Intraplaque Neovascularization, CD68+ and iNOS2+ Macrophage Infiltrate Intensity Are Associated with Atherothrombosis and Intraplaque Hemorrhage in Severe Carotid Atherosclerosis.

BACKGROUND: Atherosclerosis is a progressive disease that results from endothelial dysfunction, inflammatory arterial wall disorder and the formation of the atheromatous plaque. This results in carotid artery stenosis and is responsible for atherothrombotic stroke and ischemic injury. Low-grade plaque inflammation determines biological stability and lesion progression. METHODS: Sixty-seven cases with active perilesional inflammatory cell infiltrate were selected from a larger cohort of patients undergoing carotid endarterectomy. CD68+, iNOS2+ and Arg1+ macrophages and CD31+ endothelial cells were quantified around the atheroma lipid core using digital morphometry, and expression levels were correlated with determinants of instability: ulceration, thrombosis, plaque hemorrhage, calcification patterns and neovessel formation. RESULTS: Patients with intraplaque hemorrhage had greater CD68+ macrophage infiltration (p = 0.003). In 12 cases where iNOS2 predominated over Arg1 positivity, the occurrence of atherothrombotic events was significantly more frequent (p = 0.046). CD31 expression, representing neovessel formation, correlated positively with atherothrombosis (p = 0.020). CONCLUSIONS: Intraplaque hemorrhage is often described against the background of an intense inflammatory cell infiltrate. Atherothrombosis is associated with the presence of neovessels and pro-inflammatory macrophages expressing iNOS2. Modulating macrophage polarization may be a successful therapeutic approach to prevent plaque destabilization.

Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis.

Osteoarthritis (OA) is a complex disease of whole joints with progressive cartilage matrix degradation and chondrocyte transformation. The inflammatory features of OA are reflected in increased synovial levels of IL-1ß, IL-6 and VEGF, higher levels of TLR-4 binding plasma proteins and increased expression of IL-15, IL-18, IL-10 and Cox2, in cartilage. Chondrocytes in OA undergo hypertrophic and senescent transition; in these states, the expression of Sox-9, Acan and Col2a1 is suppressed, whereas the expression of RunX2, HIF-2α and MMP-13 is significantly increased. NF-kB, which triggers many pro-inflammatory cytokines, works with BMP, Wnt and HIF-2α to link hypertrophy and inflammation. Altered carbohydrate metabolism and the upregulation of GLUT-1 contribute to the formation of end-glycation products that trigger inflammation via the RAGE pathway. In addition, a glycolytic shift, increased rates of oxidative phosphorylation and mitochondrial dysfunction generate reactive oxygen species with deleterious effects. An important surveyor mechanism, the YAP/TAZ signaling system, controls chondrocyte differentiation, inhibits ageing by protecting the nuclear envelope and suppressing NF-kB, MMP-13 and aggrecanases. The inflammatory microenvironment and synthesis of key matrix components are also controlled by SIRT1 and mTORc. Senescent chondrocytes represent the functional end stage of hypertrophic differentiation and characteristically upregulate p16 and p21, but also a variety of inflammatory cytokines, chemokines and metalloproteinases, developing the senescence-associated secretory phenotype. Senolysis with dendrobin, miR29b-5p and other agents has been shown to be efficient under experimental conditions, and appears to be a promising tool for the treatment of OA, as it restores COL2A1 and aggrecan synthesis, suppressing NF-kB and destructive metalloproteinases.

Intimal CD31-Positive Relative Surfaces Are Associated with Systemic Inflammatory Markers and Maturation of Arteriovenous Fistula in Dialysis Patients.

BACKGROUND: Arteriovenous fistula dysfunction is a widely disputed subject in the scientific literature on end-stage kidney disease (ESKD). The main cause of mortality and morbidity in these patients is the non-maturation or dysfunction of the arteriovenous fistula. Despite the many complications, the native arteriovenous fistula remains the gold standard in the treatment of these patients requiring renal replacement. This study aims to discuss the predictive role of some systemic inflammatory biomarkers (NLR, PLR, SII, IL-6), intimal hyperplasia, and neoangiogenesis (characterized by intimal-media CD31-positive relative surface) in arteriovenous fistula maturation failure. METHODS: The present study was designed as an observational, analytical, and prospective study which included patients diagnosed with ESKD with indications of radio-cephalic arteriovenous fistula (RCAVF). Demographic data, comorbidities, preoperative laboratory data and histological/digital morphometry analysis results were processed. The patients included were divided into two groups based on their AVF maturation status at 8 weeks: "Maturation" (Group 1) and "Failed Maturation" (Group 2). RESULTS: There was no difference in the demographic data. In terms of comorbidities, the second group had a greater incidence of heart failure (p = 0.03), diabetes (p = 0.04), peripheral artery disease (p = 0.002), and obesity (p = 0.01). Additionally, regarding the laboratory findings, these patients had higher levels of serum uric acid (p = 0.0005), phosphates (p < 0.0001), and creatinine (p = 0.02), as well as lower levels of total calcium (p = 0.0002), monocytes (p = 0.008), and lymphocytes (p < 0.0001). Moreover, all inflammatory markers (p = 0.001; p < 0.0001; p = 0.006, and p = 0.03) and Ca-P product (p < 0.0001) had higher baseline values in Group 2. Upon immunohistochemical analysis, regarding the density of neoformed vessels, there was a higher incidence of CD31-positive surfaces (p = 0.006) and CD31-positive relative surfaces (p = 0.001); the NLR (r = 0.323; p = 0.03), PLR (r = 0.381; p = 0.04), SII (r = 0.376; p = 0.03), and IL-6 (r = 0.611; p < 0.001) are all significantly correlated with vascular density, as evidenced by CD31. CONCLUSIONS: Heart failure, peripheral artery disease, obesity, and diabetes, as well as the systemic inflammatory markers (NLR, PLR, SII, IL-6), intimal hyperplasia, and CD31-positive relative surfaces are predictors of arteriovenous fistula maturation failures.

Inflammation, Microcalcification, and Increased Expression of Osteopontin Are Histological Hallmarks of Plaque Vulnerability in Patients with Advanced Carotid Artery Stenosis.

BACKGROUND: severe carotid artery stenosis is a major cause of ischemic stroke and consequent neurological deficits. The most important steps of atherosclerotic plaque development, leading to carotid stenosis, are well-known; however, their exact timeline and intricate causal relationships need to be more characterized. METHODS: in a cohort of 119 patients, who underwent carotid endarterectomy, we studied the histological correlations between arterial calcification patterns and localization, the presence of the inflammatory infiltrate and osteopontin expression, with ulceration, thrombosis, and intra-plaque hemorrhage, as direct signs of vulnerability. RESULTS: in patients with an inflammatory infiltrate, aphasia was more prevalent, and microcalcification, superficial calcification, and high-grade osteopontin expression were characteristic. Higher osteopontin expression was also correlated with the presence of a lipid core. Inflammation and microcalcification were significantly associated with plaque ulceration in logistic regression models; furthermore, ulceration and the inflammatory infiltrate were significant determinants of atherothrombosis. CONCLUSION: our results bring histological evidence for the critically important role of microcalcification and inflammatory cell invasion in the formation and destabilization of advanced carotid plaques. In addition, as a calcification organizer, high-grade osteopontin expression is associated with ulceration, the presence of a large lipid core, and may also have an intrinsic role in plaque progression.

Cellular FXIII in Human Macrophage-Derived Foam Cells.

Macrophages express the A subunit of coagulation factor XIII (FXIII-A), a transglutaminase which cross-links proteins through Nε-(γ-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque; they may stabilize the plaque by cross-linking structural proteins and they may become transformed into foam cells by accumulating oxidized LDL (oxLDL). The combination of oxLDL staining by Oil Red O and immunofluorescent staining for FXIII-A demonstrated that FXIII-A is retained during the transformation of cultured human macrophages into foam cells. ELISA and Western blotting techniques revealed that the transformation of macrophages into foam cells elevated the intracellular FXIII-A content. This phenomenon seems specific for macrophage-derived foam cells; the transformation of vascular smooth muscle cells into foam cells fails to induce a similar effect. FXIII-A containing macrophages are abundant in the atherosclerotic plaque and FXIII-A is also present in the extracellular compartment. The protein cross-linking activity of FXIII-A in the plaque was demonstrated using an antibody labeling the iso-peptide bonds. Cells showing combined staining for FXIII-A and oxLDL in tissue sections demonstrated that FXIII-A-containing macrophages within the atherosclerotic plaque are also transformed into foam cells. Such cells may contribute to the formation of lipid core and the plaque structurization.

Neutrophil­to­lymphocyte, platelet­to­lymphocyte and lymphocyte­to­monocyte ratios are associated with amputation rates in patients with peripheral arterial disease and diabetes mellitus who underwent revascularization: A Romanian regional center study.

Inflammation plays an important role in peripheral artery disease (PAD), contributing to the onset and progression of atherosclerosis, as well as to the rupture of atherosclerotic plaques. Studies have revealed that due to their inflammatory nature, leucocytes play an important role in the development of atherosclerosis. A retrospective study was conducted involving 203 patients with PAD admitted to Targu Mures Emergency County Hospital for revascularization surgery between January 2017 and June 2019 (of which 47 were treated by endovascular intervention, and 156 underwent classical surgical intervention). Among all patients included in the study, 47 patients required amputation following the revascularization intervention. The results indicated that though the mean patient age in the non-amputation group was higher than that in the amputation group, that the difference was not significant. With regard to sex distribution, 72% of the patients from the amputation group were male, while from the non-amputation group, 74% were male. The neutrophil-to-lymphocyte ratio (NLR) cut-off value for the prediction of amputation in PAD was 3.485 (sensitivity, 60.42%; specificity 72.44%), whereas the platelet-to-lymphocyte ratio (PLR) value was 152, (sensitivity, 54.17%; specificity, 71.79%), and was 2.55 for the lymphocyte-to-monocyte ration (LMR; sensitivity, 56.25%; specificity, 66.88%). The study concluded that in patients with PAD, the NLR and PLR were increased, while the LMR was decreased, which was also associated with a higher rate of amputation after revascularization, despite the lack of correlation between these factors, Fontaine classification and the number of damaged vessels. Therefore, pre-operative alterations in NLR, PLR and LMR may predict the need for amputation in patients with PAD, or those who underwent a revascularization intervention.

The Predictive Value of Systemic Inflammatory Markers, the Prognostic Nutritional Index, and Measured Vessels' Diameters in Arteriovenous Fistula Maturation Failure.

Background: An arteriovenous fistula (AVF) is the first-line vascular access pathway for patients diagnosed with end-stage renal disease (ESRD). In planning vascular access, it is necessary to check the diameters of the venous and arterial components for satisfactory long-term results. Furthermore, the mechanism underlying the maturation failure and short-term patency in cases of AVFs is not fully known. This study aims to verify the predictive role of inflammatory biomarkers (the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic inflammatory index (SII), and C-reactive protein (CRP)), Ca-P product, the prognostic nutritional index (PNI), and the diameters of the venous and arterial components in the failure of AVF maturation. Methods: The present study was designed as an observational, analytical, and retrospective cohort study with a longitudinal follow-up, and included all patients with a diagnosis of ESRD that were admitted to the Vascular Surgery Clinic of the Targu Mures Emergency County Hospital, Romania, between January 2019 and December 2021. Results: The maturation of AVF at 6 weeks was clearly lower in cases of patients in the high-NLR (31.88% vs. 91.36%; p < 0.0001), high-PLR (46.94% vs. 85.55%; p < 0.0001), high-SII (44.28% vs. 88.89%; p < 0.0001), high-CRP (46.30% vs. 88.73%; p < 0.0001), high-Ca-P product (40.43% vs. 88.46%; p < 0.0001), and low-PNI (34.78% vs. 91.14%; p < 0.0001) groups, as well as in patients with a lower radial artery (RA) diameter (40% vs. 94.87%; p = 0.0009), cephalic vein (CV) diameter (44.82% vs. 97.14%; p = 0.0001) for a radio-cephalic AVF (RC-AVF), and brachial artery (BA) diameter (30.43% vs. 89.47%; p < 0.0001) in addition to CV diameter (40% vs. 94.59%; p < 0.0001) for a brachio-cephalic AVF (BC-AVF), respectively. There was also a significant increase in early thrombosis and short-time mortality in the same patients. A multivariate analysis showed that a baseline value for the NLR, PLR, SII, CRP, Ca-P product, and PNI was an independent predictor of adverse outcomes for all of the recruited patients. Furthermore, for all patients, a high baseline value for vessel diameter was a protective factor against any negative events during the study period, except for RA diameter in mortality (p = 0.16). Conclusion: Our findings concluded that higher NLR, PLR, SII, CRP, Ca-P product, and PNI values determined preoperatively were strongly predictive of AVF maturation failure, early thrombosis, and short-time mortality. Moreover, a lower baseline value for vessel diameter was strongly predictive of AVF maturation failure and early thrombosis.

Uncommon Surgical Management by AVF between the Great Saphenous Vein and Anterior Tibial Artery for Old Radiocephalic AVF Failure.

INTRODUCTION: Autologous native arteriovenous fistula (AVF) created in the non-dominant arm is the gold standard vascular access for dialysis in end-stage renal disease, but the post-surgical vascular access dysfunction causes a reduction in the patient's quality of life. Creating a functional upper extremity permanent arteriovenous access is limited by the upper limb's vascular resources, so good management of a complicated arteriovenous fistula may improve patient outcomes. This article highlights the importance of new surgical options in treating complicated AVFs. CASE REPORT: We present the case of a patient with a 17-year-old complex radio-cephalic arterio-venous fistula and a series of surgical interventions performed for life salvage in the first place and functional vascular access in the second place. Furthermore, we describe a successfully created uncommon type of fistula in the lower extremity between the great saphenous vein and the anterior tibial artery as the last possible access for hemodialysis in this patient. RESULTS: The patient underwent the first successful dialysis using the newly created lower limb fistula 1 month after the surgery. CONCLUSION: Applying new surgical techniques to manage AVFs gives a unique chance to improve the quality of life and reduce morbidity and mortality in these patients.

Calcification patterns in femoral and carotid atheromatous plaques: A comparative morphometric study.

This comparative study was designed to focus on the mineral patterns in human atherosclerotic plaques based on quantitative measurements of calcium deposits through the morphometric method. A total of 101 atherosclerotic plaques were harvested by conventional transluminal angioplasty from the carotid artery (CA) and different segments of the femoral-popliteal axis (FPA), fixed in formalin and sent for histological processing. The histological grade of the atherosclerotic plaque and the calcification pattern were evaluated, followed by a morphometric analysis of the mineral deposits. Regarding the localization, the advanced plaques (VII and VIII types) developed predominantly at the level of the superficial femoral artery (SFA) compared to the CA (P<0.001). This significant difference was maintained even if they were divided into low grade (IV and V) and high grade categories (VI, VII and VIII) (P<0.05). Compared with that in the carotid plaques, in the FPA plaques the mineralized surface increased in parallel with the narrowing of the vascular lumen diameter. The image analysis of the total pathological calcification score (pCS) showed a significant difference between the CA plaques and distal SFA (dSFA) plaques (P=0.038) and between the proximal SFA (pSFA) and dSFA plaques (P=0.013). In the case of the simple nodular pattern, calcification occupied significantly larger areas in the plaques developed in the dSFA and popliteal artery (PA) in comparison with the CA plaques (P=0.0007 and P=0.0009). pCSs calculated in plaques with extensive calcification pattern showed a lower value in the CA vs. the pSFA plaques (P=0.004). A less pronounced, but significant difference was observed between the pCS of pSFA and dSFA plaques (P=0.017). Femoral and carotid plaques exhibited different morphology and tendency for calcification. In parallel with the narrowing of the vascular lumen diameter, the mineralized surface increased at the level of different FPA segments. These results suggest that the mechanism is site-specific, and wall structure-dependent.

Neuroinflammation and microglia/macrophage phenotype modulate the molecular background of post-stroke depression: A literature review.

Increasing evidence hints to the central role of neuroinflammation in the development of post-stroke depression. Danger signals released in the acute phase of ischemia trigger microglial activation, along with the infiltration of neutrophils and macrophages. The increased secretion of proinflammatory cytokines interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor α (TNFα) provokes neuronal degeneration and apoptosis, whereas IL-6, interferon γ (IFNγ), and TNFα induce aberrant tryptophane degradation with the accumulation of the end-product quinolinic acid in resident glial cells. This promotes glutamate excitotoxicity via hyperexcitation of N-methyl-D-aspartate receptors and antagonizes 5-hydroxy-tryptamine, reducing synaptic plasticity and neuronal survival, thus favoring depression. In the post-stroke period, CX3CL1 and the CD200-CD200R interaction mediates the activation of glial cells, whereas CCL-2 attracts infiltrating macrophages. CD206 positive cells grant the removal of excessive danger signals; the high number of regulatory T cells, IL-4, IL-10, transforming growth factor ß (TGFß), and intracellular signaling via cAMP response element-binding protein (CREB) support the M2 type differentiation. In favorable conditions, these cells may exert efficient clearance, mediate tissue repair, and might be essential players in the downregulation of molecular pathways that promote post-stroke depression.

A rare association of cutaneous leukocytoclastic angiitis (hypersensitivity vasculitis) and hypersensitivity pneumonia (extrinsic allergic alveolitis) in a pigeon breeder - case report and literature review.

Extrinsic allergic alveolitis is an occupational condition intensively studied and published about, unlike cutaneous leukocytoclastic angiitis. The coexistence of these two diseases is even more rare in the same patient with exposure to occupational pollutants of animal origin. We present the case of a 44-year-old man, a pigeon breeder admitted to hospital with a pruritic purpuric eruption and lower limb paresthesia, dyspnea on exertion, polymyalgia rheumatica, mixed polyarthralgias. Based on the clinical, paraclinical and laboratory investigations (electroneuromyography, plethysmography, computed tomography scan, musculocutaneous biopsy, current laboratory tests and immunoassays), the main diagnoses of extrinsic allergic alveolitis and leukocytoclastic vasculitis were determined. The patient underwent treatment with corticosteroids with a favorable outcome, but which becomes aggravated by the occurrence of necrotic skin lesions at the cessation of corticosteroid therapy on the patient's own initiative. After the resumption of the corticosteroid therapy, the lesions and symptoms improve. To our knowledge, this case report is the first one that describes an association of two major conditions, extrinsic allergic alveolitis and cutaneous leukocytoclastic angiitis, in the same clinical context of an occupational exposure to specific pollutants. Long-term corticosteroid therapy has proved to be useful in preventing relapses and improving the patient's clinical status with the association of cutaneous leukocytoclastic angiitis and extrinsic allergic alveolitis. Considering our findings in this case report, we may suggest the inclusion of systemic vasculitis on the list of recognized professional diseases.

Atypical onset of total colonic Hirschsprung disease in a small female infant: A case report.

RATIONALE: Hirschsprung disease (HD) or colonic aganglionosis is a congenital disorder, which results from the abnormal migration of neuronal cells of the neural crest leading to a disorder of the enteric nervous system consisting in the absence of ganglion cells within the submucosal and myenteric plexus. PATIENT CONCERNS: We report the case of a 7-month-old female infant admitted in our clinic for constipation and failure to thrive. At the age of 6 months, she was examined in our clinic for the same reasons, and we recommended symptomatic treatment without improvements. The clinical examination revealed pallor of the skin and mucosa, distended abdomen, and abdominal tenderness at palpation. DIAGNOSES: The abdominal ultrasound showed abdominal bloating, and the barium enema was normal. The patient's evolution worsened progressively within the following 3 days after admission associating sings of toxic megacolon. INTERVENTIONS: She underwent a surgical intervention with total colectomy and ileostomy, and the final diagnosis confirmed by the histological examination was of total colonic aganglionosis (TCA). OUTCOMES: The evolution immediately after the surgery and the follow-up examination after approximately 3 months pointed out normal weight gain and the laboratory tests were within normal limits. LESSONS: TCA can also manifest in older infants. Barium enemas can guide the diagnosis in most cases of HD. Nevertheless, in patients with TCA, it can be normal. Moreover, it could represent a trigger for toxic megacolon.

Ischemic damage and early inflammatory infiltration are different in the core and penumbra lesions of rat brain after transient focal cerebral ischemia.

Clinical and experimental observations emphasize that inflammation is a direct risk factor for stroke. We performed a detailed histological and immunohistochemical analysis, assisted by digital morphometry, to compare the representative brain lesions in the ischemic core and penumbra in a rat model. Focal neuronal necrosis and degeneration were significantly more intense in the core, whereas inflammatory infiltration, MPO, CD68, CD3, FXIII, Cox-2, iNOS2, Arg-1 expressions were stronger in the penumbra. Our findings indicate that neuroinflammation affects the penumbra more than the core and suggest that targeted modulation of the cellular infiltrate could be exploited to save brain volume.

Non-Hodgkin lymphoma, diagnostic, and prognostic particularities in children - a series of case reports and a review of the literature (CARE compliant).

RATIONALE: Non-Hodgkin lymphoma remains an unpredictable condition in pediatric patients. PATIENT CONCERNS: Our first case describes an 8-year-old boy with a history of iron deficiency anemia, admitted in our clinic for recurrent abdominal pain, weight loss, loss of appetite, diarrheic stools, and fever. The second case also describes an 8-year-old boy admitted for abdominal pain and vomiting. The 3rd case refers to a 4 years and 10 months old boy admitted in our clinic with abdominal pain and loss of appetite, who was initially admitted in the Pediatrics Surgery Clinic with the suspicion of appendicitis. Our 4th patient was a 5-year-old boy admitted in our clinic for abdominal pain and intermittent diarrheic stools. DIAGNOSES: In the first case, the laboratory tests showed anemia, thrombocytosis, elevated inflammatory biomarkers, a low level of iron, and hypoproteinemia. The abdominal ultrasound and CT exam revealed an abdominal mass, and the histopathological exam established the diagnosis of diffuse large B-cell lymphoma of the bowel. In the second case, the laboratory tests pointed out anemia, elevated ESR and lactate dehydrogenase level, while both abdominal ultrasound and CT exams showed an abdominal mass. The histopathological exam confirmed the diagnosis of Burkitt lymphoma. Regarding our 3rd case, the laboratory findings revealed leukocytosis, anemia, thrombocytosis, increased inflammatory biomarkers, elevated LDH, and a low level of iron. The abdominal ultrasound and the CT scan revealed an abdominal mass which, according to the histopathological exam, was a Burkitt lymphoma. Due to the cranial CT findings the patient was diagnosed with IV stage Burkitt lymphoma with central nervous system metastases. In our 4th patients we found leukocytosis, anemia, mildly increased inflammatory biomarkers, a high level of LDH, hypoproteinemia, and a low level of serum Ir. Both ultrasound and abdominal CT exams were negative, but the exploratory laparotomy identified an abdominal mass, and according to the histopathological exam the patient was diagnosed with Burkitt lymphoma. INTERVENTIONS: All the patients followed chemotherapy (B-NHL BFM 04 protocol) and supportive treatment. OUTCOMES: The first patient died approximately 4 months after the completion of chemotherapy due to tumor relapse, the second patient died after the first cure of chemotherapy and the fourth patient died at approximately 2 years after the diagnosis. The third patient is recurrence-free after 2 years. LESSONS: Despite the advances in the management, NHL remains a fatal condition in pediatrics.

Complete progressive ophthalmoplegia and numb chin syndrome, the first clinical manifestations of a lethal abdominal Burkitt lymphoma.

A 57-year-old patient was admitted to the Neurology Clinic for hypoesthesia, intense pain in the right chin and double vision. During the hospitalization, the patient developed progressive complete bilateral ophthalmoplegia and numbness of both sides of the chin. Brain CT and MRI scans with gadolinium were normal. Standard laboratory tests on admission were normal. The cerebral spinal fluid examination and the infectious and autoimmune workup were also normal. A thoracic-abdominal and pelvic CT scan revealed two hypodense lesions in the liver, irregular thickening of the gastric and ileal wall, and multiple abdominal adenopathies. Meanwhile, the patient developed marked fatigue, fever, sweats, nausea, vomiting and abdominal pain. An exploratory laparotomy was performed that showed multiple tumours of the small intestinal wall, stomach wall, multiple liver masses in both lobes and appendicular tumour. Histopathological findings of the liver biopsy and appendicular walls revealed Burkitt lymphoma. The patient died two days after surgery by cardiopulmonary arrest. This case underscores the importance of keeping BL in the differential diagnosis of patients with rapidly progressive ophthalmoplegia and numb chin syndrome, with normal brain MRI and CSF examinations.

Meloxicam ameliorates the cartilage and subchondral bone deterioration in monoiodoacetate-induced rat osteoarthritis.

OBJECTIVE: This study aimed to quantify the cartilage- and subchondral bone-related effects of low-dose and high-dose meloxicam treatment in the late phase of mono-iodoacetate-induced osteoarthritis of the stifle. METHODS: Thirty-four male Wistar rats received intra-articular injection of mono-iodoacetate to trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono-iodoacetate-injected rats were assigned to three groups and treated from week 4 to the end of week 7 with placebo (Grp P, n = 11), low-dose (GrpM Lo, 0.2 mg/kg, n = 12) or high-dose (GrpM Hi, 1 mg/kg, n = 11) meloxicam. After a period of 4 additional weeks (end of week 11) the animals were sacrificed, and the stifle joints were examined histologically and immunohistochemically for cyclooxygenase 2, in conformity with recommendations of the Osteoarthritis Research Society International. Serum cytokines IL-6, TNFα and IL-10 were measured at the end of weeks 3, 7, and 11. RESULTS: Compared with saline-treated controls, animals treated with mono-iodoacetate developed various degrees of osteoarthritis. The cartilage degeneration score and the total cartilage degeneration width were significantly lower in both the low-dose (p = 0.012 and p = 0.014) and high-dose (p = 0.003 and p = 0.006) meloxicam-treated groups than in the placebo group. In the subchondral bone, only high-dose meloxicam exerted a significant protective effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated animals was abolished in both meloxicam groups. Increase with borderline significance of TNFα in GrpP from week 3 to week 7 (p = 0.049) and reduction of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed. CONCLUSION: In this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a chondroprotective effect, and the high dose also protected against subchondral bone lesions. The results suggest a superior protection of the high-dose meloxicam arresting the low-grade inflammatory pathway accompanied by chronic cartilage deterioration.

Diagnostic pitfalls in a young Romanian ranger with an acute psychotic episode.

The identification and distinction of the pathological conditions underlying acute psychosis are often challenging. We present the case of a 35-year-old ranger who had no history of acute or chronic infectious disease or any previous neuropsychiatric symptoms. He arrived at the Psychiatry Clinic and was admitted as an emergency case, displaying bizarre behavior, hallucinations, paranoid ideation, and delusional faults. These symptoms had first appeared 7 days earlier. An objective examination revealed abnormalities of behavior, anxiety, visual hallucinations, choreiform, and tic-like facial movements. After the administration of neuroleptic and antidepressant treatment, he showed an initial improvement, but on day 10 entered into a severe catatonic state with signs of meningeal irritation and was transferred to the intensive care unit. An electroencephalogram showed diffuse irritative changes, raising the possibility of encephalitis. Taking into consideration the overt occupational risk, Borrelia antibody tests were prescribed and highly positive immunoglobulin (Ig)M and IgG titers were obtained from serum, along with IgG and antibody index positivity in cerebrospinal fluid. In parallel, anti-N-methyl-D-aspartate receptor antibodies and a whole battery of other autoimmune encephalitis markers showed negative. A complex program of treatment was applied, including antibiotics, beginning with ceftazidime and ciprofloxacin - for suspected aspiration bronchopneumonia - and thereafter with ceftriaxone. A gradual improvement was noticed and the treatment continued at the Infectious Disease Clinic. Finally, the patient was discharged with a doxycycline, antidepressant, and anxiolytic maintenance treatment. On his first and second control (days 44 and 122 from the disease onset), the patient was stable with no major complaints, Borrelia seropositivity was confirmed both for IgM and IgG while the cerebrospinal fluid also showed reactivity for IgG on immunoblot. On the basis of the putative occupational risk, acute psychotic episode, and the success of antibiotic therapy, we registered this case as a late neuroborreliosis with atypical appearance.

The TRAP (twin reversed arterial perfusion) sequence - case presentation.

We present a particular case of TRAP (twin reversed arterial perfusion) syndrome, which has a very rarely association of the simultaneous existence of a rudimentary malformed heart and brain, and also other malformations like abdominal wall abnormality, absent bladder with present kidneys, and absence of the lungs, which appear only in a few cases on the receptor twin from this sequence, malformations incompatible with life. A Caucasian 26-year-old pregnant woman, at the first pregnancy, with a monochorionic-diamniotic pregnancy, 26 weeks of gestation was referred to our hospital, for polyhydramnios. The patient delivered a living female newborn, weighing 950 g, with an Apgar score of 2 at one minute - the donor fetus and a second female newborn with multiple malformations, no signs of life and who weighed 2300 g - the receptor fetus. The anatomopathological examination confirmed the TRAP sequence associated with severe facial dysmorphism, bilateral phocomelia and cardiac malformations (rudimentary hypoplastic, univentricular) and a vascular anastomosis between the two umbilical cords. Anemia and cardiac complications which can lead to cardiac failure, appear early during pregnancy and caused the death of the pumping twin. We emphasize that in our case of TRAP sequence, the ultrasound examination established the diagnosis of the syndrome with high accuracy. Therefore, we can conclude that the existence of a rudimentary heart and a vascular anastomosis between the two umbilical cords supports the apparition of TRAP sequence. The early diagnosis of this pathology, the observation of the pregnancy with the help of weekly ultrasounds and the intrauterine interventions can increase the survival chances of the donor fetus from the TRAP sequence.

Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease.

Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient's case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died.