Gastric neobladders: surgical outcomes of 91 cases using different techniques.

INTRODUCTION: We report on the surgical results of a series of 91 patients who received gastric neobladders as urinary diversion after radical cystectomies performed for the treatment of muscle-invasive bladder cancers. MATERIALS AND METHODS: We report on a retrospective case series of 91 patients who received gastric neobladders as urinary diversion after radical cystectomies performed for the treatment of muscle-invasive bladder cancers. Different techniques of gastric neobladders were employed from 1988 to 2013 at a university hospital in the South of Brazil. RESULTS: Initial outcomes utilizing Leong (Antral) and Nguyen-Mitchell (Wedge) technique were unsatisfactory, yielding high pressure, low capacity reservoirs. Further developments of these techniques, with the detubularized gastric neobladder and the "spherical" gastric neobladders resulted in low pressure, high capacity reservoirs, with better surgical and urodynamic outcomes. Complication and perioperative mortality rates of our series of gastric neobladders were significantly higher than historical results of techniques using ileum or colon. CONCLUSIONS: Stomach is an exceptional option for the creation of neobladders after radical cystectomies, but due to the increased complication rates it should be reserved for specific situations (e.g., renal insufficiency, previous pelvic/abdominal radiotherapy, short bowel syndromes).

Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin.

BACKGROUND: The B subunit of Escherichia coli heat-labile enterotoxin (LTB) is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant. OBJECTIVES: We aimed at evaluating and better understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral immune response induced by this construct and comparing it to that generated when aluminium hydroxide is used as adjuvant instead. METHODS: BALB/c mice were immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1, IgG2a, and IgA) were assessed by enzyme-linked immunosorbent assay (ELISA). The ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2 immune response. FINDINGS: Western blot confirmed rR1, either alone or fused to LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its activity when expressed in a heterologous system. Mice immunised with the rLTBR1 fusion protein produced approximately twice as much anti-rR1 immunoglobulins as mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed Th1/Th2 immune response. We speculate this might be a result of rR1 immune modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced approximately 1.5-fold more serum IgA than animals immunised with rR1 and aluminium hydroxide. MAIN CONCLUSIONS: The results suggest that rLTB is a more powerful parenteral adjuvant than aluminium hydroxide when administered intraperitoneally as it induced higher antibody titres. Therefore, we recommend that rLTB be considered an alternative adjuvant, even if different administration routes are employed.

Protective potential of recombinant non-purified botulinum neurotoxin serotypes C and D.

Botulinum neurotoxin (BoNT) serotypes C and D are responsible for cattle botulism, a fatal paralytic disease that results in great economic losses in livestock production. Vaccination is the main approach to prevent cattle botulism. However, production of commercially available vaccines (toxoids) involves high risk and presents variation of BoNT production between batches. Such limitations can be attenuated by the development of novel nontoxic recombinant vaccines through a simple and reproducible process. The aim of this study was to evaluate the protective potential of recombinant non-purified botulinum neurotoxin serotypes C and D. Bivalent vaccines containing 200 µg rHCC and rHCD each were formulated in three different ways: (1) purified antigens; (2) recombinant Escherichia coli bacterins; (3) recombinant E. coli cell lysates (supernatant and inclusion bodies). Guinea pigs immunized subcutaneously with recombinant formulations developed a protective immune response against the respective BoNTs as determined by a mouse neutralization bioassay with pooled sera. Purified recombinant antigens were capable of inducing 13 IU/mL antitoxin C and 21 IU/mL antitoxin D. Similarly, both the recombinant bacterins and the cell lysate formulations were capable of inducing 12 IU/mL antitoxin C and 20 IU/mL antitoxin D. These values are two times as high as compared to values induced by the commercial toxoid used as control, and two to ten times as high as the minimum amount required by the Brazilian Ministry of Agriculture, Livestock and Food Supply (MAPA), respectively. Therefore, we used a practical, industry-friendly, and efficient vaccine production process that resulted in formulations capable of inducing protective immune response (neutralizing antitoxins) against botulism serotypes C and D.

Special Considerations for Brazilian Transgender Patients in the United States: A Commentary.

Despite facing many social and structural challenges inside and outside of health systems, transgender and gender diverse (TGD) Brazilian immigrants in the U.S. are understudied, and their barriers to care are largely unnamed. In this commentary, we build on existing literature and our experiences at a safety-net community health system that sees a high volume of Brazilian patients to discuss challenges facing TGD Brazilian immigrant populations. We highlight that while Brazilian TGD populations face discrimination in Brazil, major challenges persist upon immigrating to the U.S., and include: difficulty updating identity documents and changing immigration status, barriers seeking general and specialized health care (including finding bilingual and bicultural providers), challenges navigating complex health and insurance systems, and a lack of community supports. We end by recommending more coordinated efforts between health care and community organizations to help ensure the health and wellness of TGD Brazilian immigrants in the United States.

Applying enhanced recovery principles to emergency laparotomy in penetrating abdominal trauma: a case-matched study.

PURPOSE: The implementation of enhanced recovery after surgery programs (ERPs) has significantly improved outcomes within various surgical specialties. However, the suitability of ERPs in trauma surgery remains unclear. This study aimed to (1) design and implement an ERP for trauma laparotomy patients; (2) assess its safety, feasibility, and efficacy; and (3) compare the outcomes of the proposed ERP with conventional practices. METHODS: This case-matched study prospectively enrolled hemodynamically stable patients undergoing emergency laparotomy after penetrating trauma. Patients receiving the proposed ERP were compared to historical controls who had received conventional treatment from two to eight years prior to protocol implementation. Cases were matched for age, sex, injury mechanism, extra-abdominal injuries, and trauma scores. Assessment of intervention effects were modelled using regression analysis for outcome measures, including length of hospital stay (LOS), postoperative complications, and functional recovery parameters. RESULTS: Thirty-six consecutive patients were enrolled in the proposed ERP and matched to their 36 historical counterparts, totaling 72 participants. A statistically significant decrease in LOS, representing a 39% improvement in average LOS was observed. There was no difference in the incidence of postoperative complications. Opioid consumption was considerably lower in the ERP group (p < 0.010). Time to resumption of oral liquid and solid intake, as well as to the removal of nasogastric tubes, urinary catheters, and abdominal drains was significantly earlier among ERP patients (p < 0.001). CONCLUSION: The implementation of a standardized ERP for the perioperative care of penetrating abdominal trauma patients yielded a significant reduction in LOS without increasing postoperative complications. These findings demonstrate that ERPs principles can be safely applied to selected trauma patients.

Trauma surgery workforce in the state of Rio Grande do Sul, Brazil.

OBJECTIVE: to describe the current scope of certified trauma surgeons trained in the state of Rio Grande do Sul, including demographic data, geographic distribution, remuneration, and perspectives related to this specialty. METHOD: cross-sectional survey based on information collected through an electronic questionnaire sent to potential participants. RESULTS: the response rate was 64% (n=75). There was a predominance of males (72%) with a mean age of 43 years. Most surgeons graduated from the Hospital de Pronto Socorro de Porto Alegre, and work in referral centers for trauma surgery in the capital and metropolitan region. More than 60% did not have any other training in a surgical subspecialty, though only a third stated that trauma surgery is their main source of income. CONCLUSION: trauma centers are poorly distributed and most surgeons work in referral hospitals in the metropolitan region of Porto Alegre. Due to the lack of recognition, limited financial income and shift work patterns, the career in trauma surgery care is unattractive, with only one third of surgeons performing most of their activities in this specialty.

Predictive factors of mortality in damage control surgery for abdominal trauma.

INTRODUCTION: damage control surgery (DCS) is well recognized as a surgical strategy for patients sustaining severe abdominal trauma. Literature suggests the indications, operative times, therapeutic procedures, laboratory parameters and intraoperative findings have a direct bearing on the outcomes. OBJECTIVE: to analyze the clinical profile of patients undergoing DCS and determine predictors of morbidity and mortality. METHODS: a retrospective cohort study was conducted on all patients undergoing DCS following abdominal trauma from November 2015 and December 2021. Data on subjects' demographics, baseline presentation, mechanism of injury, associated injuries, injury severity scores, laboratory parameters, operative details, postoperative complications, length of stay and mortality were assessed. A binary logistic regression analysis was performed to determine potential risk factors for mortality. RESULTS: During the study period, 696 patients underwent trauma laparotomy. Of these, 8.9% (n=62) were DCS, with more than 80% due to penetrating mechanisms. Overall mortality was 59.6%. In the logistic regression stratified by survival, several variables were significantly associated with mortality, including hypotension, and altered mental status at admission, intraoperative cardiorespiratory arrest, need for resuscitative thoracotomy, metabolic acidosis, hyperlactatemia, coagulopathy, fibrinolysis, and severity of the trauma injury scores. CONCLUSION: DCS may be appropriate in critically injured patients; however, it remains associated with significant morbidity and high mortality, even at specialized trauma care centers. From pre and postoperative clinical and laboratory parameters, it was possible to predict the risk of death in the studied sample.

Portocath insertion technique: retrospective study & step-by-step surgical description without tunneling in a high-complexity service.

OBJECTIVE: to demonstrate that the use of the portocath implantation technique without tunneling the catheter is not associated with a higher rate of complications in the short or long term. In addition, we aim to improve the implantation technique of the portocath device, with the presentation of a step-by-step guide for surgeons in training. METHODS: this is a retrospective descriptive study, with analytical components. Data were analyzed using information extracted from electronic medical records linked to the National Health Care procedure code between the years 2019-2020. RESULTS: none of the 94 procedures resulted in complications on the day they were performed. Complications were recorded seven days after the procedure in only two patients (2.13%). Intraoperative radioscopy had been performed in both cases. Thirty days afters the procedure, complications were observed in two patients among the remaining 92 (2.17%), both undergoing catheter implantation without tunneling. There were no complications in the six months after portocath implantation in 57.4% of patients and there is no information about the other 42.6%. CONCLUSION: the portocath insertion technique without tunneling is a safe outpatient procedure, with a low risk of complications, and can be adopted to shorten procedure time and patient discomfort, without functional or safety impairments. There was no association of not tunneling the catheter, laterality of the punctured vein and performing radioscopy in the transoperative period with the rate of complications.

[The profile of victims attended by the Pernambuco prehospital air service]. / Perfil da vítima atendida pelo serviço pré-hospitalar aéreo de Pernambuco.

This descriptive, exploratory study was performed using a quantitative approach to address the profile of victims attended by the Pernambuco prehospital air service. The events were evaluated from August 2007 to July 2008, corresponding to the first year of the hangar working in Recife. In the studied period, 283 event forms were studied, with an average 23 events per month. Regarding the flights, 66% were rescue flights with an answer-time of 11 minutes. As for the causes, 79% were external, mainly traffic accidents. Most victims were male, with a median age range of 34 years. The rescue of severe cases should be fast and effective, thus this study analyzed the association between the severity of a victim and the answer-time.

Depression and dry eye: a narrative review.

Dry eye disease (DED) is a multifactorial disease affecting tear quality and/or production and eye surface and is one of the most common eye disorders found in clinical practice. The association between psychiatric disorders and dry eye has been the subject of several studies since patients with this syndrome present a tendency toward a depressive mood. This narrative review aims to demonstrate the relationship between depression and DED, which is due to the side effects of psychotropic drugs or the tendency of the low pain threshold of the depressive patient. The work was produced from the analysis of 13 articles published during the last decade on this subject and demonstrated that the depressive state is linked to the appearance or worsening of DED resulting from chronic eye pain. Also, the treatment of depression with selective inhibitors of serotonin receptors causes inflammatory cytokine secretion with subsequent inflammation and apoptosis of cells on the ocular surface. The need for new studies on optimization of psychiatric treatment in patients with ophthalmic diseases, such as DED, was verified, aiming at the relief of symptoms and the reduction of psychological and eye damage caused by them.

Ocular manifestations of COVID-19: a literature review.

Coronavirus disease 2019 (COVID-19) caused by the highly pathogenic SARS-Cov-2 virus, was declared as a pandemic by the World Health Organization (WHO) in March 2020. Its main clinical manifestations are related to airway involvement; however, there is extrapulmonary impairment in some cases. Given this context, this literature review aims to identify the ophthalmological conditions caused by infection with the novel coronavirus. Although ocular findings do not include the standard clinical presentation of the disease, there are reports of some ophthalmological changes in COVID-19 patients, and conjunctivitis is the most common among these.

Electroanalysis Applied to Compatibility and Stability Assays of Drugs: Carvedilol Study Case.

Carvedilol (CRV) is a non-selective blocker of α and ß adrenergic receptors, which has been extensively used for the treatment of hypertension and congestive heart failure. Owing to its poor biopharmaceutical properties, CRV has been incorporated into different types of drug delivery systems and this necessitates the importance of investigating their compatibility and stability. In this sense, we have investigated the applicability of several electroanalytical tools to assess CRV compatibility with lipid excipients. Voltammetric and electrochemical impedance spectroscopy techniques were used to evaluate the redox behavior of CRV and lipid excipients. Results showed that Plurol® isostearic, liquid excipient, and stearic acid presented the greatest anode peak potential variation, and these were considered suitable excipients for CRV formulation. CRV showed the highest stability at room temperature and at 50 °C when mixed with stearic acid (7% w/w). The results also provided evidence that electrochemical methods might be feasible to complement standard stability/compatibility studies related to redox reactions.

Assessment of trauma scoring systems in patients subjected to exploratory laparotomy.

OBJECTIVE: to assess the epidemiological profile of patients undergoing exploratory trauma laparotomy based on severity and prognosis criteria, and to determine the predictive accuracy of trauma scoring systems in terms of morbidity and mortality. METHODS: retrospective cohort study and review of medical records of patients undergoing exploratory laparotomy for blunt or penetrating trauma at the Hospital de Pronto Socorro de Porto Alegre, from November 2015 to November 2019. Demographic data, mechanism of injury, associated injuries, physiological (RTS and Shock Index), anatomical (ISS, NISS and ATI) and combined (TRISS and NTRISS) trauma scores, intraoperative findings, postoperative complications, length of stay and outcomes. RESULTS: 506 patients were included in the analysis. The mean age was 31 ± 13 years, with the majority being males (91.3%). Penetrating trauma was the most common mechanism of injury (86.2%), predominantly by firearms. The average RTS at hospital admission was 7.5 ± 0.7. The mean ISS and NISS was 16.5 ± 10.1 and 22.3 ± 13.6, respectively. The probability of survival estimated by TRISS was 95.5%, and by NTRISS 93%. The incidence of postoperative complications was 39.7% and the overall mortality was 12.8%. The most accurate score for predicting mortality was the NTRISS (88.5%), followed by TRISS, NISS and ISS. CONCLUSION: the study confirms the applicability of trauma scores in the studied population. The NTRISS seems to be the best predictor of morbidity and mortality.

Catalytic properties of recombinant dipeptidyl carboxypeptidase from Escherichia coli: a comparative study with angiotensin I-converting enzyme.

Dipeptidyl carboxypeptidase from Escherichia coli (EcDcp) is a zinc metallopeptidase with catalytic properties closely resembling those of angiotensin I-converting enzyme (ACE). However, EcDcp and ACE are classified in different enzyme families (M3 and M2, respectively) due to differences in their primary sequences. We cloned and expressed EcDcp and studied in detail the enzyme's S(3) to S(1)' substrate specificity using positional-scanning synthetic combinatorial (PS-SC) libraries of fluorescence resonance energy transfer (FRET) peptides. These peptides contain ortho-aminobenzoic acid (Abz) and 2,4-dinitrophenyl (Dnp) as donor/acceptor pair. In addition, using FRET substrates developed for ACE [Abz-FRK(Dnp)P-OH, Abz-SDK(Dnp)P-OH and Abz-LFK(Dnp)-OH] as well as natural ACE substrates (angiotensin I, bradykinin, and Ac-SDKP-OH), we show that EcDcp has catalytic properties very similar to human testis ACE. EcDcp inhibition studies were performed with the ACE inhibitors captopril (K(i)=3 nM) and lisinopril (K(i)=4.4 microM) and with two C-domain-selective ACE inhibitors, 5-S-5-benzamido-4-oxo-6-phenylhexanoyl-L-tryptophan (kAW; K(i)=22.0 microM) and lisinopril-Trp (K(i)=0.8 nM). Molecular modeling was used to provide the basis for the differences found in the inhibitors potency. The phylogenetic relationship of EcDcp and related enzymes belonging to the M3 and M2 families was also investigated and the results corroborate the distinct origins of EcDcp and ACE.

How to get the magic triangle and the MAD triangle into your protein crystal.

The magic triangle 5-amino-2,4,6-triiodoisophthalic acid (I3C) and the MAD triangle 5-amino-2,4,6-tribromoisophthalic acid (B3C) are two representatives of a novel class of compounds that combine heavy atoms for experimental phasing with functional groups for protein interactions. These compounds are readily available and provide easy access to experimental phasing. The preparation of stock solutions and the incorporation of the compounds into protein crystals are discussed. As an example of incorporation via cocrystallization, the incorporation of B3C into bovine trypsin, resulting in a single site with high occupancy, is described.

Viability of mobile applications for remote support of radiotherapy patients.

BACKGROUND: Technological advances of the 21st century have provided greater communication, regardless of socioeconomic class and age group. Actions to promote the development of health applications are emerging around the world. OBJECTIVE: To provide a perspective on the viability and usability of mobile applications dedicated to radiotherapy patients for remote support to health professionals proposing solutions to encourage Brasil in the development of these digital tools. METHODS: Cross-sectional exploratory study by systematic review and literature review. We searched the PubMed, BVS, IBGE, and WHO databases, from 2014 to 2018. RESULTS: 6 articles were found with topics related to the use of mobile applications in the health area, two of which were published in Portuguese and four in the English, on oncology, from 2014 to 2018. CONCLUSIONS: We did not find an expressive number of works on this subject in Brasil. Mobile applications have the potential to assist in the remote support of radiotherapy patients. The latest studies suggest the need for a regulation of data protection protocols to be deployed.

Evaluation of different strategies to promote a protective immune response against leptospirosis using a recombinant LigA and LigB chimera.

Leptospirosis is a zoonosis of worldwide distribution, caused by infection with pathogenic Leptospira species. The vaccines that are currently available are bacterins, with limited human use, that confer short-term, serovar-specific immunity. Lig proteins are considered to be the best vaccine candidates to date. Here, we aimed to construct a recombinant Lig chimera (LC) comprised of LigAni and LigBrep fragments, and to evaluate it as subunit or DNA vaccine using different administration strategies. Vaccines were formulated with 50 µg of recombinant LC associated with different adjuvants or with 100 µg of pTARGET/LC. Four-week-old hamsters received two doses of vaccine with different strategies and were challenged with 5 × DL50Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. The immune response generated by Lig chimera conferred 100% protection to hamsters treated with at least one dose of recombinant LC. Despite the high levels of antibodies that vaccinated animals produced, a sterilizing immunity was not achieved. The lack of a sterilizing immunity could indicate the importance of a mixed humoral and cellular immune response. The present study generated insights that will be useful in the future development of improved subunit vaccines against leptospirosis.

A standardized BioBrick toolbox for the assembly of sequences in mycobacteria.

For more than 25 years, recombinant Mycobacterium bovis BCG has been genetically engineered for use as a vehicle for antigen expression and immunomodulation, typically through introducing or deleting a gene from BCG genome. However, BCG transformation efficacy is still unpredictable, and cloning and expression of sequences from mycobacteria is difficult to predict due to the lack of standardization. To overcome such limitations, we have employed the BioBrick format to construct a toolbox of several mycobacterial parts, including coding sequences, reporter genes, selective markers, promoters, and other regulatory sequences. Additionally, we have developed and characterized BioBrick-compatible episomal vectors that are able to replicate in M. bovis BCG to enable expression of heterologous antigens. The availability of a BCG Biobrick toolbox will enable any coding sequence to be optimally expressed in BCG. We believe that this mycobacterial toolbox represents a standardized and useful kit to enhance the efficacy and use of recombinant BCG.

Recombinant BCG strains expressing chimeric proteins derived from Leptospira protect hamsters against leptospirosis.

Leptospirosis is a zoonosis that is responsible for one million human cases per year. Fusing multiple immunogenic antigens represents a promising approach to delivering an effective vaccine against leptospirosis. Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a potential vaccine vector due to its adjuvant properties and safety. Two chimeric genes based on genic sequences of ligANI, ligBrep, lipL32, and lemA, were individually cloned into five BioBrick vectors with different promoters (pAN, Hsp60, 18 kDa, Ag85B and Ag85B plus signal sequence) for antigen expression in BCG. Groups of ten hamsters were vaccinated with recombinant BCG (rBCG) strains in two doses of 106 CFU and challenged with 5 × LD50 of L. interrogans serovar Copenhageni. All rBCG vaccines expressing chimera 1, based on antigens LipL32, LigANI, and LemA, under the control of any promoter, protected 80-100% of the hamsters from challenge (P < 0.05) and four of them also protected from renal carrier status; for chimera 2, based on LigANI and LigBrep antigens, the only vaccine that afforded survival rates statistically different from the control was the vaccine that incorporated the pAN promoter (60% of survival). A single vaccine dose was sufficient to induce significant IgG levels by all vaccine compositions evaluated; however, humoral response was not related to protection. These findings suggest that the combination of potential vaccine candidates in chimeric antigens and the use of BCG as a live vector are promising strategies by which it is possible to obtain an effective and sterilizing vaccine against leptospirosis.

Voltammetric Evaluation of Diclofenac Tablets Samples through Carbon Black-Based Electrodes.

Diclofenac (DIC) is a non-steroidal anti-inflammatory drug of wide use around the world. Electroanalytical methods display a high analytical potential for application in pharmaceutical samples but the drawbacks concerning electrode fouling and reproducibility are of major concern. Henceforth, the aim of this work was to propose the use of alternative low-cost carbon black (CB) and ionic liquid (IL) matrix to modify the surface of pencil graphite electrodes (PGE) in order to quantify DIC in raw materials, intermediates, and final products, as well as in stability assays of tablets. The proposed method using CB+IL/PGE displayed good recovery (99.4%) as well as limits of detection (LOD) of 0.08 µmol L-1 and limits of quantification (LOQ) of 0.28 µmol L-1. CB+IL/PGE response was five times greater than the unmodified PGE. CB+IL-PGE stands as an interesting alternative for DIC assessment in different pharmaceutical samples.