Advancements in the Management of Postoperative Air Leak following Thoracic Surgery: From Traditional Practices to Innovative Therapies.

Background: Postoperative air leak (PAL) is a frequent and potentially serious complication following thoracic surgery, characterized by the persistent escape of air from the lung into the pleural space. It is associated with extended hospitalizations, increased morbidity, and elevated healthcare costs. Understanding the mechanisms, risk factors, and effective management strategies for PAL is crucial in improving surgical outcomes. Aim: This review seeks to synthesize all known data concerning PAL, including its etiology, risk factors, diagnostic approaches, and the range of available treatments from conservative measures to surgical interventions, with a special focus on the use of autologous plasma. Materials and Methods: A comprehensive literature search of databases such as PubMed, Cochrane Library, and Google Scholar was conducted for studies and reviews published on PAL following thoracic surgery. The selection criteria aimed to include articles that provided insights into the incidence, mechanisms, risk assessment, diagnostic methods, and treatment options for PAL. Special attention was given to studies detailing the use of autologous plasma in managing this complication. Results: PAL is influenced by a variety of patient-related, surgical, and perioperative factors. Diagnosis primarily relies on clinical observation and imaging, with severity assessments guiding management decisions. Conservative treatments, including chest tube management and physiotherapy, serve as the initial approach, while persistent leaks may necessitate surgical intervention. Autologous plasma has emerged as a promising treatment, offering a novel mechanism for enhancing pleural healing and reducing air leak duration, although evidence is still evolving. Conclusions: Effective management of PAL requires a multifaceted approach tailored to the individual patient's needs and the specifics of their condition. Beyond the traditional treatment approaches, innovative treatment modalities offer the potential to improve outcomes for patients experiencing PAL after thoracic surgery. Further research is needed to optimize treatment protocols and integrate new therapies into clinical practice.

Pathophysiology and Clinical Management of Dyslipidemia in People Living with HIV: Sailing through Rough Seas.

Infections with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst HAART regimens, darunavir and atazanavir, tenofovir disoproxil fumarate, nevirapine, rilpivirine, and especially integrase inhibitors have demonstrated the most favorable lipid profile, emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug-drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates, or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options.

Primary Adrenal Lymphomas with Cushing's Syndrome: Two Cases with Evidence of Endogeneous Cortisol Production by the Neoplastic Lymphoid Cells.

Primary adrenal lymphoma (PAL) is a rare entity that presents as unilateral or bilateral rapidly growing adrenal masses, with signs and symptoms most commonly related to adrenal insufficiency due to the mass effect on the surrounding tissues. Although steroeidogenesis has not been previously described in PAL, we herein report two cases of PAL presenting as adrenal incidentalomas (AIs) that demonstrated autonomous cortisol production. A 52-year-old woman presented with lumbar pain; a computed tomography (CT) scan demonstrated a left AI measuring 8.5 × 15 × 10 cm. Similarly, an 80-year-old woman presented with lumbar pain, demonstrating in a CT scan a bilateral AI (right: 9 × 6.5 cm, left: 3.6 × 3.2 cm). Both cases underwent a full hormonal evaluation according to the algorithm for the investigation of AIs, demonstrating increased 24-h cortisol excretion, suppressed fasting adrenocorticotropic hormone (ACTH) levels, and non-suppressed serum cortisol levels in both the overnight and the low-dose dexamethasone suppression tests, indicating autonomous cortisol secretion and Cushing's syndrome. In a relatively short time, both patients developed night sweats, and their clinical picture deteriorated, while the CT scans showed increased dimensions of the masses with radiological characteristics compatible to lymphoma. Both patients underwent ultrasound-guided biopsies (FNBs), revealing infiltration of the left adrenal by diffuse large B-cell lymphoma in the first case, whereas bilateral adrenal infiltration from the same histological type was noted in the second case. Subsequently, they were treated with immunochemotherapy, but the second patient died from an infection shortly after the initiation of the treatment. To our knowledge, this is the first report of PAL presenting with Cushing's syndrome due to autonomous cortisol production, indicating that neoplastic lymphoid cells in PAL might acquire the potential for steroidogenesis; therefore, more cases of PAL should be analyzed so as to further elucidate the complex pathogenesis and the natural course of this entity.

Mortality due to Multidrug-Resistant Gram-Negative Bacteremia in an Endemic Region: No Better than a Toss of a Coin.

The incidence of multidrug-resistant (MDR) bloodstream infections (BSIs) is associated with high morbidity and mortality. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy in endemic regions. Novel diagnostic tests (RDTs) may facilitate and improve patient management. Data were assessed from patients with MDR Gram-negative bacteremia at a university tertiary hospital over a 12-month period. In total, 157 episodes of MDR Gram-negative BSI were included in the study. The overall mortality rate was 50.3%. Rapid molecular diagnostic tests were used in 94% of BSI episodes. In univariate analysis, age (OR 1.05 (95% CI 1.03, 1.08) p < 0.001), Charlson Comorbidity Index (OR 1.51 (95% CI 1.25, 1.83) p < 0.001), procalcitonin ≥ 1(OR 3.67 (CI 95% 1.73, 7.79) p < 0.001), and monotherapy with tigecycline (OR 3.64 (95% CI 1.13, 11.73) p = 0.030) were the only factors associated with increased overall mortality. Surprisingly, time to appropriate antimicrobial treatment had no impact on mortality. MDR pathogen isolation, other than Klebsiella pneumoniae and Acinetobacter baumanii, was associated with decreased mortality (OR 0.35 (95% CI 0.16, 0.79) p = 0.011). In multivariate analysis, the only significant factor for mortality was procalcitonin ≥ 1 (OR 2.84 (95% CI 1.13, 7.11) p = 0.025). In conclusion, in an endemic area, mortality rates in MDR BSI remain notable. High procalcitonin was the only variable that predicted death. The use of rapid diagnostics did not improve mortality rate.

COVID-19 presenting with persistent hiccup and myocardial infarction in a peritoneal dialysis patient: A case report.

BACKGROUND: Persistent hiccups, lasting more than 48 h, have been described as an atypical presentation of coronavirus disease 19 (COVID-19) in the general population. To the best of our knowledge, this is the first report of persistent hiccups and non-ST elevation myocardial injury (NSTEMI) as an atypical presentation of COVID-19 in a peritoneal dialysis (PD) patient. CASE SUMMARY: A 70-year old man, who had been on PD for 3 years with a history of ischemic heart failure and reduced ejection fraction, presented for a scheduled radionuclide myocardial scan. Upon arrival, he complained of anorexia, nausea for 5 d, and unremitting hiccups for the previous 48 h. Clinical and laboratory examinations revealed an NSTEMI plus a positive nasopharyngeal reverse transcriptase polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2. COVID-19 lung involvement was mild and was resolved without specific treatment. Myocardial injury was managed by coronary catheterization and stenting, while hiccups responded only to baclofen per os. CONCLUSION: Persistent hiccups and NSTEMI can be atypical presentations of COVID-19 in peritoneal dialysis patients, which may be due to involvement of the central nervous system and myocardial injuries.

Escrever-como-sonhar a prática profissional de um coordenador da ULIS: a repetição de uma realidade não sonhada / Escribir-como-soñar la práctica profesional de un coordinador ULIS: la repetición de una realidad no soñada / Writing-as-dreaming the professional practice of an ULIS coordinator: the repetition of an undreamt reality / Écrire-rêver le rapport à la pratique professionnelle d'un coordonnateur d'ULIS college: la répétition d'une réalitéinrêvée

Para minha pesquisa de doutorado, explorei a relação de certos coordenadores das ULIS Colégio (Unidades Localizadas para a Inclusão Escolar -em colégios) com suas próprias práticas profissionais na França. No âmbito do projeto nacional para uma escola inclusiva, os coordenadores das ULIS são professores especializados que oferecem um ensino adaptado a alunos reconhecidos como portadores de necessidades especiais. Eles também implementam o PPS (Projeto Personalizado de Escolarização), concebido para cada aluno, em estreita colaboração com os outros professores e atores médico-sociais. A partir de uma abordagem clínica de orientação psicanalítica em ciências da educação e da formação, quis explorar como os professores especializados que ocupam essa função complexa vivenciam seu quotidiano no plano psíquico. Nessa perspectiva, realizei entrevistas de pesquisa clínica com quatro profissionais. Aqui, exponho o dispositivo de análise das entrevistas implementado no a posteriori e o lugar particular da escrita como modalidade de elaboração psíquica. Inspirado no trabalho de T. Ogden (1994, 2005), o termo "escrever-como-sonhar" designa o devaneio [rêverie] subjacente ao processo de escrita nesse dispositivo, o que permite a representatividade do vínculo entrevistador-entrevistado em relação à prática profissional. Para ilustrar esse ponto, apresento a análise de uma única entrevista com um coordenador de uma ULIS. Mostro precisamente o caminho que me levou à hipótese da atualização de uma realidade "insonhável" (Ogden, 2005) na entrevista, em relação ao vínculo do coordenador com os demais professores do colégio

Para mi investigación de doctorado, exploré la relación de ciertos coordinadores universitarios de ULIS (unidad localizada para la educación inclusiva) con sus propias prácticas profesionales en Francia. Como parte del proyecto nacional por una escuela inclusiva, los coordinadores de ULIS son docentes que ofrecen enseñanza adaptada a alumnos con discapacidad reconocida. También implementan el PPS (proyecto de escolarización personalizada), diseñado para cada alumno, en estrecha colaboración con otros docentes y actores médico-sociales. Desde un enfoque clínico orientado psicoanalíticamente en ciencias de la educación, quise explorar cómo los profesores especializados que ocupan esta función experimentan su vida cotidiana en el nivel psíquico. En esta perspectiva, realicé entrevistas de investigación clínica con cuatro profesionales. Aquí expongo el dispositivo de análisis de las entrevistas y el lugar particular de la escritura como modalidad de elaboración psíquica. Inspirado en el trabajo de T. Ogden (1994, 2005), el término "escribir-como-soñar" designa la ensoñación que subyace al proceso de escritura, que permite la representabilidad del vínculo entrevistador-entrevistado en relación con la práctica profesional. Para ilustrar este punto, presento el análisis de una sola entrevista con un coordinador de ULIS. Precisamente muestro el camino que me llevó a la hipótesis de una realidad "no soñada" (Ogden, 2005) que puede afectar la colaboración del entrevistado con los demás profesores de su facultad

For my PhD research, I explored the relationship of certain ULIS college coordinators (localized unit for inclusive education) to their own professional practices in France. As part of the national project for an inclusive school, coordinators of ULIS are teachers who offer adapted teaching to pupils recognized as having disabilities. They also implement the PPS (personalized schooling project), designed for each pupil, in close collaboration with other teachers and medico-social actors. From a psychoanalytically oriented clinical approach in educational sciences, I wanted to explore how specialized teachers occupying this function experience their everyday life on the psychic level. In this perspective, I conducted clinical research interviews with four professionals. Here, I expose the device of interviews analysis and the particular place of writing as a modality of psychic elaboration. Inspired by the work of T. Ogden (1994, 2005), the term "writing-as-dreaming" designates the reverie underlying the process of writing, which allows representability of the interviewer-interviewee link in relation to the professional practice. To illustrate this point, I present the analysis of a single interview with a ULIS coordinator. I precisely show the path that led me to the hypothesis of an "undreamt" reality (Ogden, 2005) that may affect the interviewee's collaboration with the other teachers of his college

Pour ma recherche doctorale, j'ai exploré le rapport de certains coordonnateurs d'ULIS collège (Unité localisée pour l'inclusion scolaire) à leurs propres pratiques professionnelles en France. Dans le cadre du projet national pour une école inclusive, les coordonnateurs d'ULIS sont des enseignants spécialisésqui proposent un enseignement adapté auprès des élèves reconnus en situation de handicap et mettent en œuvre le PPS (Projet personnalisé de scolarisation), conçu pour chacun d'entre eux, en collaboration étroite avec les autres enseignants et acteurs du médico-social. À partir d'une approche clinique d'orientation psychanalytique en sciences de l'éducation et de la formation, j'ai souhaité explorer comment les enseignants spécialisés occupant cette fonction complexe vivaient leur métier sur le plan psychique. Dans cette perspective, j'ai mené des entretiens cliniques de recherche avec quatre professionnels. Ici, j'expose le dispositif d'analyse des entretiens mis en place dans l'après-coup et la place particulière de l'écriture comme une modalité d'élaboration psychique. Inspiré des travaux de T. Ogden (1994, 2005), le terme « écrire-rêver ¼ désigne la rêverie sous-tendant le processus de l'écriture dans ce dispositif, qui permet la représentabilité du lien interviewer-interviewé en rapport avec la pratique professionnelle. Pour illustrer ce propos, je présente l'analyse d'un seul entretien avec un coordonnateur, en restituant le chemin qui m'a amené à l'hypothèse de l'actualisation d'une réalité «inrêvée¼ (Ogden, 2005) dans l'entretien en rapport avec son lien aux autres enseignants du collège

Lipoprotein-Associated Phospholipase A2: A Novel Contributor in Sjögren's Syndrome-Related Lymphoma?

Background: B-cell non-Hodgkin's lymphoma (B-NHL) is one of the major complications of primary Sjögren's syndrome (SS). Chronic inflammation and macrophages in SS minor salivary glands have been previously suggested as significant predictors for lymphoma development among SS patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2)-a product mainly of tissue macrophages-is found in the circulation associated with lipoproteins and has been previously involved in cardiovascular, autoimmune, and malignant diseases, including lymphoma. Objective: The purpose of the current study was to investigate the contributory role of Lp-PLA2 in B-NHL development in the setting of primary SS. Methods: Lp-PLA2 activity in serum samples collected from 50 primary SS patients with no lymphoma (SS-nL), 9 primary SS patients with lymphoma (SS-L), and 42 healthy controls (HC) was determined by detection of [3H]PAF degradation products by liquid scintillation counter. Moreover, additional sera from 50 SS-nL, 28 SS-L, and 32 HC were tested for Lp-PLA2 activity using a commercially available ELISA kit. Lp-PLA2 mRNA, and protein expression in minor salivary gland (MSG) tissue samples derived from SS-nL, SS-L patients, and sicca controls (SC) were analyzed by real-time PCR, Western blot, and immunohistochemistry. Results: Serum Lp-PLA2 activity was significantly increased in SS-L compared to both SS-nL and HC by two independent methods implemented [mean ± SD (nmol/min/ml): 62.0 ± 13.4 vs 47.6 ± 14.4 vs 50.7 ± 16.6, p-values: 0.003 and 0.04, respectively, and 19.4 ± 4.5 vs 15.2 ± 3.3 vs 14.5 ± 3.0, p-values: <0.0001, in both comparisons]. ROC analysis revealed that the serum Lp-PLA2 activity measured either by radioimmunoassay or ELISA has the potential to distinguish between SS-L and SS-nL patients (area under the curve [AUC]: 0.8022, CI [95%]: 0.64-0.96, p-value: 0.004 for radioimmunoassay, and AUC: 0.7696, CI [95%]: 0.66-0.88, p-value: <0.0001, for ELISA). Lp-PLA2 expression in MSG tissues was also increased in SS-L compared to SS-nL and SC at both mRNA and protein level. ROC analysis revealed that both MSG mRNA and protein Lp-PLA2 have the potential to distinguish between SS-nL and SS-L patients (area under the curve [AUC] values of 0.8490, CI [95%]: 0.71-0.99, p-value: 0.0019 and 0.9444, CI [95%]: 0.79-1.00, p- value: 0.0389 respectively). No significant difference in either serum Lp-PLA2 activity or MSG tissue expression was observed between SS-nL and HC. Conclusions: Lp-PLA2 serum activity and MSG tissue mRNA/protein expression could be a new biomarker and possibly a novel therapeutic target for B-cell lymphoproliferation in the setting of SS.

Feasibility of non-invasive measurement of central blood pressure and arterial stiffness in shock.

BACKGROUND: Patients in haemodynamic shock are in need for an intensive care treatment. Invasive haemodynamic monitoring is state of the art for these patients. However, evolved, non-invasive blood pressure monitoring devices offer advanced functions like the assessment of central blood pressure and arterial stiffness. We analysed the feasibility of two oscillometric blood pressure devices in patients with shock. METHODS: We performed a monocentre prospective study, enrolling 57 patients admitted to the intensive care unit (ICU), due to septic and/or cardiogenic shock. We assessed invasive and non-invasive peripheral and central blood pressure <24 hours and 48 hours after admission on the ICU. Additional haemodynamic parameters such as pulse wave velocity (PWV), augmentation pressure and augmentation index were obtained through Mobil-o-Graph PWA (IEM) and SphygmoCor XCEL (AtCor Medical). RESULTS: A complete haemodynamic assessment was successful in all patients (48) with the Mobil-o-Graph 24 hours PWA and in 29 patients with the SphygmoCor XCEL (P = .001), when cases of death or device malfunction were excluded. Reasons for failure were severe peripheral artery disease, haemodynamic instability, oedema and agitation. Invasive blood pressure showed a sufficient correlation with both devices; however, large differences between invasive and non-invasive techniques were recorded in Bland-Altmann analysis (P < .05 for all parameters). PWV differed between the two devices. CONCLUSION: Non-invasive peripheral blood pressure measurement remains a rescue technique. However, non-invasive assessment of arterial stiffness and central blood pressure is possible in patients with septic or cardiogenic shock. Further studies are required to assess their clinical significance for patients in shock.

Red Blood Cell Abnormalities as the Mirror of SARS-CoV-2 Disease Severity: A Pilot Study.

PURPOSE: Unraveling the pathophysiology of COVID-19 disease is of crucial importance for designing treatment. The purpose of this study is to investigate the effects of the disease on erythrocytes (RBCs) and to correlate the findings with disease severity. MATERIALS AND METHODS: Hospitalized patients (n = 36) with COVID-19 and control group of healthy volunteers (n = 18) were included in the study. Demographic data, clinical, laboratory and chest Computed Tomography (CT) findings at time of admission were recorded. Laboratory measurements included: Hemoglobin (H b), indirect billirubin, LDH, D-Dimers, and plasma free hemoglobin (plasma free-Hb). On RBCs were performed: osmotic fragility (MCF), Free-Hb after mechanical stress (Free-Hb-MECH), intracellular RBC concentration of calcium ions (iCa2+), intracellular ROS (iROS), G6PD, intracellular active caspase-3 (RBC-caspase-3), IgG immunoglobulins (RBC-IgGs), which are bound on RBCs' senescent neo-antigen proteins and RBC surface phosphatidylserine (RBC-PS). RESULTS: The percentage of males was 50 and 66% and the mean age was 65.16 ± 14.24 and 66.33 ± 13.48 years among patients and controls respectively (mean ± SD, p = 0.78). Upon admission patients' PO2/FiO2 ratio was 305.92 ± 76.75 and distribution of infiltration extend on chest CT was: 0-25% (N = 19), 25-50%: (N = 7), and 50-75% (N = 9). Elevated hemolysis markers (LDH and plasma free-Hb) were observed in patients compared to the control group. Patients' RBCs were more sensitive to mechanical stress, and exhibited significantly elevated apoptotic markers (iCa2+, RBC-PS). Plasma free Hb levels correlated with the extend of pulmonary infiltrates on chest CT in COVID-19 patients. Surprisingly, patients' RBC-iROS were decreased, a finding possibly related with the increased G6PDH levels in this group, suggesting a possible compensatory mechanism against the virus. This compensatory mechanism seemed to be attenuated as pulmonary infiltrates on chest CT deteriorated. Furthermore, RBC-IgGs correlated with the severity of pulmonary CT imaging features as well as the abnormality of lung function, which are both associated with increased disease severity. Lastly, patients' D-Dimers correlated with RBC surface phosphatidylserine, implying a possible contribution of the red blood cells in the thrombotic diathesis associated with the SARS-CoV-2 disease. CONCLUSION: This pilot study suggests that SARS-CoV-2 infection has an effect on red blood cells and there seems to be an association between RBC markers and disease severity in these patients.

Competing Effects of Renin Angiotensin System Blockade and Sodium-Glucose Cotransporter-2 Inhibitors on Erythropoietin Secretion in Diabetes.

BACKGROUND: Anaemia is a common finding in diabetes, particularly in those patients with albuminuria or renal dysfunction and is associated with impaired erythropoietin (EPO) secretion. This review focuses on mechanisms involved in the regulation of erythropoiesis in diabetic patients in an effort to elucidate the competing effects of the renin angiotensin system (RAS) blockade and sodium-glucose cotransporter-2 (SGLT2) inhibitors on haemoglobin concentration and hematocrit values. SUMMARY: The RAS shows significant activation in diabetic subjects. Angiotensin II, its active octapeptide, causes renal tubulointerstitial hypoxia, which stimulates hypoxia-inducible factors (HIF) and increases EPO secretion and erythropoiesis. As expected, drugs that inactivate RAS, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB) are associated with a significant hematocrit-lowering effect and/or anaemia in various clinical conditions, including diabetes. Dual blockade by a combination of ACEi and ARB in diabetic patients achieves a better RAS inhibition, but at the same time a worse drop of haemoglobin concentration. Increased glucose reabsorption by SGLTs in diabetic subjects generates a high-glucose environment in renal tubulointerstitium, which may impair HIF-1, damage renal erythropoietin-producing cells (REPs) and decrease EPO secretion and erythropoiesis. SGLT2 inhibitors, which inhibit glucose reabsorption, may attenuate glucotoxicity in renal tubulointerstitium, allowing REPs to resume their function and increase EPO secretion. Indeed, EPO levels increase within a few weeks after initiation of therapy with all known SGLT2 inhibitors, followed by increased reticulocyte count and a gradual elevation of haemoglobin concentration and hematocrit level, which reach zenith values after 2-3 months. Key Messages: The competing effects of RAS blockade and SGLT2 inhibitors on erythropoiesis may have important clinical implications. The rise of hematocrit values by SGLT2 inhibitors given on top of RAS blockade in recent outcome trials may significantly contribute to the cardiorenal protection attained. The relative contribution of each system to erythropoiesis and outcome remains to be revealed in future studies.

An Engineered E.†coli Strain for Direct in Vivo Fluorination.

Selectively fluorinated compounds are found frequently in pharmaceutical and agrochemical products where currently 25-30 % of optimised compounds emerge from development containing at least one fluorine atom. There are many methods for the site-specific introduction of fluorine, but all are chemical and they often use environmentally challenging reagents. Biochemical processes for C-F bond formation are attractive, but they are extremely rare. In this work, the fluorinase enzyme, originally identified from the actinomycete bacterium Streptomyces cattleya, is engineered into Escherichia coli in such a manner that the organism is able to produce 5'-fluorodeoxyadenosine (5'-FDA) from S-adenosyl-l-methionine (SAM) and fluoride in live E. coli cells. Success required the introduction of a SAM transporter and deletion of the endogenous fluoride efflux capacity in order to generate an E. coli host that has the potential for future engineering of more elaborate fluorometabolites.

The Endothelial Glycocalyx as a Key Mediator of Albumin Handling and the Development of Diabetic Nephropathy.

The endothelial glycocalyx is a complex mesh of proteoglycans, glycoproteins and other soluble components, which cover the vascular endothelium. It plays an important role in many physiological processes including vascular permeability, transduction of shear stress and interaction of blood cells and other molecules with the vascular wall. Its complex structure makes its precise assessment challenging, and many different visualization techniques have been used with varying results. Diabetes, one of the main disease models where disorders of the glycocalyx are present, causes degradation of the glycocalyx through a variety of molecular pathways and especially through oxidative stress due to the action of reactive oxygen species. As the glycocalyx has been primarily studied in the glomerular endothelium, more evidence points towards a vital role in albumin handling and, consequently, in diabetic nephropathy. Therefore, the maintenance or restoration of the integrity of the glycocalyx seems a promising therapeutic target. In this review, we consider the structural and functional capacities of the endothelial glycocalyx, the available methods for its evaluation, the mechanisms through which diabetes leads to glycocalyx degradation and albuminuria, and possible treatment options targeting the glycocalyx.

Effect of Nebivolol and Olmesartan on 24-Hour Brachial and Aortic Blood Pressure in the Acute Stage of Ischemic Stroke.

BACKGROUND: Elevated blood pressure (BP) in the acute phase of ischemic stroke is associated with heightened risk of early disability and death. However, whether BP-lowering in this setting is beneficial and the exact levels at which BP should be targeted remain unclear. This study aimed to evaluate the effect of nebivolol, olmesartan, and no-treatment on 24-hour BP in patients with hypertension during the acute poststroke period. METHODS: In a single-blind fashion, 60 patients with acute ischemic stroke and clinic systolic BP (SBP) 160-220 mmHg were randomized to nebivolol (5 mg/day), olmesartan (20 mg/day), or no-treatment between Day 4 and Day 7 of stroke onset. BP-lowering efficacy was assessed through 24-hour BP monitoring using the Mobil-O-Graph device (IEM, Germany). RESULTS: Between baseline and Day 7, significant reductions in 24-hour brachial SBP were noted with nebivolol and olmesartan, but not with no-treatment. Change from baseline (CFB) in 24-hour brachial SBP was not different between nebivolol and olmesartan groups (between-group difference: -3.4 mmHg; 95% confidence interval (CI): -11.2, 4.3), whereas nebivolol was superior to no-treatment in lowering 24-hour brachial SBP (between-group difference: -7.8 mmHg; 95% CI: -7.8 mmHg; 95% CI: -15.6, -0.1). Similarly, nebivolol and olmesartan equally lowered 24-hour aortic SBP (between-group difference: -1.9 mmHg; 95% CI: -10.1, 6.2). Nebivolol and olmesartan provoked similar reductions in 24-hour heart rate-adjusted augmentation index and pulse wave velocity. CONCLUSION: This study suggests that during the acute phase of ischemic stroke, nebivolol is equally effective with olmesartan in improving 24-hour aortic pressure and arterial stiffness indices. ClinicalTrials.gov identifier number: NCT03655964.

Continuous Subcutaneous Insulin Infusion Initiation Is Associated With Blood Pressure Reduction in Adults With Type 1 Diabetes.

BACKGROUND: In type 1 diabetes (T1D) continuous subcutaneous insulin infusion (CSII) use has been associated with lower risks for mortality and diabetes-related complications when compared to multiple daily injections. There are limited data on the effect of CSII on blood pressure (BP). We aimed to evaluate the relationship between CSII initiation and BP changes. METHODS: We performed a retrospective, single-center, observational study including all adults with T1D who initiated CSII between 2001 and 2014. Mean systolic BP levels were calculated from values obtained up to 15 months before and up 15 months after CSII initiation. RESULTS: We studied 436 adults (46% male; mean [95% CI] age: 45 [36, 54] years, duration of diabetes: 20.3 [19.1, 21.5] years). CSII was associated with the following changes (post minus pre CSII levels) in mean (95% CI) SBP and DBP levels, respectively: whole cohort (N = 436): -2 (-1, -3), P < .001 and -2 (-1, -2), P < .001; those taking stable antihypertensive medication (n = 118): -4 (-6, -2), P < .001 and -2 (-3, -1), P < .001; antihypertensive treatment-naïve patients (n = 279): -1 (-2, 0), P = .147 and -1 (-2, 0), P = .002. In multivariate regression analysis including age, sex, diabetes duration, pre-CSII BP, HbA1c and weight changes, only pre-CSII BP showed an independent association with BP drop in all patients' groups. Once adjusted for pre-CSII BP there was no significant difference between those on antihypertensive drugs and antihypertensive treatment-naïve individuals. CONCLUSIONS: We showed BP reduction in association with CSII therapy particularly in those on antihypertensive medication. These original findings may partly explain the cardiovascular and mortality benefits associated with CSII therapy.

Effects of late cyclosporine withdrawal on renal graft function and survival.

OBJECTIVE: Attempts to discontinue calcineurin inhibitors (CNIs) early after renal transplantation without conversion to an alternative immunosuppressive have failed due to high rates of acute rejection. Data on "late" CNI withdrawal are lacking so far. DESIGN AND METHOD: We carried out a matched case-control study on the effects of CNI withdrawal on graft loss and mortality in 90 patients (1500 screened) with advanced graft dysfunction (serum creatinine > 3.5 mg/dl) and a cyclosporine-based triple immunosuppressive regimen at the Charité University Hospital, Berlin. RESULTS: Cyclosporine was withdrawn at a mean of 54.0 ± 32.8 months post-transplant in 45 subjects. Whereas estimated glomerular filtration rate (eGFR) did not significantly differ between the groups at this time (12.4 ± 2.7 vs. 14.7 ± 8.9 in the control group, p = 0.08), it was significantly higher in subjects undergoing withdrawal after 120 months (Δ 4.1 ml/min; p < 0.001). In a Cox regression analysis adjusted for age, gender and eGFR, patients with CNI withdrawal showed better survival rates for the combined endpoint death/graft loss (hazard ratio, HR [95% confidence interval]: 0.19 [0.12-0.33], p = 0.001) compared to matched controls. The survival benefit was significant for the endpoints death (p = 0.01) and graft loss (p = 0.001). CONCLUSIONS: CNI withdrawal was associated with improved survival rates in patients with advanced graft dysfunction in this retrospective analysis.

The impact of blood pressure variability and pulse pressure on graft survival and mortality after kidney transplantation.

BACKGROUND: Blood pressure variability and pulse pressure are strong and independent predictors of cardiovascular morbidity and mortality in the general population. So far, there are no data on the impact of blood pressure variability on mortality and graft survival after renal transplantation. METHODS: We performed a retrospective analysis of 877 patients who underwent kidney transplantation between 1997 and 2011 in two transplant centers in Germany (Berlin and Bochum) with a follow-up of 12-266 months. Visit-to-visit blood pressure variability over the first 12 months after transplantation (3 visits) and during the first 120 months after transplantation (7 visits) was calculated as the coefficient of variation (CV = standard deviation (SD)/mean blood pressure). Patient and graft survival was defined as composite endpoint. RESULTS: Cumulative survival was significantly higher for those patients with lower systolic blood pressure and pulse pressure within both the first 12 months and the 120 months posttransplant. After adjustment of data for gender, age, body mass index, and coronary artery disease, the cumulative incidence of the combined endpoint did not significantly differ between patients with lower vs higher CV (12 months CV hazard ratio (HR) (95% CI) = 0.90 (0.66-1.23), P = 0.51; 120 months CV HR (95% CI) = 0.92 (0.67-1.26), P = 0.60). A lower systolic blood pressure remained highly predictive for better survival in adjusted analyses. CONCLUSION: Visit-to-visit blood pressure variability is not associated with mortality or graft loss after kidney transplantation in this retrospective analysis. In analogy to the general population, however, there is an inverse relationship of survival and pulse pressure as a marker of arterial stiffness.

Local Antibiotic Delivery Systems: Current and Future Applications for Diabetic Foot Infections.

Foot infections are common among diabetic patients with peripheral neuropathy and/or peripheral arterial disease, and it can be the pivotal event leading to a minor or major amputation of the lower extremity. Treatment of diabetic foot infections, especially deep-seated ones, remains challenging, in part because impaired blood perfusion and the presence of biofilms can impair the effectiveness of systemic antibiotics. The local application of antibiotics is an emerging field in the treatment of diabetic foot infections, with demonstrable advantages. These include delivery of high concentrations of antibiotics in the affected area, limited systemic absorption, and thus negligible side effects. Biodegradable vehicles, such as calcium sulfate beads, are the prototypical system, providing a good elution profile and the ability to be impregnated with a variety of antibiotics. These have largely superseded the nonbiodegradable vehicles, but the strongest evidence available is for calcium bead implantation for osteomyelitis management. Natural polymers, such as collagen sponge, are an emerging class of delivery systems, although thus far, data on diabetic foot infections are limited. There is recent interest in the novel antimicrobial peptide pexiganan in the form of cream, which is active against most of the microorganisms isolated in diabetic foot infections. These are promising developments, but randomized trials are required to ascertain the efficacy of these systems and to define the indications for their use. Currently, the role of topical antibiotic agents in treating diabetic foot infections is limited and outside of routine practice.

Aortic Valve Replacement as a Trigger of Atypical Hemolytic Uremic Syndrome.

Mechanical hemolysis is a frequent but usually harmless complication of aortic valve replacement. The most common reason is valvular leakage. This report presents atypical hemolytic uremic syndrome (aHUS) as an alternative cause of mechanical hemolysis after this procedure. aHUS is a complement-mediated disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. It necessitates immediate specific treatment including plasma exchange or complement inhibition to avoid an adverse outcome. The present case identifies aortic valve replacement as a trigger of aHUS and shows that this disease must be taken into account in the differential diagnosis of hemolysis after valve surgery.