Atherosclerosis and rheumatoid arthritis : more than a simple association

In the last decades a large amount of evidences linked rheumatoid arthritis (RA) to atherosclerosis. In particular, it is well established that RA patients have an increased risk of cardiovascular events that is not fully explained by smoke and other classic cardiovascular risk factors. In fact, RA and atherosclerosis may share several common pathomechanisms; inflammation undoubtedly plays a primary role in these settings, being involved in the appearance and progression of both diseases. In fact, proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, involved in the pathogenesis of RA, are also independently predictive of subsequent cardiovascular disease (CVD) events in these patients. In RA inflammation may alter HDL constituents and the concentration of LDL and HDL, thus facilitating atherosclerosis and CVD events. On the other hand, also the increase of oxidative processes, frequently observed in RA, may induce atherosclerosis. Interestingly some genetic polymorphisms associated with RA occurrence may enhance atherosclerosis, thus confirming the link between these diseases; however there are some polymorphisms associated with RA susceptibility which do not increase CVD risk; this behavior is a further confirmation that several mechanisms may influence atherosclerotic processes in RA. Moreover, atherosclerosis may be directly mediated also by underlying autoimmune processes, and indirectly by the occurrence of metabolic syndrome and impaired physical activity. Finally, the effects of RA therapies on cardiovascular system in general and on atherosclerosis in particular, are really wide and different. Therefore, RA treatment comprehends drugs that may either increase or reduce CVD. However, the starting point of every RA treatment is that disease control, or better remission, is the best way we have for the reduction of cardiovascular morbidity and mortality in these patients

Carbapenemase-producing klebsiella pneumoniae colonization and infection in solid organ transplant recipients: A single-center, retrospective study

Carbapenemase-KPC producing Klebsiella pneumoniae (CP-Kp) infection represents a serious threat to solid organ transplant (SOT). All patients admitted between 1 May 2011 and 31 August 2014 undergoing SOT were included in the retrospective study. The primary outcomes included a description of the association of enteric colonization and invasive infections by CP-Kp with one-year mortality. Secondary outcomes were the study of risk factors for colonization and invasive infections by CP-Kp. Results: A total of 5.4% (45/828) of SOT recipients had at least one positive rectal swab for CP-Kp, with most (88.9%) occurring after transplantation. 4.5% (35/828) of patients developed a CP-Kp-related invasive infection, with 68.6% (24/35) being previously colonized. The 1-year mortality was 31.1% in patients with enteric colonization with CP-Kp and, it was 51.4% among patients with CP-Kp-related invasive infections. At univariate analysis, colonization, invasive infections, sepsis, severe sepsis, and septic shock were significantly associated with 1-year mortality. At multivariate analysis, only invasive infections and the combination of sepsis, severe sepsis, or septic shock were significantly associated with 1-year mortality, whereas gastrointestinal colonization was significantly associated with survival. In this population, the 1-year mortality was significantly associated with invasive infections; otherwise, gastrointestinal colonization was not associated with increased 1-year mortality

Biosimilars : lights and shadows in rheumatology

In the last 10 years, the growing approval and marketing of biological agents has significantly ameliorated the outcomes of rheumatoid arthritis and spondyloarthritis patients suffering from active and refractory disease despite conventional treatments. As patent protection of many biopharmaceuticals will expire in the next years, biosimilars could be proximally introduced. Such agents could be marked only when they will be proven, through in vitro and in vivo studies, to be similar enough to the original comparator in term of quality, efficacy and safety. As biosimilars are less expensive than corresponding originators, a wider use of these drugs may substantially cut off the expenditure of biopharmaceuticals. Nevertheless, ongoing debate exists in scientific community: the intrinsic complex and large structure of biologic molecules besides the natural variability in the manufacturing processes might lead to a slightly different product respect to the original one, so that relevant implications for efficacy and safety concerns might arise, especially in the long-term period. Immunogenicity and extended indications of biosimilars represent further matter of discussion, too. Thus, before their approval and marketing, specific guidelines and steps imposed by national and/or international regulatory agencies should be followed along with the respect of scientific societies position in each specific contest

Lung Transplantation for Primary Ciliary Dyskinesia and Kartagener Syndrome: A Multicenter Study.

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population

Spinal non-Hodgkin’s lymphoma mimicking a flare of disease in a patient with ankylosing spondylitis treated with anti-TNF agents : case report and review of the literature

We report the case of a 52-year-old man with long-standing HLAB27-positive ankylosing spondylitis treated with anti-tumour necrosis factor (TNF) alpha therapy who was admitted to our rheumatology department complaining of increasing lumbar and buttock pain radiating to the posterior thigh, associated with numbness in the leg, gait disturbance and low-grade fever. The clinical picture was initially interpreted as a flare of disease but was not responsive to treatment. A contrast-enhanced spinal MRI was performed with evidence of a diffuse signal abnormality involving the sacroiliac joints and the spine, with evidence of spondylodiscitis of L5 and with a lesion causing L5-S1 root compression and infiltrating the iliopsoas muscle. These findings confirmed the possibility of a reactivation of disease associated with an infectious process. The most frequent causes of infectious spondylodiscitis were excluded, and a biopsy was then performed. Histological analysis revealed a high-grade B-cell non-Hodgkin\u2019s lymphoma of the spine. This case highlights how a differential diagnosis of low back pain with neurological symptoms can be particularly troublesome in ankylosing spondylitis and that continuous vigilance is warranted in patients treated with long-term immunosuppressive therapies

Early disease control by low-dose prednisone comedication may affect the quality of remission in patients with early rheumatoid arthritis.

In order to identify rate and stability of remission induced by low-dose prednisone comedication in early rheumatoid arthritis (RA), we evaluated patients with early RA (<1 year) who were randomized to receive (P) or not (non-P) low-dose prednisone in association with step-up disease-modifying antirheumatic drug therapy over 2 years. Prevalence and duration of clinical remission were evaluated in the first and second year. Each treatment group included 105 patients; no significant differences were found at baseline. During the first year, P patients achieved higher rates of clinical remission with a time-averaged odds ratio (OR) of 1.965 (CI 95% 1.214-3.182, P= 0.006). Moreover, they showed a higher probability of sustained remission during the second year (OR 4.480, CI 95% 1.354-14.817, P= 0.014). In conclusion, we found as in early RA low-dose prednisone comedication is associated with higher rate of clinical remission, earlier disease activity control and more stable remission over time

Pulmonary hypertension in COPD and lung transplantation : timing and procedures

The prevalence of pulmonary hypertension (PH) in the general chronic obstructive pulmonary disease (COPD) population is undefined because stable COPD patients do not routinely undergo screening echocardiogram and right heart catheterization. Most studies published on this topic are focused on a highly selected group of patients with moderate to severe disease awaiting lung transplantation, since hemodynamic data from cardiac catheterization are part of the standard transplant evaluation. In a very recent article, Hurdman et al. studied the characteristics and outcomes, with a particular focus on mortality, of extensively phenotyped, consecutive patients with PH-COPD over a 9-year period. This article offers the opportunity to update the role of PH in COPD as a timer to propose lung transplantation, based on solid literature data on survival, and to select the best procedure (single or double lung transplant), since the outcome indexes based on the old GOLD classification according to FEV1 (1-4) and the new GOLD classification (A-D) have failed in purpose to define the correct timing, due to the lack of functional (6 minutes walking test) and nutritional (Body Mass Index) data. After a revision of available literature including the recent paper of Hurdman et al. we conclude that the timing for lung transplantation is easy to manage in case of severe PH-COPD. On the other hand mild and moderate PH-COPD are still object of debate for therapy, procedure timing and choice and rehabilitation. In other words, we have some confirms for a little percentage of patients, whilst many doubts still exist for the rest

Atherosclerosis and rheumatoid arthritis: more than a simple association

In the last decades a large amount of evidences linked rheumatoid arthritis (RA) to atherosclerosis. In particular, it is well established that RA patients have an increased risk of cardiovascular events that is not fully explained by smoke and other classic cardiovascular risk factors. In fact, RA and atherosclerosis may share several common pathomechanisms; inflammation undoubtedly plays a primary role in these settings, being involved in the appearance and progression of both diseases. In fact, proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, involved in the pathogenesis of RA, are also independently predictive of subsequent cardiovascular disease (CVD) events in these patients. In RA inflammation may alter HDL constituents and the concentration of LDL and HDL, thus facilitating atherosclerosis and CVD events. On the other hand, also the increase of oxidative processes, frequently observed in RA, may induce atherosclerosis. Interestingly some genetic polymorphisms associated with RA occurrence may enhance atherosclerosis, thus confirming the link between these diseases; however there are some polymorphisms associated with RA susceptibility which do not increase CVD risk; this behavior is a further confirmation that several mechanisms may influence atherosclerotic processes in RA. Moreover, atherosclerosis may be directly mediated also by underlying autoimmune processes, and indirectly by the occurrence of metabolic syndrome and impaired physical activity. Finally, the effects of RA therapies on cardiovascular system in general and on atherosclerosis in particular, are really wide and different. Therefore, RA treatment comprehends drugs that may either increase or reduce CVD. However, the starting point of every RA treatment is that disease control, or better remission, is the best way we have for the reduction of cardiovascular morbidity and mortality in these patients

"Twinning procedure" in lung transplantation: influence of graft ischemia on survival and incidence of complication

Abstract The limited number of suitable lung donors is the major obstacle to clinical application of lung transplantation. The "twinning procedure" may represent one strategy to optimize the use of the small pool of available grafts. From November 1991 to May 2003, 99 single lung transplants (SLTx) were performed including 46 (46%) cases of the "twinning procedure." We divided the study population into two groups: group A (recipients of the "first" lung) and group B (recipients of the "second" lung). The ischemia time was significantly different (A: 216 +/- 48 minutes, B: 310 +/- 89 minutes, P <.001). Differences were not observed in the incidence of graft failure (A: 2, B: 0, P = NS), in the length of mechanical ventilation (A: 12.8 +/- 29.4 days, B: 7.8 +/- 15.2 days, P = NS), or ICU stay (A: 18.8 +/- 50.6 days, B: 15.2 +/- 17.1 days, P = NS), or of hospitalization (A: 37.8 +/- 56.8 days, B: 31.4 +/- 31.7 days, P = NS). Three bronchial anastomotic complications occurred in each group. The incidence of infections (A: 0.015 events/patient/month, B: 0.011 events/patient/month, P = NS) and of treated acute rejections (A: 0.011 events/patient/month, B: 0.011 events/patient/month, P = NS) was similar in the two groups. One-year survival rates were 86% +/- 7% and 72% +/- 10% in group A and B patients, respectively (P = NS). In our experience the different ischemia times related to the twinning procedure did not increase the mortality or morbidity in the early and midterm perio

PEDOT-CNT-coated low-impedance, ultra-flexible, and brain-conformable micro-ECoG arrays.

Electrocorticography (ECoG) is becoming a common tool for clinical applications, such as preparing patients for epilepsy surgery or localizing tumor boundaries, as it successfully balances invasiveness and information quality. Clinical ECoG arrays use millimeter-scale electrodes and centimeter-scale pitch and cannot precisely map neural activity. Higher-resolution electrodes are of interest for both current clinical applications, providing access to more precise neural activity localization, and novel applications, such as neural prosthetics, where current information density and spatial resolution is insufficient to suitably decode signals for a chronic brain-machine interface. Developing such electrodes is not trivial because their small contact area increases the electrode impedance, which seriously affects the signal-to-noise ratio, and adhering such an electrode to the brain surface becomes critical. The most straightforward approach requires increasing the array conformability with flexible substrates while improving the electrode performance using materials with superior electrochemical properties. In this paper, we propose an ultraflexible and conformable polyimide-based micro-ECoG array of sub-millimeter recording sites electrochemically coated with high surface area conductive polymer-carbon nanotube composites to improve their brain-electrical coupling capabilities. We characterized our devices both electrochemically and by recording from rat somatosensory cortex in vivo. The performance of the coated and uncoated electrodes was directly compared by simultaneously recording the same neuronal activity during multiwhisker deflection stimulation. Finally, we assessed the effect of electrode size on the extraction of somatosensory evoked potentials and found that in contrast to the normal high-impedance microelectrodes, the recording capabilities of our low-impedance microelectrodes improved upon reducing their size from 0.2 to 0.1 mm