Long‐term preclinical magnetic resonance imaging alterations in sporadic Creutzfeldt–Jakob disease

An asymptomatic 74‐year‐old woman, on follow‐up for a carotid body tumor, showed magnetic resonance imaging (MRI) focal restricted diffusion confined to the left temporal and occipital cortices. Thirteen months later, diffusion‐weighted images revealed a bilateral cortical ribbon sign involving all lobes. After 1 month, the patient developed gait instability and cognitive decline rapidly evolving to severe dementia and death within 3 months. Prion protein gene sequence, molecular, and neuropathological studies confirmed the diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) MM1 subtype. Here we show the kinetics of MRI changes and prion spreading in preclinical sCJD MM1. Ann Neurol 2016;80:629–632     

When the government actively faces the burden of osteoporosis: the Italian experience

Epidemiology and costs of fragility fractures in Italy

The problem of osteoporosis is emerging as growing phenomenon, with an enormous impact on quality of life and on health expenses. As a consequence, a reduction in the social and health impact of bone fragility would be associated with an improved quality of life of all elderly citizens and with valuable cost savings at the health system level.

Osteoporosis: evolution of the concept in Italy

In the last 20?years, there have been enormous advances in the knowledge of diagnostic and therapeutic options and thus we would be in the position of starting effective therapies in at risk populations. However, this not always happens.

New approaches to the fragility fractures by the Italian government

In this paper we offer to the reader the possibility to know the history of osteoporosis, its diagnosis and its therapy in Italy, a country where life expectancy is one of the highest in the world.

The future of osteoporosis in Italy

We hope that the example of Italy would serve as an inspiration to those countries where the history of osteoporosis only recently began.     

Comparative study of talc poudrage versus pleural abrasion for the treatment of primary spontaneous pneumothorax

Primary spontaneous pneumothorax is a pathology mainly affecting healthy young patients. Clinical guidelines do not specify the type of pleurodesis that should be conducted, due to the lack of comparative studies on the different techniques. The aim of this study was to compare talc poudrage and pleural abrasion in the treatment of spontaneous pneumothorax. A retrospective comparative study was performed, including 787 patients with primary spontaneous pneumothorax. The 787 patients were classified into two groups: Group A (pleural abrasion) n = 399 and Group B (talc pleurodesis) n = 388. The variables studied were recurrence, surgical time, morbidity and in-hospital length of stay. Statistical analysis was done by an unpaired t-test and Fisher's exact test (SSPS 18.0). Statistically significant differences were observed in the variables: surgical time (A: 46 ± 12.3; B: 37 ± 11.8 min; P < 0.001); length of stay (A: 4.7 ± 2.5; B: 4.3 ± 1.8 days; P = 0.01); apical air camera (A: 25; B: 4; P < 0.001); pleural effusion (A: 6; B: 0; P = 0.05). Talc poudrage shows shorter surgical times and length of stay, and lower re-intervention rates. Morbidity is lower in patients with talc poudrage. Statistically significant differences were not observed in recurrence, persistent air leaks, atelectasis and haemothorax.     

A simple technique of oblique anastomosis can prevent stricture formation in primary repair of esophageal atresia

BackgroundAnastomotic stricture is an important problem after esophageal atresia (EA) repair. This study evaluates a technique of oblique esophageal anastomosis without use of a flap in order to prevent stricture formation.MethodsMedical records of 16 patients (14 with EA type III and 2 with EA type IV Ladd-Gross classification) who underwent primary repair of EA at birth without anastomotic tension were reviewed, evaluating long-term follow-up results. All patients were studied with esophageal contrast study, pH-multichannel intraluminal impedance, and endoscopy. The incidence of complications and their management were analysed.ResultsContrast esophagogram and esophagoscopy always showed regular patency of the suture line.ConclusionsOur technique of oblique anastomosis is simple, safe, and effective in preventing stricture formation even in the long-term follow-up.     

Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial

Background

Elderly patients with metastatic renal cell carcinoma (mRCC) may require special treatment considerations, particularly when comorbidities are present. An understanding of the efficacy and safety of targeted agents in elderly patients with mRCC is essential to provide individualized therapy.

Objective

To evaluate the efficacy and safety of everolimus in elderly patients (those ≥65 and ≥70 yr of age) enrolled in RECORD-1.

Design, setting, and participants

The multicenter randomized RECORD-1 phase 3 trial (Clinicaltrials.gov identifier, NCT00410124; http://www.clinicaltrials.gov) enrolled patients with mRCC who progressed during or within 6 mo of stopping sunitinib and/or sorafenib treatment (n = 416).

Intervention

Everolimus 10 mg once daily (n = 277) or placebo (n = 139) plus best supportive care. Treatment was continued until disease progression or unacceptable toxicity.

Measurements

Median progression-free survival (PFS), median overall survival (OS), and time to deterioration in Karnofsky performance status (TTD-KPS) were assessed using the Kaplan-Meier method; the log-rank test was used to compare treatment arms. Other outcomes evaluated included reduction in tumor burden, overall response rate (ORR), and safety.

Results and limitations

In RECORD-1, 36.8% of patients were ≥65 yr and 17.5% were ≥70 yr of age. PFS, OS, TTD-KPS, reduction in tumor burden, and ORR were similar in the elderly and the overall RECORD-1 population. Everolimus was generally well tolerated in elderly patients, and most adverse events were grade 1 or 2 in severity. The toxicity profile of everolimus was generally similar in older patients and the overall population; however, peripheral edema, cough, rash, and diarrhea were reported more frequently in the elderly regardless of treatment. The retrospective nature of the analyses was the major limitation.

Conclusions

Everolimus is effective and tolerable in elderly patients with mRCC. When selecting targeted therapies in these patients, the specific toxicity profile of each agent and any patient comorbidities should be considered.     

Liver transplantation in a patient with S(beta)o-thalassemia

BACKGROUND: Patients presenting sickle cell disease may develop different types of hepatic complications. Intrahepatic cholestasis is a potentially fatal complication of the disease, and sometimes the only possible solution is transplantation. Postoperative transfusion management has not yet been well established. In this report, we describe the transfusional program of a patient presenting sickle cell disease and intrahepatic cholestasis who underwent liver transplantation 2 years ago. METHODS: Data were obtained from the chart and the blood bank records. RESULTS: The liver transplantation was performed successfully. Despite mild allograft dysfunction 3 months after surgery, secondary to intrahepatic sickling, the patient has been doing well with the transfusional management adopted (sickle-cell hemoglobin <20%). CONCLUSION: Sickle cell disease should not be a criterion for exclusion from liver transplantation. Regular transfusion with monitoring of sickle-cell hemoglobin is a very important measure to minimize the risk of intrahepatic sickling and possible rejection.     

Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice

Chemerin is an adipokine that regulates adipogenesis and metabolic functions of mature adipocytes mainly through the activation of chemokine‐like receptor 1 (CMKLR1). Elevated levels of chemerin have been found in individuals with obesity, type 2 diabetes, and osteoporosis. This adipokine was identified as an inflammatory and metabolic syndrome marker. Considering that the association between metabolic syndrome and bone health remains unclear, the present study aimed to clarify the role of chemerin in the pathophysiology of bone loss induced by dyslipidemia, particularly modulating osteoclastogenesis. In vitro analyses showed a downregulation of CMKLR1 at the early stage of differentiation and a gradual increase at late stages. Strikingly, chemerin did not modify osteoclast differentiation markers or osteoclast formation; however, it increased the actin‐ring formation and bone resorption activity in mature osteoclasts. The increased bone resorption activity induced by chemerin was effectively inhibited by CMKLR1 antagonist (CCX832). Chemerin boosting mature osteoclast activity involves ERK5 phosphorylation. Moreover, two models of dyslipidemia (high‐fat diet [HFD]‐treated C57/BL6 and db/db mice) exhibited significantly increased level of chemerin in the serum and gingival tissue. Morphometric analysis showed that HFD‐treated and db/db mice exhibited increased alveolar bone loss compared to respective control mice, which was associated with an up‐regulation of chemerin, CMKLR1 and cathepsin K mRNA expression in the gingival tissue. The treatment of db/db mice with CCX832 effectively inhibited bone loss. Antagonism of chemerin receptor also inhibited the expression of cathepsin K in the gingival tissue. Our results show that chemerin not only increases osteoclasts activity in vitro, but also that increased level of chemerin in dyslipidemic mice plays a critical role in bone homeostasis. © 2016 American Society for Bone and Mineral Research.     

Survival Rates and Cause of Death in 174 Patients with Chronic Pancreatitis

Background  The natural history after surgery for chronic pancreatitis is rarely reported. Methods  Between 1970 and 1999, 174 patients underwent surgery for chronic pancreatitis and were followed until December 2006. They were divided in four groups: (1) resection 62; (2) drainage 82; (3) external drainage 7; (4) non-pancreas-directed surgery 23. A second procedure was required by 25 patients and a third by four: group 1 = 6 + 0, group 2 = 10 + 2, group 3 = 3 + 1, group 4 = 6 + 1. Results  Hospital mortality was four of 174 (2.3%). Fifty-seven patients are alive; 49 of 170 developed cancer, and 38 died: lung (22), oral, pharynx, larynx (eight), esophagus, kidney, pancreas, colon, liver (two each), breast, stomach, mediastinum, prostate, melanoma, chronic myelogenous leukemia, squamous cancer of the auricle (one each), liver metastasis from unknown primary (two). Fifteen patients died of liver cirrhosis, 13 of myocardial infarction/decompensation, six of vascular problems, five each of acute renal insufficiency or cerebral diseases, four each of acute pancreatitis, accidental trauma, complications of diabetes, bronchopneumonia, and 19 of other causes. The overall 5-, 10-, 15-, 20-, 25-, and 30-year survival rate was 84.7, 65.6, 51.6, 38.0, 28.1, and 23.5. Conclusions  Incidence of pancreatic cancer was 1.2%. The high incidence of smoking cancers (18.8%) is explained by the smoking habits of almost 100% of our patients. Eliminating smoking and increasing tests on organs at risk may prolong survival. Grant support: This study has been supported by the Ministero dell’Università e Ricerca Scientifica (Cofin 2005060715_001), Rome, Italy.