High frequency of endoluminal thrombus in patients with ischaemic stroke following AARS-CoV-2 infection.

BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with COVID-19 who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.

High frequency of endoluminal thrombus in patients with ischaemic stroke following SARS-CoV-2 infection. / Alta frecuencia de trombo endoluminal en pacientes con ictus isquémico tras la infección por coronavirus 2019.

BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with SARS-CoV-2 infection who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.

Impact of the internet on veterinary surgery.

The advent of the internet, and the technological innovations associated with it, have driven significant advances in surgical teaching and learning. The ease of access to information and the variety of online resources allow rapid sharing of surgical knowledge, promoting new teaching and learning patterns. Educational content from online platforms adds theoretical and practical knowledge to accelerate the learning curve and continuing education of surgeons. This study reviews how the advent of the Internet has influenced the teaching and dissemination of knowledge in veterinary surgery.

Post-COVID symptoms of potential peripheral nervous and muscular origin.

Many patients report persistent symptoms attributable to dysfunction of the peripheral nervous and muscular systems after acute COVID-19. These symptoms may constitute part of the so-called post-acute COVID-19 syndrome (PACS), or may result from neuromuscular complications of hospitalisation in intensive care units (ICUs). This article provides an updated review of symptoms of potential neuromuscular origin in patients with PACS, differentiating symptoms according to muscle, peripheral nerve, or autonomic nervous system involvement, and analyses the forms of neuromuscular involvement in patients who were admitted to the ICU due to severe COVID-19.

Los pacientes que han padecido COVID-19 frecuentemente refieren síntomas persistentes atribuibles a disfunción del sistema nervioso periférico y muscular. Estos síntomas pueden formar parte del denominado síndrome COVID-19 post-agudo (post-acute COVID-19 syndrome o PACS) o pueden surgir como consecuencia de las complicaciones neuromusculares del ingreso en unidades de cuidados intensivos (UCI). En este manuscrito se realiza una revisión actualizada de los síntomas de potencial origen neuromuscular en pacientes afectos de PACS, diferenciándolos en función de su posible origen a nivel de músculo, nervio periférico o sistema nervioso autónomo, así como las formas de afectación neuromuscular en pacientes que precisaron ingreso en UCI por COVID-19 grave.

Dialysis dose scaled to body surface area and size-adjusted, sex-specific patient mortality.

BACKGROUND AND OBJECTIVES: When hemodialysis dose is scaled to body water (V), women typically receive a greater dose than men, but their survival is not better given a similar dose. This study sought to determine whether rescaling dose to body surface area (SA) might reveal different associations among dose, sex, and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Single-pool Kt/V (spKt/V), equilibrated Kt/V, and standard Kt/V (stdKt/V) were computed using urea kinetic modeling on a prevalent cohort of 7229 patients undergoing thrice-weekly hemodialysis. Data were obtained from the Centers for Medicare & Medicaid Services 2008 ESRD Clinical Performance Measures Project. SA-normalized stdKt/V (SAN-stdKt/V) was calculated as stdKt/V × ratio of anthropometric volume to SA/17.5. Patients were grouped into sex-specific dose quintiles (reference: quintile 1 for men). Adjusted hazard ratios (HRs) for 1-year mortality were calculated using Cox regression. RESULTS: spKt/V was higher in women (1.7 ± 0.3) than in men (1.5 ± 0.2; P<0.001), but SAN-stdKt/V was lower (women: 2.3 ± 0.2; men: 2.5 ± 0.3; P<0.001). For both sexes, mortality decreased as spKt/V increased, until spKt/V was 1.6-1.7 (quintile 4 for men: HR, 0.62; quintile 3 for women: HR, 0.64); no benefit was observed with higher spKt/V. HR for mortality decreased further at higher SAN-stdKt/V in both sexes (quintile 5 for men: HR, 0.69; quintile 5 for women: HR, 0.60). CONCLUSIONS: SA-based dialysis dose results in dose-mortality relationships substantially different from those with volume-based dosing. SAN-stdKt/V analyses suggest women may be relatively underdosed when treated by V-based dosing. SAN-stdKt/V as a measure for dialysis dose may warrant further study.

Hemoglobin A(1c) levels and mortality in the diabetic hemodialysis population: findings from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

OBJECTIVE: Lowering hemoglobin A(1c) to <7% reduces the risk of microvascular complications of diabetes, but the importance of maintaining this target in diabetes patients with kidney failure is unclear. We evaluated the relationship between A(1c) levels and mortality in an international prospective cohort study of hemodialysis patients. RESEARCH DESIGN AND METHODS: Included were 9,201 hemodialysis patients from 12 countries (Dialysis Outcomes and Practice Patterns Study 3 and 4, 2006-2010) with type 1 or type 2 diabetes and at least one A(1c) measurement during the first 8 months after study entry. Associations between A(1c) and mortality were assessed with Cox regression, adjusting for potential confounders. RESULTS: The association between A(1c) and mortality was U-shaped. Compared with an A(1c) of 7-7.9%, the hazard ratios (95% CI) for A(1c) levels were 1.35 (1.09-1.67) for <5%, 1.18 (1.01-1.37) for 5-5.9%, 1.21 (1.05-1.41) for 6-6.9%, 1.16 (0.94-1.43) for 8-8.9%, and 1.38 (1.11-1.71) for ≥9.0%, after adjustment for age, sex, race, BMI, serum albumin, years of dialysis, serum creatinine, 12 comorbid conditions, insulin use, hemoglobin, LDL cholesterol, country, and study phase. Diabetes medications were prescribed for 35% of patients with A(1c) <6% and not prescribed for 29% of those with A(1c) ≥9%. CONCLUSIONS: A(1c) levels strongly predicted mortality in hemodialysis patients with type 1 or type 2 diabetes. Mortality increased as A(1c) moved further from 7-7.9%; thus, target A(1c) in hemodialysis patients may encompass values higher than those recommended by current guidelines. Modifying glucose-lowering medicines for dialysis patients to target A(1c) levels within this range may be a modifiable practice to improve outcomes.

Mouse bioassay for palytoxin. Specific symptoms and dose-response against dose-death time relationships.

Nowadays, a variety of protocols are applied to quantitate palytoxin. However, there is not desirable agreement among them, the confidence intervals of the basic toxicological parameters are too wide and the formal descriptions lack the necessary generality to establish comparisons. Currently, the mouse bioassay is the most accepted one to categorize marine toxins and it must constitute the reference for other methods. In the present work, the mouse bioassay for palytoxin is deeply analyzed and carefully described showing the initial symptoms of injected mice which are presented here in the first time. These symptoms clearly differ from the more common marine toxins described up to now. Regarding to the toxicological aspects two considerations are taking into account: (i) the empiric models based in the dose-death time relationships cause serious ambiguities and (ii) the traditional moving average method contains in its regular use any inaccuracy elements. Herein is demonstrated that the logistic equation and the accumulative function of Weibull's distribution (with the modifications proposed) generate satisfactory toxicological descriptions in all the respects.

Niveles de IgE Sérica total y factores asociados al desarrollo de atopía en estudiantes de medicina / evels of IgE total Sérica and factors associated to the atopía development in medicine students

Las enfermedades alérgicas son las menos estudiadas en nuestro medio, no se tienen estudios sobre los niveles de la IgE sérica total, ni su relación con los factores que pueden predisponer al desarrollo de Atopia. Este trabajo pretende establecer el diagnóstico de la Atopía en individuos predispuestos dentro de una población estudiantil de 4° año de la carrera de Medicina de la UMSA, comprendidos entre 20 y 30 años de edad de ambos sexos, durante la gestión 2001. El cálculo de tamaño muestral se realizó por EPINFO 6.0 para un estudio de corte transversal con casos y controles. De una población de 3.000 alumnos, 114 fueron seleccionados mediante un cuestionario dirigido evaluando antecedentes elérgios personales, alimenticios, ambientales y familiares, de los cuales 57 sujetos presentaron alguno de los factores asociados (casos) y 57 sujetos no presentaron ningún factor (controles), excluyendo a embarazadas y sujetos con antecedentes de zonas endémicas parasitariasd. Se aplicó una prueba de ELISA para determinar los niveles de IgE sérica total, obsercándose que el grupo control presentó todos los niveles de IgE sérica total menores a 100 UI/ml; el grupo atópico, 38 sujetos presentaron valores menores de 100 UI/ml y 19 mayores a 100 UI/ml. Se observó también que los factores asociados alimenticios, ambientales y familiares inciden en el desarrollo de la Atopia, determinándose que cuanto más asociados existen mayor es la manifestación.

Blakeslea trispora genes for carotene biosynthesis.

We cloned the carB and carRA genes involved in beta-carotene biosynthesis from overproducing and wild-type strains of Blakeslea trispora. The carB gene has a length of 1,955 bp, including two introns of 141 and 68 bp, and encodes a protein of 66.4 kDa with phytoene dehydrogenase activity. The carRA gene contains 1,894 bp, with a single intron of 70 bp, and encodes a protein of 69.6 kDa with separate domains for lycopene cyclase and phytoene synthase. The estimated transcript sizes for carB and carRA were 1.8 and 1.9 kb, respectively. CarB from the beta-carotene-overproducing strain B. trispora F-744 had an S528R mutation and a TAG instead of a TAA stop codon. The overproducing strain also had a P143S mutation in CarRA. Both B. trispora genes could complement mutations in orthologous genes in Mucor circinelloides and could be used to construct transformed strains of M. circinelloides that produced higher levels of beta-carotene than did the nontransformed parent. The results show that these genes are conserved across the zygomycetes and that the B. trispora carB and carRA genes are functional and potentially useable to increase carotenoid production.

Taking a public health approach to the prevention of end-stage renal disease: the NKF Singapore Program.

The National Kidney Foundation Singapore (NKFS) provides subsidized dialysis care to approximately 70% of the country's total end-stage renal disease (ESRD) population, based entirely on charitable donations. Because of the exponential increase in prevalent dialysis patients receiving care through the NKFS' chronic dialysis program, and with the anticipated epidemic rise in incident ESRD patients, an accelerated comprehensive strategy for the prevention of renal and its associated chronic diseases was developed. Presented is the NKFS' public health plan, which incorporates primary, secondary and tertiary approaches to the prevention of chronic kidney disease. Components of this comprehensive strategy include: screening populations at risk for the development and progression of renal disease, the documentation of existing standards of care for chronic diseases associated with renal disease, and the institution of disease management programs that facilitate the systematic management of patients with chronic diseases that lead to ESRD, including the development of community-based "Prevention Centers." Finally, longitudinal follow-up of the participating population is being performed in order to provide benchmarks for improvement and to determine future directions of the program. Such long-term monitoring also will facilitate the establishment of its efficacy in improving clinical outcomes, reducing the cost of care, and delaying the development and progression of chronic kidney disease.

Paradigms of public-private partnerships in end-stage renal disease care: the National Kidney Foundation Singapore.

Novel forms of funding chronic renal replacement therapy and other chronic kidney disease programs are urgently required in order to address the increasing global burden of end-stage renal disease (ESRD). For areas of infectious disease control in less-developed countries, the formation of public-private partnerships has successfully yielded short-term improvement in clinical outcomes. This article reviews the concept of public-private partnerships and its various formats. We argue that similar partnerships play an important role in addressing the public health problem of chronic kidney disease. Through its establishment of numerous paradigms of partnerships with private for-profit corporations in building a nationwide chronic dialysis program and through partnerships with other non-governmental institutions and healthcare institutions in order to create a new entity characterized by a separate management structure, the NKFS has been able to provide chronic dialysis care to over 70% of the country's total ESRD population. This extensive network of partnerships is currently being applied as the NKFS continues to expand its programs to focus on the prevention of chronic kidney disease at a nationwide level.

A comprehensive public health approach to address the burden of renal disease in singapore.

With the epidemic rise of ESRD in multiple regions of the world, there is an urgent need to implement programs to address this increasing burden of kidney disease. We illustrate a public health approach using the program of the National Kidney Foundation of Singapore that incorporates stepwise primary, secondary, and tertiary strategies for prevention. Components of the program include an aggressive public education program, routine surveillance for kidney disease and associated chronic diseases, the implementation of a disease management program to improve physician practice patterns, and the provision of comprehensive services in the community through a network of Prevention Centers designed to optimize the care of patients at risk for kidney disease. Finally, an equally important aspect is the clinical and epidemiologic research component, because this will provide clear benchmarks to determine the program's effect on ESRD as well as generate information that can be used to identify future directions for this evolving program.

Second trimester abortion by laminaria followed by vaginal misoprostol or intrauterine prostaglandin F2alpha: a randomized trial.

Intra-amniotic injection, as well as intravaginal application of prostaglandins, have been used to terminate second trimester pregnancies. There is as yet no consensus as to the most efficient protocol of such late abortions. Our goal was to compare the efficacy of intra-amniotic injection of prostaglandin F2 alpha (PGF2alpha) and intravaginal application of misoprostol in terminating second trimester pregnancies after pretreatment with intracervical laminaria. Women with live fetuses and requesting second trimester abortions were randomized into two groups. Eighteen hours following the insertion of intracervical laminaria, women were treated with either intra-amniotic injection of 40 mg PGF2alpha, or 12 hourly doses (to a maximum of 4 doses) of 200 mcg misoprostol. Fifty women were randomly assigned to each group. Failure to abort within 24 h of initiation of treatment occurred in 6 patients (12%) in the misoprostol group and 14 (28%) of the PGF2alpha group (p = 0.04). Mean time of induction of pharmacologic treatment to abortion was 13.6 h in the misoprostol group and 10.7 h in the PGF2alpha group (p = 0.03). The mean number of analgesic injections given were 0.8 in the misoprostol group and 1.6 in the PGF2alpha group (p = 0.0001). Only the method of abortion was predictive of abortion success and not other variables such as patient age, gestational age, gravidity, or parity. Following intracervical laminaria, vaginal misoprostol has been found to be more effective and less painful, compared with intra-amniotic PGF2alpha, for the termination of second trimester pregnancies with live fetuses.

Risk factors for proteinuria in a large, multiracial, southeast Asian population.

The factors associated with proteinuria were examined in a large multiracial Asian population participating in a screening program aimed at the early detection of renal disease. Of 213,873 adults who participated, 189,117 with complete data were included. Malay race, increasing age, both extremes of body mass index (BMI), self-reported family history of kidney disease (FKD), and higher systolic and diastolic BP measurements (even at levels classified as being within the normal range) were independently associated with dipstick-positive proteinuria. The odds ratios (OR) for proteinuria increased progressively with age. There was a J-shaped relationship between BMI and proteinuria (OR of 1.3, 1.00, 1.3, 1.6, and 2.5 for BMI of < or =18.00, 23.00 to 24.99, 25.00 to 27.49, 27.50 to 29.99, and > or =30.00 kg/m(2), respectively, compared with BMI of 18.01 to 22.99 kg/m(2)). OR for proteinuria according to systolic and diastolic BP were significantly increased beginning at levels of 110 and 90 mmHg, respectively. In addition, the Malay race was associated with a significantly higher OR for proteinuria, compared with the Chinese race (OR of 1.3). Finally, FKD was significantly associated with proteinuria (OR of 1.7), whereas a family history of diabetes mellitus and a family history of hypertension were not. When family histories were analyzed by clustering, isolated FKD remained a significant determinant of proteinuria and the magnitude of the effect was not significantly different from that observed in the presence of a coexisting family history of diabetes mellitus or hypertension. This is the first study to evaluate factors associated with proteinuria in an Asian population. The epidemiologic study of renal disease in this population suggests that risk factors for renal disease might differ significantly among racial groups.

Clinical manifestations of gastrointestinal granulocytic sarcoma requiring surgical treatment.

Granulocytic sarcoma is a rare extramedullary soft-tissue tumor of granulocytic lineage with an incidence of 3 to 5 per cent in patients with acute myelogenous leukemia. The most common sites of involvement are bone, soft tissue, lymph nodes, and skin. Here we report three unusual cases of granulocytic sarcoma involving the gastrointestinal tract that required surgical intervention.

Consideraciones de diseño de las instalaciones para producciiones estériles de alto riesgo / Considerations of design of the installations for sterile productions of tall risk

En las empresas dedicacas a producciones de alto riesgo, el aseguramiento de la calidad no se limita a la obtención de un producto que satisfaga todas las pexpectativas del cliente, sino que debe involucrar aspectos tan importantes como son la protección del hombre y del medio ambiente, minimizando el riesgo que pueda implicar la manipulación del agente tóxicos.Este trabajo tiene como objetivo fundamental el análisis de los requerimientos de las buenas prácticas de producción aplicadas a instalaciones de producciones stériles de alto riesgo, así como de normas y recomendaciones relacionadas con el diseño de las instalaciones y de esta forma obtener un documento de referencia que contenga los requerimientos exigidos para estas producciones, para ser aplicadas desde la etapa de diseño de las mismas.Conjuntamente se definen las regulaciones aplicables haciendo énfasis en los aspectos más importantes que garantizan el cumplimiento de las buenas prácticas

Phase I trial of intraperitoneal iododeoxyuridine with and without intravenous high-dose folinic acid in the treatment of advanced malignancies primarily confined to the peritoneal cavity: flow cytometric and pharmacokinetic analysis.

In this Phase I study, the maximally tolerated doses (MTDs) of i.p. iododeoxyuridine (IdUrd) alone and in combination with i.v. calcium leucovorin (LV) were determined. The pharmacokinetics and pharmacological advantage of IdUrd were evaluated, and flow cytometric analysis allowed examination of the extent of incorporation of IdUrd into tumor cells with and without the addition of i.v. LV. Thirty-nine patients with advanced neoplasms primarily confined to the peritoneal space were enrolled in a dose-escalation trial using 4-h dwells of IdUrd administered i.p. daily for 4 days with and without an i.v. infusion of LV 500 mg/m2/day for 4.5 days. Twenty-three patients received single-agent therapy, and 13 patients received i.p. IdUrd in combination with i.v. LV. The MTD of single-agent IdUrd administered on this schedule was 4125 mg/m2/day for 4 days; and that of the IdUrd in combination was 3438 mg/m2/day. Dose-limiting toxicities were myelosuppression and stomatitis. During the period of the dwell, the peritoneal AUC (area under the curve) of IdUrd exceeded the plasma AUC of IdUrd by one or two orders of magnitude in all patients at all doses tested; there was a possible effect of LV on peritoneal AUC. The geometric mean pharmacological advantage (AUCperitoneal/ AUCplasma) was 181 at 625 mg/m2/day and 90 at 4538 mg/m2/day. Flow cytometric analysis suggests saturation of IdUrd measured in DNA at the 2500-3125 mg/m2 dose level, without an increase after the addition of LV. Twelve patients received 4-12 courses of therapy. One patient with recurrent ovarian cancer who received 16 courses of therapy experienced complete resolution of her ascites, near normalization of CA-125 levels, and improved quality of life; two patients with high-risk tumors receiving "adjuvant" therapy are disease-free at 3 and 6 years after treatment; other patients experienced transient clearing of ascites. The recommended Phase II dose of i.p. IdUrd using a 4-h dwell daily for 4 days is 3750 mg/m2/day alone or 3125 mg/m2/day in combination with continuous i.v. LV at 500 mg/m2/day for 4.5 days. Although flow cytometric data suggest that DNA incorporation of IdUrd is not affected by the addition of LV, the cytotoxicity of the combination regimen may be increased due to LV-enhanced, IdUrd-related inhibition of thymidylate synthase. For this reason, we recommend that efficacy studies of the combination continue in parallel with studies of IdUrd alone.