Therapeutic Targeting of DNA Repair Pathways in Pediatric Extracranial Solid Tumors: Current State and Implications for Immunotherapy.

DNA damage is fundamental to tumorigenesis, and the inability to repair DNA damage is a hallmark of many human cancers. DNA is repaired via the DNA damage repair (DDR) apparatus, which includes five major pathways. DDR deficiencies in cancers give rise to potential therapeutic targets, as cancers harboring DDR deficiencies become increasingly dependent on alternative DDR pathways for survival. In this review, we summarize the DDR apparatus, and examine the current state of research efforts focused on identifying vulnerabilities in DDR pathways that can be therapeutically exploited in pediatric extracranial solid tumors. We assess the potential for synergistic combinations of different DDR inhibitors as well as combinations of DDR inhibitors with chemotherapy. Lastly, we discuss the immunomodulatory implications of targeting DDR pathways and the potential for using DDR inhibitors to enhance tumor immunogenicity, with the goal of improving the response to immune checkpoint blockade in pediatric solid tumors. We review the ongoing and future research into DDR in pediatric tumors and the subsequent pediatric clinical trials that will be critical to further elucidate the efficacy of the approaches targeting DDR.

Impact of COVID-19 Infection on Pancreato-Biliary Diseases Requiring Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Viral infections are known to impact the pancreato-biliary system; however, there are limited data showing that the same is true of COVID-19. Endoscopic retrograde cholangiopancreatography (ERCP) can safely be performed in patients with COVID-19 infection, but outcomes of patients with COVID-19 infections and concomitant pancreatic and biliary disease requiring endoscopic intervention are unknown. AIMS: This study aims to evaluate the severity of pancreaticobiliary diseases and post-ERCP outcomes in COVID-19 patients. METHODS: Patients with pancreato-biliary disease that required inpatient ERCP from five centers in the United States and South America between January 1, 2020, and October 31, 2020 were included. A representative cohort of patients from each month were randomly selected from each site. Disease severity and post-ERCP outcomes were compared between COVID-19 positive and COVID-19 negative patients. RESULTS: A total of 175 patients were included: 95 COVID positive and 80 COVID negative. Mean CTSI score for the patients who had pancreatitis was higher in COVID-positive cohort by 3.2 points (p < .00001). The COVID-positive group had more cases with severe disease (n = 41) versus the COVID-negative group (n = 2) (p < .00001). Mortality was higher in the COVID-19 positive group (19%) compared to COVID-negative group (7.5%) even though the COVID-19-negative group had higher incidence of malignancy (n = 17, 21% vs n = 7, 7.3%) (p = 0.0455). CONCLUSIONS: This study shows that patients with COVID infection have more severe pancreato-biliary disease and worse post-ERCP outcomes, including longer length of stay and higher mortality rate. These are important considerations when planning for endoscopic intervention. CLINICALTRIALS: gov: (NCT05051358).

Accurate and safe diagnosis and treatment of neoplastic biliary lesions using a novel 9F and 11F digital single-operator cholangioscope.

Background and study aims Digital single-operator cholangioscopy (DSOC) allows the diagnosis of biliary duct disorders and treatment for complicated stones. However, these technologies have limitations such as the size of the probe and working channel, excessive cost, and low image resolution. Recently, a novel DSOC system (eyeMAX, Micro-Tech, Nanjing, China) was developed to address these limitations. We aimed to evaluate the usefulness and safety of a novel 9F and 11F DSOC system in terms of neoplastic diagnostic accuracy based on visual examination, ability to evaluate tumor extension and to achieve complete biliary stone clearance, and procedure-related adverse events (AEs). Patients and methods Data from ≥ 18-year-old patients who underwent DSOC from July 2021 to April 2022 were retrospectively recovered and divided into a diagnostic and a therapeutic cohort. Results A total of 80 patients were included. In the diagnostic cohort (n = 49/80), neovascularity was identified in 26 of 49 patients (46.9%). Biopsy was performed in 65.3% patients with adequate tissue sample obtained in 96.8% of cases. Biopsy confirmed neoplasia in 23 of 32 cases. DSOC visual impression achieved 91.6% sensitivity and 87.5% specificity in diagnosing neoplasms. In the therapeutic cohort (n = 43/80), 26 of 43 patients required lithotripsy alone. Total stone removal was achieved in 71% patients in the first session. Neither early nor late AEs were documented in either the diagnostic or therapeutic cohort. Conclusions The novel DSOC device has excellent diagnostic accuracy in distinguishing neoplastic biliary lesions as well as therapeutic benefits in the context of total stone removal, with no documented AEs.

Assessing Endoscopic Ultrasound-Guided Radiofrequency Ablation in Unresectable Pancreatic Ductal Adenocarcinoma: A Single-Center Historic Cohort Study.

BACKGROUND: /aims: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as an alternative for the local treatment of unresectable pancreatic ductal adenocarcinoma (PDAC). We aim to assess the feasibility and safety of EUS-RFA in patients with unresectable PDAC. METHODS: The following was a historic cohort compounded by locally advanced (LA) and metastatic (m) PDAC naïve patients, who underwent EUS-RFA between October 2019 to March 2022. EUS-RFA was performed with a 19-g needle electrode with a 10 mm active tip for energy delivery. Study primary endpoints were feasibility, safety, and clinical follow-up; secondary endpoints were performance status (PS), local control (LC) and overall survival (OS). RESULTS: Twenty-six patients were selected: 15/26 LA-PDAC and 11/26 mPDAC. Technical success was achieved in all patients with no major adverse events. Six months after EUS-RFA, OS was 11/26 (42.3%), with significant PS improvement (P=.03). LC was achieved, with tumor reduction from 39.5 to 26 mm (P=.04). Post-treatment hypodense necrotic area was observed at six-month follow-up in 11/11 alive cases. Metastatic disease was a significant factor for OS worsening (HR 5.021; IC 95% 1.589 - 15.87; P=.004) CONCLUSIONS: EUS-RFA of pancreatic adenocarcinoma is a minimally invasive and safe technique that may have an important role as targeted therapy for local treatment of unresectable cases, as well as an alternative for poor surgical candidates. Also, RFA may play a role in downstaging cancer with potential OS increase in non-metastatic cases. Large prospective cohorts are required to evaluate this technique in clinical practice.

Full-depth evaluation of the bile duct with a 7F cholangioscope and its possibility for guiding therapeutics.

Background and Aims: Digital single-operator cholangioscopy (DSOC) plays a critical role in directly visualizing and treating the bile duct system. Although various cholangioscopes with different external diameters are available for DSOC, certain challenging scenarios persist in which existing scopes fail to complete a thorough evaluation of the bile ducts. To overcome these limitations, we aimed to introduce and highlight the application of a novel 7F cholangioscope. Methods: In this review article we describe the novel 7F cholangioscope, provide its assembly and setup, and review cases in which the 7F cholangioscope was used for diagnostic and therapeutic guidance. Results: Four cases involving challenging biliary assessments were presented, all of which achieved technical and clinical success. No procedure-related adverse events were reported in any of these cases. Conclusions: The 7F cholangioscope can provide additional information regarding the biliary tree and guidance for treatment, overcoming the challenging assessment of small pancreatobiliary ducts and its strictures. Its potential use in cases of severe bile duct stenosis is recommended. However, further studies evaluating safety and efficacy are needed.

ESRU-ESU-YAU_UROTECH Survey on Urology Residents Surgical Training: Are We Ready for Simulation and a Standardized Program?

Background: Currently, the landscape of surgical training is undergoing rapid evolution, marked by the initial implementation of standardized surgical training programs, which are further facilitated by the emergence of new technologies. However, this proliferation is uneven across various countries and hospitals. Objective: To offer a comprehensive overview of the existing surgical training programs throughout Europe, with a specific focus on the accessibility of simulation resources and standardized surgical programs. Design setting and participants: A dedicated survey was designed and spread in May 2022 via the European Association of Urology (EAU) mail list, to Young Urologist Office (YUO), Junior membership, European Urology Residents Education Program participants between 2014 and 2022, and other urologists under 40 yr, and via the EAU Newsletter. Intervention: A 64-item, online-based survey in accordance with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) using the platform of Survey Monkey (Portland, OR, USA) was realized. Outcome measurements and statistical analysis: The study involved an assessment of the demographic characteristics. Additionally, it explored the type of center, availability of various surgical approaches, presence of training infrastructure, participation in courses, organization of training, and participants' satisfaction with the training program. The level of satisfaction was evaluated using a Likert-5 scale. The subsequent sections delved into surgical training within the realms of open, laparoscopic, robotic, and endoscopic surgery, each explored separately. Finally, the investigation encompassed the presence of a structured training course and the availability of a duly validated final evaluation process. Results and limitations: There were 375 responders with a completion rate of 82%. Among them, 75% were identified as male, 50.6% were young urologists, 31.7% were senior residents, and 17.6% were junior residents. A significant majority of participants (69.6%) were affiliated with academic centers. Regarding the presence of dry lab training facilities, only 50.3% of respondents indicated its availability. Among these centers, 46.7% were primarily focused on laparoscopy training. The availability of virtual and wet lab training centers was even more limited, with rates of 31.5% and 16.2%, respectively. Direct patient involvement was reported in 80.5% of cases for open surgery, 58.8% for laparoscopy, 25.0% for robotics, and 78.6% for endourology. It is worth noting that in <25% of instances, training followed a well-defined standardized program comprising both preclinical and clinical modular phases. Finally, the analysis of participant feedback showed that 49.7% of respondents expressed a satisfaction rating of either 4 or 5 points with respect to the training program. The limitations of our study include the low response rate, predominance of participants from academic centers, and absence of responses from individuals not affiliated with the EAU network. Conclusions: The current distribution of surgical training centers falls short of ensuring widespread access to standardized training programs. Although dry lab facilities are relatively well spread, the availability of wet lab resources remains restricted. Additionally, it appears that many trainees' initial exposure to surgery occurs directly with patients. There is a pressing need for continued endeavors to establish uniform training routes and assessment techniques across various surgical methodologies. Patient summary: Nowadays, the surgical training landscape is heterogeneous across different countries. The implementation of a standardized training methodology to enhance the overall quality of surgical training and thereby improving patient outcomes is needed.

The impact of outdoor pollution and extreme temperatures on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma.

Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma-related outcomes of short-term exposure to outdoor air pollutants (PM2.5, PM10, NO2 , SO2 , O3 , and CO), heavy traffic, outdoor pesticides, and extreme temperatures. Additionally, the SR evaluated the impact of the efficacy of interventions reducing outdoor pollutants. The risk of bias was assessed using ROBINS-E tools and the certainty of the evidence by using GRADE. Short-term exposure to PM2.5, PM10, and NO2 probably increases the risk of asthma-related hospital admissions (HA) and emergency department (ED) visits (moderate certainty evidence). Exposure to heavy traffic may increase HA and deteriorate asthma control (low certainty evidence). Interventions reducing outdoor pollutants may reduce asthma exacerbations (low to very low certainty evidence). Exposure to fumigants may increase the risk of new-onset asthma in agricultural workers, while exposure to 1,3-dichloropropene may increase the risk of asthma-related ED visits (low certainty evidence). Heatwaves and cold spells may increase the risk of asthma-related ED visits and HA and asthma mortality (low certainty evidence).

Reproducibility and Repeatability of Intravoxel Incoherent Motion MRI Acquisition Methods in Liver.

BACKGROUND: Intravoxel incoherent motion (IVIM) diffusion weighted MRI (DWI) has potential for evaluating hepatic fibrosis but image acquisition technique influence on diffusion parameter estimation bears investigation. PURPOSE: To minimize variability and maximize repeatably in abdominal DWI in terms of IVIM parameter estimates. STUDY TYPE: Prospective test-retest and image quality comparison. SUBJECTS: Healthy volunteers (3F/7M, 29.9 ± 12.9 years) and Family Study subjects (18F/12M, 51.7 ± 16.7 years), without and with liver steatosis. FIELD STRENGTH/SEQUENCE: Abdominal single-shot echo-planar imaging (EPI) and simultaneous multi-slice (SMS) DWI sequences with respiratory triggering (RT), breath-holding (BH), and navigator echo (NE) at 3 Tesla. ASSESSMENT: SMS-BH, EPI-NE, and SMS-RT data from twice-scanned healthy volunteers were analyzed using 6 × b-values (0-800 s⋅mm-2 ) and lower (LO) and higher (HI) b-value ranges. Family Study subjects were scanned using SMS and standard EPI sequences. The biexponential IVIM model was used to estimate fast-diffusion coefficient (Df ), fraction of fast diffusion (f), and slow-diffusion coefficient (Ds ). Scan time, estimated signal-to-noise ratio (eSNR), eSNR per acquisition, and distortion ratio were compared. STATISTICAL TESTS: Coefficients of variation (CoV) and Bland Altman analyses were performed for test-retest repeatability. Interclass correlation coefficient (ICC) assessed interobserver agreement with P < 0.05 deemed significant. RESULTS: Within-subject CoVs among volunteers (N = 10) for f and Ds were lowest in EPI-NE-LO (11.6%) and SMS-RT-HI (11.1%). Inter-observer ICCs for f and Ds were highest for EPI-NE-LO (0.63) and SMS-RT-LO (0.76). Df could not be estimated for most subjects. Estimated eSNR (EPI = 21.9, SMS = 4.7) and eSNR time (EPI = 6.7, SMS = 16.6) were greater for SMS, with less distortion in the liver region (DR-PE: EPI = 23.6, SMS = 13.1). DATA CONCLUSION: Simultaneous multislice acquisitions had significantly less variability and higher ICCs of Ds , higher eSNR, less distortion, and reduced scan time compared to EPI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Liver-restricted Type I IFN Signature Precedes Liver Damage in Chronic Hepatitis B Patients Stopping Antiviral Therapy.

Immune-mediated liver damage is the driver of disease progression in patients with chronic hepatitis B virus (HBV) infection. Liver damage is an Ag-independent process caused by bystander activation of CD8 T cells and NK cells. How bystander lymphocyte activation is initiated in chronic hepatitis B patients remains unclear. Periods of liver damage, called hepatic flares, occur unpredictably, making early events difficult to capture. To address this obstacle, we longitudinally sampled the liver of chronic hepatitis B patients stopping antiviral therapy and analyzed immune composition and activation using flow cytometry and single-cell RNA sequencing. At 4 wk after stopping therapy, HBV replication rebounded but no liver damage was detectable. There were no changes in cell frequencies at viral rebound. Single-cell RNA sequencing revealed upregulation of IFN-stimulated genes (ISGs) and proinflammatory cytokine migration inhibitory factor (MIF) at viral rebound in patients that go on to develop hepatic flares 6-18 wk after stopping therapy. The type I IFN signature was only detectable within the liver, and neither IFN-α/ß or ISG induction could be detected in the peripheral blood. In vitro experiments confirmed the type I IFN-dependent ISG profile whereas MIF was induced primarily by IL-12. MIF exposure further amplified inflammatory cytokine production by myeloid cells. Our data show that innate immune activation is detectable in the liver before clinically significant liver damage is evident. The combination of type I IFN and enhanced cytokine production upon MIF exposure represent the earliest immunological triggers of lymphocyte bystander activation observed in hepatic flares associated with chronic HBV infection.

Antitumor efficacy of a sequence-specific DNA-targeted γPNA-based c-Myc inhibitor.

Targeting oncogenes at the genomic DNA level can open new avenues for precision medicine. Significant efforts are ongoing to target oncogenes using RNA-targeted and protein-targeted platforms, but no progress has been made to target genomic DNA for cancer therapy. Here, we introduce a gamma peptide nucleic acid (γPNA)-based genomic DNA-targeted platform to silence oncogenes in vivo. γPNAs efficiently invade the mixed sequences of genomic DNA with high affinity and specificity. As a proof of concept, we establish that γPNA can inhibit c-Myc transcription in multiple cell lines. We evaluate the in vivo efficacy and safety of genomic DNA targeting in three pre-clinical models. We also establish that anti-transcription γPNA in combination with histone deacetylase inhibitors and chemotherapeutic drugs results in robust antitumor activity in cell-line- and patient-derived xenografts. Overall, this strategy offers a unique therapeutic platform to target genomic DNA to inhibit oncogenes for cancer therapy.

Estudio etnobotánico de la flora medicinal de la provincia de Trujillo, Perú / Ethnobotanical study of the medicinal flora of the province of Trujillo, Peru

Trujillo, one of the main provinces of Peru, is home to a multicultural population, coming from the Coast, Sierra and Selva; of different ideologies, cultures, and ancestral knowledge about the correct use of medicinal flora. In this sense and in an effort to rescue this ancestral knowledge, the ethnobotanical study of the medicinal flora of the province of Trujillo was carried out. For which 96 semi - structured interviews were applied, using the "snowball" technique; followed by the collection, taxonomic determination and calculation of ethnobotanical indices: Use Value Index (IVU) and Informant Consensus Factor Index (FCI). It is concluded that the inhabitants of Trujillo make use of 102 species of medicinal flora, distributed in 95 genera and 46 families for the treatment and/or cure of 62 diseases. Of the total species, 24 turned out to be the most important (according to their IVU) for the cure of diseases of the Trujillo po pulation.

Trujillo, una de las principales provincias de Perú, alberga una población pluricultural, procedente de la Costa, Sierra y Selv a; de distintas ideologías, culturas, y saberes ancestrales sobre el correcto uso de la flora medicinal. En tal sentido y en el afán de rescatar ese conocimiento ancestral, se realizó el estudio etnobotánico de la flora medicinal de la provincia de Trujill o. Para lo cual se aplicaron 96 entrevistas semiestructuradas, empleando la técnica "bola de nieve"; seguido de la colecta, determinación taxonómica y cálculo de Índices etnobotánicos: Índice de valor de Uso (IVU) e Índice de Factor de Consenso del Informa nte (FCI). Se concluye que los pobladores trujillanos hacen uso de 102 especies de flora medicinal, distribuidas en 95 géneros y 46 familias para el tratamiento y/o cura de 62 enfermedades. Del total de especies, 24 resultaron ser las más importantes (segú n su IVU) para la cura de enfermedades del poblador Trujillano.

Development of convolutional neural network models that recognize normal anatomic structures during real-time radial-array and linear-array EUS (with videos).

BACKGROUND AND AIMS: EUS is a high-skill technique that requires numerous procedures to achieve competence. However, training facilities are limited worldwide. Convolutional neural network (CNN) models have been previously implemented for object detection. We developed 2 EUS-based CNN models for normal anatomic structure recognition during real-time linear- and radial-array EUS evaluations. METHODS: The study was performed from February 2020 to June 2022. Consecutive patient videos of linear- and radial-array EUS videos were recorded. Expert endosonographers identified and labeled 20 normal anatomic structures within the videos for training and validation of the CNN models. Initial CNN models (CNNv1) were developed from 45 videos and the improved models (CNNv2) from an additional 102 videos. CNN model performance was compared with that of 2 expert endosonographers. RESULTS: CNNv1 used 45,034 linear-array EUS frames and 21,063 radial-array EUS frames. CNNv2 used 148,980 linear-array EUS frames and 128,871 radial-array EUS frames. Linear-array CNNv1 and radial-array CNNv1 achieved a 75.65% and 71.36% mean average precision (mAP) with a total loss of .19 and .18, respectively. Linear-array CNNv2 obtained an 88.7% mAP with a .06 total loss, whereas radial-array CNNv2 achieved an 83.5% mAP with a .07 total loss. CNNv2 accurately detected all studied normal anatomic structures with a >98% observed agreement during clinical validation. CONCLUSIONS: The proposed CNN models accurately recognize the normal anatomic structures in prerecorded videos and real-time EUS. Prospective trials are needed to evaluate the impact of these models on the learning curves of EUS trainees.

Hospitalization and mortality during the pandemic in chronic hemodialysis patients and the general population in Peru / Hospitalização e mortalidade durante a pandemia em pacientes em hemodiálise crônica e na população em geral no Peru

ABSTRACT Background: Patients with chronic kidney disease have a higher risk of severe disease and mortality from COVID-19 than the general population. Objective: To compare hospitalization and mortality rates during the pandemic among chronic hemodialysis (HD) patients and the general population in Lima (Peru). Methods: This retrospective cohort included an assessment of the database of chronic HD patients of the health service providers of the social health insurance benefit networks of Lima and Callao between 2019 and 2021. Hospitalization and mortality rates were obtained for every 1,000 individuals, and variations in the percentages of COVID-19 cases and deaths were calculated. These rates were compared with those of the general population data and standardized by age and sex. Results: An average of 3,937 chronic HD patients were evaluated each month. Of these, 4.8% had COVID-19 and 64.97% were mild cases. The hospitalization rates per 1,000 patients were 19.5, 29.28, and 36.7 in 2019, 2020, and 2021, respectively. The mortality rates per 1,000 patients were 5.9, 9.74, and 11.49 in 2019, 2020, and 2021, respectively. When compared to the standardized general population, the peaks of both rates coincided with the plateaus of the waves during the pandemic. The hospitalization rate for COVID-19 was 12 times higher in HD patients than in the general population, and the mortality rate for COVID-19 was twice as high. Conclusion: HD patients had higher hospitalization and standardized mortality rates than the general population. Peaks in hospitalizations and mortality coincided with the plateaus of the first and second waves of the pandemic.

Resumo Histórico: Pacientes com DRC apresentam maior risco de doença grave e mortalidade por COVID-19 do que a população geral. Objetivo: Comparar taxas de hospitalização e mortalidade durante a pandemia entre pacientes em hemodiálise crônica (HD) e a população geral em Lima (Peru). Métodos: Esta coorte retrospectiva incluiu avaliação do banco de dados de pacientes em HD crônica dos prestadores de serviços de saúde das redes de benefícios do seguro social de saúde de Lima e Callao, entre 2019-2021. Obteve-se taxas de hospitalização e mortalidade para cada 1.000 indivíduos, e foram calculadas variações nas porcentagens de casos de COVID-19 e óbitos. Estas taxas foram comparadas com os dados da população geral e padronizadas por idade e sexo. Resultados: Uma média de 3.937 pacientes em HD crônica foram avaliados mensalmente. Destes, 4,8% tinham COVID-19, 64,97% eram casos leves. As taxas de hospitalização por 1.000 pacientes foram 19,5; 29,28; e 36,7 em 2019, 2020, e 2021, respectivamente. As taxas de mortalidade por 1.000 pacientes foram 5,9; 9,74 e 11,49 em 2019, 2020, e 2021, respectivamente. Quando comparados à população geral padronizada, os picos das taxas coincidiram com os platôs das ondas da pandemia. A taxa de hospitalização para COVID-19 foi 12 vezes maior em pacientes em HD do que na população geral e a taxa de mortalidade por COVID-19 foi duas vezes maior. Conclusão: Pacientes em HD apresentaram taxas de hospitalização e mortalidade padronizada mais elevadas do que a população geral. Os picos das hospitalizações e mortalidade coincidiram com os platôs da primeira e segunda ondas da pandemia.

Robust SMC-PSS and AVR design: A grid connected solar concentrated OTEC system application.

This work analyzes the stability and performance of an offshore solar-concentrated ocean thermal energy conversion system (SC-OTEC) tied to an onshore AC grid. The OTEC is a system where electricity is generated using small temperature differences between the warm surface and deep cold ocean water. Existing control methods for SC-OTEC systems lack coordination, hindering dynamic stability and effective damping for the synchronous generator (SG). These methods struggle to quickly adapt to sudden disturbances and lack the capability to adequately reject or compensate for such disturbances due to complex control constraints and computational demands. To this regard, a control strategy combining sliding mode control (SMC) and a power system stabilizer (PSS) to improve the SC-OTEC dynamic stability and damping features for the SG. Moreover, an auxiliary secondary automatic voltage regulator is assembled with a non-linear exciter system to provide damping features. The proposed PID-PSS and secondary AVR controller gains are adaptively tuned using a modified whale optimization algorithm with the balloon effect modulation. The studied SC-OTEC is tested through MATLAB/Simulink under a severe 3ϕ short-circuit fault, solar radiation variations, and a change in surface seawater temperature as well as changes in local loads. The final findings approved that the proposed control strategy preserves a strong performance and can mimic effectively the proposed SC-OTEC damping compared to the conventional system.

Use of an adapted bronchoscope for peroral endoscopic myotomy in a pediatric patient weighing less than 10 kg.

Video 1Customization of pediatric bronchoscope and peroral endoscopic myotomy settings.

Medellín, lecciones de un cambio en seguridad ciudadana / Medellín, lessons of a change in citizen security / Medellín, lições de uma mudança na segurança cidadã

Medellín fue considerada la ciudad más violenta del mundo durante los años noventa con una tasa de homicidios superior a 370 por cada 100 000 habitantes. En las últimas tres décadas, los asesinatos en la ciudad disminuyeron en un 90 %. Esta transformación ha sido celebrada internacionalmente como un ejemplo de gobernanza local exitosa de centros urbanos que sufren altos índices criminales. Ahora bien, este artículo sostiene que dicha recuperación ­catalogada por algunos como "milagro"­ no fue sólo producto de acciones exitosas del gobierno local, sino también el resultado de dos factores más: primero, la política del Estado colombiano a nivel nacional para fortalecer su aparato de seguridad y desmantelar grupos ilegales armados; y segundo, los acuerdos informales entre las autoridades y las bandas locales, así como la decisión de estas últimas de evitar confrontaciones violentas para facilitar la extracción de sus rentas ilegales.

Medellín was considered the most violent city in the world during the 1990s with a homicide rate of over 370 per 100 000 inhabitants. In the last three decades, murders in the city have decreased by 90 %. This transformation has been celebrated internationally as an example of successful local governance of urban centres suffering from high crime rates. However, this article argues that this recovery - labelled by some as a "miracle" - was not only the product of successful local government actions, but also the result of two other factors: first, the Colombian state's policy at the national level to strengthen its security apparatus and dismantle illegal armed groups; and second, the informal agreements between the authorities and local gangs, as well as the latter's decision to avoid violent confrontations in order to facilitate the extraction of their illegal rents.

Medellín foi considerada a cidade mais violenta do mundo durante a década de 1990, com uma taxa de homicídios superior a 370 por 100 000 habitantes. Nas últimas três décadas, os assassinatos na cidade diminuíram 90 %. Esta transformação tem sido celebrada internacionalmente como um exemplo de governação local bem-sucedida de centros urbanos que sofrem de elevadas taxas de criminalidade. Ora, este artigo sustenta que esta recuperação ­ catalogada por alguns como um "milagre" ­ não foi apenas o produto de ações bem-sucedidas do governo local, mas também o resultado de mais dois fatores: primeiro, a política do Estado colombiano no a nível nacional para reforçar o seu aparelho de segurança e desmantelar grupos armados ilegais; e em segundo lugar, os acordos informais entre as autoridades e os gangues locais, bem como a decisão destes últimos de evitar confrontos violentos para facilitar a extracção das suas rendas ilegais.

Impacto de la cardiomiotomía laparoscópica de Heller en la función del esfínter esofágico inferior y el diámetro del esófago / Impact of laparoscopic Heller cardiomyotomy on lower esophageal sphincter function and esophageal diameter

Introducción. La acalasia es un trastorno motor del esófago caracterizado por la ausencia de peristalsis y la alteración en la relajación del esfínter esofágico inferior. La cardiomiotomía laparoscópica de Heller más funduplicatura parcial es el tratamiento estándar. La mejoría sintomática ha sido bien documentada, pero no hay suficiente información objetiva respecto a los cambios fisiológicos y radiográficos luego del procedimiento. Métodos. Estudio de cohorte bidireccional de pacientes llevados a cardiomiotomía laparoscópica de Heller, entre los años 2018 y 2021, en el Hospital Universitario San Vicente Fundación de Medellín, Colombia. Se describen variables demográficas y clínicas. Se realizaron puntaje sintomático de Eckardt, manometría esofágica y radiografía de esófago en el pre y postoperatorio. Se hizo comparación de síntomas, presión basal del esfínter esofágico inferior, presión de relajación integrada y diámetro del esófago antes y después de la intervención. Resultados. Se incluyeron 24 pacientes. El 63 % fueron mujeres y la edad promedio fue de 44 años. Los valores promedio preoperatorios vs postoperatorios fueron: puntaje de Eckardt 10,6 vs 1,4 puntos (p<0,001), presión basal de 41,4 vs 18,1 mmHg (p=0,004) y presión de relajación integrada de 28,6 vs 12,5 mmHg (p=0,001). El diámetro del esófago no presentó cambios. No hubo correlación de síntomas con los cambios de presión del esfínter esofágico inferior. El tiempo de seguimiento fue de 20 meses. Conclusiones. La cardiomiotomía de Heller es un procedimiento altamente efectivo para el tratamiento definitivo de la acalasia, logrando una mejoría subjetiva y objetiva basada en síntomas y en parámetros de manometría, respectivamente

Introduction. Achalasia is a motor disorder of the esophagus characterized by the absence of peristalsis and impaired relaxation of the lower esophageal sphincter. Laparoscopic Heller ́s cardiomyotomy plus partial fundoplication is the standard treatment. Symptomatic improvement has been well documented, but there is insufficient objective information regarding physiologic and radiographic changes after the procedure. Methods. Bidirectional cohort study of patients underwent laparoscopic Heller ́s cardiomyotomy between 2018 and 2021 at the San Vicente Fundación University Hospital in Medellín, Colombia. Demographic and clinical variables are described. Eckardt symptom score, esophageal manometry, and esophageal radiography were performed pre and postoperatively. A comparison of symptoms, baseline lower esophageal sphincter pressure, integrated relaxation pressure, and esophageal diameter before and after intervention were performed.Results. 24 patients were included. 63% were women and the average age was 44 years. The preoperative vs. postoperative mean values were: Eckardt score 10.6 vs. 1.4 points (p<0.001), basal pressure of 41.4 vs. 18.1 mmHg (p=0.004) and integrated relaxation pressure of 28.6 vs. 12.5 mmHg (p=0.001). The diameter of the esophagus did not present changes. There was no correlation of symptoms with lower esophageal sphincter pressure changes. The follow-up time was 20 months. Conclusions. Heller cardiomyotomy is a highly effective procedure for the definitive treatment of achalasia, achieving subjective and objective improvements, based on symptoms and manometry parameters, respectively