Long-term outcomes of patients bridged to recovery with venoarterial extracorporeal life support.

OBJECTIVE: Our study examines the long-term outcomes of patients discharged from the hospital without heart replacement therapy (HRT) after recovery from cardiogenic shock using venoarterial extracorporeal life support (VA-ECLS). METHODS: We retrospectively reviewed 615 cardiogenic shock patients who recovered from VA-ECLS at our institution between January 2015 and July 2021. Of those, 166 patients (27.0%) who recovered from VA-ECLS without HRT were included in this study. Baseline characteristics, discharge labs, vitals, electrocardiograms and echocardiograms were assessed. Patients were contacted to determine vital status. The primary outcome was post-discharge mortality. RESULTS: Of 166 patients, 158 patients (95.2%) had post-discharge follow-up, with a median time of follow-up of 2 years (IQR: [1 year, 4 years]). At discharge, the median ejection fraction (EF) was 52.5% (IQR: [32.5, 57.5]). At discharge, 92 patients (56%) were prescribed ß-blockers, 28 (17%) were prescribed an ACE inhibitor, ARB or ARNI, and 50 (30%) were prescribed loop diuretics. Kaplan-Meier analysis showed a 1-year survival rate of 85.6% (95% CI: [80.1%, 91.2%]) and a 5-year survival rate of 60.6% (95% CI: [49.9%, 71.3%]). A Cox regression model demonstrated that a history of congestive heart failure (CHF) was strongly predictive of increased mortality hazard (HR = 1.929; p = 0.036), while neither discharge EF nor etiology of VA-ECLS were associated with increased post-discharge mortality. CONCLUSIONS: Patients discharged from the hospital after full myocardial recovery from VA-ECLS support without HRT should have close outpatient follow-up due to the risk of recurrent heart failure and increased mortality in these patients.

Immune cell subsets in interface cutaneous immune-related adverse events associated with anti-PD-1 therapy resemble acute graft versus host disease more than lichen planus.

BACKGROUND: Checkpoint immunotherapy is frequently associated with cutaneous immune-related adverse events (cirAEs), and among those, the most common subtype shows interface reaction patterns that have been likened to lichen planus (LP); however, cutaneous acute graft versus host disease (aGVHD) may be a closer histopathologic comparator. We used quantitative pathology to compare the immunologic composition of anti-PD-1-associated interface reactions to LP and aGVHD to assess for similarities and differences between these cutaneous eruptions. METHODS: Immunohistochemistry for CD4, CD8, CD68, PD-1, and PD-L1 was performed on formalin-fixed paraffin-embedded tissue from patients with anti-PD-1 interface cirAEs (n = 4), LP (n = 9), or aGVHD (n = 5). Densities of immune cell subsets expressing each marker were quantified using the HALO image analysis immune cell module. Plasma cell and eosinophil density were quantified on routine H&E slides. RESULTS: Specimens from patients with anti-PD-1 interface cirAEs showed equivalent total cell densities and immune cell composition to those with aGVHD. Patients with LP showed higher total immune cell infiltration, higher absolute T-cell densities, increased CD8 proportion, and reduced histiocytic component. The cases with the highest plasma cell counts were all anti-PD-1 interface cirAEs and aGVHD. CONCLUSION: The composition of immune cell subsets in anti-PD-1 interface cirAEs more closely resembles the immune response seen in aGVHD than LP within our cohort. This warrants a closer look via advanced analytics and may have implications for shared pathogenesis and potential treatment options.

Rational Design of a Thermostable 2'-Deoxyribosyltransferase for Nelarabine Production by Prediction of Disulfide Bond Engineering Sites.

One of the major drawbacks of the industrial implementation of enzymatic processes is the low operational stability of the enzymes under tough industrial conditions. In this respect, the use of thermostable enzymes in the industry is gaining ground during the last decades. Herein, we report a structure-guided approach for the development of novel and thermostable 2'-deoxyribosyltransferases (NDTs) based on the computational design of disulfide bonds on hot spot positions. To this end, a small library of NDT variants from Lactobacillus delbrueckii (LdNDT) with introduced cysteine pairs was created. Among them, LdNDTS104C (100% retained activity) was chosen as the most thermostable variant, displaying a six- and two-fold enhanced long-term stability when stored at 55 °C (t1/255 °C ≈ 24 h) and 60 °C (t1/260 °C ≈ 4 h), respectively. Moreover, the biochemical characterization revealed that LdNDTS104C showed >60% relative activity across a broad range of temperature (30−90 °C) and pH (5−7). Finally, to study the potential application of LdNDTS104C as an industrial catalyst, the enzymatic synthesis of nelarabine was successfully carried out under different substrate conditions (1:1 and 3:1) at different reaction times. Under these experimental conditions, the production of nelarabine was increased up to 2.8-fold (72% conversion) compared with wild-type LdNDT.

Magnetic Multi-Enzymatic System for Cladribine Manufacturing.

Enzyme-mediated processes have proven to be a valuable and sustainable alternative to traditional chemical methods. In this regard, the use of multi-enzymatic systems enables the realization of complex synthetic schemes, while also introducing a number of additional advantages, including the conversion of reversible reactions into irreversible processes, the partial or complete elimination of product inhibition problems, and the minimization of undesirable by-products. In addition, the immobilization of biocatalysts on magnetic supports allows for easy reusability and streamlines the downstream process. Herein we have developed a cascade system for cladribine synthesis based on the sequential action of two magnetic biocatalysts. For that purpose, purine 2'-deoxyribosyltransferase from Leishmania mexicana (LmPDT) and Escherichia coli hypoxanthine phosphoribosyltransferase (EcHPRT) were immobilized onto Ni2+-prechelated magnetic microspheres (MagReSyn®NTA). Among the resulting derivatives, MLmPDT3 (activity: 11,935 IU/gsupport, 63% retained activity, operational conditions: 40 °C and pH 5-7) and MEcHPRT3 (12,840 IU/gsupport, 45% retained activity, operational conditions: pH 5-8 and 40-60 °C) emerge as optimal catalysts for further synthetic application. Moreover, the MLmPDT3/MEcHPRT3 system was biochemically characterized and successfully applied to the one-pot synthesis of cladribine under various conditions. This methodology not only displayed a 1.67-fold improvement in cladribine synthesis (compared to MLmPDT3), but it also implied a practically complete transformation of the undesired by-product into a high-added-value product (90% conversion of Hyp into IMP). Finally, MLmPDT3/MEcHPRT3 was reused for 16 cycles, which displayed a 75% retained activity.

Physician-perceived utility of the EORTC QLQ-GINET21 questionnaire in the treatment of patients with gastrointestinal neuroendocrine tumours: a multicentre, cross-sectional survey (QUALINETS).

BACKGROUND AND OBJECTIVE: Patient-reported outcome measures can provide clinicians with valuable information to improve doctor-patient communication and inform clinical decision-making. The aim of this study was to evaluate the physician-perceived utility of the QLQ-GINET21 in routine clinical practice in patients with gastrointestinal neuroendocrine tumours (GI-NETs). Secondary aims were to explore the patient, clinician, and/or centre-related variables potentially associated with perceived clinical utility. METHODS: Non-interventional, cross-sectional, multicentre study conducted at 34 hospitals in Spain and Portugal (NCT02853422). Patients diagnosed with GI-NETs completed two health-related quality of life (HRQoL) questionnaires (QLQ-C30, QLQ-GINET21) during a single routine visit. Physicians completed a 14-item ad hoc survey to rate the clinical utility of QLQ-GINET21 on three dimensions: 1)therapeutic and clinical decision-making, 2)doctor-patient communication, 3)questionnaire characteristics. RESULTS: A total of 199 patients at 34 centres were enrolled by 36 participating clinicians. The highest rated dimension on the QLQ-GINET21 was questionnaire characteristics (86.9% of responses indicating "high utility"), followed by doctor-patient communication (74.4%), and therapeutic and clinical decision-making (65.8%). One physician-related variable (GI-NET patient volume > 30 patients/year) was associated with high clinical utility and two variables (older age/less experience treating GI-NETs) with low clinical utility. CONCLUSIONS: Clinician-perceived clinical utility of QLQ-GINET21 is high. Clinicians valued the instruments' capacity to provide a better understanding of patient perspectives and to identify the factors that had the largest influence on patient HRQoL.

Recovery of motor function after traumatic spinal cord injury by using plasma-synthesized polypyrrole/iodine application in combination with a mixed rehabilitation scheme.

Traumatic spinal cord injury (TSCI) can cause paralysis and permanent disability. Rehabilitation (RB) is currently the only accepted treatment, although its beneficial effect is limited. The development of biomaterials has provided therapeutic possibilities for TSCI, where our research group previously showed that the plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical characteristics than those of the PPy synthesized by conventional methods, promotes recovery of motor function after TSCI. The present study evaluated if the plasma-synthesized PPy/I applied in combination with RB could increase its beneficial effects and the mechanisms involved. Adult rats with TSCI were divided into no treatment (control); biopolymer (PPy/I); mixed RB by swimming and enriched environment (SW/EE); and combined treatment (PPy/I + SW/EE) groups. Eight weeks after TSCI, the general health of the animals that received any of the treatments was better than the control animals. Functional recovery evaluated by two scales was better and was achieved in less time with the PPy/I + SW/EE combination. All treatments significantly increased ßIII-tubulin (nerve plasticity) expression, but only PPy/I increased GAP-43 (nerve regeneration) and MBP (myelination) expression when were analyzed by immunohistochemistry. The expression of GFAP (glial scar) decreased in treated groups when determined by histochemistry, while morphometric analysis showed that tissue was better preserved when PPy/I and PPy/I + SW/EE were administered. The application of PPy/I + SW/EE, promotes the preservation of nervous tissue, and the expression of molecules related to plasticity as ßIII-tubulin, reduces the glial scar, improves general health and allows the recovery of motor function after TSCI. The implant of the biomaterial polypyrrole/iodine (PPy/I) synthesized by plasma (an unconventional synthesis method), in combination with a mixed rehabilitation scheme with swimming and enriched environment applied after a traumatic spinal cord injury, promotes expression of GAP-43 and ßIII-tubulin (molecules related to plasticity and nerve regeneration) and reduces the expression of GFAP (molecule related to the formation of the glial scar). Both effects together allow the formation of nerve fibers, the reconnection of the spinal cord in the area of injury and the recovery of lost motor function. The figure shows the colocalization (yellow) of ßIII-tubilin (red) and GAP-43 (green) in fibers crossing the epicenter of the injury (arrowheads) that reconnect the rostral and caudal ends of the injured spinal cord and allowed recovery of motor function.

Effect of the combined treatment of albumin with plasma synthesised pyrrole polymers on motor recovery after traumatic spinal cord injury in rats.

Traumatic spinal cord injury (TSCI) is a health problem for which there is currently no treatment or definitive therapy. Medicine has explored therapeutic options for patients with TSCI with the aim to improve their quality of life. One alternative has been the development of biomaterials that offer neuroprotection or neuroregeneration of damaged nerve tissue. The microinjection of iodine-doped polypyrrole particles synthesised by plasma (PPPy/I) has shown neuroprotective effects that favour motor function recovery in experimental animals with TSCI. However, their ability to migrate into the tissue has led to the need to test a suspension vehicle that enables the concentration of particles at the site of injury. To achieve this, two biomaterials of PPPy/I (P1 and P2) were studied. The superficial physicochemical characterisation of the polymers was performed by infrared spectroscopy, X-ray photoelectron spectroscopy and contact angle. The rheological performance under oscillatory shear rate of suspensions containing both polymers alone and in combination with bovine serum albumin was also studied. In vivo tests were performed on animals with and without TSCI that were microinjected with particles of P1 or P2 in suspension using a solution of rat serum albumin. Exposure to the protein solutions generates a protein multilayer on the surface of the biomaterials that can drastically change the behaviour of both P1 and P2, which led to severe repercussions in the in vivo assays. The results showed that surface chemistry plays an important role in the performance and that it is possible to treat TSCI with these materials. The interaction of the surface of materials PPPy/I.1 (P1) and PPPy/I.2 (P2) with bovine serum albumin (BSA) resulted in a series of changes in the surface chemistry of both biomaterials. The contact angle study (Fig. A) showed the presence of a critical BSA concentration ([BSA]c), in which a monolayer was formed on both polymers and then a stable protein multilayer, as evidenced by the establishment of a plateau in the determination of the contact angle. In vivo tests showed that this interaction may be beneficial in the treatment of traumatic spinal cord injury (TSCI), depending on the surface characteristics with or without rat serum albumin (RSA). The TSCI + P1 and TSCI + P2 + RSA groups obtained significant differences in functional recovery compared with the control group according to the Basso, Beattie and Bresnahan scale (BBB).

Functional recovery in spinal cord injured rats using polypyrrole/iodine implants and treadmill training.

Currently, there is no universally accepted treatment for traumatic spinal cord injury (TSCI), a pathology that can cause paraplegia or quadriplegia. Due to the complexity of TSCI, more than one therapeutic strategy may be necessary to regain lost functions. Therefore, the present study proposes the use of implants of mesoparticles (MPs) of polypyrrole/iodine (PPy/I) synthesized by plasma for neuroprotection promotion and functional recovery in combination with treadmill training (TT) for neuroplasticity promotion and maintenance of muscle tone. PPy/I films were synthesized by plasma and pulverized to obtain MPs. Rats with a TSCI produced by the NYU impactor were divided into four groups: Vehicle (saline solution); MPs (PPy/I implant); Vehicle-TT (saline solution + TT); and MPs-TT (PPy/I implant + TT). The vehicle or MPs (30 µL) were injected into the lesion site 48 h after a TSCI. Four days later, TT was carried out 5 days a week for 2 months. Functional recovery was evaluated weekly using the BBB motor scale for 9 weeks and tissue protection using histological and morphometric analysis thereafter. Although the MPs of PPy/I increased nerve tissue preservation (P = 0.03) and promoted functional recovery (P = 0.015), combination with TT did not produce better neuroprotection, but significantly improved functional results (P = 0.000) when comparing with the vehicle group. So, use these therapeutic strategies by separately could stimulate specific mechanisms of neuroprotection and neuroregeneration, but when using together they could mainly potentiate different mechanisms of neuronal plasticity in the preserved spinal cord tissue after a TSCI and produce a significant functional recovery. The implant of mesoparticles of polypyrrole/iodine into the injured spinal cord displayed good integration into the nervous tissue without a response of rejection, as well as an increased in the amount of preserved tissue and a better functional recovery than the group without transplant after a traumatic spinal cord injury by contusion in rats. The relevance of the present results is that polypyrrole/iodine implants were synthesized by plasma instead by conventional chemical or electrochemical methods. Synthesis by plasma modifies physicochemical properties of polypyrrole/iodine implants, which can be responsible of the histological response and functional results. Furthermore, no additional molecules or trophic factors or cells were added to the implant for obtain such results. Even more, when the implant was used together with physical rehabilitation, better functional recovery was obtained than that observed when these strategies were used by separately.

Development and Characterization of Electrodes Coated with Plasma-Synthesized Polypyrrole Doped with Iodine, Implanted in the Rat Brain Subthalamic Nucleus.

Biological treatments involve the application of metallic material coatings to enhance biocompatibility and properties. In invasive therapies, metallic electrodes are utilized, which are implanted in patients. One of these invasive therapeutic procedures is deep brain stimulation (DBS), an effective therapy for addressing the motor disorders observed in patients with Parkinson's disease (PD). This therapy involves the implantation of electrodes (IEs) into the subthalamic nucleus (STN). However, there is still a need for the optimization of these electrodes. Plasma-synthesized polypyrrole doped with iodine (PPPy/I) has been reported as a biocompatible and anti-inflammatory biomaterial that promotes nervous system regeneration. Given this information, the objective of the present study was to develop and characterize a PPPy/I-coated electrode for implantation into the STN. The characterization results indicate a uniform coating along the electrode, and physical-chemical characterization studies were conducted on the polymer. Subsequently, the IEs, both coated and uncoated with PPPy/I, were implanted into the STN of male rats of the Wistar strain to conduct an electrographic recording (EG-R) study. The results demonstrate that the IE coated with PPPy/I exhibited superior power and frequency signals over time compared to the uncoated IE (p < 0.05). Based on these findings, we conclude that an IE coated with PPPy/I has optimized functional performance, with enhanced integrity and superior signal quality compared to an uncoated IE. Therefore, we consider this a promising technological development that could significantly improve functional outcomes for patients undergoing invasive brain therapies.

Allowing Standing and Assisted Steps in a Patient With Renshaw Type IV Sacral Agenesis: A Case Report of a Novel Surgical Approach.

CASE: A 6-year-old boy with a Renshaw type 4 sacral agenesis presented paraplegia and rigid, "Buddha-like" lower-limb contractures, including severe knee pterygia, which made crawling and sitting difficult. Staged surgical treatment involved bilateral knee disarticulation, soft tissue surgery, and bifocal femoral osteotomies for lower-limb reorientation. At 18 months postoperatively and after prosthetic fitting, the patient can stand and take steps with assistance. CONCLUSION: This effective surgical strategy achieves standing in a troublesome orthopaedic congenital condition. The intervention should be tailored to specific orthopaedic disorders and the wishes of patients and families, aiming to improve function.

Gene expression and locomotor recovery in adult rats with spinal cord injury and plasma-synthesized polypyrrole/iodine application combined with a mixed rehabilitation scheme.

Introduction: Spinal cord injury (SCI) can cause paralysis, for which effective therapeutic strategies have not been developed yet. The only accepted strategy for patients is rehabilitation (RB), although this does not allow complete recovery of lost functions, which makes it necessary to combine it with strategies such as plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical properties than PPy synthesized by conventional methods. After SCI in rats, PPy/I promotes functional recovery. Therefore, the purpose of this study was to increase the beneficial effects of both strategies and identify which genes activate PPy/I when applied alone or in combination with a mixed scheme of RB by swimming and enriched environment (SW/EE) in rats with SCI. Methods: Microarray analysis was performed to identify mechanisms of action underlying the effects of PPy/I and PPy/I+SW/EE on motor function recovery as evaluated by the BBB scale. Results: Results showed robust upregulation by PPy/I in genes related to the developmental process, biogenesis, synapse, and synaptic vesicle trafficking. In addition, PPy/I+SW/EE increased the expression of genes related to proliferation, biogenesis, cell development, morphogenesis, cell differentiation, neurogenesis, neuron development, and synapse formation processes. Immunofluorescence analysis showed the expression of ß-III tubulin in all groups, a decreased expression of caspase-3 in the PPy/I group and GFAP in the PPy/I+SW/EE group (p < 0.05). Better preservation of nerve tissue was observed in PPy/I and PPy/SW/EE groups (p < 0.05). In the BBB scale, the control group scored 1.72 ± 0.41, animals with PPy/I treatment scored 4.23 ± 0.33, and those with PPy/I+SW/EE scored 9.13 ± 0.43 1 month after follow-up. Conclusion: Thus, PPy/I+SW/EE could represent a therapeutic alternative for motor function recovery after SCI.

Plasma polypyrrole implants recover motor function in rats after spinal cord transection.

We studied the use of three biocompatible materials obtained by plasma polymerization of pyrrole (PPy), pyrrole doped with iodine (PPy/I) and a copolymer formed with pyrrole and polyethylene glycol (PPy/PEG), implanted, separately, after a complete spinal cord transection in rats. Motor function assessed with the BBB scale and somatosensory evoked potentials (SEPs) in the implanted rats were studied. Results showed that the highest motor recovery was obtained in rats with PPy/I implants. They also showed a significant reduction in the latency of SEPs. Histological analyses showed no signs of implant rejection; on the contrary, implants based on PPy improved the SEPs conduction and motor function after lesion.

Evolution of Spinal Cord Transection of Rhesus Monkey Implanted with Polymer Synthesized by Plasma Evaluated by Diffusion Tensor Imaging.

In spinal cord injury (SCI) there is damage to the nervous tissue, due to the initial damage and pathophysiological processes that are triggered subsequently. There is no effective therapeutic strategy for motor functional recovery derived from the injury. Several studies have demonstrated neurons growth in cell cultures on polymers synthesized by plasma derived from pyrrole, and the increased recovery of motor function in rats by implanting the polymer in acute states of the SCI in contusion and transection models. In the process of transferring these advances towards humans it is recommended to test in mayor species, such as nonhuman primates, prioritizing the use of non-invasive techniques to evaluate the injury progression with the applied treatments. This work shows the ability of diffusion tensor imaging (DTI) to evaluate the evolution of the SCI in nonhuman primates through the fraction of anisotropy (FA) analysis and the diffusion tensor tractography (DTT) calculus. The injury progression was analysed up to 3 months after the injury day by FA and DTT. The FA recovery and the DTT re-stabilization were observed in the experimental implanted subject with the polymer, in contrast with the non-implanted subject. The parameters derived from DTI are concordant with the histology and the motor functional behaviour.

Effectiveness of lanreotide autogel 120 mg at extended dosing intervals for acromegaly.

PURPOSE: Recent data indicate that extended dosing intervals (EDIs) with lanreotide autogel 120 mg are effective and well-received among patients with acromegaly who have achieved biochemical control with monthly injections of long-acting somatostatin analogues (SSAs). We further evaluated the effectiveness of lanreotide autogel 120 mg delivered at EDIs (>4 weeks) in routine clinical practice. METHODS: Cross-sectional, multicentre, observational study conducted to determine the effectiveness-measured by control of serum insulin-like growth factor 1 (IGF-1)-of lanreotide autogel 120 mg at dosing intervals >4 weeks for ≥6 months in selected patients with acromegaly treated in routine clinical practice (NCT02807233). Secondary assessments included control of growth hormone (GH) levels, treatment adherence, patient satisfaction, and quality of life (QoL) using validated questionnaires (EQ-5D, AcroQoL, and TSQM-9). Patients who received radiotherapy within the last 6 months were excluded. RESULTS: Among 109 patients evaluated, mean (SD) age was 59.1 (13.2) years. IGF-1 values were normal (mean [SD]: 175.0 [74.5], 95% CI: 160.8 -189.1) in 91.7% of cases and normal in 91.4% of patients without previous radiotherapy treatment (n = 81). GH levels were ≤2.5 and ≤1 ng/mL, respectively, in 80.6% and 58.3%. Most patients were treated either every 5-6 (57.8%) or 7-8 weeks (38.5%), with 2.8% treated greater than every 8 weeks. The mean AcroQoL score was 63.0 (20.1). The mean global treatment satisfaction score (TSQM-9) was 75.1 (16.6). Treatment adherence (defined as no missed injections) was 94.5%. CONCLUSION: Lanreotide autogel 120 mg at intervals of >4 weeks provided IGF-1 control in more than 90% of patients with acromegaly. Treatment satisfaction and adherence were good. These findings support use of extended dosing intervals in patients who have achieved good biochemical control with long-acting SSAs.

Effect of varying the crosslinking degree of a pericardial implant with oligourethane on the repair of a rat full-thickness abdominal wall defect.

The stability and bioactivity of biologic implants rely mainly on the control of the crosslinking process of collagen. However, the most common methods have no control on the crosslinking degree producing it excessively. This study outlines the role of crosslinking of collagen-based implants with oligourethane on the host response following reconstruction of a rat full-thickness abdominal wall defect. We decellularized and crosslinked bovine pericardial tissue to achieve two crosslinking degrees. For the decellularized implants, named as non-crosslinked (N-CL), the collagen-amines were 0.42 ± 0.02 mmol/mg. Crosslinking by the oligourethane reduced the primary amine concentration to 0.28 ± 0.01 and 0.19 ± 0.01 mmol/mg; these values were classified as low (∼30%, L-CL) and medium crosslinking (∼50%, M-CL), respectively. By imaging the implants using second harmonic generation microscopy, we observed undulated bundles of collagen fibers organized in multi-directed layers localized in N-CL and L-CL samples. Post-implantation, a negligible change in the organization of collagen fibers in the crosslinked implants was observed, suggesting that the in vivo biodegradation was delayed. An enlargement of the implant area was also observed, without rupture, in all three (N-CL, L-CL, M-CL) materials, whereas adhesion to the omentum, but not to the bowel, was observed. The number of blood vessels after 90-day implantation in N-CL and L-CL was 13 ± 1 and 12 ± 1 per field, respectively, while the number significantly decreased to 2 ± 1 in M-CL. The results suggest that the controlled degree of crosslinking in oligourethane-modified biologic implants can be used as a strategy to balance biodegradation and remodeling in surgical repair of soft tissues.

Adequate restitution in primary hypothyroidism depending on levothyroxine formulations / Restitución adecuada en hipotiroidismo primario según las presentaciones de levotirotiroxina

Background: The prevalence of primary hypothyroidism (PH) is around 3.8%-4.6% in general population. Out of patients under treatment with levothyroxine, approximately 40% show altered levels of thyroid-stimulating hormone (TSH). Objective: To determine the prevalence of euthyroid sick syndrome in patients under treatment for PH in two local clinics, considering that the number of formulations of levothyroxine could be a contributing factor to the inadequate restitution. Methods: Descriptive, comparative cohort conducted with PH patients who were treated with a stable dose of levothyroxine for at least six months. Patients treated with mixtures of liothyronine/levothyroxine, with postsurgical hypothyroidism, pregnant, breastfeeding or mentally ill were discarded. Medical clinic 1 was a public center that had only access to levothyroxine of 100 µg, and medical clinic 2 was a private clinic with access to 25, 50, 75 and 100 µg levothyroxine formulations. Results: A total of 350 patients were evaluated. 190 patients were obtained at clinic 1, and 160 patients at clinic 2. At clinic 1, only 63% received the appropriate dose, while at clinic 2, 75% were medicated with the correct dose (p = 0.033). Conclusion: In the public center, 39% of patients did not receive appropriate dose of levothyroxine; however, in the private clinic, which had more drug formulations, the percentage of patients lowered to 25%. Therefore, the number of formulations could be a factor for the risk of inadequate restitution.

Introducción: La prevalencia de hipotiroidismo primario (HP) en la población general oscila entre 3.8 y 4.6%. De los pacientes que están bajo tratamiento con levotiroxina, aproximadamente 40% muestra una hormona estimulante de la tiroides (TSH) anormal. Objetivo: Conocer la prevalencia de eutiroidismo en pacientes tratados por HP en dos clínicas de nuestra localidad, considerando que las presentaciones de levotiroxina pudiesen ser un factor contribuyente. Métodos: Cohorte comparativa de pacientes con HP tratados con levotiroxina en dosis estable por más de seis meses. Se descartaron los pacientes tratados con mezclas de liotironina/levotiroxina, hipotiroidismo postquirúrgico, embarazadas o en lactancia e individuos con enfermedades mentales. La clínica 1 (entidad pública) contó con levotiroxina de 100 µg y la clínica 2 (entidad privada) con pastillas de 25, 50, 75 y 100 µg. Resultados: Evaluamos 350 pacientes. De la clínica 1 se obtuvieron 190 y de la clínica 2 fueron 160. En la clínica 1, el 63% recibió la dosis adecuada, mientras que en la clínica 2, el 75% eran medicados con la dosis correcta (p = 0.033). Conclusiones: En la entidad pública, 39% no recibió la dosis adecuada de levotiroxina; sin embargo, en la entidad privada, con más presentaciones del medicamento, el número disminuye a 25%. Por lo tanto el número de presentaciones podría ser un factor influyente para lograr el eutiroidismo.

Neutral protamine hagedorn/regular insulin in the treatment of inpatient hyperglycemia: Comparison of 3 basal-bolus regimens.

AIM: To compare the safety and efficacy or 3 basal-bolus regimens of neutral protamine hagedorn (NPH)/regular insulin in the management of inpatient hyperglycemia. METHODS: We randomized 105 patients with blood glucose levels between 140 and 400 mg/dL to a basal-bolus regimen of NPH insulin given once (n = 30), twice (n = 40) or three times (n = 35) daily, in addition to pre-meal regular insulin. Major outcomes included were differences in glycemic control, frequency of hypoglycemia and total insulin dose. RESULTS: NPH insulin given in a once-daily regimen was associated with better glycemic control (58.3%) compared to twice daily (42.4%) and three times daily (48.9) regimens (P = 0.031). The frequency of hypoglycemia was similar between the three groups (2.0%, 0.7% and 1.2%, P = 0.21). The mean insulin dose at discharge was 0.48 ± 0.14 U/kg in the once-daily group compared to 0.69 ± 0.28 in the twice-daily, and 0.65 ± 0.20 in the three times daily regimens (P < 0.001). CONCLUSION: NPH insulin administered in a once-daily regimen resulted in improvement in glycemic control with similar rates of hypoglycemia compared to a twice-daily and a three times-daily regimen. Further studies are needed to evaluate whether this regimen could be implemented in all hospitalized patients with hyperglycemia.

Delayed injection of polypyrrole doped with iodine particle suspension after spinal cord injury in rats improves functional recovery and decreased tissue damage evaluated by 3.0 Tesla in vivo magnetic resonance imaging.

BACKGROUND CONTEXT: Traumatic spinal cord injury (SCI) causes irreversible damage with loss of motor, sensory, and autonomic functions. Currently, there is not an effective treatment to restore the lost neurologic functions. PURPOSE: Injection of polypyrrole-iodine(PPy-I) particle suspension is proposed as a therapeutic strategy. STUDY DESIGN: This is an in vivo animal study. METHODS: This study evaluates the use of such particles in rats after SCI by examining spared nervous tissue and the Basso, Beattie, and Bresnahan (BBB) scale to evaluate the functional outcome. Diffusive magnetic resonance imaging (MRI) was employed to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) as non-invasive biomarkers of damage after SCI. RESULTS: Fractional anisotropy decreased, whereas ADC increased in all groups after the lesion. There were significant differences in FA when compared with the SCI-PPy-I group versus the SCI group (p<.05). Significant positive correlations between BBB and FA (r2=0.449, p<.05) and between FA and preserved tissue (r2=0.395, p<.05) were observed, whereas significant negative associations between BBB and ADC (r2=0.367, p<.05) and between ADC and preserved tissue (r2=0.421, p<.05) were observed. CONCLUSIONS: The results suggested that PPy-I is neuroprotective as it decreased the amount of damaged tissue while improving the motor function. Non-invasive MRI proved to be useful in the characterization of SCI and recovery.

Noise-induced fluctuations of period lengths of stable periodic orbits.

We discuss a class of one-dimensional maps, which possesses a globally attracting stable periodic orbit. Despite a strongly negative Lyapunov exponent, a small amount of noise can introduce fluctuations of the period length. It is shown that this is a reasonable model for the observed dynamics of a bubble formation experiment in a heated capillary embedded in boiling water.

Fluoride content by ion chromatography using a suppressed conductivity detector and osmolality of bitterns discharged into the Pacific Ocean from a saltworks: feasible causal agents in the mortality of green turtles (Chelonia mydas) in the Ojo de Liebre lagoon, Baja California Sur, Mexico.

On December 1997, 94 corpses of green turtles, Chelonia mydas, were found at the Ojo de Liebre lagoon (OLL) adjacent to the industrial operation of Exportadora de Sal S. A (ESSA), the largest saltworks in the world, owned by the Mexican Government and Mitsubishi Corporation, located in Baja California Sur, Mexico. Every year about 551 x 10(6) m3 of seawater is solar evaporated, producing 7 x 10(6) tons of salt and 24.6 x 10(6) m3 of bitterns, the latter being discharged into the OLL, which is a costal lagoon of the Pacific Ocean. ESSA claimed that bitterns contain the same salts present in seawater, but 20-fold more concentrated than the former. Ion chromatography with a conductivity detector and ion suppression was used to determine the F-, Cl-, SO4(2-) and CO3(2-) contents of seawater, brines and bitterns collected at ESSA. Furthermore, the osmolality of brines and bitterns from ESSA was measured. F- content in bitterns was 60.5-fold more than that in seawater. The bitterns osmolality was 11,000 mosm/kg of water, whereas the turtle's plasma osmolality was about 400 mosm/kg of water. We concluded that the dumping of bitterns into the ocean should be avoided.