Catecholamines for inflammatory shock: a Jekyll-and-Hyde conundrum

Catecholamines are endogenous neurosignalling mediators and hormones. They are integral in maintaining homeostasis by promptly responding to any stressor. Their synthetic equivalents are the current mainstay of treatment in shock states to counteract myocardial depression and/or vasoplegia. These phenomena are related in large part to decreased adrenoreceptor sensitivity and altered adrenergic signalling, with resultant vascular and cardiomyocyte hyporeactivity. Catecholamines are predominantly used in supraphysiological doses to overcome these pathological consequences. However, these adrenergic agents cause direct organ damage and have multiple ‘off-target’ biological effects on immune, metabolic and coagulation pathways, most of which are not monitored or recognised at the bedside. Such detrimental consequences may contribute negatively to patient outcomes. This review explores the schizophrenic ‘Jekyll-and-Hyde’ characteristics of catecholamines in critical illness, as they are both necessary for survival yet detrimental in excess. This article covers catecholamine physiology, the pleiotropic effects of catecholamines on various body systems and pathways, and potential alternatives for haemodynamic support and adrenergic modulation in the critically ill

Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

Mobilidade e a rastreabilidade da ferrugem asiática da soja no Brasil.

A ferrugem asiática da soja, causada pelo fungo Phakopsora pachyrhizi possui fácil disseminação e pode causar perdas de 30% à 75% na produção. O monitoramento da ferrugem e sua identificação nos estádios iniciais são essenciais para um controle eficiente (YORINORI, 2005). Afim de permitir uma rápida visualização sobre a dispersão desta doença no Brasil, foi desenvolvida uma versão móvel para a plataforma iOS do sistema Web do Consórcio Antiferrugem. O usuário, com o uso do aplicativo em um iPhone, iPod Touch ou iPad, pode ter acesso às informações sobre a dispersão da doença diretamente no seu dispositivo, a qualquer hora e lugar, podendo perceber a aproximação dos focos da doença na sua região e adiantar-se na procura por sinais de infecção na sua lavoura, evitando grandes perdas na produção. O aplicativo traz como diferencial, além da sua mobilidade, a possibilidade de apresentação de informações completas sobre as ocorrências da doença, registradas por laboratórios conveniados ao consórcio. Permite, também, a rastreabilidade sobre a evolução da doença no decorrer das safras, apresentando pontos geolocalizados para os focos da doença. O aplicativo foi desenvolvido sob uma arquitetura de serviços disponíveis na plataforma Web do Consórcio Antiferrugem. Desde que foi disponibilizado, o aplicativo já foi baixado centenas de vezes por usuários do mundo todo, deixando claro o interesse pelas informações não só por produtores e técnicos brasileiros, mas também pelo mercado comprador de soja. Objetivando proporcionar maior agilidade na disseminação das informações, suporte a tecnologia push, para notificações automáticas, está sendo implementado e disponibilizado na loja de aplicativos da Apple (APPLE, 2011).SBIAGRO

McKean–Vlasov limit for interacting systems with simultaneous jumps

Motivated by several applications, including neuronal models, we consider the McKean–Vlasov limit for a general class of mean-field systems of interacting diffusions characterized by an interaction via simultaneous jumps. We focus our interest on systems where the rate of the jumps is unbounded, which are rarely treated in the mean-field literature, and we prove well-posedness of the McKean–Vlasov limit together with propagation of chaos via a coupling technique. To highlight the role of simultaneous jumps, we introduce an intermediate process which is close to the original particle system but does not display simultaneous jumps. This shows in particular that the simultaneous jumps contribute to the overall rate of convergence of the N-particle empirical measures by a term of order 1/√N

Noise-induced periodicity in a frustrated network of interacting diffusions

We investigate the emergence of a collective periodic behavior in a frustrated network of interacting diffusions. Particles are divided into two communities depending on their mutual couplings. On the one hand, both intra-population interactions are positive; each particle wants to conform to the average position of the particles in its own community. On the other hand, inter-population interactions have different signs: the particles of one population want to conform to the average position of the particles of the other community, while the particles in the latter want to do the opposite. We show that this system features the phenomenon of noise-induced periodicity: in the infinite volume limit, in a certain range of interaction strengths, although the system has no periodic behavior in the zero-noise limit, a moderate amount of noise may generate an attractive periodic law

Strong existence and uniqueness of the stationary distribution for a stochastic inviscid dyadic model

We consider an inviscid stochastically forced dyadic model, where the additive noise acts only on the first component. We prove that a strong solution for this problem exists and is unique by means of uniform energy estimates. Moreover, we exploit these results to establish strong existence and uniqueness of the stationary distribution

Cervical cystic lymphangioma in a young dog: CT findings

Lymphangioma is a rare lymphatic disorder; in veterinary medicine it is still considered a benign tumour, while in human medicine has been recently classified as a Lymphatic Malformation (LM), in fact it probably origins from a failure in development of connections between lympatic and venous system. Reported localizations of canine lymphangioma include skin, subcutaneous and fascial tissue of axilla, limbs, inguinal and mammary regions; lymph nodes; retroperitoneal space; nasopharynx. In the present report we describe the computed tomographic (CT) features of a cervical cystic lymphangioma in a young dog. A 1-year-old intact male Italian Shepherd dog was referred to the primary care veterinarian with a 1-month history of left ventrolateral neck swelling. No other clinical signs were present. Ultrasonographic (US) examination revealed a mass with hyperechoic thick wall, hypoechoic content with hyperechoic fluctuating areas. Fine needle aspiration biopsy (FNAB) revealed a cloudy pinkish fluid, citologically referable to serous-hematic fluid with chronic inflamation. For better assessment of the morphology and of the margins of the lesion, the dog was referred for CT examination. Pre- and post-contrast CT scan of head, neck and thorax were made. A mass located between the muscles of the caudal neck and thoracic/axillary regions (from the level of C4 to the level of T2) was found, which partially occupied the left visceral space of the neck and bulged into the thoracic inlet. The mass was ellipsoid-shaped (40x45x140 mm), with well-defined margins and heterogeneous soft tissue attenuation. It was apparently capsulated, with fluid-like content and soft tissue attenuating septa and small areas within the fluid. Adjacent to the mass three areas of soft tissue mineralization, smoothly marginated, were found. It was responsible for mild mass effect, without significant compression on the surrounding structures. Mild left axillary and left medial retropharyngeal lymphadenomegaly was noted, with normal shape and attenuation of the limph nodes. Post-contrast images showed moderate enhancement of the mass wall and the soft-tissue-attenuating areas/septa within it; no enhancement of the fluid was noted. No other abnormalities were found. The mass was completely surgically excised and submitted for histopathologic analysis, with a definitive diagnosis of cystic lymphangioma. In human literature CT features of lymphangioma are widely described, while in veterinary literature there are no reports about its CT appearance; moreover, human lymphangioma is described as preferentially located in the neck and axillary regions, while, to our knowledge, cervical localization has never been reported before for canine lymphangioma

Anakinra-Dependent Recurrent Pericarditis: The Role of the R202Q Variant of the MEFV Gene

Background: the role of the R202Q (c.605G>A, p.Arg202Gln) missense variant of the MEFV gene has been debated as either a benign polymorphism or a potentially pathogenic mutation. We report and discuss here the case of a young female with corticosteroid-dependent recurrent pericarditis carrying the homozygous R202Q variant, exhibiting distinctive clinical features possibly influenced by this genetic variant. Methods: a 30-year-old woman with a previous diagnosis of cancer and recent respiratory infection presented with severe pleuritic chest pain, hypotension, tachycardia, and fever. Initial diagnostic evaluation indicated cardiac tamponade, and emergent pericardiocentesis was performed. Despite initial treatment with NSAIDs, colchicine, and corticosteroids, the patient experienced multiple recurrences. Genetic testing identified homozygous R202Q variant in the MEFV gene. Given the corticosteroid dependency and recurrent nature of her condition, IL-1 inhibitor anakinra was introduced, leading to significant improvement, although tapering below 150 mg per week failed to prevent recurrences. Results: the introduction of anakinra resulted in rapid symptom relief and resolution of pericardial effusion. However, attempts to taper or discontinue anakinra led to pericarditis recurrences. Ultimately, a maintenance dose of 50 mg every three days was established, which maintained remission for 18 months without recurrence. Despite multiple tapering attempts, further reduction in anakinra dosage was unsuccessful without triggering relapses. Conclusions: the R202Q variant, although typically considered benign, may contribute to an autoinflammatory phenotype resembling familial Mediterranean fever. This case underscores the potential pathogenicity of the homozygous R202Q variant in recurrent pericarditis and its responsiveness to IL-1 inhibition. In patients with corticosteroid-dependent recurrent pericarditis, genetic testing for the R202Q variant should be considered when anti-IL-1 drugs cannot be withdrawn. Further studies are warranted to elucidate the variant’s role in pericardial inflammation and guide personalized treatment strategies

Planar bone scintigraphy and CT findings in dogs with forelimb lameness

Scintigraphy has been used for many years in veterinary medicine, due to its high sensitivity, for the localization of lameness of unknown origin in horses and for the assessment of thyroid/skeletal neoplasia in dogs. In the last few years bone scintigraphy (BS) has become increasingly used in dogs for the localization of occult lameness, when clinical examination and radiographic exam are inconclusive [1]. This study describes BS and computed tomographic (CT) findings in dogs referred for monolateral forelimb obscure lameness, for which a precise localization had not been found by clinical examination nor radiographic exam (no abnormalities at all, mild radiological abnormalities which could not be related to the grade of lameness or symmetrical bilateral alterations). Eight dogs matched inclusion criteria: 3 mixed breed, 1 Bernese mountain dog, 1 Amstaff, 1 Labrador retriever, 1 Australian shepherd and 1 Boxer. BS images showed intense IRU (Increased Radiopharmaceutical Uptake) of elbow joint in 6 cases; these findings coincided to CT alterations of proximal ulna in 5 dogs (mostly located in the medial coronoid process - MCP region: bone density alterations, evidence of fragmentation, new bone formation). In one of these cases, an intense IRU was observed in correspondence of the region of the flexors attachment, with no concurrent abnormalities on CT examination. These findings were suggestive of an obscure form of flexor enthesopathy. In one case we observed diffuse and intense IRU of the carpus joint; this coincided with arthrosis and the presence of a subchondral cyst. One dog showed only mild IRU of the elbow joint, not compatible with the degree of lameness. Because of lack of significant IRU, CT and MRI examination were performed and revealed the presence of an expansive lesion in correspondence of the brachial plexus roots compatible with PNST (Peripheral Nerve Sheath Tumor). BS' high sensitivity allowed the localization of the lameness thanks to the assessment of functional bone state, as already stated in literature [2]. However, its low specificity required additional imaging (CT, MRI), targeted on the region identified on scintigraphic examination. In our experience, the combined use of functional and morphologic diagnostic imaging techniques (bone scintigraphy and computed tomography- magnetic resonance) has been helpful to reach a definitive diagnosis. Further studies, with an increased sample size, are needed to evaluate whether there is a correlation between bone density changes and grade of IRU in limbs affected by different pathologies