions (MPDE) from viral exanthema (VE). PATIENTS/METHODS: Children with confirmed MPDE (group I), VE (group II), and drug rashes with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) (group III) were included. Serum sFasL levels and peripheral blood lymphocyte subtypes were analyzed in groups I-III on admission, and repeated twice (only once for group IV - controls). RESULTS: There were no significant serum soluble FasL level differences among the groups for all the samples. In the initial samples, CD19+ cell numbers in group II were significantly higher than in group IV, and the CD4+/CD8+ ratio was higher than groups I and IV. In the second samples, CD4+ and CD19+ cell numbers were significantly higher in group II than group I. In the final samples, CD4+ cell numbers in group II were significantly higher than group I and group III. CD19+ cells numbers in group III were significantly lower than the other groups for all samples. CONCLUSION: Serum sFasL levels were not found to be useful in discriminating viral exanthemas from other drug rashes. The significant differences between MPDE, VE, and DRESS were high CD4+ and CD19+ cell-count numbers in VE but low B-cell numbers in DRESS. This might be important for discriminating VE from DRESS, and the low B-cell count in early symptoms might be a useful predictor of DRESS development.

Antimicrobial Stewardship Reduces Surgical Site Infection Rate, as well as Number and Severity of Pancreatic Fistulae after Pancreatoduodenectomy.

Background: Surgical site infections (SSIs) remain a major source of morbidity after pancreatoduodenectomy (PD). We noted a higher than anticipated incidence of SSI in our patients undergoing PD, and after an internal audit and detailed analysis of the microflora of SSIs, as well as a multidisciplinary discussion, the local prophylactic antibiotic policy was changed based on sensitivities to the bacteria isolated from post-operative infections. The hypothesis was that a targeted change in antibiotic prophylaxis would reduce the rate of SSIs. The aim of the current study was to analyze the results of a change in prescribing policy on SSI rates, and in addition, on the occurrence and severity of post-operative pancreatic fistulae (POPF) because this complication is often linked to the presence of an organ/space SSI. Methods: After implementing a change of prophylaxis policy from cefalexin to ceftriaxone and metronidazole, and educating staff and residents, a prospectively maintained departmental database was used to identify consecutive patients undergoing PD pre- and post-institution of policy change. Incidence data relating to SSIs and POPF were obtained from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) data set and the details of culture results and organism sensitivity extracted from the electronic medical record, as were details on the severity of fistulae, and verified by the senior author. Results: The pre- and post-implementation cohorts consisted of 111 and 216 patients, respectively, and were matched in terms of all demographic features. After the change in the antibiotic prophylaxis policy, there was a reduction in the overall SSI rate (26.4% vs. 14.8%; p = 0.01) and the organ/space SSI rate (OS-SSI; 15.3% vs. 8.6%; p = 0.03). There were also reductions in the POPF rate (38.2% vs. 19%; p = 0.002) and in the clinically relevant POPF (CR-POPF; 23.4% vs. 6.0%; p = 0.001). The rate of Clostridium difficile infections also decreased (8.1% vs.1.9%; p = 0.006) as did the median length of hospital stay (7 vs. 6 days; p = 0.003). After excluding patients with a penicillin allergy (n = 24) from the post-implementation cohort, cases compliant (158/192) and non-compliant (34/192) to the new antibiotic policy were compared. The overall SSI (26.4% vs. 10.7%; p = 0.025), OS-SSI (17.6% vs. 5.1%; p = 0.021), overall POPF (32.4 vs. 14.6; p = 0.023); CR-POPF (10.8% vs. 5.5%; p = 0.047) and Clostridium difficile (8.8% vs. 1.3%; p = 0.040) were all lower in the compliant patient cohort. Conclusions: A change in antibiotic prophylaxis prior to PD based on the local microflora, resulted in reductions in SSI, POPF, and Clostridium difficile rates.

Placement of double-J stent in patients with malignant ureteral obstruction: antegrade or retrograde approach?

AIM: To determine whether antegrade or retrograde methods should be preferred for double-J stent placement in patients with malignant ureteral obstruction (MUO). MATERIAL AND METHODS: The medical records of patients treated for MUO in the Urology and Interventional Radiology Clinic, Konya Training and Research Hospital, were reviewed retrospectively. Patients with benign aetiology were excluded from the study. Reports of the procedures, ultrasonography findings, computed tomography (CT), angiography, and pyelography images and the follow-up records of patients with MUO were assessed. A total of 111 patients and 114 ureteral stenting treatments were included in the study; 63 (55.3%) were operated on using the antegrade ureteral stenting (AUS) method, whereas 51 (44.7%) were operated on using the retrograde ureteral stenting (RUS), method, and the characteristics of these groups were evaluated. The presence of hydroureteronephrosis and ureteral tortuosity were determined. RESULTS: Overall success rates were found to be 95.2% using the AUS method and 47.1% using the RUS method. The technical success of the antegrade method was significantly higher in patients with or without tortuosity (respectively: p=0.005, Z shape p=0.001, pigtail shape p=0.035″). The technical success of the antegrade method was significantly higher in patients with hydroureteronephrosis (p=0.001). CONCLUSION: The AUS technique should be the first choice for double-J stent placement in patients with MUO.

Is da Vinci Xi Better than da Vinci Si in Robotic Rectal Cancer Surgery? Comparison of the 2 Generations of da Vinci Systems.

BACKGROUND: We aimed to compare perioperative outcomes for procedures using the latest generation of da Vinci robot versus its previous version in rectal cancer surgery. PATIENTS AND METHODS: Fifty-three patients undergoing robotic rectal cancer surgery between January 2010 and March 2015 were included. Patients were classified into 2 groups (Xi, n=28 vs. Si, n=25) and perioperative outcomes were analyzed. RESULTS: The groups had significant differences including operative procedure, hybrid technique and redocking (P>0.05). In univariate analysis, the Xi group had shorter console times (265.7 vs. 317.1 min, P=0.006) and total operative times (321.6 vs. 360.4 min, P=0.04) and higher number of lymph nodes harvested (27.5 vs. 17.0, P=0.008). In multivariate analysis, Xi robot was associated with a shorter console time (odds ratio: 0.09, P=0.004) with no significant differences regarding other outcomes. CONCLUSIONS: Both generations of da Vinci robot led to similar short-term outcomes in rectal cancer surgery, but the Xi robot allowed shorter console times.

Trimetazidine for prevention of induced ischemia and reperfusion of guinea pig retina.

OBJECTIVE: Trimetazidine (TMZ) has been used to protect against ischemia/reperfusion (I/R) injury of many tissues. We aimed to evaluate the effect of TMZ during retinal I/R in a guinea pig model. STUDY DESIGN/PATIENTS AND METHODS: An experimental study in retinal I/R. Three groups of five guinea pigs were studied to include a control, placebo, and drug test groups. Prior to the application of 90 minutes of high intraocular pressure (IOP) to induce retinal ischemia followed by 24 hours of reperfusion, we applied intraperitoneal saline to the placebo group and 3 mg/kg of TMZ for the drug test group and repeated the injections at intervals of six hours for four cycles. Both eyes of the animals were enucleated at the end of the reperfusion period. Biochemical assay and histopathologic evaluation was performed on one randomly selected eye of each animal. The level of retinal-free malondialdehyde (MDA) and retinal layer thicknesses were determined and comparisons were then made with the control group. RESULTS: The mean free MDA level increased in the placebo group (P = 0.006) but not in the drug group (P > 0.05). We observed polymorphonucleated leukocyte infiltration, retinal edema and hydropic degeneration in the retina of the placebo group. However, significant histopathologic change was not observed in specimens of the drug group. CONCLUSIONS: This study suggests TMZ has a beneficial effect on retinal lipid peroxidation and histopathologic changes due to I/R injury.

Leptin and resistin levels in serum of patients with hematologic malignancies: correlation with clinical characteristics.

AIM: To evaluate leptin and resistin levels in patients with various hematologic malignancies. METHODS: We included 21 patients with lymphoma, 14 with multiple myeloma (MM), 14 with acute leukemia, 13 with chronic lymphocytic leukemia (CLL), and 25 healthy control subjects into our study. The subjects' body mass indexes (BMI) were calculated; hematological and acute phase response parameters, serum lipid were determined; serum leptin and resistin levels were determined by ELISA. RESULTS: Serum leptin level was significantly increased in CLL and MM groups when compared to the control group (p less, similar 0.01). Resistin level was significantly higher in lymphoma patients than in CLL, acute leukemia and control groups (p less, similar 0.01). In the control group, leptin level was negatively correlated with hemoglobin level (r = -0.44, p = 0.047); and in all patients with hematologic malignancies, leptin level was correlated with BMI (r = 0.32, p = 0.02). Leptin in lymphoma subjects correlated with hemoglobin level (r = 0.64, p = 0.005), resistin level correlated with the platelet count in patients with hematologic malignancies (r = 0.26, p = 0.044). In addition, leptin level had negative correlations with international prognostic score (IPS) in Hodgkin lymphoma (r = -0.9, p = 0.002) and with international prognostic index (IPI) in non-Hodgkin lymphoma (r = -0.77, p = 0.03). In CLL patients, leptin level had a correlation with the poor prognostic marker - CD38 level (r = 0.68, p = 0.03). CONCLUSION: We found higher leptin levels in MM and CLL patients, and higher resistin levels in lymphoma patients: this fact demonstrates that changes in adipose tissue and metabolism occur in these disease states.

Secondary amyloidosis causing nephrotic syndrome in a patient with non-Hodgkin's lymphoma: quite a rare diagnosis.

Secondary amyloidosis is usually a complication of chronic inflammation. Amyloidosis cases during the course of non-Hodgkin's lymphoma (NHL) are usually of AL-type, only one NHL patient with secondary amyloidosis has been reported. Our 79-year-old male patient visited us with multiple lymphadenopathies, and he was diagnosed with nodal marginal zone B-cell lymphoma. After four cycles of combined chemotherapy; his urea, creatinine levels started to increase and he developed nephrotic-range proteinuria. His rectal biopsy demonstrated amyloid deposition in submucosal vessel walls. The patient has been under hemodialysis for 10 months and his lymphoma is still in partial remission. We presented this case because it is the second NHL patient who developed secondary amyloidosis during his disease course.

Increased adiponectin level in non-Hodgkin lymphoma and its relationship with interleukin-10. Correlation with clinical features and outcome.

It was reported that interleukin-10 (IL-10) level increased in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) patients; moreover this was associated with poor prognosis. In addition, it was stated that adiponectin induced the antiinflammatory cytokine IL-10. We evaluated adiponectin and IL-10 levels in NHL and CLL patients. We included newly diagnosed 28 NHL, 23 CLL patients, and 17 healthy subjects. In NHL patients, adiponectin level was higher than in CLL group and controls (p values < 0.05). In CLL group, IL-10 level was lower than in NHL, and control groups (p values < 0.05). Adiponectin level had a positive correlation with IL-10 level in the NHL patients (r = 0.41, p = 0.04). In the NHL group, the median survival of patients with high IL-10 levels was shorter (22 months vs. not reached, p = 0.03). Increased IL-10 levels helped to predict poor outcome in our NHL patients. High adiponectin levels and a relationship between adiponectin/IL-10 in newly diagnosed NHL patients might suggest a role for both in the immunodysregulation in NHL.

The possible effect of clinical recovery on regional cerebral blood flow deficits in fibromyalgia: a prospective study with semiquantitative SPECT.

OBJECTIVES: Regional deficits in cerebral blood flow have been reported in a few studies of fibromyalgia; however, there is no information on the effects of treatment and clinical recovery on these abnormalities. We evaluated the effects of amitriptyline treatment and consequent clinical recovery on cerebral blood flow changes in fibromyalgia. METHODS: We assessed cerebral blood flow with a semiquantitative functional brain mapping technique of single-photon emission computed tomography in 14 patients with primary fibromyalgia before and after 3 months of amitriptyline treatment. Patients were followed by visual analog scale, tender point count, and Beck Depression Inventory for clinical improvement. RESULTS: There was statistically significant improvement in visual analog scale and tender point count after treatment. Beck Depression Inventory did not change significantly. Statistically significant blood flow increase in bilateral hemithalami and basal ganglia and decrease in bilateral temporal, left temporo-occipital, and right occipital lobes were observed on single-photon emission computed tomography after treatment. CONCLUSIONS: We speculate that these findings could indicate that deficits in cerebral blood flow in fibromyalgia improve parallel to clinical recovery.

An interesting presentation of intrathoracic extramedullary hematopoiesis in a patient with thalassemia intermedia.

Extramedullary hematopoiesis (EMH) occurs as a compensatory mechanism for bone marrow dysfunction in severe thalassemia. In addition to the more common locations, such as liver, spleen and lymph nodes, a mass of EMH may occasionally occur in the thorax. Intrathoracic EMH is usually asymptomatic. A 69-year-old woman who initially presented with hematuria, dysuria, and left inguinal pain was found to have paravertebral masses in the thorax. Histopathologic examination of a CT-guided needle aspiration biopsy of the masses showed the presence of trilineage hematopoiesis. We present this unusual case, in which EMH was diagnosed by chance in an elderly patient with no symptoms related to thalassemia.

Thrombosis in systemic lupus erythematosus: effect of inherited thrombophilic mutations.

Thrombosis in the venous or arterial system is quite common in systemic lupus erythematosus (SLE). We describe a young female patient whose first presentation was in the form of deep venous thrombosis of the right lower extremity. Her family history for thrombosis was positive and further studies revealed her to have SLE. Genetic studies showed that she had thrombophilic mutations of factor V, prothrombin and methylene tetrahydrofolate reductase genes. Her therapeutic response to anticoagulant therapy was satisfactory. The presence of inherited thrombophilic mutations must be searched for in SLE patients with thrombosis, especially in cases with a positive family history.

Metastatic squamous cell carcinoma of the skin in chronic myeloid leukaemia: complication of hydroxyurea therapy.

Hydroxyurea is a ribonucleotide diphosphate reductase inhibitor used in the treatment of patients with myeloproliferative disorders. Hydroxyurea has some dermatological side-effects. It has recently been recognized that hydroxyurea can induce squamous cell and basal cell carcinomas of skin. We present the case of an elderly man with chronic myeloid leukaemia who was treated with hydroxyurea for 4 years, with good control of his disease. However, in addition to the appearance of various skin lesions and cutaneous squamous cell carcinoma after 3 years of therapy, he was found to have a metastatic squamous cell carcinoma after 4 years. Hydroxyurea was discontinued, and he underwent surgery and radiotherapy. The patient subsequently died of ventricular fibrillation. We present this case to draw attention to the association between hydroxyurea and secondary skin cancers and to emphasize the need for dermatological examination before and during the course of hydroxyurea therapy.

Candida arthritis in a patient with chronic myelogenous leukemia (CML) in blastic transformation, unresponsive to fluconazole, but treated effectively with liposomal amphotericin B.

Candida arthritis is quite rare and might be caused either by direct intra-articular inoculation of Candida or secondary to hematogeneous seeding of Candida in immunocompromised hosts. Until now less than 50 cases of Candida arthritis have been reported in the literature. We report a case of Candida arthritis, which occurred in a patient with chronic myelogenous leukemia (CML) in blastic transformation. Aggressive chemotherapy and broad-spectrum antibiotics for a prolonged period for febrile neutropenia had been given to the patient. Arthritis of the left knee appeared during the recovery phase of leukopenia. Despite treatment with fluconazole, no clinical or microbiological improvement was obtained. Thus, administration of liposomal amphotericin B was started and after 3 days there was improvement. We can conclude that fluconazole might not be sufficient in some Candida arthritis cases and liposomal amphotericin B might be a good alternative in these resistant cases.

A rare cause of acute abdomen: splenic infarction.

Splenic infarction is a rare disorder. We have treated 4 patients during the last year. Abdominal pain in the left upper quadrant was the common complaint. Other complaints were fever, nausea and vomiting. Computed tomography showed infarcted areas in the spleen in all of the patients. Splenectomy was applied to three of the patients with recurring symptoms. The other patient had the first episode treated medically. Pulmonary embolism in one and surgical wound infection occurred in another patient during postoperative follow-up for nine (range: 4-14) months.

A clinically variant fibrosis syndrome in a Turkish family maps to the CFEOM1 locus on chromosome 12.

OBJECTIVES: To describe the phenotype of a Turkish family with variably expressed congenital fibrosis of the extraocular muscles (CFEOM), and to determine the genetic location of their disorder. METHODS: Participants were examined and had blood extracted for genetic analysis. The clinical features of the family's disorder were studied, and the disorder was tested for linkage to the 3 known CFEOM loci (CFEOM1, CFEOM2, and CFEOM3). RESULTS: Twenty-nine affected and 31 unaffected family members participated in the study. Eighteen affected individuals had congenital bilateral ptosis and restrictive infraductive (downward) ophthalmoplegia, consistent with the published descriptions of classic CFEOM families linked to the CFEOM1 locus. Eleven affected individuals, however, had eye(s) in a neutral primary position, residual upgaze, and/or absence of ptosis, thus deviating from previous descriptions of CFEOM1-linked families. Analysis of the autosomal dominant variably expressed disorder in this family revealed linkage to the CFEOM1 locus on chromosome 12 with a maximum lod score of 10.8 at D12S85. CONCLUSIONS: This Turkish family segregates a variably expressed form of CFEOM that most closely resembles CFEOM3-linked CFEOM, but maps to the CFEOM1 locus. CLINICAL RELEVANCE: These data establish that there is much greater phenotypic heterogeneity at the CFEOM1 locus than previously reported, and this may blur our ability to distinguish the different CFEOM loci based solely on clinical presentation. Arch Ophthalmol. 2000;118:1090-1097