Unraveling the RAGE-NF-κB pathway: implications for modulating inflammation in diabetic neuropathy through photobiomodulation therapy.

Diabetic peripheral neuropathy (DPN) is a primary complication observed in diabetes that severely affects quality of life. Recent evidence suggests that photobiomodulation (PBM) is a promising therapy against painful conditions and nerve damage. However, the effects of PBM on DPN remains mostly unknown. In the present study, we investigated the efficacy of PBM therapy in modulating proinflammatory cytokine expression in both central and peripheral nervous systems of rats with Streptozotocin (STZ)-induced type 1 diabetes. Male Wistar rats were allocated into control (naïve), diabetic (STZ), and treatment (STZ + PBM) groups. A single intraperitoneal (i.p.) injection of STZ (85 mg/kg) was administered for the induction of diabetes. Animals were subjected to 10 treatment sessions, every other day. The results herein presented indicate that PBM treatment diminishes Receptor for Advanced Glycation End-products (RAGE) and Nuclear Factor Kappa B (NF-Ï°B) expression in peripheral nervous system and suppresses TNF-α expression in central nervous system tissues. Furthermore, PBM-therapy in diabetic rats also induces increased levels of the anti-inflammatory protein IL-10 in both peripheral and central nervous system. Collectively, our findings demonstrate compelling evidence that PBM-therapy modulates cytokine dynamics and influences RAGE/NF-Ï°B axis in a STZ-induced model of type 1 diabetes.

Prevention and reversal of neuropathic pain by near-infrared photobiomodulation therapy in male and female rats.

Pathological nociception arising from peripheral nerve injury impacts quality of life. Current therapeutics are generally ineffective. However, photobiomodulation therapy (PBMT) has shown promise in addressing this issue. We aimed to assess the potential anti-allodynic effects of 2 p.m. protocols, each applied transcutaneously over the peripheral nerve injury. In addition to evaluating nociceptive behavior, we also conducted morphological analysis using electron microscopy (EM) to investigate potential ultrastructural changes at the cellular level. We sought to determine, using the chronic constriction injury (CCI) model, whether our parameters could alleviate established allodynia and/or dampen allodynia development. Adult male and female rats with CCI or sham were treated with PBMT (850-nm wavelength) for 2 min, 3 times a week over three or four weeks across three studies, where PBMT began either before or after CCI. Allodynia was assessed prior to surgery and across weeks and, at the conclusion of the third study, sciatic nerve was processed for EM and histomorphometrically evaluated. The results showed that PBMT before versus after CCI injury yielded similar behaviors, effectively decreasing allodynia. Interestingly, these positive effects of PBMT do not appear to be accounted by protection of the sciatic injury site, based on EM. CCI reliably decreased axon size and the number of myelinated axons present in both PBMT and control groups. While PBMT reduced the number of C-fibers in CCI samples, no improvement in any measure was observed in response to PBMT.

THE COMBINATORY EFFECTS OF ESSENTIAL OIL FROM Lippia macrophylla ON MULTIDRUG RESISTANT Acinetobacter baumannii CLINICAL ISOLATES.

To assess the antibacterial effectiveness of Lippia macrophylla essential oil (LMEO) against multidrug-resistant Acinetobacter baumannii isolates, both as a standalone treatment and in combination with conventional antibiotics. LMEO demonstrated a significant inhibitory effect on the growth of A. baumannii, with a minimum inhibitory concentration (MIC) below 500µg/mL. Notably, LMEO was capable of reversing the antibiotic resistance of clinical isolates or reducing their MIC values when used in combination with antibiotics, showing synergistic (FICI ≤ 0.5) or additive effects. The combination of LMEO and imipenem was particularly effective, displaying synergistic interactions for most isolates. Ultrastructural analyses supported these findings, revealing that the combination of LMEO + ceftazidime compromised the membrane integrity of the Acb35 isolate, leading to cytoplasmic leakage and increased formation of Outer Membrane Vesicles (OMVs). Taken together our results point for the use of LMEO alone or in combination as an antibacterial agent against A. baumannii. These findings offer promising avenues for utilizing LMEO as a novel antibacterial strategy against drug-resistant infections in healthcare settings, underscoring the potential of essential oils in enhancing antibiotic efficacy.

Comparative efficacy and safety of sodium fluorescein-guided surgery versus standard white light for resection of brain metastases: a systematic review and meta-analysis.

PURPOSE: Recent studies have investigated if the sodium fluorescein-guided (SFg) improves the extent of resection of BMs when compared to standard white light (sWL). Therefore, we aimed to assess the comparative efficacy and safety of SFg and sWL for resection of BMs. METHODS: We searched Medline, Embase, and Cochrane Library databases following Cochrane and PRISMA guidelines for studies reporting comparative data of SFg and WL resection of BMs. We pooled odds ratios (OR) with 95% confidence intervals under random effects and applied I² statistics and leave-one-out sensitivity analysis to assess heterogeneity. I² > 40% was considered significant for heterogeneity. RESULTS: Five studies involving 816 patients were included, of whom 390 underwent BMs resection with SFg and 426 with sWL, and ages ranging between 26 and 86.2 years old. Analysis revealed a statistically significant higher likelihood of complete resection in the SFg group when compared to the sWL group (OR = 2.15, 95%CI: 1.18-3.92, p = 0.01; I² = 47%). Sensitivity analysis revealed a consistent result in all five scenarios, with low heterogeneity in two of the five scenarios. Three studies reported significant improvement in OS in the SFg group, and the qualitative assessment of complications and procedure-related mortality did not provide sufficient information for conclusions. CONCLUSION: This systematic review and meta-analysis identified a higher likelihood of complete resection in the SFg group when compared to the standard sWL group. This study is the first to directly compare the impact of SFg and sWL on resection outcomes for BMs.

CYP broth: a tool for Yersinia pestis isolation in ancient culture collections and field samples.

We developed a simple new selective LB-based medium, named CYP broth, suitable for recovering long-term stored Y. pestis subcultures and for isolation of Y. pestis strains from field-caught samples for the Plague surveillance. It aimed to inhibit the growth contaminating microorganisms and enrich Y. pestis growth through iron supplementation. The performance of CYP broth on microbial growth from different gram-negative and gram-positive strains from American Type Culture Collection (ATCC®) and other clinical isolates, field-caught rodent samples, and more importantly, on several vials of ancient Y. pestis subcultures was evaluated. Additionally, other pathogenic Yersinia species such as Y. pseudotuberculosis and Y. enterocolitica were also successfully isolated with CYP broth. Selectivity tests and bacterial growth performance on CYP broth (LB broth supplemented with Cefsulodine, Irgasan, Novobiocin, nystatin and ferrioxamine E) were evaluated in comparison with LB broth without additive; LB broth/CIN, LB broth/nystatin and with traditional agar media including LB agar without additive, and LB agar and Cefsulodin-Irgasan-Novobiocin Agar (CIN agar) supplemented with 50 µg/mL of nystatin. Of note, the CYP broth had a recovery twofold higher than those of the CIN supplemented media or other regular media. Additionally, selectivity tests and bacterial growth performance were also evaluated on CYP broth in the absence of ferrioxamine E. The cultures were incubated at 28 °C and visually inspected for microbiological growth analysis and O.D.625 nm measurement between 0 and 120 h. The presence and purity of Y. pestis growth were confirmed by bacteriophage and multiplex PCR tests. Altogether, CYP broth provides an enhanced growth of Y. pestis at 28 °C, while inhibiting contaminant microorganisms. The media is a simple, but powerful tool to improve the reactivation and decontamination of ancient Y. pestis culture collections and for the isolation of Y. pestis strains for the Plague surveillance from various backgrounds. KEY POINTS: • The newly described CYP broth improves the recuperation of ancient/contaminated Yersinia pestis culture collections • CYP broth was also efficient in reducing environmental contamination in field-capture samples, improving Y. pestis isolation • CYP broth can also be used for the isolation of Y. enterocolitica and Y. pseudotuberculosis.

Identification and characterization of bacterial biofilm production in clinical isolates of Staphylococcus spp. against antimicrobials / Identificação e caracterização da produção de biofilme bacteriano em isolados clínicos de Staphylococcus spp. frente aos antimicrobianos / Identificación y caracterización de la producción de biopelículas bacterianas en aislamientos clínicos de Staphylococcus spp. contra los antimicrobianos

Justification and Objectives: Circulating blood is sterile and the presence of microorganisms can be of clinical interest, especially in the hospital environment, being able to cause infectious processes and substantially increase morbidity and mortality. The objective of this work was to characterize the isolates of the genus Staphylococcus spp. from bloodstream infections as to the production of bacterial biofilm and resistance to the main antimicrobials used in clinical practice. Methods: Blood cultures were collected with an indication of positivity for bacterial growth from multiple sectors of the study hospital, which were subsequently processed to identify the bacterial genus through the use of phenotypic tests for Gram positive bacteria. The verification of the resistance profile was performed following the Kirby-Bauer disk diffusion. The identification of the production and quantification of the bacterial biofilm occurred following the protocol described by O'toole (2010). Results: The most frequent clinical isolate was Coagulase negative Staphylococci 38 (54.29%), followed by Staphylococcus aureus 32 (45.71%). Resistance to erythromycin, norfloxacin, levofloxacin and azithromycin was observed in most isolates (70%). Regarding methicillin, more MRSA (59.38%) than MR-CONS (47.37%) were isolated. The ICU was the place where the formation of the biofilm showed indicative data of greater adherence, which was associated with MRSA strains. Conclusion: The bacterial isolates associated with bloodstream infections showed high resistance to antimicrobials. The presence of MRSA and MR-CONS with strong and/or moderate biofilm production capacity represents a greater risk to the health of patients affected by infections caused by these agents.(AU)

Justificativa e Objetivos: O sangue circulante é estéril e a presença de microrganismos pode ter interesse clínico, especialmente no ambiente hospitalar, sendo capaz de causar processos infecciosos e aumentar substancialmente a morbimortalidade. O objetivo deste trabalho foi caracterizar os isolados do gênero Staphylococcus spp. oriundos de infecções de corrente sanguínea quanto à produção de biofilme bacteriano e resistência aos principais antimicrobianos utilizados na prática clínica. Métodos: Foram coletadas hemoculturas com indicação de positividade para o crescimento bacteriano de múltiplos setores do hospital de estudo, as quais posteriormente foram processadas para identificação do gênero bacteriano através da utilização de testes fenotípicos para bactérias Gram positivas. A verificação do perfil de resistência foi realizada seguindo a metodologia de disco difusão de Kirby-Bauer. A identificação da produção e quantificação do biofilme bacteriano ocorreu seguindo o protocolo descrito por O'toole (2010). Resultados: O isolado clínico mais frequente foi o Staphylococcus coagulase negativo 38 (54,29%), seguido pelo Staphylococcus aureus 32 (45,71%). A resistência à eritromicina, norfloxacina, levofloxacina e azitromicina foi observada na maioria dos isolados (70%). Em relação à meticilina, foram isolados mais Staphylococcus aureus resistente à meticilina (MRSA) (59,38%) que Staphylococcus coagulase negativa resistente à meticilina (MR-CONS) (47,37%). A UTI foi o local onde a formação do biofilme apresentou dados indicativos de maior aderência, sendo essa associada às cepas MRSA. Conclusão: Os isolados bacterianos associados às infecções da corrente sanguínea apresentaram elevada resistência aos antimicrobianos. A presença de MRSA e MR-CONS com forte e/ou moderada capacidade de produção de biofilme representa maior risco à saúde dos pacientes acometidos por infecções causadas por estes agentes.(AU)

Justificación y objetivos: la sangre circulante es estéril y la presencia de microorganismos puede ser de interés clínico, especialmente en el entorno hospitalario, ya que puede causar procesos infecciosos y aumentar sustancialmente la morbilidad y la mortalidad. El objetivo de este trabajo fue caracterizar los aislamientos del género Staphylococcus spp. de infecciones del torrente sanguíneo en cuanto a la producción de biopelículas bacterianas y la resistencia a los principales antimicrobianos utilizados en la práctica clínica. Métodos: Se recogieron hemocultivos con una indicación de positividad para el crecimiento bacteriano de múltiples sectores del hospital de estudio, que posteriormente se procesaron para identificar el género bacteriano mediante el uso de pruebas fenotípicas para bacterias Gram positivas. La verificación del perfil de resistencia se realizó siguiendo la metodología de difusión de disco de Kirby-Bauer. La identificación de la producción y cuantificación de la biopelícula bacteriana se produjo siguiendo el protocolo descrito por O'toole (2010). Resultados: El aislado clínico más frecuente fue Staphylococcus coagulasa negativo 38 (54.29%), seguido de Staphylococcus aureus 32 (45.71%). Se observó resistencia a la eritromicina, norfloxacina, levofloxacina y azitromicina en la mayoría de los aislamientos (70%). Con respecto a la meticilina, se aislaron más MRSA (59,38%) que MR-CONS (47,37%). La UCI fue el lugar donde la formación de la biopelícula mostró datos indicativos de una mayor adherencia, que se asoció con las cepas de MRSA. Conclusión: los aislamientos bacterianos asociados con infecciones del torrente sanguíneo mostraron una alta resistencia a los antimicrobianos. La presencia de MRSA y MR-CONS con una capacidad de producción de biopelículas fuerte y / o moderada representa un mayor riesgo para la salud de los pacientes afectados por infecciones causadas por estos agentes.(AU)

Production, characterization, evaluation and toxicity assessment of a Bacillus cereus UCP 1615 biosurfactant for marine oil spills bioremediation.

In this study, Bacillus cereus was cultivated in a mineral medium composed of 2% frying oil and 0.12% peptone to produce a biosurfactant. The production was scaled up from flasks to 1.2-, 3.0- and 50-L bioreactors, where surface tension achieved 28.7, 27.5 and 32 mN/m and biosurfactant concentration 4.3, 4.6 and 4.7 g/L, respectively. The biosurfactant was characterized as anionic, while nuclear magnetic resonance, thin-layer chromatography and gas chromatography analyses revealed its lipopeptide nature. Toxicity tests showed survival rates of the fish Poecilia vivipara and the bivalve Anomalocardia brasiliana higher than 90% and 55%, respectively, thus suggesting the use of this biosurfactant in marine environment depollution. Moreover, the biosurfactant stimulated the growth of autochthonous microorganisms independently of the presence of motor oil in bioassays performed in seawater. These results demonstrate that the biosurfactant is biocompatible and has potential for industrial-scale production and application to bioremediation of oil spills-polluted marine environment.

Multidrug-resistant Acinetobacter baumannii clones persist on hospital inanimate surfaces

ABSTRACT Acinetobacter baumannii is one of the most frequent Gram-negative opportunistic pathogens associated with hospital-acquired infection worldwide. We briefly describe A. baumannii isolates that were recovered from surrounding ICU bed surfaces, exhibiting multidrug resistance phenotype and belonging to some widely spread clonal complexes of clinical A. baumannii isolates.

Photobiostimulation reverses allodynia and peripheral nerve damage in streptozotocin-induced type 1 diabetes.

For better evaluation of the efficacy of low-level laser therapy in treating painful diabetic neuropathy and in protecting nerve fiber damage, we conducted a study with type 1 diabetic rats induced by streptozotocin. It is well known that diabetic peripheral neuropathy is the leading cause of pain in those individuals who suffer from diabetes. Despite the efficacy of insulin in controlling glucose level in blood, there is no effective treatment to prevent or reverse neuropathic damage for total pain relief.Male Wistar rats were divided into saline, vehicle, and treatment groups. A single intraperitoneal (i.p.) injection of streptozotocin (STZ) (85 mg/kg) was administered for the induction of diabetes. The von Frey filaments were used to assess nociceptive thresholds (allodynia). Behavioral measurements were accessed 14, 28, 48, and 56 days after STZ administration. Rats were irradiated with GaAs Laser (Gallium Arsenide, Laserpulse, Ibramed Brazil) emitting a wavelength of 904 nm, an output power of 45 mWpk, beam spot size at target 0.13 cm2, a frequency of 9500 Hz, a pulse time 60 ns, and an energy density of 6,23 J/cm2.The application of four sessions of low-level laser therapy was sufficient to reverse allodynia and protect peripheral nerve damage in diabetic rats.The results of this study indicate that low-level laser therapy is feasible to treat painful diabetic condition in rats using this protocol. Although its efficacy in reversing painful stimuli and protecting nerve fibers from damage was demonstrated, this treatment protocol must be further evaluated in biochemical levels to confirm its biological effects.

Resistência de bactérias isoladas em equipamentos em unidade de terapia intensiva / Resistance of bacteria isolated from equipment in an intensive care unit

Objetivo: Avaliar a resistência microbiana a medicamentos de bactérias isoladas de equipamentos próximos aos pacientes da Unidade de Terapia Intensiva. Métodos Trata-se de um estudo transversal. As amostras foram coletadas com swabs umedecidos em Trypticase Soy Broth, semeados posteriormente em Ágar Sangue de Carneiro e MacConkey. A identificação fenotípica ocorreu com base na morfologia das cepas e resultados bioquímicos. A análise da resistência aos medicamentos foi baseada no método de disco-difusão de Kirby-Bauer. Resultados Apresentaram-se contaminados 94,4% dos equipamentos analisados. Os microrganismos isolados mais frequentes foram: Acinetobacter sp., Staphylococcus aureus e Pseudomonas sp. Cerca de 75% de Acinetobacter sp. apresentaram resistência à piperacilina associada a tazobactam, meropenem e levofloxacina. Da mesma forma, 36,3% de S. aureus apresentaram-se resistentes à oxacilina e 10% dos isolados de Pseudomonas sp. foram resistentes aos medicamentos testados. Conclusão A maioria dos isolados apresentaram elevadas taxas de resistência microbiana aos medicamentos.

Objective: Evaluate drug resistance of bacteria isolated from equipment placed close to patients in an Intensive Care Unit of a hospital in Caruaru/Pernambuco, Brazil. Methods This is a cross-sectional study. The samples were collected with swabs moistened with Trypticase Soy Broth, which were then cultured in sheep blood agar and MacConkey agar. The phenotypic identification performed was based on the morphology of the strains and biochemical results. The drugs resistance analysis was based on Kirby-Bauer’s Disk Diffusion protocol. Results A rate of 94.4% of the analyzed equipment was contaminated. The most frequently isolated microorganisms were: Acinetobacter sp., Staphylococcus aureus and Pseudomonas sp. Just about 75% of Acinetobacter sp. was resistant to piperacillin associated to tazobactam, meropenem and levofloxacin. Similarly, 36.3% of S. aureus showed resistance to oxacillin and 10% of Pseudomonas sp. was resistant to the drugs tested. Conclusion Most of the microorganisms presented high levels of resistance to the drugs.

Reprodutibilidade das classificações AO/ASIF e Gartland para fraturas supracondilianas de úmero em crianças / Reproducibility of the AO/ASIF and Gartland classifications for supracondylar fractures of the humerus in children

OBJETIVO:Avaliar a reprodutibilidade das classificações radiográficas de Gartland e Association for Osteosynthesis/Association for the Study of Internal Fixation (AO/ASIF) para fraturas supracondilianas de úmero em crianças.MÉTODOS:Em duas ocasiões foram avaliadas por três cirurgiões ortopedistas pediátricos 50 radiografias nas incidências anteroposteriores e perfil de acordo com as classificações de Gartland e AO/ASIF pediátrica. As respostas foram submetidas à análise estatística pelo cálculo do coeficiente κ para avaliar a concordância intra- e interobservador, em ambas as classificações.RESULTADOS:A força de concordância intraobservador foi grande ou quase perfeita para os três examinadores nos dois sistemas de classificação. A força de concordância interobservador foi grande nos dois sistemas, com coeficiente κ de 0,756 para classificação de Gartland e de 0,766 para classificação AO/ASIF.CONCLUSÃO:Os sistemas de classificação de Gartland e AO/ASIF mostraram reprodutibilidade e desempenho similar. Observou-se grande força de concordância nas análises intra- e interobservador.

OBJECTIVE: To evaluate the reproducibility of the radiographic classifications of Gartland and the Association for Osteosynthesis/Association for the Study of Internal Fixation (AO/ASIF) for supracondylar fractures of the humerus in children. METHODS: On two occasions, 50 radiographs in anteroposterior and lateral views were evaluated by three pediatric orthopedists in accordance with the Gartland and AO/ASIF pediatric classifications. Their responses were subjected to statistical analysis consisting of calculation of the κ coefficient to assess the intra- and interobserver concordance, in both classifications. RESULTS: The strength of the intraobserver concordance was high or near perfect for the three examiners in the two classification systems. The strength of the interobserver concordance was high in the two systems, with κ coefficients of 0.756 for the Gartland classification and 0.766 for the AO/ASIF classification. CONCLUSION: The Gartland and AO/ASIF classification systems showed similar reproducibility and performance. High strength of concordance was seen in the intra- and interobserver analyses.

Morbidity and mortality of pancreatic tumors undergoing surgical treatment / Morbimortalidade do tratamento cirúrgico dos tumores do pâncreas

BACKGROUND: Pancreatic cancer has a high mortality rate due to late diagnosis and aggressive behavior. The prognosis is poor, with 5-year survival occurring in less than 5% of cases. AIM: To analyze demographic characteristics, comorbidities, type of procedure and early postoperative complications of patients with pancreatic cancer submitted to surgical treatment. METHODS: Cross-sectional study with analysis of 28 medical records of patients with malignant tumors of the pancreas in a 62 month. Data collection was performed from the medical records of the hospital. RESULTS: Of the total, 53,6% were male and the mean age was 60.25 years. According to the procedure, 53,6% was submitted to duodenopancreactectomy the remainder to biliodigestive derivation or distal pancreatectomy. The ductal adenocarcinoma occurred in 82,1% and 92,9% of tumors were located in the pancreatic head. Early postoperative complications occurred in 64,3% of cases and the most prevalent was intra-abdominal abscess (32,1%). Among duodenopancreactectomies 77,8% had early postoperative complications. CONCLUSION: Its necessary to encourage early detection of tumors of the pancreas to raise the number operations with curative intent. Refinements in surgical techniques and surgical teams can diminish postoperative complications and, so, operative morbimortality can also decrease over time. .

RACIONAL: O câncer de pâncreas apresenta alta taxa de mortalidade por conta do diagnóstico tardio e comportamento agressivo. O prognóstico é reservado com sobrevida de cinco anos em menos de 5% dos casos. OBJETIVO: Analisar as características demográficas, as comorbidades, o tipo de procedimento e as intercorrências pós-operatórias precoces dos pacientes de câncer de pâncreas submetidos ao tratamento cirúrgico. MÉTODOS: Estudo transversal, que analisou 28 prontuários de pacientes portadores de tumores malignos do pâncreas, no período de 62 meses. A coleta de dados foi realizada a partir dos prontuários médicos do hospital. RESULTADOS: Do total de participantes 53,6% eram do sexo masculino. A média de idade foi de 60,25 anos. Em relação ao procedimento, 53,6% foram submetidos à duodenopancreactectomia e o restante à derivação biliodigestiva ou pancreatectomia corpo-caudal. O adenocarcinoma ductal ocorreu em 82,1% e 92,9% dos tumores estavam localizados na cabeça do pâncreas. As complicações pós-operatórias precoces ocorreram em 64,3%, e a mais prevalente foi abscesso intra-abdominal (32,1%). Entre as duodenopancreatectomias, 77,8% apresentaram complicações pós-operatórias precoces. CONCLUSÃO: Há necessidade de se incentivar a detecção precoce dos tumores de pâncreas para que se consiga realizar mais operações com intenção curativa. Também, é necessário o aprimoramento das técnicas operatórias e das equipes cirúrgicas para que as complicações pós-operatórias e a morbimortalidade operatória diminuam ao longo do tempo. .

Morbidity and mortality of pancreatic tumors undergoing surgical treatment.

BACKGROUND: Pancreatic cancer has a high mortality rate due to late diagnosis and aggressive behavior. The prognosis is poor, with 5-year survival occurring in less than 5% of cases. AIM: To analyze demographic characteristics, comorbidities, type of procedure and early postoperative complications of patients with pancreatic cancer submitted to surgical treatment. METHODS: Cross-sectional study with analysis of 28 medical records of patients with malignant tumors of the pancreas in a 62 month. Data collection was performed from the medical records of the hospital. RESULTS: Of the total, 53,6% were male and the mean age was 60.25 years. According to the procedure, 53,6% was submitted to duodenopancreactectomy the remainder to biliodigestive derivation or distal pancreatectomy. The ductal adenocarcinoma occurred in 82,1% and 92,9% of tumors were located in the pancreatic head. Early postoperative complications occurred in 64,3% of cases and the most prevalent was intra-abdominal abscess (32,1%). Among duodenopancreactectomies 77,8% had early postoperative complications. CONCLUSION: Its necessary to encourage early detection of tumors of the pancreas to raise the number operations with curative intent. Refinements in surgical techniques and surgical teams can diminish postoperative complications and, so, operative morbimortality can also decrease over time.