Noninvasive biomarkers for the detection of GERD-induced pulmonary injury.

BACKGROUND: The role of gastroesophageal reflux in progressive lung damage is increasingly recognized. We have proposed, based on our work with lung transplant recipients, a novel immune mechanism of pulmonary injury after aspiration of gastric contents, during which higher levels of normally sequestered lung self-antigens (SAgs) collagen V (Col-V) and K-alpha-1 tubulin (Kα1T) in circulating small extracellular vesicles (EVs) induce the production of self-antibodies (SAbs) anti-Col-V and anti-Kα1T. Thus, we aimed to determine whether levels of SAbs or SAgs increased in an animal model of aspiration-induced lung damage in a nontransplant setting. METHODS: We created a murine model of repetitive lung aspiration using C57BL/6J mice. Mice were aspirated weekly with 1 mL/kg of hydrochloric acid (n = 9), human gastric contents (n = 9), or combined (1:1) fluid (n = 9) once, three, or six times (n = 3 in each subgroup; control group, n = 9). Blood samples were periodically obtained, and all animals were sacrificed at day 90 for pathological assessment. SAbs were measured using an enzyme-linked immunosorbent assay; SAgs and NF-κB contained in small EVs were assessed by western blot. RESULTS: Aspirated mice weighed significantly less than controls throughout the study and had histological evidence of pulmonary injury at day 90. Overall, aspirated mice developed higher concentrations of anti-Col-V at day 28 (53.9 ± 28.7 vs. 29.9 ± 4.5 ng/mL, p < 0.01), day 35 (42.6 ± 19.8 vs. 28.6 ± 7.2 ng/mL, p = 0.038), and day 90 (59.7 ± 27.7 vs. 34.1 ± 3.2 ng/mL, p = 0.014) than the control group. Circulating small EVs isolated from aspirated mice on day 90 contained higher levels of Col-V (0.7 ± 0.56 vs. 0.18 ± 0.6 m.o.d., p = 0.009) and NF-κB (0.42 ± 0.27 vs. 0.27 ± 0.09 m.o.d., p = 0.095) than those from controls. CONCLUSIONS: This experimental study supports the theory that gastroesophageal reflux leads to the development of lung damage and an increase of humoral markers that may serve as noninvasive biomarkers to detect asymptomatic lung injury among patients with gastroesophageal reflux disease.

Mesenchymal Stem/Stromal Cells Derived from Dental Tissues Mediate the Immunoregulation of T Cells through the Purinergic Pathway.

Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for potential clinical applications because of their accessibility and anti-inflammatory capacity. We previously demonstrated that DT-MSCs from dental pulp (DP-MSCs), periodontal ligaments (PDL-MSCs), and gingival tissue (G-MSCs) show immunosuppressive effects similar to those of BM, but to date, the DT-MSC-mediated immunoregulation of T lymphocytes through the purinergic pathway remains unknown. In the present study, we compared DP-MSCs, PDL-MSCs, and G-MSCs in terms of CD26, CD39, and CD73 expression; their ability to generate adenosine (ADO) from ATP and AMP; and whether the concentrations of ADO that they generate induce an immunomodulatory effect on T lymphocytes. BM-MSCs were included as the gold standard. Our results show that DT-MSCs present similar characteristics among the different sources analyzed in terms of the properties evaluated; however, interestingly, they express more CD39 than BM-MSCs; therefore, they generate more ADO from ATP. In contrast to those produced by BM-MSCs, the concentrations of ADO produced by DT-MSCs from ATP inhibited the proliferation of CD3+ T cells and promoted the generation of CD4+CD25+FoxP3+CD39+CD73+ Tregs and Th17+CD39+ lymphocytes. Our data suggest that DT-MSCs utilize the adenosinergic pathway as an immunomodulatory mechanism and that this mechanism is more efficient than that of BM-MSCs.

Food-Related Quality of Life Is Impaired in Latinx and Non-Latinx Patients With Inflammatory Bowel Disease.

Background and Aims: Anxiety over food choices and symptoms related to food consumption diminish quality of life (QoL) in inflammatory bowel disease (IBD) patients. However, the specific factors that impact QoL among IBD patients remain unclear. In this study, we analyzed the relationships of demographic and disease factors with food-related QoL (FRQoL) in a large, diverse US cohort of IBD patients. Methods: In this cross-sectional analysis of 1108 IBD patients aged ≥18 years, we measured FRQoL with the 29-item Food-Related Quality of Life Questionnaire (FR-QoL-29) and disease activity with the Harvey-Bradshaw index in Crohn's disease (CD) patients or the Simple Clinical Colitis Activity Index in ulcerative colitis (UC) patients. Latinx immigrants completed a Spanish translation of the FR-QoL-29. A subset of patients had colonoscopy and inflammatory marker data available. We used univariate, multivariate, and subgroup analyses to examine the factors that influence FRQoL. Results: In our cohort, 55% of IBD patients self-identified as Latinx. Latinx and non-Latinx patients had similar FR-QoL-29 scores. Female patients had significantly lower FRQoL than male patients (P = .001). Increasing age and IBD duration correlated with higher FRQoL (P < .0001). In UC patients, higher Simple Clinical Colitis Activity Index scores (P < .0001), higher Mayo scores (P = .0009), and longer disease duration (P = .03) predicted significantly lower FRQoL. Disease activity and FRQoL were not significantly related in CD patients. Conclusion: This is the largest study to date to examine FRQoL in American IBD patients, and the first to include Latinx patients. Disease-related factors had a greater impact on FRQoL than ethnicity. Clinical and endoscopic disease activity had a more detrimental impact on FRQoL in UC than in CD. Diet intervention studies are needed to alleviate symptoms and improve FRQoL in the IBD population.

Endoscopic assessment of failed fundoplications differs between endoscopists.

BACKGROUND: Despite excellent long-term outcomes, a small proportion of patients who undergo fundoplication with hiatal hernia repair (laparoscopic antireflux surgery [ARS]) for treatment of gastroesophageal reflux disease (GERD) may require reoperation. Esophagogastroduodenoscopy (EGD) assessment in patients presenting with symptom recurrence plays a critical role in surgical planning of redo-ARS by confirming failure of the fundoplication and revealing the pattern of failure. We aimed to compare the findings documented by external endoscopists (i.e., outside physicians) to those documented by internal endoscopists (i.e., operating foregut or thoracic surgeons) before redo-ARS. METHODS: After IRB approval, we conducted a retrospective chart review of patients who underwent redo-ARS at a tertiary surgical center between November 2016 and March 2023. Patients with both external and internal EGD reports were included, and findings from the two reports were compared. RESULTS: Of 197 patients who underwent redo-ARS, both preoperative EGD reports were available for 181 (136 [75.1%] women; median age, 61 years [IQR 53-69]; median BMI, 27.9 kg/m2 [IQR 24.9-31.3]). The median time between primary and redo-ARS was 89 months (IQR 38-153), and the median time between external and internal endoscopic evaluation was 5 months (IQR 2-12). Only 38.9% of external reports mentioned a prior fundoplication. Compared to the operating surgeons, external physicians reported a significantly lower proportion of Barrett's esophagus (52.4%, p < .001), slipped fundoplications (28.8%, p < .001), paraesophageal hernias (20.5%, p < .001), disrupted fundoplications (20%, p < .001), intrathoracic fundoplications (0%, p < .001), and twisted fundoplications (0%, p < .001). CONCLUSIONS: External endoscopists' reports of failed fundoplications are often incomplete and lack relevant details. Discrepancies between nonsurgical endoscopists and experienced surgeons are likely explained by a lack of training and experience to discern and document fundoplication changes accurately. To reduce this gap, we strongly recommend the adoption of standard definitions describing post-fundoplication endoscopic changes and the inclusion of relevant training within educational programs.

Development of a biodegradable prosthesis through tissue engineering, for the organ-replacement or substitution of the extrahepatic bile duct.

INTRODUCTION AND OBJECTIVES: There are different situations in which an extrahepatic bile duct replacement or substitute is needed, such as initial and localized stages of bile duct cancer, agenesis, stenosis, or bile duct disruption. MATERIALS AND METHODS: A prosthesis obtained by electrospinning composed of Poly (D,L-lactide-co-glycolide) (PGLA) - Polycaprolactone (PCL) - Gelatin (Gel) was developed, mechanical and biological tests were carried out to evaluate resistance to tension, biocompatibility, biodegradability, cytotoxicity, morphological analysis and cell culture. The obtained prosthesis was placed in the extrahepatic bile duct of 15 pigs with a 2-year follow-up. Liver function tests and cholangioscopy were evaluated during follow-up. RESULTS: Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable. The prosthesis implanted in the experimental model allowed cell adhesion, migration, and proliferation, maintaining bile duct permeability without altering liver function tests. Immunohistochemical analysis indicates the presence of biliary epithelium. CONCLUSIONS: A tubular scaffold composed of electrospun PGLA-PCL-Gel nanofibers was used for the first time to replace the extrahepatic bile duct in pigs. Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable, making it an excellent candidate for use in bile ducts and potentially in other tissue engineering applications.

Unraveling microbial processes involved in carbon and nitrogen cycling and greenhouse gas emissions in rewetted peatlands by molecular biology.

Restoration of drained peatlands through rewetting has recently emerged as a prevailing strategy to mitigate excessive greenhouse gas emissions and re-establish the vital carbon sequestration capacity of peatlands. Rewetting can help to restore vegetation communities and biodiversity, while still allowing for extensive agricultural management such as paludiculture. Belowground processes governing carbon fluxes and greenhouse gas dynamics are mediated by a complex network of microbial communities and processes. Our understanding of this complexity and its multi-factorial controls in rewetted peatlands is limited. Here, we summarize the research regarding the role of soil microbial communities and functions in driving carbon and nutrient cycling in rewetted peatlands including the use of molecular biology techniques in understanding biogeochemical processes linked to greenhouse gas fluxes. We emphasize that rapidly advancing molecular biology approaches, such as high-throughput sequencing, are powerful tools helping to elucidate the dynamics of key biogeochemical processes when combined with isotope tracing and greenhouse gas measuring techniques. Insights gained from the gathered studies can help inform efficient monitoring practices for rewetted peatlands and the development of climate-smart restoration and management strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s10533-024-01122-6.

Comparison of Pain Management Strategies to Reduce Opioid Use Postoperatively in Free Flap Breast Reconstruction: Pain Catheter versus Nerve Block in Addition to Refinements in the Oral Pain Management Regime.

Background Perioperative management in autologous breast reconstruction has gained focus in recent years. This study compares two pain management protocols in patients undergoing abdominal-based free flap breast reconstruction: a past protocol (PP) and a current protocol (CP)-both intended to reduce opioid consumption postoperatively. The PP entails use of a pain catheter in the abdominal wound and the CP consists of an intraoperative nerve block in addition to refinements in the oral pain management. We hypothesize that the CP reduces opioid consumption compared to PP. Methods From December 2017 to January 2020, 102 patients underwent breast reconstruction with an abdominal-based free flap. Two postoperative pain management strategies were used during the period; from December 2017 to September 2018, the PP was used which entailed the use of a pain catheter with ropivacaine applied in the abdominal wound with continuous distribution postoperatively in addition to paracetamol orally and oxycodone orally pro re nata (PRN). From October 2018 to January 2020, the CP was used. This protocol included a combination of intraoperative subfascial nerve block and a postoperative oral pain management regime that consisted of paracetamol, celecoxib, and gabapentin as well as oxycodone PRN. Results The CP group ( n = 63) had lower opioid consumption compared to the PP group ( n = 39) when examining all aspects of opioid consumption, including daily opioid usage in morphine milligram equivalents and total opioid usage during the stay ( p < 0.001). The CP group had shorter length of hospital stay (LOS). Conclusion Introduction of the CP reduced opioid use and LOS was shorter.

Global Equity in Clinical Trials: An ASCO Policy Statement.

ASCO is a global professional society representing more than 50,000 physicians, other health care professionals, and advocates in over 100 countries specializing in cancer treatment, diagnosis, prevention, and advocacy. ASCO strives, through research, education, and promotion of the highest quality of patient care, to create a world where cancer is prevented or cured, and every survivor is healthy. In this pursuit, health equity remains the guiding institutional principle that applies to all its activities across the cancer care continuum. This ASCO policy statement emphasizes the urgent need for global equity in clinical trials, aiming to enhance access and representation in cancer research as it not only improves cancer outcomes but also upholds principles of fairness and justice in health care.

Cruroplasty with or without mesh? A systematic literature review with a novel time-organized proportion meta-analysis.

BACKGROUND: Improved outcomes with the use of non-absorbable mesh (NAM) for inguinal hernia repairs led to its rapid adoption for hiatal hernia (HH) repairs; however, feared complications occurred, and the trend shifted toward using absorbable mesh (AM). We aimed to analyze the literature assessing objective HH recurrence rates after primary laparoscopic cruroplasty with or without the use of different mesh types. METHODS: A systematic literature review with both pairwise and time-organized proportion meta-analyses of articles published between January 1993 and September 2022 was performed using the MEDLINE, EMBASE, and Taylor & Francis databases to identify relevant studies comparing groups undergoing cruroplasty with suture repair (SR) alone, AM, NAM, or partially absorbable mesh (PAM). Studies documenting an objective follow-up ≥ 6 months were included. The primary outcome was the HH recurrence rate confirmed by barium esophagram or upper GI endoscopy. RESULTS: A total of 34 studies met the inclusion criteria, including 6 randomized clinical trials, 25 retrospectives studies, and 3 prospective cohort studies. A total of 2170 subjects underwent laparoscopic HH repair and completed an objective follow-up ≥ 6 months after surgery; the objective recurrence rate was 20.8% (99/477) at a mean follow-up of 25.8 ± 16.4 months for the SR group, 20.6% (244/1187) at 28.1 ± 13.8 months for the AM group, 13.7% (65/475) at 30.8 ± 15.3 months for the NAM group, and 0% (0/31) at 32.5 ± 13.5 months for the PAM group. However, the pairwise meta-analysis revealed that overall mesh use was not superior to SR in preventing long-term HH recurrence. CONCLUSION: The use of AM does not appear to reduce HH recurrence compared to SR alone. Although the data favors NAM to decrease objective HH recurrence in the mid-term, the long-term (≥ 48 months) recurrence rate was similar with or without any type of mesh.

Prevalence and severity of abdominal bloating in patients with gastroesophageal reflux disease.

Abdominal bloating (AB) is a common symptom among patients with gastroesophageal reflux disease (GERD); however, in clinical practice, its prevalence is likely underestimated due to the lack of objective tools to measure its frequency and severity. It is associated with dissatisfaction and worse quality of life, but data on its prevalence before and after mechanical control of GERD (i.e. fundoplication, magnetic sphincter augmentation, and antireflux mucosectomy) are lacking. To assess and determine the pre- and postoperative prevalence and severity of AB among patients with GERD, we conducted a structured literature search using MeSH and free-text terms in MEDLINE (via Pubmed), EMBASE, and Taylor & Francis Online between January 1977 and October 2022. Fifteen articles reporting the prevalence or severity of AB using quality-of-life questionnaires before or after antireflux surgery (ARS) were included. Overall, a high prevalence of AB before ARS was found. A decline in the prevalence and severity of AB was documented postoperatively in most cases independent of the surgical approach. Among surgical approaches, a complete fundoplication had the highest reported postoperative AB. Overall, patients reported less severe and less frequent AB after ARS than before. The traditional belief that postoperative bloating is a sequela of ARS should be reevaluated.

Pulmonary and esophageal function in lung transplantation: Fundamental principles and clinical application.

The lungs and esophagus have a close anatomical and physiological relationship. Over the years, reflux-induced pulmonary injury has gained wider recognition, but the full effects of pulmonary disease on esophageal function are still unknown. Intrathoracic pressure dynamics potentially affect esophageal function, especially in patients with end-stage lung disease, both obstructive and restrictive. Lung transplantation is the only viable option for patients with end-stage pulmonary disease and has provided us with a unique opportunity to study these effects as transplantation restores the intrathoracic environment. Esophageal and foregut functional testing before and after transplantation provide insights into the pathophysiology of the foregut-pulmonary axis, such as how underlying pulmonary disease and intrathoracic pressure changes affect esophageal physiology. This review summarizes the available literature and shares the research experience of a lung transplant center, covering topics such as pre- and posttransplant foregut function, esophageal motility in lung transplant recipients, immune-mediated mechanisms of graft rejection associated with gastroesophageal reflux, and the role of antireflux surgery in this population.

The Brain Tumor Segmentation (BraTS) Challenge 2023: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs).

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

Maculopatía paracentral aguda media y neurorretinopatía macular aguda / Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy

La neurorretinopatía macular aguda es una condición rara con patogenia microvascular. Se presenta con un inicio agudo con escotomas paracentrales correspondientes a lesiones paramaculares evidentes. Los avances en las imágenes multimodales permitieron caracterizar este trastorno de retina y crear nuevos conceptos. Serraf, en el 2013, identificó dos formas por medio de la tomografía de coherencia óptica dominio espectral: el tipo 1 conocido como maculopatía paracentral aguda media en la cual se observa una banda hiperreflectiva en la capa nuclear interna, y el tipo 2 en el cual la banda hiperreflectiva se ubica en la capa nuclear externa, que involucra la zona elipsoide y la zona de interdigitación con el epitelio pigmentario de la retina. Hasta el momento no existe cura; pero se puede actuar sobre los factores de riesgo. Por ser una condición rara y por no existir reportes hasta el momento en Cuba es que se presentan a continuación dos pacientes con cuadros clínicos similares de estas dos variantes; concluyendo la importancia que presentan las imágenes multimodales como medio auxiliar diagnóstico(AU)

Acute macular neuroretinopathy is a rare condition with complex pathogenesis and microvascular cause. It appears with acute onset, with paracentral scotomas corresponding to obvious paramacular lesions. Advances in multimodal imaging made it possible to characterize this retinal disorder and to create new concepts. Serraf, in 2013, identified two forms by spectral domain optical coherence tomography: type 1, known as paracentral acute middle maculopathy, in which a hyperreflective band is observed in the inner nuclear layer; and type 2, in which the hyperreflective band is located in the outer nuclear layer, involving the ellipsoid zone and the zone of interdigitation with the retinal pigment epithelium. Up to this moment, there is no cure; but it is possible to act on the risk factors. Because it is a rare condition and because there are no reports so far in Cuba, two patients with similar clinical pictures of these two variants are presented; concluding the importance of multimodal images as an auxiliary diagnostic tool(AU)

Prehabilitation programs for individuals with cancer: a systematic review of randomized-controlled trials.

BACKGROUND: Prehabilitation programs focusing on exercise training as the main component are known as a promising alternative for improving patients' outcomes before cancer surgery. This systematic review determined the benefits and harms of prehabilitation programs compared with usual care for individuals with cancer. METHODS: We searched CENTRAL, MEDLINE, and EMBASE from inception to June 2022, and hand searched clinical trial registries. We included randomized-controlled trials (RCTs) in adults, survivors of any type of cancer, that compared prehabilitation programs that had exercise training as the major component with usual care or other active interventions. Outcome measures were health-related quality of life (HRQL), muscular strength, postoperative complications, average length of stay (ALOS), handgrip strength, and physical activity levels. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias and the certainty of the evidence. RESULTS: Twenty-five RCTs (2682 participants) published between 2010 and 2022 met our inclusion criteria. Colorectal and lung cancers were the most common diagnoses. The studies had methodological concerns regarding outcome measurement, selective reporting, and attrition. Five prehabilitation programs were compared to usual care (rehabilitation): combined training, aerobic training, respiratory muscle training plus aerobic training, respiratory muscle training plus resistance training, and pelvic floor training. The studies provided no clear evidence of an effect between groups. We assessed the overall certainty of the evidence as very low, downgraded due to serious study limitations and imprecision. CONCLUSION: Prehabilitation programs focusing on exercise training may have an effect on adults with cancer, but the evidence is very uncertain. We have very little confidence in the results and the true effect is likely to be substantially different from these. Further research is needed before we can draw a more certain conclusion. SYSTEMATIC REVIEW REGISTRATION: CRD42019125658.

Generalized Lymphatic Anomaly as a Differential Diagnosis of Lytic Lesions.

Generalized lymphatic anomaly (GLA) is an infrequent multiorgan disease characterized by the presence of abnormal proliferation of lymphatic vessels. The diagnosis requires histological confirmation, and the treatment is controversial. We are presenting a case of a 28-year-old male patient who was diagnosed with an extragonadal mediastinal nonseminomatous germ cell tumor. He underwent chemotherapy, and during this treatment, radiologic findings evidenced lytic lesions. Multiple biopsies were performed, which revealed the presence of abnormal lymphatic vessels, characteristic of GLA. There are different etiologies of osteolytic lesions, and on some occasions, they mimic a tumoral entity. The clinical suspicion of GLA is the first step in approaching the diagnosis, particularly in young adult patients.

Diagnosis and management of anastomotic leaks after Ivor Lewis esophagectomy: a single-center experience.

PURPOSE: Esophageal anastomotic leaks (ALs) after esophagectomy are a common and serious complication. The incidence, diagnostic approach, and management have changed over time. We described the diagnosis and management of patients who developed an esophageal AL after an Ivor Lewis esophagectomy at our center. METHODS: After IRB approval, we queried our prospectively maintained database for patients who developed an esophageal AL after esophagectomy from August 2016 through July 2022. Data pertaining to demographics, comorbidities, surgical and oncological characteristics, and clinical course were extracted and analyzed. RESULTS: During the study period, 145 patients underwent an Ivor Lewis esophagectomy; 10 (6.9%) developed an AL, diagnosed a median of 7.5 days after surgery, and detected by enteric contents in wound drains (n = 3), endoscopy (n = 3), CT (n = 2), and contrast esophagogram (n = 2). Nine patients (90%) had an increasing white blood cell count and additional signs of sepsis. One asymptomatic patient was identified by contrast esophagography. All patients received enteral nutritional support, intravenous antibiotics, and antifungals. Primary treatment of ALs included endoscopic placement of a self-expanding metal stent (SEMS; n = 6), surgery (n = 2), and SEMS with endoluminal vacuum therapy (n = 2). One patient required surgery after SEMS placement. The median length of ICU and total hospital stays were 11.5 and 22.5 days, respectively. There was no 30-day mortality. CONCLUSION: The incidence of esophageal ALs at our center is similar to that of other high-volume centers. Most ALs can be managed without surgery; however, ALs remain a significant source of postoperative morbidity despite clinical advancements that have improved mortality.

Essential Oil of Bursera morelensis Promotes Cell Migration on Fibroblasts: In Vitro Assays.

Essential oils (EOs) are complex mixtures of volatile natural compounds. We have extensively studied the EO of Bursera morelensis, which demonstrates antibacterial, antifungal, anti-inflammatory, and wound-healing activities. The objective of this work was to determine the effect of this EO on fibroblast migration in a three-dimensional in vitro model. For the three-dimensional in vitro model, a series of fibrin hydrogel scaffolds (FSs) were built in which fibroblasts were cultured and subsequently stimulated with fibroblast growth factor (FGF) or EO. The results demonstrated that these FSs are appropriate for fibroblast culture, since no decrease in cell viability or changes in cell proliferation were found. The results also showed that this EO promotes cell migration four hours after stimulation, and the formation of cell projections (filopodia) outside the SF was observed. From these results, we confirmed that part of the mechanism of action of the essential oil of B. morelensis during the healing process is the stimulation of fibroblast migration to the wound site.

Surgical Repair of Large Hiatal Hernias: Insight from a High-Volume Center.

BACKGROUND: Laparoscopic-assisted hiatal hernia (HH) repair is safe and effective; however, it is unclear whether hernia size affects perioperative outcomes and whether a watch-and-wait strategy is appropriate for patients with asymptomatic large HHs. We aimed to investigate these issues. METHODS: After IRB approval, we queried our prospectively maintained database for patients who underwent primary laparoscopic HH repair at our center between August 2016 and December 2019. All procedures were performed by a single surgeon (SKM). According to the intraoperative findings, HHs were divided into four groups: small (S-HH), medium (M-HH), large (L-HH), or giant (G-HH) when the percentage of herniated stomach was 0% (sliding), < 50%, 50-75%, or > 75%, respectively. Perioperative and mid-term outcomes were analyzed. RESULTS: A total of 170 patients were grouped: S-HH (n = 46), M-HH (n = 69), L-HH (n = 20), and G-HH (n = 35) with mean age of 58.5.6 ± 11.0, 61.9 ± 11.3, 70.7 ± 10.3, and 72.6 ± 9.7 years (p < 0.001), respectively. Compared to M-HH patients, L-HH patients had significantly longer hospital stays (mean 2.8 ± 3.2 vs 1.4 ± 0.91 days; p = 0.001) and more postoperative complications (6/20 [30.0%] vs 3/69 [4.3%]; OR 6.9, 95% CI 5.4-8.4, p < 0.001). At a mean follow-up time of 43.1 ± 25.0 and 43.5 ± 21.6 months for the combined S/M-HH and L/G-HH groups, GERD-Health-Related Quality of Life scores were comparable (S/M-HH: 6.5 ± 10.9 vs L/G-HH: 7.1 ± 11.3; p = 0.63). There was no perioperative mortality. CONCLUSIONS: HHs likely grow with age, reflecting their progressive nature. Laparoscopic L-HH repair was associated with higher morbidity than M-HH repair. Thus, patients with M-HH, even if less symptomatic, should be evaluated by a foregut surgeon. Regardless of HH size, good mid- and long-term quality of life outcomes can be achieved.

Atypical pattern of response in rectal cancer after neoadjuvant pembrolizumab treatment: a case report, literature review, and proposed management model.

Background: Immunotherapy is the first-line treatment in patients with advanced microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) colorectal cancer (CRC). Although immune checkpoint inhibitors (ICIs) for locally advanced rectal cancer (LARC) are not yet a standard, the results are very encouraging and raise the question of whether patients with clinical complete response (cCR) could receive nonoperative management (NOM). However, different patterns of response have challenged management strategies. Case Description: A 34-year-old woman diagnosed with dMMR LARC started treatment with capecitabine 2,000 mg/m2 on day 1 to 14 and oxaliplatin 130 mg/m2 on day 1 and every 21 days. Magnetic resonance imaging (MRI), performed three cycles later, showed local progression of the primary rectal lesion, which at that time had new peritoneal reflex involvement. A new hepatic lesion in segment V was observed. Due to disease progression, she was administered pembrolizumab 200 mg every 21 days. After three cycles, a discordant radiological response was observed on a new MRI scan that showed a complete response of the liver lesion and magnetic resonance tumor regression grade (mrTRG) 1 in the rectum. However, new involvement of the mesentery and enlargement of the regional lymph nodes (LNs) were also evident. A new colonoscopic biopsy was performed, showing no cancerous cells. She underwent surgery on the rectum and liver lesion. Pathology showed a complete response of the rectal wall and liver lesion, but 1 of 22 LNs was positive for adenocarcinoma (ypT0 N1 M0). The patient continued on pembrolizumab, and 14 months after surgery, she had not relapsed. Conclusions: Neoadjuvant immunotherapy for rectal cancer requires new recommendations for the assessment of clinical response. Pseudoprogression should be ruled out as an atypical response before deciding on surgical treatment. We propose an algorithm to address pseudoprogression in this setting.