Challenges of Differential Diagnosis Between Primary Hyperparathyroidism and Bone Metastases of Breast Cancer.

Breast cancer might be complicated by distant metastases accompanied by hypercalcemia, but hyperparathyroidism is not commonly considered in the differential diagnosis. We present a case of 38 years old female patient who was diagnosed with ductal breast carcinoma. Eight months after the initial diagnosis the patient was diagnosed with distant bone metastases. However, this diagnosis was reconsidered at follow up, because we identified elevation of PTH 137.2 pg/ml, Ca2+ 1.19 mmol/l, albumin corrected calcium 2.42 mmol/l, 25(OH)D 39.4 nmol/l, indicating hyperparathyroidism. Scintigraphy with 99mTC-sestamibi confirmed parathyroid adenoma. Postoperative histopathology confirmed 1.2 g chief-cell PTA. Two months after the operation both PTH and Ca2+ levels were within the normal ranges. This study emphasizes the importance of considering possible hyperparathyroidism in patients with breast cancer and hypercalcemia. Routine evaluation of PTH is considered as a reasonable test in patients with breast cancer accompanied by bone lesions.

Percutaneous treatment of vascular access-site complications: a ten years' experience in two centres.

BACKGROUND: The spread of percutaneous arterial catheterization in diagnostic and therapeutic procedures has led to a parallel increase of vascular access site complications. The incidence of these events is between 0.2-1%. A detailed analysis of injuries by type of procedure shows a higher incidence of injuries after therapeutic procedures (3%) than those observed for diagnostic ones (1%), due to the greater size of the vascular devices used and the necessity to frequently administer anticoagulant and antiplatelet therapy during procedures. The iatrogenic arterial injuries requiring treatment are the pseudoaneurysm, arteriovenous fistula, arterial rupture and dissection. Less frequent complications include distal embolization of the limbs, nerve damage, abscess and lymphocele. Moreover, the use of percutaneous vascular closure devices (VCD) has further expanded the types of complications, with an increased risk of stenosis, thrombosis, distal embolism and infection. Our work aims to bring the personal 10 years' experience in the percutaneous treatment of vascular access-site complications. RESULTS: Ninety-two pseudoaneurysms (PSA), 12 arteriovenous fistulas (AVF), 15 retrograde dissections (RD) and 11 retroperitoneal bleedings (RB) have been selected and treated. In 120/130 cases there were no periprocedural complications with immediate technical success (92.3%). Nine femoral PSA, treated with percutaneous ultrasound-guided thrombin injection, showed a failure to close the sac and therefore they were treated by PTA balloon inflation with a contralateral approach and cross-over technique. Only one case of brachial dissection, in which the prolonged inflation of the balloon has not led to a full reimbursement of the dissection flap, was then surgically repaired. At the 7 days follow-up, complications were two abscesses in retroperitoneal bleedings, treated by percutaneous drainage. At 3 months, acute occlusion of 3 covered femoral stents occurred, then treated by loco-regional thrombolysis and PTA. A total of 18 major complications was recorded at 2 years, with a complication rate at 2 years of 13.8%. CONCLUSIONS: The percutaneous treatment of vascular access-site complications is the first-choice treatment. It represents a safe and effective option, validated by a high technical success rate and a low long-term complication rate, that allows avoiding the surgical approach in most cases.

Evaluation of the effects of liraglutide on the development of epilepsy and behavioural alterations in two animal models of epileptogenesis.

Liraglutide (LIR) is a novel long-lasting glucagon-like peptide-1 (GLP-1) analogue that facilitates insulin signalling and shows also neuroprotective properties in different brain disease models. In this study, we explored the potential antiepileptogenic effects of LIR in two different animal models; namely, the mouse intrahippocampal kainic acid (KA) model of temporal lobe epilepsy and the WAG/Rij rat model of absence epileptogenesis. Moreover, we evaluated LIR effects on comorbidities in various behavioural tests. Mice with kainate-induced epilepsy were treated with LIR (300 µg/kg/day s.c.) for 4 weeks after status epilepticus and then evaluated for drug effects on seizure development and behavioural alterations, whereas WAG/Rij rats were treated for 17 weeks (starting at 30 days of age, before seizure onset) with LIR (300 µg/kg/day s.c.) in order to investigate whether an early chronic treatment was able to reduce the development of absence seizures and related comorbidities. Our results indicate that LIR was effective in reducing the development of spontaneous seizures in kainate-induced epilepsy; moreover, in this model, it prevented memory impairment and related anxiety-like behaviour in the open field (OF) test while in the forced swimming test (FST), LIR displayed an apparent pro-depressant effect that was instead related to reduced endurance as confirmed by rotarod test. In contrast, LIR was unable to modify the epileptogenic process underlying the development of absence seizures in WAG/Rij rats while being antidepressant in the FST in this strain. Our results indicate that LIR may represent a promising novel treatment to prevent and treat the epileptogenic process and its associated behavioural and cognitive alterations in some models of convulsive epilepsy characterized by neurodegeneration, since LIR effects are likely secondary to its recognised neuroprotective properties.

Evaluation of a New Interface Combining High-Flow Nasal Cannula and CPAP.

BACKGROUND: This study assessed the effects of a new interface that combined CPAP 10 cm H2O by using a helmet with high-flow nasal cannula (HFNC) at varying flows in healthy volunteers. Outcome measures included pharyngeal pressures, diaphragm kinetics, breathing frequency, the temperature inside the helmet, and comfort. METHODS: After baseline assessment during spontaneous breathing, HFNC was applied at flows of 30, 40, and 50 L/min. Successively, the volunteers underwent helmet CPAP at 10 cm H2O and CPAP + HFNC at flows of 30, 40, and 50 L/min. We measured the variations of pharyngeal pressures at end-expiration and end-inspiration, referenced to spontaneous breathing for HFNC and to CPAP for CPAP + HFNC, diaphragm displacement and thickness at end-expiration and thickness at end-inspiration, breathing frequency, the temperature inside the helmet, the occurrence of the fog effect, and comfort. RESULTS: Variations of pharyngeal pressures at end-inspiration changes were small overall and clinically unimportant. With the mouth closed, at increasing HFNC flow, variations of pharyngeal pressures at end-expiration increased during both HFNC (from 2.8 up to 7.7) and, to a lesser extent, CPAP + HFNC (from 2.7 up to 3.8) (P < .001 for all comparisons). These variations were attenuated during open-mouth breathing. HFNC ≥ 40 L/min and CPAP + HFNC ≥ 40 L/min compared with spontaneous breathing and CPAP, respectively, increased diaphragm displacement (P = .001), thickness at end-inspiration and thickness at end-expiration (P < .003 for both). At all flows, breathing frequency was slightly, although significantly, lower with CPAP + HFNC than with HFNC alone (P < .003). The temperature inside the helmet increased slightly and insignificantly at flows of ≤40 L/min with CPAP + HFNC compared with CPAP alone. The fog effect never occurred, whereas comfort was always rated as optimal, without differences between trials. CONCLUSIONS: CPAP + HFNC was well tolerated, with no adverse effects. Based on our findings, there was no need to vary the CPAP level when adding HFNC. At least in healthy subjects, CPAP + HFNC at 30 L/min seemed to be the best combination.

Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP).

INTRODUCTION: Post-marketing surveillance activities (namely pharmacovigilance) are crucial to favor the early detection of unexpected adverse events (AEs) and/or serious adverse reactions (SAEs). Indeed, spontaneous reporting of AEs has been demonstrated to underestimate the number of events in different clinical settings. Aim of the present study is to report the preliminary data of a Regional (Calabria, Italy) Pharmacovigilance Program (CBPP) aimed at improving AEs' reporting associated with biologics use in rheumatology. MATERIALS AND METHODS: We developed a simple, cost-effective pharmacovigilance program based on regular training sessions for physicians (stimulated reporting), periodical phone calls by a clinical pharmacologist aimed at identifying new events and stimulating self-awareness and encouraging reporting to the physician during the subsequent follow-up visit for minor AEs. To test this approach, all consecutive patients undergoing treatment with one biologic agent at eight rheumatology centers during a two-years period were invited to participate. Collected AEs were compared to the number of AEs spontaneously reported for the same molecules in the same centers before starting the protocol. RESULTS: During the study period, 399 patients (245 females; mean age: 58 ± 11 years) were started on treatment with biologics for active RA (n = 211, 52.9%), PsA (n = 119, 29.8%) or AS (n = 69, 17.3%) at eight rheumatology centers. A total of 125 AEs (31.3%) and 9 SAEs (2.3%) were reported during the two-years study period. In the control cohort (comprising 368 consecutive patients started on treatment with bDMARDs during a two-years period before CBPP study) only 42 (11.4%) AEs and no SAEs were reported (p < 0.0001). The most common AEs were injection site reactions and skin disorders. CONCLUSIONS: In conclusion, our study provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology.

Skin grafting for the treatment of chronic leg ulcers - a systematic review in evidence-based medicine.

Skin grafting is one of the most common surgical procedures in the area of non-healing wounds by which skin or a skin substitute is placed over a wound to replace and regenerate the damaged skin. Chronic leg ulcers are an important problem and a major source of expense for Western countries and for which many different forms of treatment have been used. Skin grafting is a method of treatment that decreases the area of chronic leg ulcers or heals them completely, thus improving a patient's quality of life. Skin grafting is an old technique, rediscovered during the first and second world wars as the main treatment for wound closure. Nowadays, skin grafting has a pivotal role in the context of modern wound healing and tissue regeneration. The aim of this review was to track and to analyse the specific outcomes this technique achieved, especially in the last decade, in relation to venous, arterial, diabetic, rheumatoid and traumatic leg ulcers. Our main findings indicate that autologous split-thickness skin grafting still remains the gold standard in terms of safety and efficacy for chronic leg ulcers; skin grafting procedures have greater success rates in chronic venous leg ulcers compared to other types of chronic leg ulcers; skin tissue engineering, also supported by genetic manipulation, is quickly expanding and, in the near future, may provide even better outcomes in the area of treatments for long-lasting chronic wounds.

Pulsatile perfusion with intra-aortic balloon pumping ameliorates whole body response to cardiopulmonary bypass in the elderly.

OBJECTIVE: The growing life expectancy has led the elderly to be increasingly referred to coronary artery bypass grafting. Preexisting comorbidities may benefit from theoretical advantages of pulsatile perfusion during cardiopulmonary bypass (CPB). DESIGN: Prospective randomized trial. SETTING: Cardiac surgery unit in a university hospital. PATIENTS: Eighty consecutive patients older than 70 years. INTERVENTIONS: Elective coronary artery bypass grafting on CPB, randomizing to conventional linear CPB (40 patients, group A) or intra-aortic balloon pump (IABP)-induced pulsatile CPB (40 patients, group B). MEASUREMENTS AND MAIN RESULTS: We evaluated hemodynamic response by pulmonary artery flotation catheter, metabolic/splanchnic response by lactate and transaminase, bilirubin, amylase, and renal function (creatinine clearance, creatinine, incidence of renal insufficiency and failure), respiratory response by Pao2/Fio2, respiratory compliance, scoring of chest radiograph, intubation time, and need for noninvasive positive-pressure ventilation, hematologic response by chest drainage, hemocoagulative and fibrinolytic cascades, and transfusions. IABP-related complications were recorded. Two minor IABP-related complications (2.5%) were registered. Hemodynamics was comparable, except for a slightly better cardiac index and indexed systemic vascular resistances at the end of CPB and at intensive therapy unit (ITU) admission (p < 0.05). Transaminases, bilirubin, amylase, proved lower in group B (p < 0.05 from ITU admission to 48 hours). Creatinine clearance, serum creatinine, and lactate were better in group B (p < 0.05), and acute renal insufficiency was accordingly lower (p = 0.02). Respiratory response demonstrated better Pao2/Fio2 and respiratory compliance from aortic declamping to 48 hours, with better scoring of chest radiograph (p < 0.05 from ITU admission to 48 hours), lower noninvasive positive-pressure ventilation (p = 0.002) and intubation time (p = 0.031) in group B. Lower chest drainage (p < 0.05 at first and second day), transfusions (p < 0.05), activated partial thromboplastin time, international normalized ratio, white blood cells, and D-dimer (p < 0.05 from ITU admission to 48 hours), together with higher platelets, fibrinogen, and antithrombin III (p < 0.05 from ITU admission to 48 hours) were demonstrated in the pulsated group. CONCLUSIONS: IABP-induced pulsatile flow significantly improves whole body perfusion in the elderly undergoing CPB.

Preoperative intraaortic balloon pumping improves outcomes for high-risk patients in routine coronary artery bypass graft surgery.

BACKGROUND: We evaluated the association between the preoperative use of intraaortic balloon pumping and in-hospital and long-term outcomes in high-risk patients undergoing coronary artery bypass grafting. METHODS: From 714 total patients undergoing coronary artery bypass grafting during a 4-year period, we compared the clinical, biochemical, and echocardiographic findings up to 1 year after surgery between 111 patients who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 12 or greater and received intraaortic balloon pumping preoperatively (group A) and 130 patients who had a EuroSCORE of 5 or less and received no preoperative intraaortic balloon pumping (group B). RESULTS: Group A patients were significantly older, had significantly more comorbid conditions, and had a significantly lower mean preoperative ejection fraction (all p < 0.001). Intraoperative data were comparable between groups, as were lactate and troponin I levels sampled from the coronary sinus. Lactate, troponin I, creatine kinase, and creatine kinase-MB mass showed comparable leakage at all postoperative times. The incidences of in-hospital mortality, perioperative myocardial damage, and acute myocardial infarction and duration of hospital stay were comparable. High-risk patients showed significant improvements in ejection fraction (p < 0.001) and wall-motion score index (p = 0.06) after surgery, but low-risk patients showed no significant change in these variables. The incidences of death, recurrent angina, myocardial infarction, and repeat coronary procedures did not differ significantly between groups. CONCLUSIONS: The preoperative use of intraaortic balloon pumping appears to shift high-risk patients undergoing coronary artery bypass grafting into a lower-risk category and is associated with comparable perioperative troponin leakage and short-term and long-term outcomes similar to low-risk patients not receiving intraaortic balloon pumping.

Early intra-aortic balloon pumping following perioperative myocardial injury improves hospital and mid-term prognosis.

We evaluated the impact of immediate intra-aortic balloon pumping (IABP) on hospital and mid-term outcome of coronary artery bypass graft (CABG) whenever perioperative acute complications developed. We compared clinical, biochemical, echocardiographic in-hospital results and two-year follow-up outcome of 30 low-risk (EuroSCORE<5) CABG (group A) who immediately received perioperative IABP when acute complications were suspected, to a contemporary, uncomplicated case-matched group (30 patients; Group B). Two in-hospital deaths were recorded in group A with no deaths in controls (P=0.492). Group A showed significantly higher lactate only at ICU arrival (P=0.001). Troponin I was always higher, but never reached values diagnostic for myocardial infarction (P<0.001). Worse left ventricular ejection fraction (P<0.001) and wall motion score index (P=0.008) were recorded at ICU arrival in group A, although an almost complete recovery was registered at discharge. Two-year actuarial survival was similar between the two groups (P=0.598). No differences were observed in freedom from acute myocardial infarction (P=0.503) and from overall cardiac complications (P=0.410). Early IABP should be established whenever cardiac complications are suspected, because of its beneficial impact on enzymatic leakage, myocardial recovery at echocardiography, hospital outcome, mid-term follow-up survival and freedom from cardiovascular events.