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Abstract Context Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality. Objective Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX. Methods Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = –0.48, –0.88 to –0.07, P = .022). Conclusion Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.

Since the advent of insulin, the improvements in diabetes detection and the therapies to treat hyperglycemia have reduced the mortality of acute metabolic emergencies, such that today chronic complications are the major cause of morbidity and mortality among diabetic patients. More than half of the mortality that is seen in the diabetic population can be ascribed to cardiovascular disease (CVD), which includes not only myocardial infarction due to premature atherosclerosis but also diabetic cardiomyopathy. The importance of renin-angiotensin-aldosterone system (RAAS) antagonism in the prevention of diabetic CVD has demonstrated the key role that the RAAS plays in diabetic CVD onset and development. Today, ACE inhibitors and angiotensin II receptor blockers represent the first line therapy for primary and secondary CVD prevention in patients with diabetes. Recent research has uncovered new dimensions of the RAAS and, therefore, new potential therapeutic targets against diabetic CVD. Here we describe the timeline of paradigm shifts in RAAS understanding, how diabetes modifies the RAAS, and what new parts of the RAAS pathway could be targeted in order to achieve RAAS modulation against diabetic CVD.

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.

TNF-related apoptosis-inducing ligand (TRAIL) is a protein that induces apoptosis in cancer cells but not in normal ones, where its effects remain to be fully understood. Previous studies have shown that in high-fat diet (HFD)-fed mice, TRAIL treatment reduced body weight gain, insulin resistance, and inflammation. TRAIL was also able to increase skeletal muscle free fatty acid oxidation. The aim of the present work was to evaluate TRAIL actions on skeletal muscle. Our in vitro data on C2C12 cells showed that TRAIL treatment significantly increased myogenin and MyHC and other hallmarks of myogenic differentiation, which were reduced by Dr5 (TRAIL receptor) silencing. In addition, TRAIL treatment significantly increased AKT phosphorylation, which was reduced by Dr5 silencing, as well as glucose uptake (alone and in combination with insulin). Our in vivo data showed that TRAIL increased myofiber size in HFD-fed mice as well as in db/db mice. This was associated with increased myogenin and PCG1α expression. In conclusion, TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake. These data shed light onto a pathway that might hold therapeutic potential not only for the metabolic disturbances but also for the muscle mass loss that are associated with diabetes.

TRAIL or tumor necrosis factor (TNF) related apoptosis-inducing ligand is a member of the TNF superfamily of proteins, whose best characterized function is the induction of apoptosis in tumor, infected, or transformed cells through activation of specific receptors. In nontransformed cells, however, the actions of TRAIL are less well characterized. Recent studies suggest that TRAIL may be implicated in the development and progression of diabetes. Here we review TRAIL biological actions, its effects on the immune system, and how and to what extent it has been shown to protect against diabetes.

Purpose. Obesity is a risk factor for severe coronavirus disease 2019 (COVID-19). Circulating adipokines have been associated with inflammatory burden and amplified or dysregulated immune responses. This study aimed to evaluate the discriminatory ability of adipokines to identify COVID-19 pneumonia and to assess disease severity. Methods. We conducted an observational case-control study, with a prospective design, and recruited patients with diagnosis of COVID-19 pneumonia (n = 48) and healthy controls (n = 36), who were matched by age, sex, and BMI. Leptin, adiponectin, IL-6, and TNF-α were measured by ELISA. Results. Patients with COVID-19 pneumonia had higher levels of leptin, lower adiponectin/leptin (Adpn/Lep) ratio, and higher expression of IL-6. Leptin had an acceptable discriminatory accuracy for COVID-19 pneumonia in patients with BMI >30 (AUC 0.74 [0.58, 0.90]) with a cutoff of 7852 pg/mL and it was associated with maximum respiratory support. By contrast, Adpn/Lep had an excellent discriminatory accuracy for COVID-19 pneumonia in patients with BMI <25 (AUC 0.9 [0.74, 1.06]) with a cutoff of 2.23. Conclusion. Our data indicate that high Adpn/Lep (>2.23) in lean patients is consistent with a state of good health, which decreases in case of inflammatory states, ranging from adipose tissue dysfunction with low-grade inflammation to COVID-19 pneumonia.

Objective. Benign thyroid nodules are a common occurrence whose only remedy, in case of symptoms, has always been surgery until the advent of new techniques, such as radiofrequency ablation (RFA). This study aimed at evaluating RFA efficacy, tolerability, and costs and comparing them to hemithyroidectomy for the treatment of benign thyroid nodules. Design and Methods. 37 patients who underwent RFA were retrospectively compared to 74 patients surgically treated, either in a standard inpatient or in a short-stay surgical regimen. Efficacy, tolerability, and costs were compared. The contribution of final pathology was also taken into account. Results. RFA reduced nodular volume by 70% after 12 months and it was an effective method for treating nodule-related clinical problems, but it was not as effective as surgery for the treatment of hot nodules. RFA and surgery were both safe, although RFA had less complications and pain was rare. RFA costed €1,661.50, surgery costed €4,556.30, and short-stay surgery costed €4,139.40 per patient. RFA, however, did not allow for any pathologic analysis of the nodules, which, in 6 patients who had undergone surgery (8%), revealed that the nodules harboured malignant cells. Conclusions. RFA might transform our approach to benign thyroid nodules.

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.

Purpose. Thermal ablations (TA) are gaining ground as alternative options to conventional therapies for symptomatic benign thyroid nodules. Little is known about the impact of nodule biology on the outcomes of TA. The aim of our study was to evaluate the baseline immunocytochemistry profile of thyroid nodules that were poorly responsive to TA in order to identify potential predictors of the treatment response. Methods. From a cohort of 406 patients with benign thyroid nodules treated with TA and followed for 5 years, we retrospectively selected two groups of patients: NONRESPONDERS (patients who did not respond to TA and were later surgically treated) and RESPONDERS (patients who responded to TA). The fine-needle aspiration cytology (FNAC) slides obtained before TA were stained for Galectin-3, HBME-1, CK-19, and Ki-67. Results. Benign nodules of NONRESPONDERS (n = 19) did not express CK-19 (p=0.03), as compared to RESPONDERS (n = 26). We combined the absence of CK-19 and the presence of Ki-67 to obtain a composite biomarker of resistance to TA, which discriminated between likelihood of retreatment and no retreatment with an AUC of 0.68 (95%CI: 0.55-0.81) and a sensitivity, specificity, PPV, and NPV of 29%, 91%, 71%, and 64%, respectively. Conclusion. In benign thyroid nodules, the absence of CK-19 was associated with resistance to TA, while the presence of CK-19 was predictive of response to TA. If confirmed, this finding could provide rapid and inexpensive information about the potential outcome of TA on benign thyroid nodules. In addition, as CK-19 can be expressed in adenomatous hyperplasia, it could be speculated that these nodules, rather than follicular adenomas, might be better candidates for TA.

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.