Drug-Coated Balloon for the Treatment of Long-Segment Femoropopliteal Artery Disease: Pooled Analysis from the BIOLUX P-III SPAIN and BIOLUX P-III All-Comers Registry Long Lesion Subgroup.

PURPOSE: To investigate the clinical performance and safety of the Passeo-18 Lux drug-coated balloon (DCB) in complex femoropopliteal Trans-Atlantic Inter-Society Consensus (TASC) C and D lesions in an all-comers patient population. MATERIAL AND METHODS: Data from BIOLUX P-III SPAIN, a prospective, national, multicenter, postmarket all-comers registry conducted from 2017 to 2019, and a matching long lesion subgroup from the BIOLUX P-III All-Comers global registry conducted from 2014 to 2018 were pooled for analysis. The primary safety end point was freedom from major adverse events (MAEs) at 6 months, and the primary performance end point was freedom from clinically driven target lesion revascularization (fCD-TLR) at 12 months, both adjudicated by an independent clinical events committee. RESULTS: A total of 159 patients, of whom 32.7% had critical limb ischemia, were included in the Passeo-18 Lux long lesion cohort. The mean lesion length was 248.5 mm ± 71.6, and the majority were occluded (54.1%), calcified (87.4%), and of type TASC C (49.1%) or TASC D (50.9%). Freedom from MAEs was 90.6% (95% CI, 84.6-94.3) at 6 months and 83.9% (95% CI, 76.7-89.0) at 12 months. fCD-TLR was 84.4% (95% CI, 77.3-89.5) at 12 months. Freedom from target limb major amputation was 98.6% (95% CI, 94.6-99.7), and all-cause mortality was 5.3% (95% CI, 2.7-10.4) at 12 months. There were no device- or procedure-related deaths or amputations up to the 12-month follow-up. CONCLUSION: Passeo-18 Lux DCB is safe and effective for the treatment of long femoropopliteal lesions in a real-word setting.

A case of co-infection with malaria and chikungunya in a returning traveler from Nigeria.

Due to globalization, physicians have to be prepared with knowledge and understanding of cases and diseases from all over the world. Vector-borne diseases are a particular group of diseases for which the clinician should be prepared, especially in the context of returning travelers with tropical fever, as the symptoms are very similar among some of the pathogens. In this report we present a case of a returning traveler from Nigeria with fever as her chief complaint and with a final diagnosis of malaria and chikungunya. We discuss how co-infection with different pathogens could change the natural history or modify the clinical course of the disease.

Long-Term Clinical and Ecological Impact of an Antimicrobial Stewardship Program on the Incidence of Carbapenem-Resistant Klebsiella pneumoniae Infections in a High-Endemic Hospital.

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is currently a serious global concern. Antimicrobial stewardship programs (ASPs) are one of the key strategies to overcome this resistance. However, evidence about the long-term clinical and ecological impacts of ASPs is scarce. A multidisciplinary team conducted a multifaceted intervention in a CR-Kp endemic hospital over a 6-year period. We assessed the monthly long-term impacts of ASPs on carbapenem use, incidence density (ID), and crude death rates of hospital-acquired CR-Kp infections. Other variables potentially related to CR-Kp incidence and healthcare activity indicators were monitored. Carbapenem use showed a sustained reduction over the long term, with a difference of -66.19% (95% CI -87.03 to -45.34) between the expected pre-intervention trend consumption value and that obtained six years after starting the program. The ID of CR-Kp also decreased significantly and was maintained over the long term, with a relative reduction of -88.14% (95% CI; -100.4 to -75.85) at the end of the study period. The crude death rate of CR-Kp at 14 and 28 days decreased significantly after the intervention and remained steady after six years. Infection control indicator trends remained stable. This mixed ASP contributed to reducing the high incidence of infections and mortality rates of CR-Kp, achieving a sustained ecological and clinical effect.

Multicentre study of ceftazidime/avibactam for Gram-negative bacteria infections in critically ill patients.

This study aimed to assess the efficacy of ceftazidime/avibactam (C/A) in the treatment of infections due to Gram-negative bacteria (GNB) in critically ill patients. A multicentre, retrospective, observational study was conducted in critically ill patients receiving C/A for GNB infections. We evaluated demographic data, localisation and severity of infection, clinical and microbiological outcomes, and mortality. A total of 68 patients received C/A for serious GNB infections. The main infections were respiratory (33.8%), intra-abdominal (22.1%) and urinary tract infections (10.3%); bacteraemia was found in 22 cases (32.4%). Most infections were complicated by septic shock (58.8%) or sepsis (36.8%) and most of them required life-supporting therapies. Enterobacterales (79.4%) and Pseudomonas aeruginosa (19.1%) were the most frequently isolated bacteria; 84.2% of isolates were carbapenem-resistant. Thirty-four patients (50.0%) received C/A in combination with other antimicrobials. Fifty patients (73.5%) presented a favourable clinical response. Microbiological eradication was documented in 25 cases (36.8%). No significant differences were found in clinical response between patients treated with monotherapy or combined therapy (79.4% vs. 67.6%; P = 0.27). Overall intensive care unit (ICU) mortality was 41.2%. Univariate analysis showed that 30-day all-cause mortality was significantly (P < 0.05) associated with bacteraemia, previous corticosteroid use and the need of life-supporting therapies. C/A appears to be an effective therapy for severe infections due to GNB, including carbapenem-resistant isolates, in critically ill patients. C/A combination therapy was not associated with a higher clinical response. Mortality correlated significantly with the presence of bacteraemia, previous corticosteroid use and the need for life-supporting therapies.

The impact of climate change on neglected tropical diseases: a systematic review.

Neglected tropical diseases (NTDs) are a diverse group of diseases that continue to affect >1 billion people, with these diseases disproportionately impacting vulnerable populations and territories. Climate change is having an increasing impact on public health in tropical and subtropical areas and across the world and can affect disease distribution and transmission in potentially diverse ways. Improving our understanding of how climate change influences NTDs can help identify populations at risk to include in future public health interventions. Articles were identified by searching electronic databases for reports of climate change and NTDs between 1 January 2010 and 1 March 2020. Climate change may influence the emergence and re-emergence of multiple NTDs, particularly those that involve a vector or intermediate host for transmission. Although specific predictions are conflicting depending on the geographic area, the type of NTD and associated vectors and hosts, it is anticipated that multiple NTDs will have changes in their transmission period and geographic range and will likely encroach on regions and populations that have been previously unaffected. There is a need for improved surveillance and monitoring to identify areas of NTD incursion and emergence and include these in future public health interventions.

Applying a One Health Approach in Global Health and Medicine: Enhancing Involvement of Medical Schools and Global Health Centers.

Background: Multidisciplinary and multisectoral approaches such as One Health and related concepts (e.g., Planetary Health, EcoHealth) offer opportunities for synergistic expertise to address complex health threats. The connections between humans, animals, and the environment necessitate collaboration among sectors to comprehensively understand and reduce risks and consequences on health and wellbeing. One Health approaches are increasingly emphasized for national and international plans and strategies related to zoonotic diseases, food safety, antimicrobial resistance, and climate change, but to date, the possible applications in clinical practice and benefits impacting human health are largely missing. Methods: In 2018 the "Application of the One Health Approach to Global Health Centers" conference held at the Albert Einstein College of Medicine convened experts involved in One Health policy and practice. The conference examined issues relevant to One Health approaches, sharing examples of challenges and successes to guide application to medical school curricula and clinical practice for human health. This paper presents a synthesis of conference proceedings, framed around objectives identified from presentations and audience feedback. Findings and Recommendations: The following objectives provide opportunities for One Health involvement and benefits for medical schools and global health centers by: 1) Improving One Health resource sharing in global health and medical education; 2) Creating pathways for information flow in clinical medicine and global health practice; 3) Developing innovative partnerships for improved health sector outcomes; and 4) Informing and empowering health through public outreach. These objectives can leverage existing resources to deliver value to additional settings and stakeholders through resource efficiency, more holistic and effective service delivery, and greater ability to manage determinants of poor health status. We encourage medical and global health educators, practitioners, and students to explore entry points where One Health can add value to their work from local to global scale.

Median raphe cyst. Report of two cases and literature review.

OBJECTIVES: To report 2 cases of median raphe cysts, 1 in the penis and the other in the perineum. METHOD: Two cases of median raphe cyst are described; the first was treated by surgery and the second required no treatment. RESULTS: The surgical patient experienced no complications and was asymptomatic with no recurrence at 2 years. CONCLUSIONS: Median raphe cysts are a rare, benign condition of uncertain etiology. Treatment consists on simple excision.

The diagnostic and prognostic value of paraoxonase-1 and butyrylcholinesterase activities compared with acute-phase proteins in septic dogs and stratified by the acute patient physiologic and laboratory evaluation score.

BACKGROUND: Sepsis is a complex syndrome that involves an increased oxidative stress status and dysregulation of cholinergic neurotransmission. Paraoxonase-1 (PON-1) and butyrylcholinesterase (BChE) activities have been identified as significant biomarkers to monitor such disorders in human septic patients. OBJECTIVE: We aimed to determine the diagnostic and prognostic value of PON-1 and BChE vs other traditional acute-phase proteins such as albumin (ALB) and C-reactive protein (CRP) in septic dogs. METHODS: This prospective observational study included 20 dogs with a diagnosis of sepsis, 27 with low-grade systemic inflammation (LGSI), and 10 healthy dogs that served as controls. Plasma samples were obtained from all dogs for analysis on admission, and then every 24-48 hours until discharge or death in the septic group. RESULTS: Dogs with sepsis had lower PON-1 activity compared with dogs in the LGSI group (1.1 ± 0.10 vs 1.6 ± 0.08 U/mL, P = .002), but no differences in BChE activity were detected between the groups. PON-1, ALB, and CRP could successfully discriminate healthy animals from those with sepsis looking at the area under the curve (AUC) of the receiver operator characteristics curves (ROCs), which were 0.828, 0.903 and 1.000, respectively. Finally, although no differences were found among the groups for PON-1 or BChE activity, the nonsurvivor septic dogs had higher CRP (P = .002), lower ALB (P = .025) levels, and tended to have lower PON-1 (P = .082) activities than the survivors at patient death or discharge. CONCLUSION: Septic dogs showed lower plasma PON-1 and higher BChE activities, but only PON-1 activity correlated with disease severity. Further studies are warranted to describe the usefulness of these new biomarkers of sepsis progression and recovery in dogs.

Increased renal vascular resistance in dogs with hepatic disease.

Doppler ultrasound is a non-invasive technique that can be used to estimate vascular resistance by calculation of resistive index (RI) and pulsatility index (PI). Liver disease may increase renal RI and PI, and in humans with liver disease the indices are monitored to attain prognostic information. Systemic hypertension has been found in dogs with hepatic disease and is also related to increased renal vascular resistance in humans. The aim of this study was to examine renal vascular resistance increases in dogs with hepatic disease and to ascertain whether these may be related to blood pressure increases and biochemical parameters. Twenty dogs with hepatic disease were evaluated. The mean renal RI, PI, and systolic blood pressure were significantly higher than in normal animals. A positive correlation was found between the indices and alkaline phosphatase but not with systolic blood pressure. It is concluded that renal vascular resistance may increase in dogs with hepatic disease and in this study was above the limit value in 50% of the animals.

Climate change and One Health.

The journal The Lancet recently published a countdown on health and climate change. Attention was focused solely on humans. However, animals, including wildlife, livestock and pets, may also be impacted by climate change. Complementary to the high relevance of awareness rising for protecting humans against climate change, here we present a One Health approach, which aims at the simultaneous protection of humans, animals and the environment from climate change impacts (climate change adaptation). We postulate that integrated approaches save human and animal lives and reduce costs when compared to public and animal health sectors working separately. A One Health approach to climate change adaptation may significantly contribute to food security with emphasis on animal source foods, extensive livestock systems, particularly ruminant livestock, environmental sanitation, and steps towards regional and global integrated syndromic surveillance and response systems. The cost of outbreaks of emerging vector-borne zoonotic pathogens may be much lower if they are detected early in the vector or in livestock rather than later in humans. Therefore, integrated community-based surveillance of zoonoses is a promising avenue to reduce health effects of climate change.

Climate change and infectious diseases.

Global changes are major determinants for infectious diseases, although attributable, part of climate change remains debatable. Vector-borne diseases are prone to be impacted by global warming, although other factors may play a substantial role, evidenced by the dramatic decrease in malaria in the last decades in places where climate change has deep and significant effects. There is now evidence that in some areas of the world, e.g. Horn of Africa, warm El Niño Southern Oscillations (ENSO), which are observed in the South Pacific Ocean, are associated with higher risk of emergence of Rift Valley fever, cholera and malaria and during cold La Niña events, dengue fever, chikungunya and yellow fever. This has been observed for these and other diseases in other parts of the world. For example, seasonal influenza outbreaks have been more intense (i.e. higher number) and more severe (i.e. higher mortality) when concomitant with La Niña events. Since climate scientists have recently observed that climate change is tied to more frequent and more intense ENSO events, we may foresee increases in frequency and severity in emerging infectious diseases in the world.

Septic arthritis by Sphingobacterium multivorum in imunocompromised pediatric patient. / Artrite séptica por Sphingobacterium multivorum em paciente pediátrico imunossuprimido.

OBJECTIVE: To report a case septic arthritis with a rare pathogen in a immunosuppressed child. CASE DESCRIPTION: Male patient, 6 years old, had liver transplant 5 and half years ago due to biliary atresia. Patient was using tacrolimus 1mg q.12hours. This patient started to have pain in left foot and ankle and had one episode of fever 3 days before hospital admission. Physical Examination showed weight 17kg, height 109cm, temperature 36,4°C, with pain, swelling and heat in the left ankle, without other clinical signs. Initial tests: hemoglobin 11,7g/dL hematocrit 36.4%, leukocyte count 17600/uL (7% banded neutrophils, 70% segmented neutrophils, 2% eosinophils, basophils 1%, 13% lymphocytes, 7% monocytes) C-reactive protein 170,88mg/L. Joint ultrasound showed moderate effusion in the site. Patient was submitted to surgical procedure and S. multivorum was isolated from the effusion. The germ was susceptible to broad spectrum cephalosporins (ceftriaxone and cefepime) and fluoroquinolones (ciprofloxacin and levofloxacin), and it was resistant to carbapenemic antibiotics and aminoglycosides. He was treated intravenously with oxacillin for 15 days and ceftriaxone for 13 days, and orally with ciprofloxacin for 15 days, with good outcome. COMMENTS: The Sphingobacterium multivorum is a gram negative bacillus that belongs to Flavobacteriaceae family and it is considered non-pathogenic. It has rarely been described as a cause of infections in humans, especially in hospital environment and in immunosuppressed patients. This case report is relevant for its unusual etiology and for the site affected, which may be the first case of septic arthritis described.

Citizen science and online data: opportunities and challenges for snake ecology and action against snakebite

The secretive behavior and life history of snakes makes studying their biology, distribution, and the epidemiology of venomous snakebite challenging. One of the most useful, most versatile, and easiest to collect types of biological data are photographs, particularly those that are connected with geographic location and date-time metadata. Photos verify occurrence records, provide data on phenotypes and ecology, and are often used to illustrate new species descriptions, field guides and identification keys, as well as in training humans and computer vision algorithms to identify snakes. We scoured eleven online and two offline sources of snake photos in an attempt to collect as many photos of as many snake species as possible, and attempt to explain some of the inter-species variation in photograph quantity among global regions and taxonomic groups, and with regard to medical importance, human population density, and range size. We collected a total of 725,565 photos—between 1 and 48,696 photos of 3098 of the world's 3879 snake species (79.9%), leaving 781 “most wanted” species with no photos (20.1% of all currently-described species as of the December 2020 release of The Reptile Database). We provide a list of most wanted species sortable by family, continent, authority, and medical importance, and encourage snake photographers worldwide to submit photos and associated metadata, particularly of “missing” species, to the most permanent and useful online archives: The Reptile Database, iNaturalist, and HerpMapper.

A comparison of traditional and quantitative analysis of acid-base imbalances in hypoalbuminemic dogs.

OBJECTIVE: To compare the traditional (HH) and quantitative approaches used for the evaluation of the acid-base balance in hypoalbuminemic dogs. DESIGN: Prospective observational study. SETTING: ICU of a veterinary teaching hospital. ANIMALS: One hundred and five client-owned dogs. MEASUREMENTS AND MAIN RESULTS: Jugular venous blood samples were collected from each patient on admission to determine: total plasma protein (TP), albumin (Alb), blood urea nitrogen (BUN), glucose (Glu), hematocrit (HCT), Na(+) , Cl(-) , K(+) , phosphate (Pi ), pH, PvCO2, bicarbonate (HCO3 (-) ), anion gap (AG), adjusted anion gap for albumin (AGalb ) or phosphate (AGalb-phos ), standardized base excess (SBE), strong ion difference (SID), concentration of nonvolatile weak buffers (Atot ), and strong ion gap (SIG). Patients were divided in 2 groups according to the severity of the hypoalbuminemia: mild (Alb = 21-25 g/L) and severe (Alb ≤20 g/L). All parameters were compared among groups. Patients with severe hypoalbuminemia showed significant decrease in TP (P = 0.011), Atot (P = 0.050), and a significant increase in adjusted AG (P = 0.048) and the magnitude of SIG (P = 0.011) compared to animals with mild hypoalbuminemia. According to the HH approach, the most frequent imbalances were simple disorders (51.4%), primarily metabolic acidosis (84.7%) associated with a high AG acidosis. However, when using the quantitative method, 58.1% of patients had complex disorders, with SIG acidosis (74.3%) and Atot alkalosis (33.3%) as the most frequent acid-base imbalances. Agreement between methods only matched in 32 cases (kappa < 0.20). CONCLUSIONS: The agreement between the HH and quantitative methods for interpretation of acid-base balance was poor and many imbalances detected using the quantitative approach were missed using the HH approach. Further studies are necessary to confirm the clinical utility of using the quantitative approach in the decision-making process of the severely ill hypoalbuminemic patients.

ß-globin gene transfer to human bone marrow for sickle cell disease.

Autologous hematopoietic stem cell gene therapy is an approach to treating sickle cell disease (SCD) patients that may result in lower morbidity than allogeneic transplantation. We examined the potential of a lentiviral vector (LV) (CCL-ßAS3-FB) encoding a human hemoglobin (HBB) gene engineered to impede sickle hemoglobin polymerization (HBBAS3) to transduce human BM CD34+ cells from SCD donors and prevent sickling of red blood cells produced by in vitro differentiation. The CCL-ßAS3-FB LV transduced BM CD34+ cells from either healthy or SCD donors at similar levels, based on quantitative PCR and colony-forming unit progenitor analysis. Consistent expression of HBBAS3 mRNA and HbAS3 protein compromised a fourth of the total ß-globin-like transcripts and hemoglobin (Hb) tetramers. Upon deoxygenation, a lower percentage of HBBAS3-transduced red blood cells exhibited sickling compared with mock-transduced cells from sickle donors. Transduced BM CD34+ cells were transplanted into immunodeficient mice, and the human cells recovered after 2-3 months were cultured for erythroid differentiation, which showed levels of HBBAS3 mRNA similar to those seen in the CD34+ cells that were directly differentiated in vitro. These results demonstrate that the CCL-ßAS3-FB LV is capable of efficient transfer and consistent expression of an effective anti-sickling ß-globin gene in human SCD BM CD34+ progenitor cells, improving physiologic parameters of the resulting red blood cells.