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Pancreas transplant (PTx) is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes types 1 and 2. The paper aims to review and analyze graft survival, patient survival, and the impact on diabetic complications. We describe that the graft survival was 82-98% at 1 year, 90% at 5 years, and 75-54% at 10 years for simultaneous pancreas-kidney recipient; 71% pancreas after kidney (PAK), and 62% PTx alone at 1 year. Patient survival: At 1 year for recipients was 96.9% simultaneous pancreas-kidney transplantation (SPK); for PAK transplantation recipients, 96.3%; and for PTx alone recipients, 98.3%. In general, the pancreas transplantation improves and reverses diabetic complications. Finally, the pancreatic transplant is a morbid procedure and emerges as a significant alternative in diabetes management, directly competing with conventional insulin therapies. Results so far suggest that the most effective transplant model is the SPK. While more patients could benefit from this procedure, surgical complications and the need for immunosuppression pose significant challenges.

El trasplante de páncreas es el único tratamiento que estabiliza los niveles normales de glucosa en los pacientes diagnosticados con diabetes tipo 1 o tipo 2. En esta revisión se analizan la supervivencia del injerto, la supervivencia del paciente y el impacto en las complicaciones diabéticas. Se describe la supervivencia del injerto: 82-98% al año para los receptores de trasplante simultáneo de páncreas y riñón, 71% para trasplante páncreas después de riñón y 62% para trasplante de páncreas solitario al año. Supervivencia de los pacientes a 1 año: 96.9% para los receptores de trasplante simultáneo de páncreas y riñón, 96.3% para los receptores de trasplante de páncreas después de riñón y 98.3% para los receptores de páncreas solitario. En general, el trasplante de páncreas mejora y revierte las complicaciones diabéticas. Finalmente, el trasplante de páncreas, un procedimiento mórbido, surge como una alternativa significativa en el manejo de la diabetes, compitiendo directamente con las terapias convencionales de insulina. Hasta ahora, los resultados indican que el modelo de trasplante más efectivo es el simultáneo de páncreas y riñón. Aunque más pacientes podrían beneficiarse de este procedimiento, las complicaciones quirúrgicas y la necesidad de inmunosupresión plantean desafíos significativos.

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Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of nanocrystals (NCs). Beyond the many advantages of formulating NCs, their incorporation into solid dosage forms remains a challenge that limits their use. In this work, we set out to load Atorvastatin NCs (ATV-NCs) in a delivery device by combining 3D scaffolds with an "in situ" loading method such as freeze-drying. When comparing two infill patterns for the scaffolds at two different percentages, the one with the highest NCs load was chosen (Gyroid 20 % infill pattern, 13.8 ± 0.5 mg). Colloidal stability studies of NCs suggest instability in acidic media, and therefore, the system is postulated for use as a sublingual device, potentially bypassing stomach and hepatic first-pass effects. An ad hoc dissolution device was developed to mimic the release of actives. The nanometric size and properties acquired in the process were maintained, mainly in the dissolution rate and speed, achieving 100 % dissolution of the content in 180 s. Based on these results, the proof of concept represents an innovative approach to converting NCs suspensions into solid dosage forms.

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The challenge of low water solubility in pharmaceutical science profoundly impacts drug absorption and therapeutic effectiveness. Nanocrystals (NC), consisting of drug molecules and stabilizing agents, offer a promising solution to enhance solubility and control release rates. In the pharmaceutical industry, top-down techniques are favored for their flexibility and cost-effectiveness. However, increased solubility can lead to premature drug dissolution in the stomach, which is problematic due to the acidic pH or enzymes. Researchers are exploring encapsulating agents that facilitate drug release at customized pH levels as a valuable strategy to address this. This study employed wet milling and spray drying techniques to create encapsulated NC for delivering the drug to the intestinal tract using the model drug ivermectin (IVM). Nanosuspensions (NS) were efficiently produced within 2 h using NanoDisp®, with a particle size of 198.4 ± 0.6 nm and a low polydispersity index (PDI) of 0.184, ensuring uniformity. Stability tests over 100 days at 4 °C and 25 °C demonstrated practical viability, with no precipitation or significant changes observed. Cytotoxicity evaluations indicated less harm to Caco-2 cells compared to the pure drug. Furthermore, the solubility of the NC increased by 47-fold in water and 4.8-fold in simulated intestinal fluid compared to the pure active compound. Finally, dissolution tests showed less than 10% release in acidic conditions and significant improvement in simulated intestinal conditions, promising enhanced drug solubility and bioavailability. This addresses a long-standing pharmaceutical challenge in a cost-effective and scalable manner.

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Atorvastatin (ATV) is a first-line drug for the treatment of hyperlipidemia. This drug presents biopharmaceutical problems, partly due to its low solubility and dissolution rate. In this work, nanocrystals of ATV stabilized with Tween 80® were designed by wet milling. A full factorial design was applied to optimize the process. Additionally, a cryoprotectant agent (maltodextrin, MTX) was identified, which allowed maintaining the properties of the nanocrystals after lyophilization. The storage stability of the nanocrystals was demonstrated for six months in different conditions. The obtained nanocrystal powder was characterized using SEM, EDXS, TEM, DSC, TGA, FT-IR, and XRD, showing the presence of irregular crystals with semi-amorphous characteristics, likely due to the particle collision process. Based on the reduction in particle size and the decrease in drug crystallinity, a significant increase in water and phosphate buffer (pH 6.8) solubility by 4 and 6 times, respectively, was observed. On the other hand, a noticeable increase in the dissolution rate was observed, with 90 % of the drug dissolved within 60 min of study, compared to 30 % of the drug dissolved within 12 h in the case of the untreated drug or the physical mixture of components. Based on these results, it can be concluded that the nano-milling of Atorvastatin stabilized with Tween 80® is a promising strategy for developing new formulations with improved biopharmaceutical properties of this widely used drug.

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OBJECTIVE AND SIGNIFICANCE: This research aims to design and develop a pilot plant-type pharmaceutical reactor with a strong focus on its volumetric capacity and heat transfer capabilities. The primary goal is to replicate design and control strategies at the laboratory or pilot scale to analyze and produce generic semisolid formulations. METHODS: Computational fluid dynamics and heat transfer modeling, utilizing the finite volume method, were employed to determine the reactor's performance and particle trajectory during the mixing and stirring. This allowed for the establishment of optimal operational parameters and variables. Furthermore, prototypes were constructed at 1:2.5 and 1:15 scales to examine the reactor's morphology, ensure volumetric versatility, and conduct mixing, homogenization, and coloration tests using varying volumes. RESULTS AND CONCLUSIONS: The outcomes of this study yielded a versatile reactor suitable for processing pharmaceutical semisolids at both laboratory and pilot-scale volumes. Notably, the reactor demonstrated exceptional volumetric capacity within a single vessel while effectively facilitating heat transfer to its interior.

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Introduction: The flaps, whose function is to reduce or redirect tension during a closure, are classified based on their primary movement: transposition, advancement, and rotation, each with its characteristics, indications, and peculiarities. Combining the qualities of the transposition flaps with those of rotation, which make up the S-Apple flap, makes it more versatile and with better aesthetic results than the bilobed flap, which denotes the archetype for the appearance of the S-Apple. Method: Having the rotation and transposition flaps as an archetype, four flaps are made in the S-Apple flap, which are rotated and transposed to close the defect. This is excised in a circular format for the oncological safety of margins. The "S" of the flap is traced at a 30º angle in relation to the defect. The arm dimension must be the same diameter as the defect, with the flaps transposed as in a z-plasty, and the flap rotated to cover the defect, resulting from the exeresis of the lesion. Results: No necrosis, infection, dehiscence, recurrences, trapdoor scars, or rotation point elevation were observed. The scars were classified as satisfactory and extremely satisfactory. Conclusion: The S-Apple flap proved versatile and easy to mark with excellent aesthetic and functional results.

Introdução: Os retalhos, com função de reduzir ou redirecionar a tensão durante um fechamento, são classificados com base em seu movimento primário: transposição, avanço e rotação, cada um com suas características, indicações e peculiaridades. O arregimentar das qualidades dos retalhos de transposição com os de rotação, que compõem o retalho S-Apple, tornam-no mais versátil e com melhores resultados estéticos em relação ao retalho bilobado, que denota o arquétipo para o surgimento do S-Apple. Método: Tendo como arquétipo os retalhos de rotação e transposição, no retalho S-Apple são confeccionados quatro retalhos, que são rotacionados e transpostos para fechamento do defeito. Este é excisado em formato circular para segurança oncológica de margens. O "S" do retalho é traçado em um ângulo de 30º em relação ao defeito. A dimensão do braço deve ser do mesmo diâmetro do defeito, sendo os retalhos transpostos como em uma zetaplastia e o retalho rotacionado para cobrir o defeito, resultante da exérese da lesão. Resultados: Não foram observadas necroses, infecção, deiscências, recidivas, cicatrizes em alçapão e elevação em ponto de rotação. As cicatrizes foram classificadas como satisfatórias e extremamente satisfatórias. Conclusão: O retalho S-Apple se mostrou um retalho versátil de fácil marcação com excelentes resultados estéticos e funcionais.

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Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for Helicobacter pylori. The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form to release them into the stomach slowly. For this purpose, NICLO-NCRs were produced by wet-milling and included in a floating Gelucire l3D printed tablet by semi-solid extrusion, applying the Melting solidification printing process (MESO-PP) methodology. The results obtained in TGA, DSC, XRD and FT-IR analysis showed no physicochemical interactions or modifications in the crystallinity of NICLO-NCR after inclusion in Gelucire 50/13 ink. This method allowed the incorporation of NICLO-NCRs in a concentration of up to 25% w/w. It achieved a controlled release of NCRs in a simulated gastric medium. Moreover, the presence of NICLO-NCRs after redispersion of the printlets was observed by STEM. Additionally, no effects on the cell viability of the NCRs were demonstrated in the GES-1 cell line. Finally, gastroretention was demonstrated for 180 min in dogs. These findings show the potential of the MESO-PP technique in obtaining slow-release gastro-retentive oral solid dosage forms loaded with nanocrystals of a poorly soluble drug, an ideal system for treating gastric pathologies such as H. pylori.

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BACKGROUND: The safety and efficacy data of the different types of available vaccines is still needed. The goal of the present analysis was to evaluate the humoral response to the COVID-19 vaccines in orthotopic liver transplant (OLT) recipients. METHODS: Participants were included from February to September 2021. No prioritized vaccination roll call applied for OLT patients. Controls were otherwise healthy people. Blood samples were drawn after 15 days of the complete vaccine doses. The samples were analyzed according to the manufacturer's instructions using the Liaison XL platform from DiaSorin (DiaSorin S.p.A., Italy), and SARS-COV-2 IgG II Quant (Abbott Diagnostics, IL, USA). RESULTS: A total of 187 participants (133 OLT, 54 controls, median age: 60 years, 58.8% women) were included for the analysis; 74.3% had at least one comorbidity. The serologic response in OLT patients was lower than in controls (median 549 AU/mL vs. 3450 AU/mL, respectively; p = 0.001). A positive humoral response was found in 133 OLT individuals: 89.2% with BNT162b2 (Pfizer-BioNTech), 60% ChAdOx1 nCOV-19 (Oxford-AstraZeneca), 76.9% with CoronaVac (Sinovac, Life Sciences, China), 55.6% Ad5-nCov (Cansino, Biologics), 68.2% Gam-COVID-Vac (Sputnik V) and 100% with mRNA-1273. In controls the serological response was 100%, except for Cansino (75%). In a multivariable model, personal history of COVID-19 and BNT162b2 inoculation were associated with the serologic response, while the use of prednisone (vs. other immunosuppressants) reduced this response. CONCLUSION: The serologic response to COVID-19 vaccines in OLT patients is lower than in healthy controls. The BNT162b2 vaccine was associated with a higher serologic response.

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Schistosomiasis is a widely distributed parasitic disease and one of the most important neglected tropical diseases globally, for which Praziquantel® (PZQ) is the only available treatment. In this context, tests with new PZQ formulations become relevant for disease control. This study evaluated the effects of PZQ treatment in the prepatent phase of schistosomiasis using two formulations: nanoencapsulated (PZQ-NANO) and active pharmaceutical ingredient (PZQ-API). Five experimental groups were established, for which the following serological parameters were evaluated: ALT, AST, ALP, and TP. Animals treated with PZQ-API at 15 and 30 days post-infection showed decreased eggs per gram of feces (EPG) compared to untreated infected animals. The same animals showed reductions of 63.6 and 65.1%, respectively, at 60 days post-infection. Animals treated with PZQ-NANO experienced no significant changes in EPG at any time of observation. Animals treated with either PZQ-API or PZQ-NANO had higher ALT and AST levels in the patent period (60 and 90 days post-infection). Treatment with PZQ, either API or NANO, at 15 days post-infection reduced AST, ALT, and TP levels. It is concluded that prepatent treatment with PZQ-API can reduce the parasite load of infected animals and that treatment at 15 days post-infection can prevent increased serum levels of ALT, AST, and TP.

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This is the first report on the inclusion of nanocrystals (NCs) within 3D-printed oral solid dosage forms -3D-printed tablets or printlets- produced by the Melting Solidification Printing Process (MESO-PP) 3D printing technique. This method allowed the incorporation of albendazole (ABZ) nanocrystals in a concentration of up to 50% w/w, something not achieved in conventional tablets. An ink of PEG 1500/propylenegycol was used as a carrier and no physicochemical interactions or crystallinity modifications were observed due to the inclusion of ABZ-NCs into the ink, as demonstrated by TGA, DSC, XRD and FT-IR. In particular, the relative crystallinity of the ink loaded with NCs was 97.8% similar to the physical mixture of the components. Moreover, the presence of NCs was observed in the surface and matrix of the printlets by SEM. In addition, the printlet NCs demonstrated to be more effective than NCs included in hard gelatin capsules in improving drug dissolution in HCl 0.1 N. The particle size, crystallinity and chemical stability of the nanocrystals was maintained before and after 180 days of storage. Thus, these findings exhibit relevant pharmaceutical potential for developing stable, fast-release, oral, solid dosage forms of poorly soluble drugs combining 3D printing and nanocrystals. Additionally, this technique could be applied for printing objects using different types of nanocrystals embedded in low melting temperature polymers.

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