Effects of a 3-month weight-bearing and resistance exercise training on circulating osteogenic cells and bone formation markers in postmenopausal women with low bone mass.

Osteoporosis is a health issue in postmenopausal women. Physical activity is recommended in these subjects, since it has positive effects on bone mass. Cellular mechanisms underlying this effect are still unclear. Osteogenic cells, released after physical exertion, could be a key factor in exercise-induced bone formation. INTRODUCTION: The aim of our research was to explore if a weight-bearing and resistance exercise program could positively affect circulating osteogenic cells (OCs), markers of bone formation and quality of life (QoL) in osteopenic postmenopausal women. METHODS: We recruited 33 postmenopausal women with a T-score at lumbar spine or femoral neck between - 1 and - 2.5 SD. Anthropometric and fitness parameters, bone-remodeling markers, OCs, and QoL were evaluated at the time of enrolment, after 1-month run-in period, and after 3 months of weight-bearing and resistance exercise. RESULTS: After 3 months of training, the pro-collagen type 1 N-terminal peptide (P1NP) and the number of OCs were significantly increased, with no significant increase of the type 1 collagen cross-linked C-telopeptide (sCTX). We also observed a significant increase in body height, one-repetition maximum (1RM) on the pull-down lat machine and leg press, and mean VO2max. The increase of immature circulating OCs was significantly correlated with the improvement of 1RM both of the upper and lower limbs. Moreover, QoL was significantly improved with regard to pain, physical function, mental function, and general QoL. The improvement in QoL, namely in the overall score and in the pain score, was significantly correlated with the increase in height. CONCLUSIONS: The exercise program we trialed is able to increase the markers of bone formation and the commitment of immature OCs with no significant increase in the markers of bone resorption. Our results confirm that combined weight-bearing and resistance physical activity is an effective tool to improve QoL of postmenopausal women with low bone mass. TRIAL REGISTRATION: NCT03195517.

Intensive lifestyle intervention is particularly advantageous in poorly controlled type 2 diabetes.

BACKGROUND AND AIMS: It is unknown whether lifestyle change is effective in people with type 2 diabetes with inadequate glucose control. The aim of this study was to asses, in a group of people with type 2 diabetes, the impact of baseline values of glycosylated haemoglobin (HbA1c) on the effects of an intensive lifestyle intervention on metabolic, clinical and strength parameters. METHODS AND RESULTS: 222 people with type 2 diabetes with mean ± standard deviation baseline HBA1c of 7.50% ± 1.27 (range 5.1-12.7%), were enrolled in a 3-month structured multidisciplinary lifestyle intervention. Anthropometric, biochemical, clinical and fitness measurements were collected at baseline, at the end of the lifestyle intervention program and at two-year follow-up visit. Significant improvements in glycometabolic control (HbA1c: p ≤ 0.0001); anthropometric parameters (BMI p ≤ 0.0001; waist circumference: p ≤ 0.0001); and systemic blood pressure (p ≤ 0.0001) were observed both at the end of the three month intensive lifestyle program and at the two-year follow up visit. In addition, defined daily doses of hypoglycaemic treatment significantly decreased (p = 0.001). Fitness measures exhibited significant increments in the whole sample at the end of the intensive intervention program (p ≤ 0.0001). When patients were divided into tertiles considering the baseline value of HbA1c, the most marked improvements in HbA1c, blood glucose and triglycerides were observed in the group with inadequate glucose control (Hba1c ≥ 7.71%), both at the three-month and two-year follow-ups. CONCLUSION: These results demonstrate that an intensive lifestyle intervention should be recommended for people with type 2 diabetes, particularly those with the most inadequate glycaemic control. REGISTRATION NUMBER: CURIAMO trial was registered in the Australian New Zealand Clinical Trials Registry, (ACTRN12611000255987).

Levels and function of regulatory T cells in patients with polymorphic light eruption: relation to photohardening.

BACKGROUND: We hypothesized that regulatory T cells (Tregs) are involved in the immunological abnormalities seen in patients with polymorphic light eruption (PLE). OBJECTIVES: To investigate the number and suppressive function of peripheral Tregs in patients with PLE compared with healthy controls. METHODS: Blood sampling was done in 30 patients with PLE [seeking or not seeking 311-nm ultraviolet (UV)B photohardening] as well as 19 healthy controls at two time points: TP1, March to June (before phototherapy); and TP2, May to August (after phototherapy). We compared the number of CD4(+) CD25(high) CD127(-) FoxP3(+) Tregs by flow cytometry and their function by assessing FoxP3 mRNA levels and effector T cell/Treg suppression assays. RESULTS: Tregs isolated from healthy controls significantly suppressed the proliferation of effector T cells at TP1 by 68% (P = 0·0156). In contrast, Tregs from patients with PLE entirely lacked the capacity to suppress effector T-cell proliferation at that time point. The medical photohardening seen in 23 patients with PLE resulted in a significant increase in the median percentage of circulating Tregs [both as a proportion of all lymphocytes; 65 6% increase (P = 0·0049), and as a proportion of CD4(+) T cells; 32.5% increase (P = 0·0049)]. This was accompanied by an increase in the expression of FoxP3 mRNA (P = 0·0083) and relative immunosuppressive function of Tregs (P = 0·083) comparing the two time points in representative subsets of patients with healthy controls tested. Seven patients with PLE not receiving 311-nm UVB also exhibited an increase in the number of Tregs but this was not statistically significant. No significant differences in Treg numbers were observed in healthy subjects between the two time points. CONCLUSIONS: An impaired Treg function is likely to play a role in PLE pathogenesis. A UV-induced increase in the number of Tregs (either naturally or therapeutically) may be a compensatory mechanism by which the immune system counteracts the susceptibility to PLE.

Photodynamic therapy plus regulatory T-cell depletion produces immunity against a mouse tumour that expresses a self-antigen.

BACKGROUND: Photodynamic therapy (PDT) can lead to development of antigen-specific immune response and PDT-mediated immunity can be potentiated by T regulatory cell (Treg) depletion. We investigated whether the combination of PDT with cyclophosphamide (CY) could foster immunity against wild-type tumours expressing self-antigen (gp70). METHODS: Mice with CT26 tumours were treated with PDT alone or in combination with low-dose CY. T regulatory cell numbers and transforming growth factor-ß (TGF-ß) levels were measured at several time points after treatment. Mice cured by PDT+CY were rechallenged with CT26 and monitored for long-term survival. RESULTS: Photodynamic therapy+CY led to complete tumour regression and long-term survival in 90% of treated mice while the absolute numbers of Treg decreased after PDT+CY and the TGF-ß levels were reduced to a level comparable to naïve mice. Sixty-five percent of the mice treated with PDT+CY that survived over 90 days tumour free rejected the rechallenge with the same tumour when a second dose of CY was administered before rechallenge but not without. CONCLUSION: Administration of CY before PDT led to depletion of Treg and potentiated PDT-mediated immunity, leading to long-term survival and development of memory immunity that was only uncovered by second Treg depletion.

Hypertrophic obstructive cardiomyopathy. Late follow-up after ventricular myotomy-myectomy.

A series of 25 patients with hypertrophic obstructive cardiomyopathy, isolated or associated with minor anomalies, were operated upon using a modified Morrow's procedure. The indication for operation was based on either the presence of severe symptoms despite treatment with beta-blocking agents, or a significant peak gradient of over 50 mmHg even in asymptomatic patients. All patients survived and none was lost to follow-up. Long-term results were evaluated with 2-dimensional echocardiography. Surgical versus pharmacological treatment is discussed, with particular consideration given to paediatric patients.

Chylothorax following cardiac surgery in children.

Eleven cases of chylothorax following cardiac surgery in children are described. Conservative treatment was carried out with success in all patients but one, who died because of the underlying cardiac pathology, with the chylothorax still present. Our results indicate that conservative treatment is effective in children, although surgery has been previously considered by some authors as the treatment of choice in this age group.

Quadricuspid aortic valve.

A case of quadricuspid aortic valve is described. The anomaly was unexpectedly found during operation for aortic valve replacement in a 70-year-old woman. Macroscopic and histological examinations of the valve showed no sign of previous inflammatory disease. Quadricuspid aortic valve must be considered, therefore, a malformation capable of leading to severe valve failure in later life.

Spontaneous rupture of the gallbladder and haemoperitoneum in a patient with cardiac valve prostheses.

A case is reported of isolated spontaneous rupture of the gallbladder with obstructed cystic duct and a stone in the cystic cavity, in a patient on anticoagulant treatment after cardiac valve replacement. The mechanism of the onset, the diagnosis and the treatment of the lesion are discussed together with a review of the literature.

Cervical aortic arch and a new type of double aortic arch. Report of a case.

A case of cervical aortic arch is reported. To the best of our knowledge, it is the first to be associated with a serious intracardiac anomaly. In addition, it is part of a new type of double aortic arch, caused by failure of reabsorption of both dorsal aortic roots and persistence of the fourth right and second (or third) left branchial arches.

Interruption of the aortic arch in an infant with left subclavian steal syndrome. Case report.

An unusual case of interruption of the aortic arch with flow to the descending aorta through the left vertebral and left subclavian arteries is described. The ductus arteriosus was functionally closed. The aortic arch was reconstructed with a PTFE graft, but the patient died because of lung problems, related to a high left-to-right shunt through a ventricular septal defect. A new surgical approach is postulated in view of the unusual hemodynamic features. Surgical control of pulmonary congestion could be the initial step, followed by aortic arch reconstruction later when insertion of a non-restrictive aortic prosthesis is possible.

The incidence of urinary tract malformations in congenital heart disease.

A statistically significant number of congenital heart disease patients were evaluated for urinary tract anomalies. Twelve percent (160 cases among 1340 patients) had such associated anomalies. However, no association between a specific congenital heart disease and a particular urinary tract anomaly could be found. The results were very similar to those reported in clinical series, but slightly higher than those found at autopsy. The percentage of urinary tract malformations varied over a wide range, with some congenital heart disease having a much higher association than others. However, the total average incidence of urinary tract malformation was similar to that of the general population.

Indirect radiographic and angiographic signs of isolated left superior vena cava in congenital heart disease.

Blood that drains into the right atrium through an isolated left superior vena cava (LSVC) can be a complicating condition during cardiac surgery. In cases of LSVC, a double shadow can be present on standard chest X-ray over the left mediastinum. A notch along the lower contour of left atrium has been previously reported by Owen et al. in 4 cases as an indirect sign of this LSVC anomaly. These two indirect signs were evaluated in 135 (4.5%) cases of LSVC, viewing 89 chest radiographs and 40 angiograms. Their incidence, separately (17-45%) or in combination (9-20%), was observed to be frequent enough to justify a systematic search of these signs in open-heart surgery candidates.

The syndrome of congenital absence of the pulmonary valve: pathological, clinical and surgical considerations.

Four cases of congenital absence of the pulmonary valve are described. Three of them underwent successful operation. The fourth case, operated on in the first days of life, died because of severe respiratory distress. After examining the embryological aspects of this malformation, its treatment is discussed in relation to particular respiratory problems in infants and to the possibility of inserting prosthetic valves in children undergoing elective surgical treatment.

Congenital coronary artery fistula: report of five patients, diagnostic problems and principles of management.

The detection of a coronary artery fistula (CAF) is usually by chance and, because of the to-and-fro characters of the murmur, a misdiagnosis of a patent ductus arteriosus is frequently made. Correct diagnosis can only be reached after hemodynamic investigation completed by angiography. This lesion is often accompanied by few or no symptoms in infancy, but may become symptomatic with aging even if the shunt is small: complications such as endocarditis, rhythm disturbances, aneurysmatic dilation and rupture have been reported. Five cases of CAF have been studied in our institution: 3 of them have been operated upon in extracorporeal circulation with good results. Principles of management are controversial: many authors advocate delay of treatment until symptoms appear: in our opinion, based on the natural history of the disease and on our experience, closure of the fistula in pediatric age, even in asymptomatic patients, is the treatment of choice.