Uniportal versus multiportal video-assisted thoracoscopic surgery for spontaneous pneumothorax.

BACKGROUND: Multiportal video-assisted thoracic surgery (mVATS) is the standard approach for the surgical treatment of spontaneous pneumothorax. However, uniportal VATS (uVATS) has emerged as an alternative aiming to minimize surgical morbidity. This study aims to strengthen the evidence on the safety and efficiency of uVATS compared to mVATS. METHODS: From January 2004 to December 2020, records of patients who had undergone surgical treatment for primary or secondary spontaneous pneumothorax were evaluated for eligibility. Patients who had undergone pleurectomy combined with bullectomy or apical wedge resection via uVATS or mVATS were included. Surgical characteristics and postoperative data were compared between patients who had undergone surgery via uVATS or mVATS. Univariable and multivariable analyses were performed to determine whether the surgical approach was associated with any complication (primary outcome), major complications (i.e., Clavien-Dindo ≥ 3), recurrence, prolonged hospitalization or prolonged chest drainage duration (secondary outcomes). RESULTS: A total of 212 patients were enrolled. Patients treated via uVATS (n = 71) and mVATS (n = 141) were significantly different in pneumothorax type (secondary spontaneous; uVATS: 54 [76%], mVATS: 79 [56%]; p = 0.004). No significant differences were observed in (major) complications and recurrence rates between both groups. Multivariable analyses revealed that the surgical approach was no significant predictor for the primary or secondary outcomes. CONCLUSIONS: This study indicates that uVATS is non-inferior to mVATS in the surgical treatment of spontaneous pneumothorax regarding safety and efficiency, and thus the uVATS approach has the potential for further improvements in the perioperative surgical care for spontaneous pneumothorax.

Satisfaction with a meal kit delivery program and feasibility of a phase I trial in the intervening in food insecurity to reduce and mitigate (InFoRM) childhood obesity study.

BACKGROUND: Food and nutrition security interventions have been demonstrated to optimize health, prevent and treat chronic diseases among adult populations. Despite the increasing prevalence and intersection of food insecurity and childhood obesity in the United States, there are few food and nutrition security interventions targeted to children and families. OBJECTIVES: The primary purpose of this phase I randomized, crossover trial was to assess the safety, acceptability and satisfaction of a meal kit delivery program among children with obesity living in households with food insecurity. Secondarily, we assessed the feasibility of our study design, recruitment and retention to inform future larger scale trials. METHODS: We delivered 6 weeks of healthy meal kits, which included fresh pre-portioned ingredients and simple picture-based recipes (two recipes/week) in English or Spanish to prepare one-pot, under 30-min meals (after preparation ~ 10 servings/week). RESULTS: Caregivers received and prepared the meal kits and reported overall satisfaction with the meal kit delivery program. CONCLUSION: A meal kit delivery intervention for children with obesity and food insecurity is acceptable and a phase I randomized, crossover trial is feasible.

Predicting Survival in Patients Presenting With Spinal Epidural Metastases: The Limburg Spinal Metastasis Score.

BACKGROUND: Patients with spinal epidural metastases (SEM) often experience a reduction in ambulatory status and, thus, the quality of life. Predicting which patients will benefit from a surgical intervention remains a challenge. Life expectancy is an essential factor to be considered in surgical decision-making, although not the only one. Prediction models can add value in surgical decision-making. The goal of this study was to develop and internally validate a novel model (Limburg spinal metastases score [LSMS]) and compare the predictive value with 2 commonly used models: modified Bauer score and Oswestry Spinal Risk Index (OSRI). METHODS: We retrospectively analyzed 144 consecutive patients who underwent surgical decompression for SEM in our centers between November 2006 and December 2020. Clinical and surgical parameters were evaluated. The novel prediction model was based on multivariate analysis and was internally validated. External validation of the 2 most commonly used prediction models was performed. RESULTS: The median survival was 17 months, 55.7% of the immobile patients regained ambulation postoperatively. In 50 patients (34.7%), at least 1 complication occurred within 30 days after surgery. The LSMS consists of 4 parameters: primary tumor type, Karnofsky performance score, presence of visceral metastases, and presence of multiple spinal metastases. Bootstrap internal validation of the model developed on this cohort yielded an optimism-corrected c-statistic of 0.75 (95% CI: 0.71-0.80). The c-statistic of the OSRI score and the Bauer score was 0.69 (95% CI: 0.64-0.74) and 0.67 (95% CI: 0.62-0.72), respectively. CONCLUSION: The LSMS consists of 4 parameters to assist surgical decision-making for patients with SEM. The score is easy to use and appears more accurate in our population in comparison with previous existing models. CLINICAL RELEVANCE: A novel prediction model was developed to aid in surgical decision-making for patients with spinal epidural metastases.

Metabolic strategies for the degradation of the neuromodulator agmatine in mammals.

Agmatine (1-amino-4-guanidinobutane), a precursor for polyamine biosynthesis, has been identified as an important neuromodulator with anticonvulsant, antineurotoxic and antidepressant actions in the brain. In this context it has emerged as an important mediator of addiction/satiety pathways associated with alcohol misuse. Consequently, the regulation of the activity of key enzymes in agmatine metabolism is an attractive strategy to combat alcoholism and related addiction disorders. Agmatine results from the decarboxylation of L-arginine in a reaction catalyzed by arginine decarboxylase (ADC), and can be converted to either guanidine butyraldehyde by diamine oxidase (DAO) or putrescine and urea by the enzyme agmatinase (AGM) or the more recently identified AGM-like protein (ALP). In rat brain, agmatine, AGM and ALP are predominantly localised in areas associated with roles in appetitive and craving (drug-reinstatement) behaviors. Thus, inhibitors of AGM or ALP are promising agents for the treatment of addictions. In this review, the properties of DAO, AGM and ALP are discussed with a view to their role in the agmatine metabolism in mammals.

Mammalian agmatinases constitute unusual members in the family of Mn2+-dependent ureahydrolases.

Agmatine (1-amino-4-guanidinobutane) plays an important role in a range of metabolic functions, in particular in the brain. Agmatinases (AGMs) are enzymes capable of converting agmatine to the polyamine putrescine and urea. AGMs belong to the family of Mn2+-dependent ureahydrolases. However, no AGM from a mammalian source has yet been extracted in catalytically active form. While in human AGM the six amino acid ligands that coordinate the two Mn2+ ions in the active site are conserved, four mutations are observed in the murine enzyme. Here, we demonstrate that similar to its human counterpart murine AGM does not appear to have in vitro catalytic activity, independent of the presence of Mn2+. However, in presence of agmatine both enzymes are very efficient in promoting cell growth of a yeast strain that is deficient in polyamine biosynthesis (Saccharomyces cerevisiae strain TRY104Δspe1). Furthermore, mutations among the putative Mn2+ binding residues had no effect on the ability of murine AGM to promote growth of the yeast culture. It thus appears that mammalian AGMs form a distinct group within the family of ureahydrolases that (i) either fold in a manner distinct from other members in this family, or (ii) require accessory proteins to bind Mn2+ in a mechanism related to that observed for the Ni2+-dependent urease.

Cloning of two LIMCH1 isoforms: characterization of their distribution in rat brain and their agmatinase activity.

Agmatine, a precursor for polyamine biosynthesis, is also associated with neurotransmitter, anticonvulsant, antineurotoxic and antidepressant actions in the brain. This molecule results from the decarboxylation of L-arginine by arginine decarboxylase, and it is hydrolyzed to urea and putrescine by agmatinase. Recently, we have described a new protein that also hydrolyzes agmatine, agmatinase-like protein (ALP), which was identified through immunohistochemical analysis in the hypothalamus and hippocampus of rats. However, its sequence differs greatly from all known agmatinases and does not contain the typical Mn(2+) ligands associated with the urea hydrolase family of proteins. ALP has a LIM-like domain close to its carboxyl terminus, and the removal of which results in a truncated variant with a tenfold increased k cat value and a threefold decreased K m value for agmatine. Analysis of the gene database revealed several transcripts, denominated LIMCH1 isoforms, with extreme 3' sequences identical to ALP. Limch1 gene products have been described as members of a multi-domain family of proteins with the biggest isoform containing a calponin homology (CH) domain at its N-terminus. Here, we cloned two LIMCH1 transcripts, one of 3177 bp and the other of 2709 bp (ALP contains 1569 bp) and analyzed LIMCH1 expression and distribution in rat brain using RT-PCR, Western blot and immunohistochemical analyses. LIMCH1 was detected mainly in the hypothalamic and hippocampal regions, which is similar to the distribution of ALP and agmatine in brain. In addition, we cloned and expressed both isoforms in E. coli and confirmed that they were catalytically active on agmatine with kinetic parameters similar to ALP. LIM domain-truncated variants of both isoforms moderately increased the k cat and catalytic efficiency. Thus, we propose that LIMCH1 is useful to regulate the intracellular concentrations of the neurotransmitter/neuromodulator, agmatine.

Insight on the interaction of an agmatinase-like protein with Mn(2+) activator ions.

Agmatinase is an enzyme that catalyzes the hydrolysis of agmatine, a compound that is associated with numerous functions in the brain of mammalian organisms such as neurotransmitter, anticonvulsant, antinociceptive, anxiolytic and antidepressant-like actions. To date the only characterized agmatinases with significant enzymatic activity were extracted from bacterial organisms. These agmatinases are closely related to another ureahydrolase, arginase; both have binuclear Mn(2+) centers in their active sites. An agmatinase-like protein (ALP) from rat brain was identified that bears no sequence homology to known agmatinases (E. Uribe, M. Salas, S. Enriquez, M.S. Orellana, N. Carvajal, Arch. Biochem. Biophys. 461(2007) 146-150). Since all known ureahydrolases contain histidines in their binuclear Mn(2+) site each of the five histidine residues in ALP was individually replaced by alanines to identify those that may be involved in metal ion binding. Reactivation assays and thermal stability measurements indicated that His206 is likely to interact with a Mn(2+) bound to a high affinity site. In contrast, His65 and possibly His435 are important for binding of a second Mn(2+) to a lower affinity site. Metal ion binding to that site is not only leading to an increase in reactivity but also enzyme stability. Thus, similar to bacterial agmatinases and some of the antibiotic-degrading, Zn(2+)-dependent metallo-ß-lactamases ALP appears to be active in the mono and binuclear form, with binding of the second metal ion increasing both reactivity and stability.

Impregnation of an intraocular lens for ophthalmic drug delivery.

In this work the possibility of impregnating P(MMA-EHA-EGDMA) with flurbiprofen using a clean and environmentally friendly technology, namely supercritical fluid technology was evaluated. P(MMA-EHA-EGDMA) has been proposed as a promising matrix to be used for intraocular delivery of anti-inflammatory drugs used in eye surgery and flurbiprofen is a non-steroidal anti-inflammatory agent. Fundamental studies like, the solubility of the drug in carbon dioxide, as well as the sorption degree of this polymeric matrix in the presence of carbon dioxide have been previously carried out. The aim of this research was to evaluate the effects of these two variables in the impregnation process. Different experimental conditions were tested and the results obtained suggest that the best impregnating conditions for this system are low temperatures and pressures, which at the same time correspond to a lower solubility of the drug in the supercritical fluid and a low swelling of the polymeric matrix. Experiments performed also indicate that the batch impregnation process leads to higher yields of impregnation and according to the release profiles obtained the drug can be released from the matrix up to three months, which presents great advantages for post-surgical treatments.

Theophylline formulation by supercritical antisolvents.

Supercritical antisolvent precipitation has been used to produce theophylline particles as pure crystals or as a solid formulation with poly lactic acid (PLA). Experiments were carried out as batch or semi-continuous process and with carbon dioxide (CO2) or trifluoromethane (CHF3) as antisolvent. Both modes led to micronized theophylline, but the semi-continuous produced smaller particles than the batch. The particle morphology was sensitive to the antisolvent, since CO2- and CHF3-samples exhibited hexagonal and triangular shape, respectively. The most distinguish feature of CO2-powders was that theophylline exhibited a different crystal lattice than the crude- or the CHF3-materials, accredited by new diffraction peaks in the XRD patterns not attributable to hydration of samples. However, neither the shape nor the new crystal lattice influenced the dissolution kinetics of Theophylline. For co-precipitation with PLA, the successful recovery of a powder occurred only in conditions of CHF3-batch and CO2-semi continuous. The powder retained the shape and the crystallinity of the corresponding pure processed theophylline, indicating that PLA did not interfere with the precipitation behavior of the drug. Moreover, only the CO2-semi continuous products exhibited a decreased release rate and a prolongation of the total release time of the drug.

Preparation of acetazolamide composite microparticles by supercritical anti-solvent techniques.

The possibility of preparation of ophthalmic drug delivery systems using compressed anti-solvent technology was evaluated. Eudragit RS 100 and RL 100 were used as drug carriers, acetazolamide was the model drug processed. Compressed anti-solvent experiments were carried out as a semi-continuous or a batch operation from a liquid solution of polymer(s)+solute dissolved in acetone. Both techniques allowed the recovery of composite particles, but the semi-continuous operation yielded smaller and less aggregated populations than the batch operation. The release behaviour of acetazolamide from the prepared microparticles was studied and most products exhibited a slower release than the single drug. Moreover, the release could be controlled to some extent by varying the ratio of the two Eudragit used in the formulation and by selecting one or the other anti-solvent technique. Simple diffusion models satisfactorily described the release profiles. Composites specifically produced by semi-continuous technique have a drug release rate controlled by a diffusion mechanism, whereas for composites produced by the batch operation, the polymer swelling also contributes to the overall transport mechanism.