Efficacy of ustekinumab in the treatment of patients with Crohn's disease with failure to previous conventional or biologic therapy: a prospective observational real-life study.

Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn's disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. This study was performed on 92 subjects with confirmed diagnosis of moderate to severe Crohn's disease and no neoplasia. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy. All patients underwent endoscopic examination and bowel MRI and ultrasonography at baseline (T0). At week 52 (T52), patients underwent colonoscopy for assessment of mucosal healing and MRI or ultrasonography for assessment of transmural healing. CDAI was used for the assessment of clinical response and clinical remission. SES-CD was used to assess endoscopic response and remission. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Clinical response at week 52 was achieved in 38 (50.5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. We observed a reduction in SES-CD of at least 50% in 34 (45%) patients as well as an SES-CD ≤ 2 in 26 (35%) patients. All patients with mucosal healing also showed transmural healing. No major TRAEs were observed during treatment. In this multicenter, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).

Detection of Cross-Correlation between Gravitational Lensing and γ Rays.

In recent years, many γ-ray sources have been identified, yet the unresolved component hosts valuable information on the faintest emission. In order to extract it, a cross-correlation with gravitational tracers of matter in the Universe has been shown to be a promising tool. We report here the first identification of a cross-correlation signal between γ rays and the distribution of mass in the Universe probed by weak gravitational lensing. We use data from the Dark Energy Survey Y1 weak lensing data and the Fermi Large Area Telescope 9-yr γ-ray data, obtaining a signal-to-noise ratio of 5.3. The signal is mostly localized at small angular scales and high γ-ray energies, with a hint of correlation at extended separation. Blazar emission is likely the origin of the small-scale effect. We investigate implications of the large-scale component in terms of astrophysical sources and particle dark matter emission.

Adjuvant chemotherapy for rectal cancer: Current evidence and recommendations for clinical practice.

While adjuvant chemotherapy is an established treatment for pathological stage II and especially stage III colon cancer, its role in the multimodal management of rectal cancer remains controversial. As a result, there is substantial variation in the use of this treatment in clinical practice. Even among centres and physicians who consider adjuvant chemotherapy as a standard treatment, notable heterogeneity exists with regard to patient selection criteria and chemotherapy regimens. The controversy around this topic is confirmed by the lack of full consensus among national and international clinical guidelines. While most of the clinical trials do not support the contention that adjuvant chemotherapy may improve survival outcomes if pre-operative (chemo)radiotherapy is also given, these suffer from many limitations that preclude drawing definitive conclusions. Nevertheless, in the era of evidence-based medicine, physicians should be guided by the available data and refrain from extrapolating results of adjuvant colon cancer trials to inform treatment decisions for rectal cancer. Patients should be informed of the evidence gap, be given the opportunity to carefully discuss pros and cons of all the possible management options and be empowered in the decision making. In this article we review the available evidence on adjuvant chemotherapy for rectal cancer and propose a risk-adapted decisional algorithm that largely relies on informed patient preferences.

Grey areas and evidence gaps in the management of rectal cancer as revealed by comparing recommendations from clinical guidelines.

BACKGROUND: While the management of nonmetastatic and oligometastatic rectal cancer has rapidly evolved over the last few decades, many grey areas and highly debated topics remain that foster significant variation in clinical practice. We aimed to identify controversial points and evidence gaps in this disease setting by systematically comparing recommendations from national and international clinical guidelines. METHODS: Twenty-six clinical questions reflecting practical challenges in the routine management of nonmetastatic and oligometastatic rectal cancer patients were selected. Recommendations from the ESMO, NCCN, JSCCR, Australian and Ontario guidelines were extrapolated and compared using a 4-tier classification system (i.e., identical/very similar, similar, slightly different, different). Overall agreement between guidelines (i.e., substantial/complete disagreement, partial disagreement, partial agreement, substantial/complete agreement) was assessed for each clinical question and compared against the highest level of available evidence by using the χ2 statistic test. RESULTS: Guidelines were in substantial/complete agreement, partial agreement, partial disagreement, and substantial/complete disagreement for 8 (30.8%), 2 (7.7%), 7 (26.9%), and 9 (34.6%) clinical questions, respectively. High level of evidence supported clinical recommendations in 3/10 cases (30%) where guidelines were in agreement and in 10/16 cases (62.5%) where guidelines were in disagreement (χ2 = 2.6, p = 0.106). Agreement was frequently reached for questions regarding diagnosis, staging, and radiology/pathology pro-forma reporting, while disagreement characterised most of the treatment-related topics. CONCLUSIONS: Substantial variation exists across clinical guidelines in the recommendations for the management of nonmetastatic and oligometastatic rectal cancer. This variation is only partly explained by the lack of supporting, high-level evidence.

Osteoporosis across chronic liver disease.

Osteoporosis is a complication of chronic liver disease, with impact on morbidity, quality of life, and survival. The progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with liver disease. So, it is fundamental to make better the quality of life and to prevent complications. Metabolic bone disorders are common complications of chronic liver disease (CLD). Patients with CLD have an increased risk of bone fractures, with significant impact on morbidity, quality of life, and even on survival. Bone diseases, including osteomalacia, osteoporosis, and osteopenia, are frequently observed in many types of liver disease. The pathogenesis of damage and the mechanisms of bone loss are different in relation to the specific liver disease. The relevance of these conditions induced many authors to create a new nosographic entity known as "hepatic osteodystrophy", although this term is rarely used anymore and it is now commonly referred to as osteopenia or osteoporosis associated with chronic liver disease. This review is based on the personal experiences of the authors and upon research done of the available literature on this subject matter. The authors searched the PubMed database for publications containing the term "liver disease" in combination with "bone disease", "hepatic osteodistrophy", "osteoporosis", "osteopenia", "osteomalacia", and "fractures". They selected publications from the past 10 years but did not exclude older seminal publications, especially for colestatic liver diseases. This review of literature shows that osteoporosis crosses all CLD. It is important to underline that the progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with CLD. It is fundamental to make better the quality of life and it is mandatory to prevent complications and in particular the osteoporotic ones, especially fractures.

Effect of immunosuppressive therapy on patients with inflammatory bowel diseases and hepatitis B or C virus infection.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

[A new technique for post-mastectomy breast reconstruction: the Muscular Flag Flap (MFF)]. / Una nuova tecnica per la ricostruzione mammaria post-mastectomia: il muscular FLAG FLAP (MFF).

The possibility of breast reconstruction after a mastectomy resulting from breast cancer is still not widely exploited, and perhaps because it is relatively uncommon and unknown, is not widely practised. The plastic surgeons who were pioneers in this field know just how hard it has been to reach the stage we are at today. This leads to longer operating times, in the context of over-worked operating theaters in which time was already at a premium, and this is expecially the case in peripheral hospitals lacking in-house resources for surgical reconstruction and dependent on outisde specialist consultants. In order to address this problem, a new single-operation surgical technique, MFF (Muscular Flag Flap) has been developed. The surgical techniques adopted at present are based on immediate reconstruction or successive reconstruction. The MFF technique was developed as a response to demand for intraoperative reconstruction even when "demolition" is extensive and the breast large. This will reduce the need to operate the contralateral breast. Upper and lower pectoralis major muscle flaps are created in order to produce a large enough pocket for the final prothesis. The elasticity of this muscle is such that a large pocket is possible. The pectoralis major muscle will then envelop at least two thirds of the prosthesis. Projection of the reconstructed cone and a more anatomically normal profile are obtained. This method gives excellent esthetic results in a single operation. Thanks to the collaboration of the hospitals of Ivrea, Pinerolo and Alba over a period of approximately one year, about 80 patients have been very successfully treated using this techhnique. Rapid functional and social recovery have been observed, with no particular problems. In view of the above, we confirm that this new surgical technique will be of considerable benefit to patients.

[Aneurysm of the hepatic artery. Case report and review of the literature]. / L'aneurisma dell'arteria epatica. Case report e revisione della letteratura.

Hepatic artery aneurysms (HAAs) are considered rare even though their reports in the literature are becoming more and more frequent. The great improvement in the diagnosis of vascular diseases and the increasing incidence of atherosclerosis have resulted in a wider recognition of these pathologies. Differently from other splanchnic locations HAAs have a high risk of rupture (up to 80%) so that an aggressive treatment is required. Different therapeutic options are currently available: simple ligation of the artery, aneurysm excision and vascular reconstruction, transcatheter embolization. However, the therapeutic choice must be evaluated in each single case, depending on the size, aspect and locations of the aneurysm, and requiring an accurate study of the collateral vascular supply. Finally, since additional aneurysms in other sites are frequent, a dose follow up of these patients is recommended.

[Cystadenocarcinoma of the pancreas. Case report and review of the literature]. / II cistoadenocarcinoma del pancreas. Caso clinico e revisione della Letteratura.

Pancreatic cystadenocarcinoma is a quite rare neoplasm. Due to the low incidence and recent nosographic arrangement, the natural evolution and the clinical development of this type of neoplasm are not well known. The Authors report their experience and a review of the Literature trying to establish the criteria for the classification, diagnosis and therapy of pancreatic cystadenocarcinoma.