Effectiveness of negative pressure wound therapy in treating diabetic foot ulcers: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Diabetic foot ulcers (DFUs) present devastating complications. Management of these wounds includes applying a vacuum device composed of a fenestrated tube embedded in a foam dressing and connected to a vacuum pump to collect the fluid in a vessel. OBJECTIVE: To review the effectiveness of negative pressure wound therapy (NPWT) in treating DFUs and evaluate the clinical outcomes of full and partial wound healing. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted after searching the PubMed, Web of Science, and Cochrane Library databases. Studies that described the use of NPWT in the management of DFUs were included and compared with different interventions for the proposed outcomes. RESULTS: A total of 14 studies were included, 1 of which was later excluded during internal validation. Wound healing outcomes were analyzed in 2 studies, showing the superiority of total wound healing in the NPWT group. Ten studies compared the effect of different interventions on wound area reduction and 8 of these results were best with NPWT. Three studies showed clinical and statistical homogeneity (I² = 100%), making it possible to conduct a meta-analysis. CONCLUSION: Although the articles included in this systematic review have limitations regarding methodological quality and clinical heterogeneity, the results showed the potential benefit of NPWT in healing and wound area reduction. These outcomes are essential in the prevention of amputation in patients with DFU.

Effects of valproic acid on wound healing of the abdominal wall musculoaponeurotic layer: an experimental study in rats.

INTRODUCTION: valproic acid (VPA), an epigenetic drug, has potential for the treatment of neoplasms. Its effects on the healing of the peritoneal-musculo-aponeurotic plane (PMA) of the abdominal wall are studied. METHOD: sixty Wistar rats were allocated into two groups: experimental (VPA) and control (0.9% sodium chloride), treated daily, starting three days before the intervention and until euthanasia. Under anesthesia, a median laparotomy was performed and repaired with two synthetic layers. Assessments took place 3, 7 and 14 days after surgery. The integrity of the wounds, the quality of the inflammatory reaction, the intensity of the leukocyte infiltrate, collagen synthesis, the intensity of angiogenesis and the presence of myofibroblasts were studied. RESULTS: there was dehiscence of the PMA plane in 11 of the 30 animals (p=0.001) in the experimental group. There was no difference in the quality and intensity of the inflammatory reaction. Immunohistochemistry revealed, in the experimental group, less collagen I (p3=0.003, p7=0.013 and p14=0.001) and more collagen III (p3=0.003, p7=0.013 and p14= 0.001). Collagen evaluated by Sirus Supra Red F3BA showed, in the experimental group, less collagen at all three times (p<0.001) with less collagen I and collagen III (p<0.001). A lower number of vessels was found on the 3rd day (p<0.001) and on the 7th day (p=0.001) and did not affect the number of myofibroblasts. CONCLUSION: VPA showed dehiscence of the PMA plane, with less deposition of total collagen and collagen I, less angiogenic activity, without interfering with the number of myofibroblasts.

Effects of valproic acid on wound healing of the abdominal wall musculoaponeurotic layer: an experimental study in rats / Os efeitos do ácido valpróico na cicatrização do plano músculoaponeurótico da parede abdominal: estudo experimental em ratos

ABSTRACT Introduction: valproic acid (VPA), an epigenetic drug, has potential for the treatment of neoplasms. Its effects on the healing of the peritoneal-musculo-aponeurotic plane (PMA) of the abdominal wall are studied. Method: sixty Wistar rats were allocated into two groups: experimental (VPA) and control (0.9% sodium chloride), treated daily, starting three days before the intervention and until euthanasia. Under anesthesia, a median laparotomy was performed and repaired with two synthetic layers. Assessments took place 3, 7 and 14 days after surgery. The integrity of the wounds, the quality of the inflammatory reaction, the intensity of the leukocyte infiltrate, collagen synthesis, the intensity of angiogenesis and the presence of myofibroblasts were studied. Results: there was dehiscence of the PMA plane in 11 of the 30 animals (p=0.001) in the experimental group. There was no difference in the quality and intensity of the inflammatory reaction. Immunohistochemistry revealed, in the experimental group, less collagen I (p3=0.003, p7=0.013 and p14=0.001) and more collagen III (p3=0.003, p7=0.013 and p14= 0.001). Collagen evaluated by Sirus Supra Red F3BA showed, in the experimental group, less collagen at all three times (p<0.001) with less collagen I and collagen III (p<0.001). A lower number of vessels was found on the 3rd day (p<0.001) and on the 7th day (p=0.001) and did not affect the number of myofibroblasts. Conclusion: VPA showed dehiscence of the PMA plane, with less deposition of total collagen and collagen I, less angiogenic activity, without interfering with the number of myofibroblasts.

RESUMO Introdução: o ácido valpróico (VPA), droga epigenética, apresenta-se com potencial para o tratamento de neoplasias. Estudam-se seus efeitos sobre a cicatrização do plano peritônio-músculo-aponeurótico (PMA) da parede abdominal. Método: sessenta ratos Wistar, foram alocados em dois grupos: o experimental (VPA) e o controle (cloreto de sódio 0,9%), tratados diariamente, iniciando três dias antes da intervenção e até a eutanásia. Sob anestesia, fez-se uma laparotomia mediana que foi reparada com dois planos de síntese. As avaliações aconteceram 3, 7 e 14 dias após a cirurgia. Estudou-se a integridade das feridas, a qualidade da reação inflamatória, a intensidade do infiltrado de leucócitos, a síntese do colágeno, a intensidade da angiogênese e a presença de miofibroblastos. Resultados: o plano PMA mostrou-se deiscente em 11 dos 30 animais (p=0,001) do grupo experimento. Não houve diferença na qualidade da reação inflamatória e nem no infiltrado de leucócitos. A imuno-histoquímica revelou, no grupo experimento, menos colágeno I (p3=0,003, p7=0,013 e p14=0,001) e mais colágeno III (p3=0,003, p7=0,013 e p14= 0,001). Colágeno avaliado pelo Sirus Supra Red F3BA mostrou, no grupo experimento,menos colágeno nos três tempo (p<0,001) com menos colágeno I e colágeno III (p<0,001). Constatou-se menor número de vasos no 3º dia (p<0,001) e no 7º dia (p=0,001) e não afetou a quantidade de miofibroblastos. Conclusão: o VPA mostrou deiscências do plano PMA, com reação inflamatória semelhante.ao controle, menor deposição de colágeno total e de colágeno I, menor atividade angiogênica, sem interferir na quantidade de miofibroblastos.

Is it possible to automate the discovery of process maps for the time-driven activity-based costing method? A systematic review.

OBJECTIVES: The main objective of this manuscript was to identify the methods used to create process maps for care pathways that utilized the time-driven activity-based costing method. METHODS: This is a systematic mapping review. Searches were performed in the Embase, PubMed, CINAHL, Scopus, and Web of Science electronic literature databases from 2004 to September 25, 2022. The included studies reported practical cases from healthcare institutions in all medical fields as long as the time-driven activity-based costing method was employed. We used the time-driven activity-based costing method and analyzed the created process maps and a qualitative approach to identify the main fields. RESULTS: A total of 412 studies were retrieved, and 70 articles were included. Most of the articles are related to the fields of orthopedics and childbirth-related to hospital surgical procedures. We also identified various studies in the field of oncology and telemedicine services. The main methods for creating the process maps were direct observational practices, complemented by the involvement of multidisciplinary teams through surveys and interviews. Only 33% of the studies used hospital documents or healthcare data records to integrate with the process maps, and in 67% of the studies, the created maps were not validated by specialists. CONCLUSIONS: The application of process mining techniques effectively automates models generated through clinical pathways. They are applied to the time-driven activity-based costing method, making the process more agile and contributing to the visualization of high degrees of variations encountered in processes, thereby making it possible to enhance and achieve continual improvements in processes.

Histological, Laboratorial, and Clinical Benefits of an Optimized Maintenance Strategy of a Potential Organ Donor-A Rabbit Experimental Model.

INTRODUCTION: Most transplanted organs are obtained from brain-dead donors. Inflammation results in a higher rate of rejection. Objectives: The objective of this animal model of brain death (BD) was to evaluate the effect of the progressive institution of volume expansion, norepinephrine, and combined hormone therapy on clinical, laboratory, and histological aspects. Methods: Twenty rabbits were divided: A (control), B (induction of BD + infusion of crystalloid), C (BD + infusion of crystalloid and noradrenaline (NA)), and D (BD + infusion of crystalloid + vasopressin + levothyroxine + methylprednisolone + NA). The animals were monitored for four hours with consecutives analysis of vital signs and blood samples. The organs were evaluated by a pathologist. Results: In Group D, we observed fewer number and lesser volume of infusions (p = 0.032/0.014) when compared with groups B and C. Mean arterial pressure levels were higher in group D when compared with group B (p = 0.008). Group D had better glycemic control when compared with group C (p = 0.016). Sodium values were elevated in group B in relation to groups C and D (p = 0.021). In Group D, the organ perfusion was better. Conclusion: The optimized strategy of management of BD animals is associated with better hemodynamic, glycemic, and natremia control, besides reducing early signs of ischemia.

Cardiopulmonary resuscitation in the prone position: a systematic review of case series/reports / Reanimação cardiopulmonar em posição prona: uma revisão sistemática de séries/relatos de casos

Abstract Introduction The prone position is frequently adopted for surgical or critically ill patients in intensive care. Cardiorespiratory arrest in these patients may pose an operational challenge, in which delays resulting from mobilization to the supine position culminate in worse outcomes. Objective To provide clinical insight based on the synthesis of evidence from reports or case series on reverse cardiopulmonary resuscitation (reverse CPR) in surgical patients or invasive ventilatory support in severe acute respiratory distress syndrome. Methods This is a systematic review of reports or case series in PubMed, Scopus, Embase, and Google Scholar databases, in addition to a search of the gray literature. Case reports published in any language, reporting at least one case of prone cardiopulmonary resuscitation in patients of any age and in any care context, were considered eligible. Results Thirteen studies of fourteen cases of successful reverse resuscitation were retrieved. Three patients died within 30 days, while the others survived without complications or neurological sequelae. Conclusion Despite limited evidence to support clinical decision-making, prone resuscitation appears to be a feasible alternative in exceptional circumstances, where patient mobilization may result in additional harm, delay or interrupt advanced life support (compressions, high-quality early chest surgery, and defibrillation) or incur occupational risks to the health team.

Resumo Introdução A posição prona é um procedimento frequente de cuidados intensivos para pacientes cirúrgicos ou doentes graves. A ocorrência de parada cardiorrespiratória nestes pacientes pode representar um desafio operacional, no qual atrasos relacionados à mobilização para decúbito dorsal implicam em piores desfechos. Objetivo Oferecer um insight clínico a partir da síntese das evidências oriundas de relatos ou séries de casos sobre a utilização de reanimação cardiopulmonar reversa em pacientes cirúrgicos ou em suporte ventilatório invasivo na síndrome do desconforto respiratório agudo grave. Métodos Trata-se de uma revisão sistemática de relatos ou séries de casos condu-zida nas bases de dados PubMed, Scopus, Embase e Google Scholar, além de busca na literatura cinzenta. Foram considerados elegíveis relatos de caso publicados em qualquer idioma, que reportaram pelo menos um caso de reanimação cardiopulmonar em posição prona em pacientes de qualquer idade e em qualquer contexto de atendimento. Resultados Foram recuperados treze estudos que relataram quatorze casos de reanimação reversa bem-sucedidos. Três pacientes faleceram em um intervalo de 30 dias, enquanto os demais sobreviveram sem complicações ou sequelas neurológicas. Conclusão Apesar de evidências limitadas para suportar a tomada de decisão clínica, a reanimação em posição prona parece ser uma alternativa factível em circunstâncias excepcionais, nas quais a mobilização do paciente pode resultar em dano adicional, atrasar ou interromper o suporte avançado de vida (compressões torácicas precoces de alta qualidade e a desfibrilação) ou, ainda, incorrer em riscos ocupacionais à equipe de saúde.

Valproic acid and bladder healing: an experimental study in rats.

PURPOSE: to recognize the effects of valproic acid (VPA), an epigenetic drug, on the bladder healing process, in rats. METHOD: twenty male Wistar rats were divided in two groups: experimental (A), treated with VPA (150mg/Kg/day), and control (B) with 0.9% sodium chloridrate. Healing was analyzed on the third and seventh days, evaluating the inflammatory reaction, collagen synthesis and angiogenesis. RESULTS: inflammatory reaction on the third day was minimal and acute in both groups. On the seventh day, it was subacute in both groups, moderate intensity in group A and minimal in group B (p=0.0476). Collagen III intensity, marked by immunohistochemistry, was similar in both groups. Collagen I intensity on the third day was similar in both groups, but on the seventh day it was higher in experimental than control (p=0.0476). Collagen evaluation by picrosiriusred allowed to verify that the presence of collagen III was similar in both groups (p=0.3312) on the third day, and it was higher in control on the seventh day (p=0.0015). Collagen I showed similarity on the third day (p=0.3100), and it was higher in control on the seventh day (p=0.0015). Vessel marked with anti-SMA counting showed fewer vessels on the third (p=0.0034) and seventh day (p=0.0087) in experimental group. The lower intensity of angiogenesis was confirmed with anti-CD34, on the third day (p=0,0006) and on the seventh day (p=0,0072). CONCLUSION: VPA determined alterations in the bladder healing process, in rats, with lower collagen density and less angiogenic activity, but without compromising the integrity of the organ.

The effects of valproic acid on skin healing: experimental study in rats.

PURPOSE: To recognize the effects of valproic acid (VPA), an epigenetic drug, on the skin healing process. METHODS: Sixty male Wistar rats were divided into two groups: the experiment treated with VPA (100 mg/kg/day); and the control, with 0.9% sodium chloride by gavage. Skin healing was studied in three moments (the third, the seventh, and the 14th day), evaluating the parameters: inflammatory reaction and its intensity (anti-LCA), angiogenesis (anti-CD34), collagen I and III (anti-collagen I, anti-collagen III and Picrosirius-red F3BA) and myofibroblasts (anti-alpha-AMS). RESULTS: The inflammatory reaction was acute or sub-acute in both groups on the third day. On the seventh and the 14th day, chronic predominated in the control (p=0.006), and sub-acute in the experiment (p=0.020). There was a greater number of leukocytes in the group treated only on the third day (p=0.036). The number of vessels was lower in the treated group at the three times (p3=0.002, p7<0.001, and p14=0.027). Myofibroblasts were rare in the third day and moderate quantity in the remaining periods. Collagen I density was higher in the control at the three times (p<0.001) and collagen III in the treated group (p<0.001). CONCLUSIONS: VPA led to a more intense inflammatory reaction, decreased angiogenesis and collagen deposition, especially type I collagen.

Use of sildenafil and L-arginine in an experimental rat model for the prevention of neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) has a 45% mortality in neonatal intensive care units. This paper aimed to evaluate the isolated and combined effects of sildenafil and L-arginine in the prevention of necrotizing enterocolitis. Neonatal rats were fed formula milk and submitted to hypoxia under a 100% N2 atmosphere for 70 s. Then, animals were subjected to hypothermia (4 °C for 10 min), twice a day for 3 days. Forty neonatal rats were divided into five groups: negative control-not submitted to the protocol (n = 5), sildenafil group-NEC protocol (n = 9), L-arginine group-NEC protocol (n = 9), L-arginine and sildenafil group-NEC protocol (n = 9) and positive control-NEC protocol and intraperitoneal saline solution (n = 8). Jejunum and terminal ileus were removed for histopathologic and immunohistochemical Ki-67 analysis. Kruskal-Wallis test was used to analyze mortality, survival, body weight, intestinal injury score and Ki-67 proliferation index. All animals submitted to the protocol developed enterocolitis. Mortality rate was higher in group that received only L-arginine (p = 0.0293). The Ki-67 analysis showed a higher proliferative index in groups that received interventional drugs (p = 0.017). In conclusion, sildenafil and L-arginine were not effective to reduce intestinal injury.

Biological compatibility of oxidized cellulose vs. porcine gelatin to control bleeding in liver lesions in rats.

PURPOSE: To compare biological compatibility, hemostasis, and adhesion formation between oxidized regenerated cellulose and lyophilized hydrolyzed porcine collagen in liver trauma. METHODS: Forty male Wistar rats constituted two groups: group A (oxidized cellulose) and group B (lyophilized hydrolyzed collagen). Standardized liver trauma was made, and the hemostatic agent was applied. Animals in subgroups A7 and B7 were submitted to euthanasia and relaparotomy after seven days, and in subgroups A14 and B14 after 14 days. Macroscopic and microscopic results were evaluated. RESULTS: There was no fluid in the cavity in any of the animals, and adhesions were present in all of them. In the analysis after seven days, the adhesions were grades 3 or 4 and consisted of omentum, small intestine, and abdominal wall (p<0.05). In both groups, the mesh was surrounded by a capsule, which was not observed after 14 days. In the evaluation after 14 days, adhesions were grades 2 or 3 (p>0.05). The microscopic examination showed subacute and chronic reactions, in both groups and in both timepoints, with similar frequency. The intensity of fibrosis always presented positive scores. Microabscesses and xanthomatous macrophages were observed in both groups. CONCLUSIONS: There was no superiority of one agent over the other.

When guidelines face reality - Lynch syndrome screening in the setting of public health system in a developing country.

Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC); however, it is still underrecognized and underdiagnosed. While international guidelines gravitate towards universal screening, the underuse of screening methods has been reported in real-world scenarios. This study aims to evaluate screening for LS among patients diagnosed with CRC in a public cancer center in Brazil and evaluate access to genetic counseling and testing for abnormal screens. For that purpose, all patients with CRC registered in our institution from July 2012 to December 2018 had their charts reviewed. Demographic and clinical characteristics were noted, as well as immunohistochemistry and microsatellite instability analysis results, when available. After applying exclusion criteria, a total of 1234 charts were reviewed. Among these, 257 patients were screened for LS, making up a 20.8% screening rate; when considering Jerusalem criteria, screening rate was 24.5%; for Bethesda criteria, it was 35.1%. Almost 80% of patients fulfilling Amsterdam criteria I/II were screened. There were 64 abnormal screens, from which 40 (62.5%) underwent genetic counseling and 12 (18.7%) underwent genetic testing. We concluded that overall screening rates for LS among CRC patients in a public cancer center in Brazil are low, and still very guided by stringent clinical criteria. Referral to genetic counseling and access to testing is limited, calling the whole process into question. Public policies aiming to raise awareness on hereditary cancer and include genetic testing in the public health system could help improve this scenario.

The effects of valproic acid on skin healing: experimental study in rats

Purpose: To recognize the effects of valproic acid (VPA), an epigenetic drug, on the skin healing process. Methods: Sixty male Wistar rats were divided into two groups: the experiment treated with VPA (100 mg/kg/day); and the control, with 0.9% sodium chloride by gavage. Skin healing was studied in three moments (the third, the seventh, and the 14th day), evaluating the parameters: inflammatory reaction and its intensity (anti-LCA), angiogenesis (anti-CD34), collagen I and III (anti-collagen I, anti-collagen III and Picrosirius-red F3BA) and myofibroblasts (anti-alpha-AMS). Results: The inflammatory reaction was acute or sub-acute in both groups on the third day. On the seventh and the 14th day, chronic predominated in the control (p=0.006), and sub-acute in the experiment (p=0.020). There was a greater number of leukocytes in the group treated only on the third day (p=0.036). The number of vessels was lower in the treated group at the three times (p3=0.002, p7<0.001, and p14=0.027). Myofibroblasts were rare in the third day and moderate quantity in the remaining periods. Collagen I density was higher in the control at the three times (p<0.001) and collagen III in the treated group (p<0.001). Conclusions: VPA led to a more intense inflammatory reaction, decreased angiogenesis and collagen deposition, especially type I collagen.

Intrauterine balloon tamponade for postpartum hemorrhage / Tamponamento por balão intrauterino no tratamento da hemorragia pós-parto

Abstract Introduction: Postpartum hemorrhage is an obstetric emergency with high prevalence and significant morbidity and mortality, especially in areas with reduced access to specialized health services. Objective: To evaluate the effectiveness of intrauterine balloon tamponade in controlling postpartum hemorrhage, with the aim to reduce the need for emergency surgical interventions and decrease maternal mortality. Methods: A systematic review of randomized clinical trials, guided by the Cochrane Handbook for Systematic Reviews of Interventions and reported through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Randomized clinical trials that evaluated the use of different types of balloons for intrauterine tamponade as a strategy for reducing or stopping postpartum hemorrhage compared to other interventions (pharmacological or surgical) were considered for inclusion. Results: Four studies evaluated 498 patients. In 80% of the reported cases, hemorrhage cessation was observed within a mean interval of 15 min after device insertion. The device permanence time was 24 h. No serious adverse events were reported. Due to clinical heterogeneity between studies, it was not possible to perform a quantitative synthesis. Conclusion: We did not find enough evidence to support the routine use of uterine tamponade devices as a protocol practice in the control of refractory postpartum hemorrhage. However, the use of these devices seems to be promising in cases where first line interventions fail and may play an important role in decreasing maternal morbidity and mortality and in uterine preservation.

Resumo Introdução: A hemorragia pós-parto trata-se de uma emergência obstétrica com elevada prevalência e morbimortalidade significativa, sobretudo em contextos de baixa acessibilidade a serviços especializados de saúde. Objetivo: Avaliar a efetividade do tamponamento por balão intrauterino no controle da hemorragia pós-parto, redução da necessidade de intervenções cirúrgicas de emergência e redução da mortalidade materna. Métodos: Revisão sistemática de ensaios clínicos randomizados, orientada pelo Cochrane Handbook for Systematic Reviews of Interventions e relatada através do Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Foram considerados como critérios de elegibilidade ensaios clínicos randomizados que avaliaram o uso de diferentes tipos de balão para tamponamento intrauterino enquanto estratégia para a redução ou cessação da hemorragia pós-parto quando comparados a outras intervenções (farmacológicas ou cirúrgicas). Resultados: Quatro estudos avaliaram 498 pacientes para os desfechos preconizados. Em 80% dos casos relatados observou-se a cessação da hemorragia em um intervalo médio de 15 minutos, após a inserção dos dispositivos. O tempo de permanência dos dispositivos foi de 24 horas. Não foram relatados eventos adversos graves. Devido à heterogeneidade clínica entre os estudos, não foi possível realizar síntese quantitativa. Conclusão: Os achados obtidos não fornecem evidências suficientes para sustentar a utilização rotineira dos dispositivos de tamponamento uterino enquanto prática protocolar no controle da hemorragia pós-parto refratária. A utilização destes dispositivos, no entanto, parece ser promissora diante da falha das intervenções de primeira linha, podendo desempenhar um importante papel em termos de redução de morbimortalidade materna e preservação uterina.

Valproic acid and bladder healing: an experimental study in rats / Ácido valpróico e cicatrização em bexiga: estudo experimental em ratos

ABSTRACT Purpose: to recognize the effects of valproic acid (VPA), an epigenetic drug, on the bladder healing process, in rats. Method: twenty male Wistar rats were divided in two groups: experimental (A), treated with VPA (150mg/Kg/day), and control (B) with 0.9% sodium chloridrate. Healing was analyzed on the third and seventh days, evaluating the inflammatory reaction, collagen synthesis and angiogenesis. Results: inflammatory reaction on the third day was minimal and acute in both groups. On the seventh day, it was subacute in both groups, moderate intensity in group A and minimal in group B (p=0.0476). Collagen III intensity, marked by immunohistochemistry, was similar in both groups. Collagen I intensity on the third day was similar in both groups, but on the seventh day it was higher in experimental than control (p=0.0476). Collagen evaluation by picrosiriusred allowed to verify that the presence of collagen III was similar in both groups (p=0.3312) on the third day, and it was higher in control on the seventh day (p=0.0015). Collagen I showed similarity on the third day (p=0.3100), and it was higher in control on the seventh day (p=0.0015). Vessel marked with anti-SMA counting showed fewer vessels on the third (p=0.0034) and seventh day (p=0.0087) in experimental group. The lower intensity of angiogenesis was confirmed with anti-CD34, on the third day (p=0,0006) and on the seventh day (p=0,0072). Conclusion: VPA determined alterations in the bladder healing process, in rats, with lower collagen density and less angiogenic activity, but without compromising the integrity of the organ.

RESUMO Objetivo: reconhecer os efeitos do ácido valpróico (VPA), uma droga epigenética, no processo de cicatrização da bexiga, em ratos. Método: vinte ratos Wistar machos foram divididos em dois grupos: experimental (A), utilizando VPA (150mg/Kg/dia), e controle (B), tratados com cloreto de sódio 0,9% por gavagem. A cicatrização da bexiga foi analisada no terceiro e sétimo dia, estudando-se a reação inflamatória, síntese de colágeno, reepitelização e angiogênese. Resultados: a reação inflamatória no terceiro dia foi mínima e aguda em ambos os grupos. No sétimo dia, foi subaguda em ambos os grupos com intensidade moderada no grupo A e mínima no grupo B (p=0,0476). A intensidade do colágeno III, marcada pela imuno-histoquímica, foi semelhante nos dois grupos, nos dois tempos estudados. A intensidade de colágeno I no terceiro dia foi semelhante nos dois grupos, e maior no sétimo dia no grupo experimental (p=0,0476). A avaliação do colágeno pelo picrosiriusred mostrou que a presença de colágeno III foi semelhante em ambos os grupos (p=0,3312) no terceiro dia, e maior no controle no sétimo dia (p=0,0015). O colágeno I foi semelhante no terceiro dia (p=0,3100), e maior no controle no sétimo dia (p=0,0015). A contagem de vasos marcados pelo anti-SMA mostrou menos vasos no terceiro (p=0,0034) e sétimo dia (p=0,0087) no grupo experimental, confirmado pelo anti-CD34, no terceiro (p=00006) e no sétimo dia (p=0,0072). Conclusão: o VPA determinou alterações no processo de cicatrização da bexiga, em ratos, com menor densidade de colágeno e menor atividade angiogênica, mas sem comprometer a integridade do órgão.

Digital PCR detection of EGFR somatic mutations in non-small-cell lung cancer formalin fixed paraffin embedded samples.

BACKGROUND: Digital PCR (dPCR) is proposed to replace real time PCR and Sanger sequencing for detection and quantification of rare mutations, frequently unnoticed in the mass of tumoral cells. Screening of endothelial growth factor receptor (EGFR) mutations is mandatory before treatment with EGFR-targeted therapy with small-molecule tyrosine kinase inhibitors, which has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC). OBJECTIVE: In order to establish a cost-effective method for detection of mutations, we optimized dPCR identification of EGFR mutations in exons 18-21, and determined dPCR sensitivity, limits of detection (LoD) and quantification (LoQ). METHODS: For clinical validation, we compared the performance of dPCR and castPCR in 57 NSCL formalin fixed paraffin embedded samples and 10 lung cancer-free formalin fixed paraffin embedded samples. RESULTS: EGFR mutations DEL19, p.L858R, p.G719X, p.L861Q and p.T790 M were detected by dPCR in 27 samples versus 11 detected by castPCR (p = 0.014). LoD was determined as 100 molecules of DNA/uL and LoQ as 1%. Most of the samples (87%) identified by competitive Allele-Specific TaqMan (castPCR) as wild-type and by dPCR as mutated, presented less than 10% mutated DNA molecules (mean 4.57%). Accuracy of dPCR was 94.44%, as measured with the assay recommended by the College of American Pathologists. CONCLUSION: These results indicated higher sensibility and specificity of dPCR for screening EGFR mutations in NSCLC biopsies, compared to castPCR.

Correlation of End-Tidal Carbon Dioxide with Arterial Carbon Dioxide in Mechanically Ventilated Neonates: A Scoping Review.

Monitoring CO2 levels in intubated neonates is highly relevant in the face of complications associated with altered CO2 levels. Thus, this review aims to present the scientific evidence in the literature regarding the correlation between arterial carbon dioxide measured by non-invasive methods in newborns submitted to invasive mechanical ventilation. The search was carried out from January 2020 to January 2021, in the Scopus, Medline, The Cochrane Library, Web of Science, CINAHL and Embase databases. Also, a manual search of the references of included studies was performed. The main descriptors used were: "capnography," "premature infant," "blood gas analysis," and "mechanical ventilation." As a result, 221 articles were identified, and 18 were included in this review. A total of 789 newborns were evaluated, with gestational age between 22.8 and 42.2 weeks and birth weight between 332 and 4790 g. Capnometry was the most widely used non-invasive method. In general, the correlation and agreement between the methods evaluated in the studies were strong/high. The birth weight did not influence the results. The gestational age of fewer than 37 weeks implied, in its majority, a moderate correlation and agreement. Therefore, we can conclude that there was a predominance of a strong correlation between arterial blood gases and non-invasive methods, although there are variations found in the literature. Even so, the results were promising and may provide valuable data for future studies, which are necessary to consolidate non-invasive methods as a reliable and viable alternative to arterial blood gasometry.

Biological compatibility of oxidized cellulose vs. porcine gelatin to control bleeding in liver lesions in rats

ABSTRACT Purpose: To compare biological compatibility, hemostasis, and adhesion formation between oxidized regenerated cellulose and lyophilized hydrolyzed porcine collagen in liver trauma. Methods: Forty male Wistar rats constituted two groups: group A (oxidized cellulose) and group B (lyophilized hydrolyzed collagen). Standardized liver trauma was made, and the hemostatic agent was applied. Animals in subgroups A7 and B7 were submitted to euthanasia and relaparotomy after seven days, and in subgroups A14 and B14 after 14 days. Macroscopic and microscopic results were evaluated. Results: There was no fluid in the cavity in any of the animals, and adhesions were present in all of them. In the analysis after seven days, the adhesions were grades 3 or 4 and consisted of omentum, small intestine, and abdominal wall (p<0.05). In both groups, the mesh was surrounded by a capsule, which was not observed after 14 days. In the evaluation after 14 days, adhesions were grades 2 or 3 (p>0.05). The microscopic examination showed subacute and chronic reactions, in both groups and in both timepoints, with similar frequency. The intensity of fibrosis always presented positive scores. Microabscesses and xanthomatous macrophages were observed in both groups. Conclusions: There was no superiority of one agent over the other.

Impact of the COVID-19 pandemic in patient admission to a high-complexity cancer center in Southern Brasil.

OBJECTIVE: The aim of our study was to investigate whether there has been a reduction in patient admission to a high-complexity cancer care center in Brasil during the COVID-19 pandemic, similar to what was reported in Europe. METHODS: We reviewed the cancer tracking database of the largest cancer center in southern Brasil and performed statistical tests to compare first-time appointments from the onset of the outbreak until the end of June to those of the equivalent period in 2019. RESULTS: We observed a dramatic reduction (-42%) in first-time appointments during the pandemic compared to the same period in the previous year (P <0.001). This reduction was observed among all medical specialties (P <0.001). CONCLUSION: The onset of COVID-19 was correlated with a reduction in admission to a high-complexity cancer care center in Brasil. Since a delay in diagnosis and treatment may influence prognosis, it is important that cancer centers and public health strategies reinforce care for non-COVID-19 patients to prevent potentially unnecessary deaths.