A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy.

BACKGROUND AND AIMS: Obesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. METHODS AND RESULTS: Thirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. CONCLUSIONS: Our study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.

Preliminary Study on the Effect of a Night Shift on Blood Pressure and Clock Gene Expression.

Night shift work has been found to be associated with a higher risk of cardiovascular and cerebrovascular disease. One of the underlying mechanisms seems to be that shift work promotes hypertension, but results have been variable. This cross-sectional study was carried out in a group of internists with the aim of performing a paired analysis of 24 h blood pressure in the same physicians working a day shift and then a night shift, and a paired analysis of clock gene expression after a night of rest and a night of work. Each participant wore an ambulatory blood pressure monitor (ABPM) twice. The first time was for a 24 h period that included a 12 h day shift (08.00-20.00) and a night of rest. The second time was for a 30 h period that included a day of rest, a night shift (20.00-08.00), and a subsequent period of rest (08.00-14.00). Subjects underwent fasting blood sampling twice: after the night of rest and after the night shift. Night shift work significantly increased night systolic blood pressure (SBP), night diastolic blood pressure (DBP), and heart rate (HR) and decreased their respective nocturnal decline. Clock gene expression increased after the night shift. There was a direct association between night blood pressure and clock gene expression. Night shifts lead to an increase in blood pressure, non-dipping status, and circadian rhythm misalignment. Blood pressure is associated with clock genes and circadian rhythm misalignement.

Long-term efficacy and safety of percutaneous ethanol injection (PEI) in cystic thyroid nodules: A systematic review and meta-analysis.

BACKGROUND: Percutaneous ethanol injection (PEI) is used for the treatment of benign cystic thyroid nodules. This systematic review and meta-analysis aimed to obtain strong evidence of its long-term efficacy and safety. METHODS: PubMed, CENTRAL, Scopus and Web of Science databases were searched until November 2020 for studies reporting data on volume reduction rate (VRR), compressive symptoms and cosmetic concerns. Associated complications were assessed. A random-effects model was designed to pool the data. RESULTS: Out of 385 papers, nine studies evaluating 1667 nodules were finally included. Overall, VRR at 6, 12, 24, 36, 60 and 120 months was 77%, 81%, 72%, 68%, 74% and 69%, respectively. Significant reductions in the compressive symptoms and cosmetic concerns were observed. No permanent complications were observed. CONCLUSIONS: The present meta-analysis showed that PEI could significantly reduce the volume of benign cystic thyroid nodules. This reduction was already effective at 6 months post-treatment, and the effect was stable over time.

Image-guided thermal ablation in autonomously functioning thyroid nodules. A retrospective multicenter three-year follow-up study from the Italian Minimally Invasive Treatment of the Thyroid (MITT) Group.

OBJECTIVES: To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years. METHODS: Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. RESULTS: A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small (< 10 mL) (74%), medium (49%), or large (> 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. CONCLUSIONS: Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. KEY POINTS: • Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

Type 1 diabetes is associated with significant changes of ACE and ACE2 expression in peripheral blood mononuclear cells.

BACKGROUND AND AIMS: The renin-angiotensin system (RAS), which is a key mediator of cardiovascular homeostasis, has two main axes. The classic one, including angiotensin-converting enzyme (ACE) and Angiotensin (Ang) II, promoting vasoconstriction, and the "alternative" one, including ACE2 and Ang1-7, with opposed actions to AngII. ACE2 has been identified as the main receptor of SARS-CoV2, whereby it enters the cells, leading to the downregulation of surface ACE2 and RAS tissue unbalance. Given that diabetes is associated with an increase in COVID-19 severity and death, we aimed at evaluating RAS expression in patients with type 1 diabetes (T1D). METHODS AND RESULTS: This is a case-control study comparing 39 T1D patients to 33 controls, with a median age of 29 and 32 years, and no comorbidities. ACE and ACE2 gene expression was assessed in peripheral blood mononuclear cells. T1D patients had higher ACE expression and circulating AngII, which were related to glucose levels. T1D patients had lower ACE2 expression. However, ACE2 expression was also related to the sex of participants, being higher in the female group. T1D women did not show the same increase of ACE2 expression that was seen in control women. CONCLUSION: T1D promotes the increase of ACE, AngII, and ACE/ACE2, which might contribute to the higher cardiovascular risk, as well as to severe tissue injury induced by SARS-CoV2 in these patients. The ratio ACE/ACE2 does not differ between men and women with T1D, which might explain why CVD or COVID-19 do not show substantial gender differences in these patients.

TRAIL treatment prevents renal morphological changes and TGF-ß-induced mesenchymal transition associated with diabetic nephropathy.

BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) has attracted attention not only as an anti-cancer agent, but also as a potential treatment for diabetes. Animal studies have shown that TRAIL delivery ameliorated glucose control in type 1 and type 2 diabetes. It is currently unknown whether TRAIL positive effects are maintained in more severe forms of type 2 diabetes, and whether they include renoprotection. Our study aimed at evaluating TRAIL effects in a severe form of type 2 diabetes with nephropathy. MATERIALS AND METHODS: A total of 20 db/db mice were treated with saline or TRAIL twice per week for 12 weeks. In parallel, renal tubular epithelial cells were cultured with TGF-ß1 in the presence and absence of TRAIL, with and without silencing TRAIL-specific receptor (DR5) and leptin receptor. RESULTS: TRAIL did not improve glucose control, but it significantly reduced circulating interleukin (IL)-6 and resistin. In the kidney, TRAIL treatment significantly ameliorated glomerular and tubular morphology with an improvement in kidney function, but no effect on proteinuria. Our in vitro studies on TGF-ß1-treated cells, showed that by binding to DR5, TRAIL rescued normal tubular cell morphology, increasing E-cadherin and reducing α-smooth muscle actin (SMA) expression, with no effects on cell viability. Interestingly, both in vivo and in vitro, TRAIL reduced the accumulation of the autophagy substrate p62. CONCLUSIONS: Our data confirm TRAIL protective effects against organ damage and shed light on to promising anti-fibrotic actions, which are independent of glucose control. TRAIL anti-fibrotic actions might be due to the rescue of autophagy in diabetes.

The Total Testing Process of Intra-Operative Parathyroid Hormone. A Narrative Review.

BACKGROUND: Primary hyperparathyroidism (pHPT) is a common endocrine disorder, due to an excessive secretion of parathyroid hormone (PTH) from one or more parathyroid gland(s), where the only cure remains surgery. The surgical approach has become less invasive over the years, thanks to the advances in the preoperative localization of the enlarged parathyroid gland, as well as to the possibility to measure intra-operative parathyroid hormone (IOPTH). After the targeted removal of a parathyroid gland, IOPTH can confirm biochemically the cure of pHPT, such that it helps the surgeon to judge if the parathyroidectomy has been successful and there is no need of additional dissection. As with all laboratory tests, the quality of IOPTH total testing process is essential to the best utilization of patients' results. However, this can be affected by errors occurring in different phases. This review aims to describe the total testing process of IOPTH. METHODS: We performed a search in Pubmed and a review of the literature on the current management of pHPT and the total testing process of IOPTH measurement. RESULTS: Compared to previous studies focusing on single aspects of the IOPTH testing process, here we have analyzed all the steps crucial for the quality of IOPTH from the "pre-pre" to the "post-post" analytical phase. CONCLUSIONS: Clinicians and laboratory scientists should be aware of all the potential sources of errors in IOPTH measurement in order to improve their daily management of pHPT.

Sex Differences in Proatherogenic Cytokine Levels.

BACKGROUND: It has been shown that sex affects immunity, including cytokine production. Given that atherosclerosis is an inflammatory disease promoted by specific cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, we aimed at evaluating whether sex could affect the levels of these proatherogenic cytokines in a group of healthy adults. In this analysis, we also included other cytokines and peptides that have been implicated in atherosclerosis development and progression. METHODS: A total of 104 healthy adults were recruited; we measured circulating levels of IL-1ß, IL-6, TNF-α, angiotensins and angiotensin-converting enzyme-2 (ACE2), as well as osteoprotegerin and receptor activator of nuclear factor κB ligand (RANKL). RESULTS: IL-1ß, IL-6, and TNF-α were significantly higher in men as compared to women. They were all associated with testosterone and the testosterone/estradiol ratio. They remained significantly associated with sex (but not with hormones) after being tested for potential confounders. CONCLUSIONS: Sex seems to influence the levels of proatherogenic cytokines. This is consistent not only with sex differences in vulnerability to infections but also with the higher cardiovascular risk exhibited by the male gender as compared to the female gender. Nevertheless, this association is only partly explained by hormone levels.

Efficacy of radiofrequency ablation in autonomous functioning thyroid nodules. A systematic review and meta-analysis.

Whether thermal ablation is effective to treat toxic thyroid nodules (TTN) is still unknown. Aim of this review was to achieve more robust evidence on the efficacy of radiofrequency ablation (RFA) in treating TTN in terms of TSH normalization, thyroid scintiscan, and volume reduction rate (VRR). A comprehensive literature search of PubMed/Medline and Scopus was performed in November 2018 to retrieve published studies. Original papers reporting TTN treated by RFA and later followed-up were eligible. Excluded were: articles not within this field, articles with unclear data, overlapping series, case/series reports. Discordances were solved in a final collegial meeting. Information was collected concerning population features, treatment procedure, follow-up, cases with TSH normalization, cases with scintiscan normalization, VRR of nodules. Pooled prevalence of patients with TSH or scintiscan normalization, and pooled VRR over time were calculated. For statistical analysis, the random-effects model was used. Eight articles published between 2008 and 2018 were included. The overall number of AFTN treated by RFA was 205. Five studies used a single session of treatment. The time of follow-up ranged from six to 24 months. The pooled rate of patients with TSH normalization was 57%. The pooled rate of patients with scintigraphically proven optimal response was 60%. The pooled VRR at 1 year was 79%. Baseline nodules volume was associated with the rate of TSH normalization. In conclusion, a moderate efficacy of RFA in treating TTN was found, and this can represent a solid starting point in this field.

Correction to: Efficacy of radiofrequency ablation in autonomous functioning thyroid nodules. A systematic review and meta-analysis.

The authors of this paper declare that their correct family and first names and their correct affiliations are shown in this correction paper.

TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?

Ligands and receptors of the tumor necrosis factor (TNF) superfamily regulate immune responses and homeostatic functions with potential diagnostic and therapeutic implications. Kidney disease represents a global public health problem, whose prevalence is rising worldwide, due to the aging of the population and the increasing prevalence of diabetes, hypertension, obesity, and immune disorders. In addition, chronic kidney disease is an independent risk factor for the development of cardiovascular disease, which further increases kidney-related morbidity and mortality. Recently, it has been shown that some TNF superfamily members are actively implicated in renal pathophysiology. These members include TNF-related apoptosis-inducing ligand (TRAIL), its decoy receptor osteoprotegerin (OPG), and TNF-like weaker inducer of apoptosis (TWEAK). All of them have shown the ability to activate crucial pathways involved in kidney disease development and progression (e.g. canonical and non-canonical pathways of the transcription factor nuclear factor-kappa B), as well as the ability to regulate cell proliferation, differentiation, apoptosis, necrosis, inflammation, angiogenesis, and fibrosis with double-edged effects depending on the type and stage of kidney injury. Here we will review the actions of TRAIL, OPG, and TWEAK on diabetic and non-diabetic kidney disease, in order to provide insights into their full clinical potential as biomarkers and/or therapeutic options against kidney disease.

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

A prospective study on the efficacy of patient simulation in heart and lung auscultation.

BACKGROUND: The use of simulation technology for skill training and assessment in medical education has progressively increased over the last decade. Nevertheless, the teaching efficacy of most technologies remains to be fully determined. The aim of this prospective study was to evaluate if a short individual training on a patient simulator could improve heart and lung auscultation skills in undergraduate students. METHODS: A group of fifth-year medical school students, who had trained on a patient simulator in their third year (EXP, n = 55), was compared to a group of fifth-year medical school students who had not previously trained on it (CNT, n = 49). Students were recruited on a voluntary basis. Students were evaluated in terms of their ability to correctly identify three heart (II sound wide split, mitral regurgitation, aortic stenosis) and five lung sounds (coarse crackles, fine crackles, pleural rubs, rhonchi, wheezes), which were reproduced in a random order on the Kyoto-Kagaku patient simulator. RESULTS: Exposure to patient simulator significantly improved heart auscultation skills, as mitral regurgitation was correctly recognized by 89.7% of EXP students as compared to 71.4% of CNT students (p = 0.02). In addition, a significantly greater percentage of EXP students correctly graphed all the heart diagnoses as compared to CNT students. There were no differences between the groups in lung auscultation. CONCLUSIONS: This study demonstrates that training medical students with a patient simulator, individually for one hour, significantly ameliorated their heart auscultation skills. Our data suggests that patient simulation might be useful for learning auscultation skills, especially when it is combined with graphic sound display.

Hemicentin 1 influences podocyte dynamic changes in glomerular diseases.

Different complex mechanisms control the morphology of podocyte foot processes and their interactions with the underlying basement membrane. Injuries to this system often cause glomerular dysfunction and albuminuria. The present study aimed at identifying early markers of glomerular damage in diabetic nephropathy. For this purpose, we performed a microarray analysis on kidneys of 3-wk-old peroxisome proliferator-activated receptor-γ (PPARγ)-null and AZIP/F1 mice, which are two models of diabetic nephropathy due to lipodystrophy. This was followed by functional annotation of the enriched clusters of genes. One of the significant changes in the early stages of glomerular damage was the increase of hemicentin 1 (HMCN1). Its expression and distribution were then studied by real-time PCR and immunofluorescence in various models of glomerular damage and on podocyte cell cultures. HMCN1 progressively increased in the glomeruli of diabetic mice, according to disease severity, as well as in puromycin aminonucleoside (PA)-treated rats. Studies on murine and human podocytes showed an increased HMCN1 deposition upon different pathological stimuli, such as hyperglycemia, transforming growth factor-ß (TGF-ß), and PA. In vitro silencing studies showed that HMCN1 mediated the rearrangements of podocyte cytoskeleton induced by TGF-ß. Finally, we demonstrated an increased expression of HMCN1 in the kidneys of patients with proteinuric nephropathies. In summary, our studies identified HMCN1 as a new molecule involved in the dynamic changes of podocyte foot processes. Its increased expression associated with podocyte dysfunction points to HMCN1 as a possible marker for the early glomerular damage occurring in different proteinuric nephropathies.

TRAIL reduces impaired glucose tolerance and NAFLD in the high-fat diet fed mouse.

Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. The present study aimed at evaluating whether TRAIL had the potential not only to prevent, but also to treat type 2 diabetes. Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD). After 4 weeks of HFD, mice were further randomized to receive either placebo or TRAIL, which was delivered weekly for 8 weeks. Body weight, food intake, fasting glucose, and insulin were measured at baseline and every 4 weeks. Tolerance tests were performed before drug randomization and at the end of the study. Tissues were collected for further analyses. Parallel in vitro studies were conducted on HepG2 cells and mouse primary hepatocytes. TRAIL significantly reduced body weight, adipocyte hypertrophy, free fatty acid levels, and inflammation. Moreover, it significantly improved impaired glucose tolerance, and ameliorated non-alcoholic fatty liver disease (NAFLD). TRAIL treatment reduced liver fat content by 47% in vivo as well as by 45% in HepG2 cells and by 39% in primary hepatocytes. This was associated with a significant increase in liver peroxisome proliferator-activated receptor (PPAR) γ (PPARγ) co-activator-1 α (PGC-1α) expression both in vivo and in vitro, pointing to a direct protective effect of TRAIL on the liver. The present study confirms the ability of TRAIL to significantly attenuate diet-induced metabolic abnormalities, and it shows for the first time that TRAIL is effective also when administered after disease onset. In addition, our data shed light on TRAIL therapeutic potential not only against impaired glucose tolerance, but also against NAFLD.

Usefulness of core needle biopsy for the diagnosis of thyroid Burkitt's lymphoma: a case report and review of the literature.

BACKGROUND: Thyroid lymphomas are an exceptional finding in patients with thyroid nodules. Burkitt's lymphoma is one of the rarest and most aggressive forms of thyroid lymphomas, and its prognosis depends on the earliness of medical treatment. Given the rarity of this disease, making a prompt diagnosis can be challenging. For instance, fine-needle aspiration (FNA) cytology, which is the first-line diagnostic test that is performed in patients with thyroid nodules, is often not diagnostic in cases of thyroid lymphomas, with subsequent delay of the start of therapy. CASE PRESENTATION: Here we report the case of a 52-year-old woman presenting with a rapidly enlarging thyroid mass. Thyroid ultrasonography demonstrated a solid hypoechoic nodule. FNA cytology was only suggestive of a lymphoproliferative disorder and did not provide a definitive diagnosis. It is core needle biopsy (CNB) that helped us to overcome the limitations of routine FNA cytology, showing the presence of thyroid Burkitt's lymphoma. Subsequent staging demonstrated bone marrow involvement. The early start of an intensive multi-agent chemotherapy resulted in complete disease remission. At 60 months after the diagnosis, the patient is alive and has not had any recurrence. CONCLUSIONS: Clinicians should be aware that thyroid Burkitt's lymphoma is an aggressive disease that needs to be treated with multi-agent chemotherapy as soon as possible. To diagnose it promptly, they should consider to order/perform a CNB in any patient with a rapidly enlarging thyroid mass that is suspicious for lymphoma.

Patient satisfaction after thyroid RFA versus surgery for benign thyroid nodules: a telephone survey.

INTRODUCTION: Minimally invasive nonsurgical techniques are gaining ground as alternatives to surgery for the treatment of benign thyroid nodules. Here, we aimed at comparing patient satisfaction after radiofrequency ablation (RFA) to that after surgery. METHODS: In this cross-sectional study, we recruited 126 patients treated with RFA and 84 treated with surgery for a single benign thyroid nodule. All patients were contacted by phone call and were asked the following questions: Are you satisfied with the symptom resolution?; Are you satisfied with the cosmetic results?; Are you satisfied overall with the procedure?; Are you taking any medication for your thyroid? Patients' general characteristics were collected from our database. RESULTS: In the surgery group, there was a higher percentage of patients fully satisfied with the resolution of nodule-related symptoms (p = .02). In the RFA group, there was a higher percentage of patients fully satisfied with the cosmetic results (p = .001). In terms of overall satisfaction, there were no differences between the groups (p = .26). Nevertheless, RFA led to differing results based on thyroid nodule function. In patients with nonfunctioning thyroid nodules, RFA was as effective as surgery in terms of satisfaction with symptom resolution, while it was not in patients with autonomously functioning thyroid nodules (AFTN). CONCLUSION: Our data on postoperative patient satisfaction support the notion that both RFA and surgery are valid therapeutic options for nonfunctioning thyroid nodules, while surgery should be still preferred for AFTN.

Hypertrophic osteoarthropathy mimicking a reactive arthritis: a case report and review of the literature.

BACKGROUND: Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by abnormal proliferation of skin and periosteal tissues of the extremities. It can be a rare hereditary disease (pachydermoperiostosis) or can be secondary to various diseases, though mostly lung malignancies. Here, we report an unusual clinical presentation of HOA. CASE PRESENTATION: A 77-year-old man presented with fever, diarrhea, and an oligoarthritis involving the left knee and the ankles. Since left knee synovial fluid aspiration revealed an aseptic synovitis and Clostridium Difficile toxin was detectable in stool samples, a reactive arthritis secondary to a Clostridium Difficile induced colitis was initially suspected. However, the presence of a worsened digital clubbing and the lack of a good clinical response to steroid therapy led us to perform a radionuclide bone scanning, which revealed HOA. This turned out to be associated with a lepidic predominant lung adenocarcinoma, which was clinically and radiologically difficult to distinguish from a relapse of pneumonia. CONCLUSION: Consistent with the literature, HOA tends to have a variable clinical presentation, mimicking that of various rheumatic diseases. This clinical case shows that HOA can present as a presumptive acute reactive arthritis, and it highlights the importance of patient's follow-up in the differential diagnosis of inflammatory arthritis, especially when a worsened digital clubbing is present.

The Complex Interplay between Lipids, Immune System and Interleukins in Cardio-Metabolic Diseases.

Lipids and inflammation regulate each other. Early studies on this topic focused on the systemic effects that the acute inflammatory response-and interleukins-had on lipid metabolism. Today, in the era of the obesity epidemic, whose primary complications are cardio-metabolic diseases, attention has moved to the effects that the nutritional environment and lipid derangements have on peripheral tissues, where lipotoxicity leads to organ damage through an imbalance of chronic inflammatory responses. After an overview of the effects that acute inflammation has on the systemic lipid metabolism, this review will describe the lipid-induced immune responses that take place in peripheral tissues and lead to chronic cardio-metabolic diseases. Moreover, the anti-inflammatory effects of lipid lowering drugs, as well as the possibility of using anti-inflammatory agents against cardio-metabolic diseases, will be discussed.

Ambulatory Arterial Stiffness Indexes in Cushing's Syndrome.

Long-standing exposure to endogenous cortisol excess is associated with high cardiovascular risk. The aim of our study was to investigate arterial stiffness, which has been recognized as an independent predictor of adverse cardiovascular outcome, in a group of patients with Cushing's syndrome. Twenty-four patients with Cushing's syndrome (3 males, mean age 49±13 years; 20 pituitary-dependent Cushing's disease and 4 adrenal adenoma) underwent 24-h ambulatory blood pressure monitoring (ABPM) and evaluation of cardiovascular risk factors. The Ambulatory Arterial Stiffness Index (AASI) and symmetric AASI (sAASI) were derived from ABPM tracings. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 16 hypertensive (HYP-CUSH) patients, and were compared with 8 normotensive (NOR-CTR) and 16 hypertensive (HYP-CTR) control subjects, matched for demographic characteristics, 24-h ABPM and cardiometabolic risk factors. The AASI and sAASI indexes were significantly higher in Cushing patients than in controls, either in the normotensive (p=0.048 for AASI and p=0.013 for sAASI) or in the hypertensive (p=0.004 for AASI and p=0.046 for sAASI) group. No difference in metabolic parameters was observed between NOR-CUSH and NOR-CTR or between HYP-CUSH and HYP-CTR groups. AASI and sAASI were both correlated with urinary cortisol in patients with endogenous hypercortisolism (Spearman's rho=0.40, p=0.05, and 0.61, p=0.003, respectively), while no correlation was found in controls. Both AASI and sAASI are increased in Cushing syndrome, independent of BP elevation, and may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in arterial stiffness has to be further clarified.