Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis.

Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated human induced pluripotent stem cells (iPSCs) from three LS patient-derived fibroblast lines. Using whole-exome and mitochondrial sequencing, we identified unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD). These LS patient-derived iPSC lines were viable and capable of differentiating into progenitor populations, but we identified several abnormalities in three-dimensional differentiation models of brain development. LS patient-derived cerebral organoids showed defects in neural epithelial bud generation, size and cortical architecture at 100 days. The double mutant MT-ATP6/PDH line produced organoid neural precursor cells with abnormal mitochondrial morphology, characterized by fragmentation and disorganization, and showed an increased generation of astrocytes. These studies aim to provide a comprehensive phenotypic characterization of available patient-derived cell lines that can be used to study Leigh syndrome.

Ocular thelaziosis: an emerging human parasitosis in Europe.

Ocular thelaziosis is a parasitosis distributed mainly in East Asia, but increasingly described in Europe in different domestic and wild animals, including dogs, different wild canids and lagomorphs, and exceptionally in humans. In Spain, in some areas, a high infection prevalence rate has been described in domestic canids, which may lead to an increase in human cases. However, the description of human cases is still exceptional, which suggests that they are probably underdiagnosed. A case of ocular thelaziosis in a 2-year-old girl from an urban environment is described.

Common molecular mechanisms of SLC6A1 variant-mediated neurodevelopmental disorders in astrocytes and neurons.

Solute carrier family 6 member 1 (SLC6A1) is abundantly expressed in the developing brain even before the CNS is formed. Its encoded GABA transporter 1 (GAT-1) is responsible for the reuptake of GABA into presynaptic neurons and glia, thereby modulating neurotransmission. GAT-1 is expressed globally in the brain, in both astrocytes and neurons. The GABA uptake function of GAT-1 in neurons cannot be compensated for by other GABA transporters, while the function in glia can be partially replaced by GABA transporter 3. Recently, many variants in SLC6A1 have been associated with a spectrum of epilepsy syndromes and neurodevelopmental disorders, including myoclonic atonic epilepsy, childhood absence epilepsy, autism, and intellectual disability, but the pathomechanisms associated with these phenotypes remain unclear. The presence of GAT-1 in both neurons and astrocytes further obscures the role of abnormal GAT-1 in the heterogeneous disease phenotype manifestations. Here we examine the impact on transporter trafficking and function of 22 SLC6A1 variants identified in patients with a broad spectrum of phenotypes. We also evaluate changes in protein expression and subcellular localization of the variant GAT-1 in various cell types, including neurons and astrocytes derived from human patient induced pluripotent stem cells. We found that a partial or complete loss-of-function represents a common disease mechanism, although the extent of GABA uptake reduction is variable. The reduced GABA uptake appears to be due to reduced cell surface expression of the variant transporter caused by variant protein misfolding, endoplasmic reticulum retention, and subsequent degradation. Although the extent of reduction of the total protein, surface protein, and the GABA uptake level of the variant transporters is variable, the loss of GABA uptake function and endoplasmic reticulum retention is consistent across induced pluripotent stem cell-derived cell types, including astrocytes and neurons, for the surveyed variants. Interestingly, we did not find a clear correlation of GABA uptake function and the disease phenotypes, such as myoclonic atonic epilepsy versus developmental delay, in this study. Together, our study suggests that impaired transporter protein trafficking and surface expression are the major disease-associated mechanisms associated with pathogenic SLC6A1 variants. Our results resemble findings from pathogenic variants in other genes affecting the GABA pathway, such as GABAA receptors. This study provides critical insight into therapeutic developments for SLC6A1 variant-mediated disorders and implicates that boosting transporter function by either genetic or pharmacological approaches would be beneficial.

Body composition and ventricular function in hemodialysis patients.

There is no evidence about the potential role of body composition on cardiovascular mortality in dialysis patients. The aim of this study was to assess the relationship between body composition and changes in ventricular function. We conducted an observational study over a population of 78 patients on chronic hemodialysis. A transthoracic echocardiogram and a bioimpedance were performed at the beginning and at the end of the study. The mean follow-up time was 30.6 months. Patients who had a higher fat tissue index (FTI > 9.20 kg/m2 ) experienced a worsening in right and left ventricular function. They developed a greater fall in tricuspid annular plane systolic excursion (TAPSE) (-1 ± 4.3 mm) and left ventricular ejection fraction (LVEF)(-4.2 ± 6.8%), compared to those with lower FTI (p = 0.032 and p = 0.045, respectively). No associations were found between any other echocardiography or body composition parameters and overall mortality. Patients with right ventricular dysfunction (determined as TAPSE) experienced a tendency to higher mortality rate along the study (HR for mortality of 13.5 (95% CI, 1.1-166.7; p = 0.041)]. A higher fat tissue index could be associated with a deleterious effect over right and left ventricular function in dialysis patients.

COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.

Human papillomavirus genotypes and P16INK4A expression in squamous penile carcinoma in Mexican patients.

BACKGROUND: Approximately 50% of cases of penile carcinoma (PeCa), a rare neoplasm worldwide, are associated with human papillomavirus (HPV). However, the detection of HPV-DNA is not sufficient to consider it the etiological factor in the development of this type of cancer. Currently, the overexpression of P16INK4A is used as a surrogate biomarker of HPV carcinogenesis. Information on PeCa in Mexico is scarce, particularly regarding cases related to HPV and genotype frequency. OBJECTIVE: To evaluate the presence of HPV, its genotypes, and the presence of multiple genotypes, and the expression of P16INK4A, as well as its clinical and histopathological parameters. METHODS: For HPV-DNA detection and P16INK4A expression, we used the INNO-LiPA® test and immunohistochemistry, respectively. RESULTS: Sixty cases of PeCa were evaluated, of which 75% were HPV-non-related histological variants. We found that 58.9% (33/56) of PeCa cases were HPV-DNA positive, while 30.9% of the cases evaluated (17/55) were positive for P16INK4A. HPV16 was the main genotype in 42.9% of the cases, followed by HPV52 in 7.1% and HPV18 in 5.4%. Within the HPV-positive cases, 27.3% had multiple genotypes. All HPV-positive patients under the age of 45 years were positive only for HPV16. CONCLUSIONS: HPV16 was the most commonly detected genotype in PeCa. HPV 31, 35 and 39 were infrequent; however, they were related to a single infection and P16INK4A overexpression; thus, they seem to be relevant in PeCa carcinogenesis. Our results suggest that P16INK4A overexpression could be useful for the classification of HPV-related PeCa. The role of multiple HPV genotypes in the development and prognosis of PeCa is still not completely understood. Thus, it is necessary to define criteria to establish reliable ways to classify HPV-related PeCa that could lead to optimal therapeutic approaches.

[Subtotal-supracrioid laryngectomy (SCSL): the importance of the histopathological analysis]. / Laringectomía subtotal supracricoidea (LSSC): la importancia del análisis histopatológico.

The purpose of conservative surgical treatment of laryngeal cancer is to obtain cancer control with preservation of laryngeal function, and in turn, the preservation of laryngeal function should be understood as the preservation of the patient's ability to ventilate in the normal way without tracheostomy and without aspiration and maintaining intelligible speech. This objective is achieved by maintaining a balance between two fundamental aspects: proper patient selection (based on tumor extension and preoperative laryngeal function) and an adequate histopathological analysis of the surgical specimen. Supracricoid subtotal laryngectomy (SCSL) is the voice conservative surgical technique which offers the best possibility of control in patients with locally advanced laryngeal cancer, and the proper histopathological analysis allows staging and selecting patients eligible for adjuvant therapy, avoiding unnecessary therapies, and allows design of a monitoring and surveillance program based on risk factors. The aim of this manuscript is to highlight key points in the histopathological evaluation of the surgical specimen of SCSL. The proper communication between the surgeon and pathologist, offering complete information on preoperative clinical evaluation and the knowledge of the key points in the evaluation of the surgical specimen (sites of tumor leakage and surgical resection margins) are fundamental parameters to achieve a proper histopathologic evaluation of the surgical specimen.

[Tenosynovitis due to Chikungunya virus]. / Tenosinovitis por virus Chikungunya.

We report the case of a man from Dominican Republic who consulted for a tenosynovitis of the right middle finger extensor; in the immediate convalescence second febrile curve, after 48 hours of no symptoms of an acute febrile illness, with marked fatigue, itchy rash, polyarthralgia, functional impairment and general stiffness. Biochemical tests did not provide useful data for diagnosis. Dengue virus serology was negative. Detection of IgM and neutralizing antibodies (PRNT) for Chikundunya virus (CHIKV) were positive.

[Uterine spontaneous secondary perforation to pyometra in a patient with cervicouterine cancer: report of a case]. / Perforación uterina espontánea secundaria a piometra en una paciente con cáncer cervicouterino: reporte de un caso.

The pyometra is a rare condition, with an incidence of less than 1%. In patients with cervical cancer, spontaneous rupture of pyometra manifests as a generalized peritonitis, which is extremely rare, in the literature only seven cases are described. This paper reports the case of a patient with a history of postmenopausal vaginal bleeding one month before her admission to the hospital; she attended because of acute abdomen. The CT scan reported air in the abdominal cavity and the uterus with air at the periphery, so she underwent an exploratory laparotomy in which purulent material was found with two perforations in the uterine fundus. She underwent total abdominal extrafacial hysterectomy with histopathological diagnosis of keratinizing squamous cell carcinoma, moderately differentiated.

Adoption of Electronic Medical Records for Chronic Disease Care in Kenyan Refugee Camps: Quantitative and Qualitative Prospective Evaluation.

Background: Noncommunicable disease (NCD) prevention and control in humanitarian emergencies is a well-recognized need, but there is little evidence to guide responses, leading to varying care delivery. The Sana.NCD mobile health (mHealth) app, initially developed in Lebanon, is the only known mHealth tool for NCD management designed to increase care quality and coverage for providers in humanitarian settings. Objective: We evaluated a specialized mHealth app consisting of an abbreviated medical record for patients with hypertension or diabetes, adapted for a Kenyan refugee camp setting. Methods: We tested an adapted version of the Sana.NCD app (diabetes and hypertension medical record) in an 11-month (May 2021 to March 2022) quantitative and qualitative prospective evaluation in Kenya's Hagadera refugee camp. Leveraging the rollout of a general electronic medical record (EMR) system in the Kakuma refugee camp, we compared a specialized NCD management app to a general EMR. We analyzed secondary data collected from the Sana.NCD app for 1539 patients, EMR data for 68 patients with NCD from Kakuma's surgical and outpatient departments, and key informant interviews that focused on Hagadera clinic staff perceptions of the Sana.NCD app. Results: The Hagadera NCD clinic reported 18,801 consultations, 42.1% (n=7918) of which were reported in the NCD app. The Kakuma EMR reported 350,776 visits, of which 9385 (2.7%) were for NCDs (n=4264, 1.2% hypertension; n=2415, 0.7% diabetes). The completeness of reporting was used as a quality-of-care metric. Age, sex, prescribed medicines, random blood sugar, and smoking status were consistently reported in both the NCD app (>98%) and EMR (100%), whereas comorbidities, complications, hemoglobin A1c, and diet were rarely reported in either platform (≤7% NCD app; 0% EMR). The number of visits, BMI, physical activity, and next visit were frequently reported in the NCD app (≥99%) but not in the EMR (≤15%). In the NCD app, the completeness of reporting was high across the implementation period, with little meaningful change. Although not significantly changed during the study, elevated blood sugar (P=.82) and blood pressure (P=.12) were reported for sizable proportions of patients in the first (302/481, 62.8%, and 599/1094, 54.8%, respectively) and last (374/602, 62.1%, and 720/1395, 51.6%, respectively) study quarters. Providers were satisfied with the app, as it standardized patient information and made consultations easier. Providers also indicated that access to historic patient information was easier, benefiting NCD control and follow-up. Conclusions: A specialized record for NCDs outperformed a more general record intended for use in all patients in terms of reporting completeness. This CommCare-based NCD app can easily be rolled out in similar humanitarian settings with minimal adaptation. However, the adaptation of technologies to the local context and use case is critical for uptake and ensuring that workflows and time burden do not outweigh the benefits of EMRs.

Impact of preoperative exercise in not initially candidates to native arteriovenous fistulas.

BACKGROUND: Native autologous arteriovenous fistula (AVFn) is the preferred vascular access for hemodialysis due to its long term patency and low complication rate. A challenging limitation is the anatomical inability to perform AVFn and failure of maturation. Preoperative isometric exercise (PIE) can increase vascular calibers and improve the rate of distal AVF. However, it is unknown whether PIE might enhance the performance of AVFn in patients who are not initially candidates. METHODS: A retrospective observational study was conducted over a population of 45 patients evaluated in vascular access clinic, 23 were not initially candidates for radiocephalic (NRC-AVF) and 22 were not candidates for autologous fistula at all (NA-AVF). They were assigned to perform PIE with handgrip device and revaluated. RESULTS: After 4-8 weeks of PIE, a AVFn was performed in 16 patients from NA-AVF group and a radiocephalic AVFn was performed in 21 patients from NRC-AVF group. Both groups experienced a significant and similar increase in venous caliber 0.91 ± 0.43 mm in NA-AVF versus 0.76 ± 0.47 mm in NRC-AVF (p = 0.336) and arterial caliber 0.18 ± 0.24 mm versus 0.18 ± 0.21 mm (p = 0.928), respectively. Nevertheless, primary failure rate was significantly higher in NA-AVF (n = 8, 50%) than in NRC-AVF group (n = 3, 14.3%) (p = 0.030). After 6 months, the fistula usability for dialysis was only 50% in NA-AVF, while 86.7% were dialyzed by fistula in NRC-AVF group (p = 0.038). CONCLUSIONS: PIE allowed the allocation of an AVFn in patients not initially candidates, but entailed a high rate of maturation failure. Patients not candidates to radiocephalic AVF benefited from PIE and preserved a long term usability of AVF for dialysis.

Slippery lubricant-infused silica nanoparticulate film processing for anti-biofouling applications.

Microbial biofilm build-up in water distribution systems can pose a risk to human health and pipe material integrity. The impact is more devastating in space stations and to astronauts due to the isolation from necessary replacement parts and medical resources. As a result, there is a need for coatings to be implemented onto the inner region of the pipe to minimize the adherence and growth of biofilms. Lubricant-infused surfaces has been one such interesting material for anti-biofouling applications in which their slippery property promotes repellence to many liquids and thus prevents bacterial adherence. Textured and porous films are suitable substrate candidates to infuse and contain the lubricant. However, there is little investigation in utilizing a nanoparticulate thin film as the substrate material for lubricant infusion. A nanoparticulate film has high porosity within the structure which can promote greater lubricant infusion and retention. The implementation as a thin film structure aids to reduce material consumption and cost. In our study, we utilized a well-studied nanoporous thin film fabricated via layer-by-layer assembly of polycations and colloid silica and then calcination for greater stability. The film was further functionalized to promote fluorinated groups and improve affinity with a fluorinated lubricant. The pristine nanoporous film was characterized to determine its morphology, thickness, wettability, and porosity. The lubricant-infused film was then tested for its lubricant layer stability upon various washing conditions and its performance against bacterial biofilm adherence as a result of its slippery property. Overall, the modified silica nanoparticulate thin film demonstrated potential as a base substrate for lubricant-infused surface fabrication that repelled against ambient aqueous solvents and as an anti-biofouling coating that demonstrated low biofilm coverage and colony forming unit values. Further optimization to improve lubricant retention or incorporation of a secondary function can aid in developing better coatings for biofilm mitigation.

Prolonged Computer Use by Office Workers Induces Ocular Symptoms Associated With Tear Film Alterations and Overexpression of Mucin 5 AC and Catalase.

OBJECTIVE: The aim of the study was to evaluate office workers for symptoms of computer vision syndrome (CVS) and alterations in the tear film relate to the hours of daily computer use. METHODS: Sixty-seven volunteers were divided into 2 groups: 2 to 6 and 7 to 12 hours of daily computer use. Computer vision syndrome symptoms, tear film stability by tear film break-up time test, and composition of mucin 5 AC, catalase, and IL-6 was assessed by relative gene expression of conjunctival impression cytology samples were examined. RESULTS: All participants exhibited moderate symptoms of CVS, whereas 90% showed reduced tear film stability. For the 7- to 12-hour (vs 2- to 6-hour) group, these effects were more pronounced and overexpression of mucin 5 AC and catalase was detected. CONCLUSIONS: Prolonged computer use induced an overexpression of mucin 5 AC and catalase and instability of the tear film, associated with ocular symptoms.

Utilizing hiPSC-derived oligodendrocytes to study myelin pathophysiology in neuropsychiatric and neurodegenerative disorders.

Oligodendrocytes play a crucial role in our central nervous system (CNS) by myelinating axons for faster action potential conduction, protecting axons from degeneration, structuring the position of ion channels, and providing nutrients to neurons. Oligodendrocyte dysfunction and/or dysmyelination can contribute to a range of neurodegenerative diseases and neuropsychiatric disorders such as Multiple Sclerosis (MS), Leukodystrophy (LD), Schizophrenia (SCZ), and Autism Spectrum Disorder (ASD). Common characteristics identified across these disorders were either an inability of oligodendrocytes to remyelinate after degeneration or defects in oligodendrocyte development and maturation. Unfortunately, the causal mechanisms of oligodendrocyte dysfunction are still uncertain, and therapeutic targets remain elusive. Many studies rely on the use of animal models to identify the molecular and cellular mechanisms behind these disorders, however, such studies face species-specific challenges and therefore lack translatability. The use of human induced pluripotent stem cells (hiPSCs) to model neurological diseases is becoming a powerful new tool, improving our understanding of pathophysiology and capacity to explore therapeutic targets. Here, we focus on the application of hiPSC-derived oligodendrocyte model systems to model disorders caused by oligodendrocyte dysregulation.

Human Papillomavirus-Related Recurrent Multiphenotypic Sinonasal Carcinoma With HPV Genotype 56 Detected by HPV Direct Flow CHIP.

Human Papillomavirus-related multiphenotypic sinonasal carcinoma is a rare, and recently described neoplasm, defined by its association with high-risk Human Papillomavirus, which exclusively affects the sinonasal tract and simulates salivary gland tumors. Due to the infrequency of this neoplasm and the lack of knowledge of its pathological characteristics, it is susceptible to diagnostic error. We describe the clinical-radiological findings of a 54-year-old man with multiphenotypic sinonasal carcinoma related to Human Papillomavirus genotype 56. The diagnosis of multiphenotypic sinonasal carcinoma was suspected by light microscopy and was corroborated by immunohistochemistry and polymerase chain reaction (PCR) analysis. The patient was subsequently treated with 63.6 gray radiotherapies. He is currently alive after a follow-up of 20 months, with a recurrence of the disease. In conclusion, multiphenotypic sinonasal carcinoma is an unusual neoplasm, which is not well recognized and can be confused with adenoid cystic carcinoma. However, multiphenotypic sinonasal carcinoma should be included in the differential diagnosis as we encounter sinonasal tumors, which by histology present tubular, cribriform, and solid growth patterns, accompanied by dysplasia or carcinoma in situ in the superficial mucosa. In this case, it is necessary to perform immunohistochemistry for p16INK4A or PCR to confirm the presence of high-risk Human Papilloma Virus, which would confirm the diagnosis.

Leptomeningeal Neural Organoid (LMNO) Fusions as Models to Study Meninges-Brain Signaling.

Neural organoids derived from human induced pluripotent stem cells (iPSCs) provide a model to study the earliest stages of human brain development, including neurogenesis, neural differentiation, and synaptogenesis. However, neural organoids lack supportive tissues and some non-neural cell types that are key regulators of brain development. Neural organoids have instead been co-cultured with non-neural structures and cell types to promote their maturation and model interactions with neuronal cells. One structure that does not form de novo with neural organoids is the meninges, a tri-layered structure that surrounds the CNS and secretes key signaling molecules required for mammalian brain development. Most studies of meninges-brain signaling have been performed in mice or using two-dimensional (2D) cultures of human cells, the latter not recapitulating the architecture and cellular diversity of the tissue. To overcome this, we developed a co-culture system of neural organoids generated from human iPSCs fused with fetal leptomeninges from mice with fluorescently labeled meninges (Col1a1-GFP). These proof-of-concept studies test the stability of the different cell types in the leptomeninges (fibroblast and macrophage) and the fused brain organoid (progenitor and neuron), as well as the interface between the organoid and meningeal tissue. We test the longevity of the fusion pieces after 30 days and 60 days in culture, describe best practices for preparing the meninges sample prior to fusion, and examine the feasibility of single or multiple meninges pieces fused to a single organoid. We discuss potential uses of the current version of the LMNO fusion model and opportunities to improve the system.

Leptomeningeal Neural Organoid (LMNO) Fusions as Models to Study Meninges-Brain Signaling.

Neural organoids derived from human induced pluripotent stem cells (iPSCs) provide a model to study the earliest stages of human brain development, including neurogenesis, neural differentiation, and synaptogenesis. However, neural organoids lack supportive tissues and some non-neural cell types that are key regulators of brain development. Neural organoids have instead been co-cultured with non-neural structures and cell types to promote their maturation and model interactions with neuronal cells. One structure that does not form de novo with neural organoids is the meninges, a tri-layered structure that surrounds the CNS and secretes key signaling molecules required for mammalian brain development. Most studies of meninges-brain signaling have been performed in mice or using two-dimensional (2D) cultures of human cells, the latter not recapitulating the architecture and cellular diversity of the tissue. To overcome this, we developed a co-culture system of neural organoids generated from human iPSCs fused with fetal leptomeninges from mice with fluorescently labeled meninges (Col1a1-GFP). These proof-of-concept studies test the stability of the different cell types in the leptomeninges (fibroblast and macrophage) and the fused brain organoid (progenitor and neuron), as well as the interface between the organoid and meningeal tissue. We test the longevity of the fusion pieces after 30 days and 60 days in culture, describe best practices for preparing the meninges sample prior to fusion, and examine the feasibility of single or multiple meninges pieces fused to a single organoid. We discuss potential uses of the current version of the LMNO fusion model and opportunities to improve the system.

Peripheral arterial disease in hemodialysis patients 10 years later.

BACKGROUND AND OBJECTIVE: Patients with chronic kidney disease (CKD) on hemodialysis present high cardiovascular comorbidity. Peripheral arterial disease (PAD) is associated with higher mortality and the interest in its early detection and treatment is increasing. The objective of this study is to determine the frequency and severity of symptomatic PAD, and to establish its relationship with mortality in HD patients that have received treated early and compare them with a cohort of our center already reported. MATERIAL AND METHODS: Retrospective study on a cohort of incident patients since 2014 and followed up until December 2019. Demographic data, cardiovascular risk, the presence of symptomatic PAD at baseline and during follow-up were collected. Trophic lesions were graded using the Rutherford scale. RESULTS: Initially, there were 91 patients and 7 cases that were not included in the study were lost to follow-up. Age 64 ±â€¯16 years, men 51.6% (47/91). The percentage of baseline PAD was 10.7% (9/84). During a median follow-up of 35 months (20-57), the diagnosis of PAD increased to 25% (21/84). Half of the patients with PAD 52.38% (11/21) obtained a score greater than 3 in the Rutherford Clinical Classification, which corresponds to severe disease. 13/21 patients required reoperation due to recurrence of symptoms (61.9% of cases with PAD). The development of PAD was significantly associated with: an elevated index of Charlson (3.9±2.1 vs. 7.7 ±â€¯3.5; P = 0.001),being male (19 vs. 2; P = 0.001), diabetic (no: 7; yes: 15; P = 0.001) and with a history of chronic ischemic heart disease (no: 13; yes: 8; P = 0.001), 38.1% (8/21) had ischemic heart disease in patients who developed PAD, while in the absence of PAD the presence of ischemic heart disease was 9.5% (6/63). Furthermore, more than half (66.7% [14/21]) of those who developed PAD were diabetic. Univariate analysis showed that age, C reactive protein, albumin, and number of surgical interventions, but not PAD, were associated with mortality. In the multivariate analysis adjusted for other factors, only C reactive protein was related to overall survival Exp ß: 2.17; P = 0.011; CI (1.19-3.97). Regarding cardiovascular mortality, in the multivariate Cox analysis, only PAD was related to mortality of cardiovascular origin Exp ß: 1.73; P = 0.006; CI (1.17-2.56). CONCLUSIONS: A significant number of patients on hemodialysis develop PAD requiring peripheral vascular surgery. PAD was not associated with overall mortality in our cohort, but it did show an association with cardiovascular mortality. Prospective studies with a larger sample size are necessary. New surgical treatments and Follow-up by vascular surgeons could improve the severity of PAD and the long-term prognosis.

Assessing pandemic preparedness, response, and lessons learned from the COVID-19 pandemic in four south American countries: agenda for the future.

Introduction: The COVID-19 pandemic emerged in a context that lacked adequate prevention, preparedness, and response (PPR) activities, and global, regional, and national leadership. South American countries were among world's hardest hit by the pandemic, accounting for 10.1% of total cases and 20.1% of global deaths. Methods: This study explores how pandemic PPR were affected by political, socioeconomic, and health system contexts as well as how PPR may have shaped pandemic outcomes in Argentina, Brazil, Colombia, and Peru. We then identify lessons learned and advance an agenda for improving PPR capacity at regional and national levels. We do this through a mixed-methods sequential explanatory study in four South American countries based on structured interviews and focus groups with elite policy makers. Results: The results of our study demonstrate that structural and contextual barriers limited PPR activities at political, social, and economic levels in each country, as well as through the structure of the health care system. Respondents believe that top-level government officials had insufficient political will for prioritizing pandemic PPR and post-COVID-19 recovery programs within their countries' health agendas. Discussion: We recommend a regional COVID-19 task force, post-pandemic recovery, social and economic protection for vulnerable groups, improved primary health care and surveillance systems, risk communication strategies, and community engagement to place pandemic PPR on Argentina, Brazil, Colombia, and Peru and other South American countries' national public health agendas.