Poor Perfusion Research Articles

Platelet rich plasma–complexed hydrogel glue enhances skin wound healing in a diabetic rat model

Diabetic patients often exhibit delayed or incomplete progress in the healing of acute wounds, owing to poor blood perfusion. Platelet-rich plasma (PRP) has attracted much attention as a means to improve wound healing, because it contains high growth factor concentrations. However, the burst-like release of PRP growth factors results in a short half-life of these therapeutic proteins, thus greatly limiting the therapeutic effect. In this study, we prepared PRP from human umbilical cord blood and developed an in situ photocrosslinkable PRP hydrogel glue (HNPRP) by adding a photoresponsive hyaluronic acid (HA-NB) into PRP. The HNPRP hydrogel allowed for controlled release of platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β (TGF-β) for up to 28 days. In vitro cell culture showed that HNPRP promoted migration of fibroblasts and keratinocytes as well as PRP and did not reveal the advantages of HNPRP. However, in a diabetic rat skin wound model, HNPRP treatment promoted faster wound closure. Furthermore, the HNPRP group, compared with the control, PRP and hydrogel only groups, showed significantly greater re-epithelialization and numbers of both newly formed and mature blood vessels. The HNPRP group also displayed higher collagen formation than did the control group. In conclusion, HNPRP enhances angiogenesis and skin regeneration and consequently achieves faster wound healing, thus extending its potential for clinical applications to treat diabetic skin wounds.

Multimodal imaging in a case of acute idiopathic maculopathy

Bacillary layer detachment (BLD) is an optical coherence tomography (OCT) finding depicting split within the inner segment of myoids. We present a case of acute idiopathic maculopathy in a young female who presented with sudden painless diminution of vision in the left eye without a prodromal viral illness. On the OCT splitting of ellipsoid and myoid zone of rod, inner segments were noted suggestive of BLD, whereas optical coherence tomography angiography showed flow void areas on choriocapillaris slab. BLD in acute idiopathic maculopathy occurs due to poor choroidal perfusion leading to stress and splitting of bacillary layer. However, once choroidal perfusion improves, BLD resolves and hence no treatment is required.

Shock Resuscitation - the Necessity and Priority of Renal Blood Perfusion Assessment.

Improving organ perfusion is the aim of shock resuscitation; therefore, improving organ blood perfusion is a direct indicator for shock resuscitation. During shock, different organs have different capacities for blood flow autoregulation. The kidney is an important organ with excellent ability to autoregulate the blood flow and with vulnerability to poor organ perfusion, which places kidney perfusion in a position of necessity and priority relative to that of other organs in shock. Critical-care ultrasonography provides the best evaluation of renal perfusion.

Necrotizing enterocolitis: a literature review

OBJECTIVE: To update the topic through a literature review. METHODS: A search was performed on the MEDLINE, PubMed, SciELO, LILACS and Cochrane platforms, using keywords on the topic and, after selecting the main articles, they were analyzed. CONCLUSION: Necrotizing enterocolitis (NEC) is an inflammation that affects the gastrointestinal tract (GIT) of newborns. The modified Bell stagind criteria classifies it, according to clinical and radiographic findings, into suspicion, confirmed or advanced. Pathogenesis is not completely understood. In term babies it occurs due to poor mesenteric perfusion. The classic form occurs in preterm infants, with multifactorial pathophysiology that includes: immaturity of the GIT, genetic predisposition, changes in the intestinal microbiota, pathogenic bacteria, characteristics of enteral nutrition and hypoxic-ischemic intestinal injury. All of these factors activate an intense inflammatory cascade, which can lead to intestinal necrosis. Risk factors are prematurity, low birth weight, sepsis, persistence of the ductus arteriosus, anemia and/or transfusion, among others. In addition to gastrointestinal symptoms (abdominal distention and pain, gastric residuals, vomiting and rectal bleeding), it has nonspecific symptoms such as temperature instability, apneas, hypoglycemia or even shock. On radiographic examination, bowel distention, pneumatosis, portal vein gas, pneumoperitoneum, intraperitoneal fluid or persistent dilated loops are found. The therapeutic approach includes fasting, broad-spectrum antibiotics, hemodynamic monitoring. Surgery is indicated when clinical worsening, perforation or suspicion of necrosis occurs. Among the preventive measures are: infection control, breastfeeding, protocols for the initiation and progression of enteral nutrition and administration of probiotics.

Prevalence and predictors of No-reflow during primary percutaneous intervention

It is now accepted that the reopening of the epicardial coronary vessels in the acute phase of the infarction using percutaneous coronary intervention (PCI) is necessary but not sufficient, because in at least 2.3% to 10% of cases, the restoration of TIMI 3 flow is an illusion of reperfusion. This phenomenon is referred to as “no reflow”. This study outlines the predictors of poor perfusion or “no reflow” in the acute phase STEMI and its impact on the mortality. Observational retrospective study, in the department of cardiology of University Hospital of Sfax, over a period of 21 months from mars 2017 to December 2018. Baseline demographi, clinical, and angiographical data were collected in order to determine the predictor factors of no reflow. A follow-up of 9 months was obtained in 75% of patients. Among the 214 patients with AMI who underwent primary PCI, only 30 patients presented slow/no-reflow phenomenon (14.01%). A total of 100 patients were included. The mean age was 59.41 ± 10.07 years in the normal flow group and 55.57 ± 10.58 years in the no-reflow group ( P = 0.08). Patients with Killip classes 3 and 4, previous coronary artery disease and left ventricle dysfunction were, respectively, more frequent in the no-reflow group 33.33% vs. 14.28%; P = 0.029; 23.33% vs. 4.28; P = 0.024 and 33.75 ± 7.44% vs. 49.30 ± 7.97%; P < 0.001. Late mortality, target lesion revascularization and readmission were more frequent in the no-reflow group after a follow-up of 9 months, respectively, 20% vs. 2.9%; P = 0.03; 40% vs. 10%; P = 0.023 and 60% vs. 17.1%; P = 0.006. Lesion length > 20 mm was an independent predictor of no-reflow (odds ratio [OR] = 3.63; 95% confidence interval [CI], 1.021-12.74; P = 0.046). No reflow is a common phenomenon, strongly correlated with mortality. The distal embolization during PCI is an important phenomenon, pharmacological intervention as well as a well deployed stent seem to limit this phenomenon.

Modulation of miR-29a and ADAM12 Reduces Post-Ischemic Skeletal Muscle Injury and Improves Perfusion Recovery and Skeletal Muscle Function in a Mouse Model of Type 2 Diabetes and Peripheral Artery Disease.

Both Type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2) are associated with an increased risk of limb amputation in peripheral arterial disease (PAD). How diabetes contributes to poor PAD outcomes is poorly understood but may occur through different mechanisms in DM1 and DM2. Previously, we identified a disintegrin and metalloproteinase gene 12 (ADAM12) as a key genetic modifier of post-ischemic perfusion recovery. In an experimental PAD, we showed that ADAM12 is regulated by miR-29a and this regulation is impaired in ischemic endothelial cells in DM1, contributing to poor perfusion recovery. Here we investigated whether miR-29a regulation of ADAM12 is altered in experimental PAD in the setting of DM2. We also explored whether modulation of miR-29a and ADAM12 expression can improve perfusion recovery and limb function in mice with DM2. Our result showed that in the ischemic limb of mice with DM2, miR-29a expression is poorly downregulated and ADAM12 upregulation is impaired. Inhibition of miR-29a and overexpression of ADAM12 improved perfusion recovery, reduced skeletal muscle injury, improved muscle function, and increased cleaved Tie 2 and AKT phosphorylation. Thus, inhibition of miR-29a and or augmentation of ADAM12 improves experimental PAD outcomes in DM2 likely through modulation of Tie 2 and AKT signalling.

Clinical profile of children with parechovirus meningitis in Singapore

Human parechovirus (HPeV) is one of the most common causes of aseptic meningitis in children worldwide. This study aims to review the epidemiology, clinical presentation, and cerebrospinal fluid (CSF) findings in HPeV meningitis and compare these with Enterovirus (EV) meningitis. This is a retrospective study of children aged ≤ 1year admitted for HPeV meningitis between November 2015 and July 2017, with positive CSF HPeV PCR and negative blood and CSF bacterial cultures. The clinical findings were compared with a historical cohort of children with EV meningitis admitted between July 2008 and July 2011. There were 71 children with HPeV meningitis, aged between 2 and 127days, with the majority (96%) being ≤ 90days old. The most common symptoms reported were poor feeding (42%), tachycardia out of proportion to fever (27%), and lethargy (20%). Only 2 patients (3%) had CSF pleocytosis. Cerebral spinal fluid white blood cell counts ranged from 0 to 28 cells/mm3, with a median of 3 cells/mm3 [interquartile range (IQR) 1-6 cells/mm3]. When compared to our historical cohort of EV meningitis ≤ 90days old, children with HPeV meningitis ≤ 90days old were less likely to have CSF pleocytosis (OR 0.008, 95% CI 0.001-0.057). HPeV and EV meningitis are known to cause sepsis-like illness in infants < 90days old. This study further supports this, with the requirement for fluid bolus therapy for tachycardia or poor perfusion noted to be higher in children with HPeV meningitis ≤ 90days old (OR 6.3, 95% CI 2.7-14.2).

Indocyanine Green to Assess Vascularity of Ileal Conduit Anastomosis During Pelvic Exenteration for Recurrent/Persistent Gynecological Cancer: A Pilot Study.

IntroductionPelvic exenteration performed for recurrent/persistent gynecological malignancies has been associated with urological short- and long-term morbidity due to altered vascularization of tissues for previous radiotherapy. The aims of the present study were to describe the use of intravenous indocyanine green (ICG) to assess vascularity of urinary diversion (UD) after pelvic exenteration for gynecologic cancers, to evaluate the feasibility and safety of this technique, and to assess the postoperative complications.MethodsProspective, observational, single-center, pilot study including consecutive patients undergoing anterior or total pelvic exenteration due to persistent/recurrent gynecologic cancers between August 2020 and March 2021 at Fondazione Policlinico Gemelli IRCCS, Rome, Italy. All patients underwent intravenous injection of 3–6 ml of ICG (1.25 mg/ml) once the UD was completed. A near-infrared camera was used to evaluate ICG perfusion of anastomoses (ileum–ileum, right and left ureter with small bowel, and colostomy or colorectal sides of anastomosis) a few seconds after ICG injection.ResultsFifteen patients were included in the study. No patient reported adverse reactions to ICG injection. Only 3/15 patients (20.0%) had an optimal ICG perfusion in all anastomoses. The remaining 12 (80.0%) patients had at least one ICG deficit; the most common ICG deficit was on the left ureter: 3 (20.0%) vs. 1 (6.7%) patient had no ICG perfusion on the left vs. right ureter, respectively (p = 0.598). 8/15 (53.3%) and 6/15 (40.0%) patients experienced grade ≥3 30-day early and late postoperative complications, respectively. Of these, two patients had early and one had late postoperative complications directly related to poor perfusion of anastomosis (UD leak, ileum–ileum leak, and benign ureteric stricture); all these cases had a suboptimal intraoperative ICG perfusion.ConclusionThe use of ICG to intraoperatively assess the anastomosis perfusion at time of pelvic exenteration for gynecologic malignancy is a feasible and safe technique. The different vascularization of anastomotic stumps may be related to anatomical sites and to previous radiation treatment. This approach could be in support of selecting patients at higher risk of complications who may need personalized follow-up.

Exercise-Induced Pulmonary Hypertension: How to Define, Diagnose, and Treat At-Risk Patients

Introduction Pulmonary hypertension is a devastating disease with a rapid progression of symptoms leading to high patient mortality. It is characterized by high blood pressure in the pulmonary vasculature and poor pulmonary perfusion, resulting in patient fatigue, dyspnea, and syncope, especially upon physical exertion. A sub-clinical form of pulmonary hypertension also exists which is referred to as exercise induced pulmonary hypertension, where patients display normal resting hemodynamic properties but abnormal pulmonary responses to exercise. Discussion Recent evidence suggests early intervention and treatment of pulmonary hypertension can improve patient outcomes. However, there is a lack of clinical evidence supporting effective treatments for exercise induced pulmonary hypertension (EIPH), arguably the earliest stage of pulmonary hypertension. This is due in part to the removal of EIPH from official guidelines such as the European Respiratory Society in 2008. EIPH was removed from clinical guidelines due to a lack of consensus on the definition and standardized testing procedures for diagnosing EIPH. Emerging evidence suggests that exercise testing following a standardized protocol of stress echocardiography or right heart catheterization of patients may allow for the classification of EIPH as a mean pulmonary artery pressure/cardiac output slope &gt; 3 mmHg/L/min, and/or mean pulmonary artery pressure &gt; 30 mmHg with a pulmonary vascular resistance &gt; 3 Wood Units. Conclusion Providing evidence for a consensus definition of EIPH, along with a validated, standardized testing procedure, will hopefully foster the progression of research on EIPH and further the development of treatments and improve patient outcomes for people with pulmonary hypertension.

Hirschsprung Disease.

Hirschsprung Disease.

Human breast tumor derived endothelial cells exhibit distinct biological properties.

Excessive angiogenesis characterized by leaky, tortuous, and chaotic vasculature is one of the hallmarks of cancers and is significantly correlated to poor prognosis. Disorganized angiogenesis leads to poor perfusion of anti-cancer drugs and limits access to immune cells. Hence, impeding angiogenesis is one of the attractive therapeutic targets to inhibit progression and metastasis in several solid tumors including breast. We have developed a robust and reproducible method for isolating and ex vivo culture of endothelial cells (EC) derived from non-malignant (Endo-N) and malignant (Endo-T) part from clinically characterized human breast tumors. RT-PCR and immunoblotting analysis indicated that these cells exhibited expression of endothelial specific genes such as PECAM-1 (CD31), Endoglin (CD105), eNOS, VE-cadherin, VCAM1, and MCAM. Vasculogenic mimicry and contamination of progenitor EC recruited in tumors was ruled out by absence of CD133 expression and normal karyotype. Both the cell types showed stable expression of CD31 and CD105 up to seven passages. Furthermore, compared to Endo-N cells, Endo-T cells showed (a) constitutively increased proliferation marked by nearly 36% of cells in mitotic phase, (b) requirement of glutamine for cell survival, (c) pro-migratory phenotype, (d) produced increased number of sprouts in 3D cultures, and (e) resistance to sorafenib. Tumor derived EC showed distinct biological properties compared to normal breast EC. Our method for isolating endothelial cell types from human breast tumors may be explored to (a) understand cellular and molecular mechanisms, (b) screen anti-angiogenic molecules, and (c) formulate organoid cultures to develop personalized medicine facilitating better clinical management of breast cancers.

Abstract 13466: In Experimental Pad miR29a Modulates Perfusion Recovery and ADAM12 Expression Through Direct Interaction With ADAM12 mRNA

Peripheral artery disease (PAD) is caused by atherosclerotic occlusion of vessels outside the heart and most commonly affects vessels of the lower extremities. Angiogenesis is a part of the post ischemic adaption involved in restoring blood flow in PAD. Previously, in a murine hind limb ischemia (HLI) model of PAD, we identified ADAM12 as a key genetic modifier of post-ischemic perfusion recovery. However, less is known about ADAM12 regulation in ischemia. MiRNAs are a class of small, non-coding, single-stranded RNAs that regulate gene expression primarily through transcriptional repression of mRNA. We showed miR29a modulates ADAM12 expression in the setting of type 1 DM and ischemia. However, how miR29a modulates ADAM12 was not known. Moreover, the physiological effects of miR29a modulation in a non-diabetic setting was not known. Here, we demonstrate that AAV-mediated ectopic overexpression of miR29a in ischemic mouse hind limbs impairs post ischemic perfusion recovery and angiogenesis. We further demonstrate that miR29a regulates ADAM12 through direct interaction with ADAM12 mRNA. Treatment of ischemic mouse hind limbs with AAV9 particles containing miR29a (pAV-miR29a) increased miR29a expression (pAV-control vs pAV-miR29a: 3.22 ± 0.36, vs 1.0 ± 0.09, p&lt;0.05, n=5-6,) and decreased ADAM12 mRNA expression (1.0 ± 0.31 vs 0.30 ± 0.08, p&lt;0.05, n=7-10) resulting in decreased angiogenesis (1.0 ± 0.07 vs 0.66 ± 0.04, p&lt;0.05, n=5), and impairment perfusion (week 3 post HLI perfusion, 101.9±5.55 vs 66.13±12.39, p&lt;0.05, n=5-6,).AGO2 miRNA/RNA-immunoprecipitation studies showed levels of miR29a and ADAM12 mRNA in the complex decreased in samples treated with antagomiR29a (4, 40, 400nM) in a dose dependent manner (miR29a: 0.87, 0.68, 0.44, and ADAM12: 0.89, 0.78, 0.67, fold) but was unchanged by control antagomir (miR29a: 0.84, 0.84, 0.87, fold, and ADAM12: 1.11, 1.12, 1.10, fold). Taken together the data shows miR29a suppresses ADAM12 expression by directly binding to its mRNA resulting in impaired angiogenesis and poor perfusion. Hence, elevated levels of miR29a as seen in diabetes likely contributes to vascular pathology and lowering miR29a could be a therapeutic target.

Abstract PO-027: Investigating unfolded protein responses in pancreatic ductal adenocarcinoma under lipid imbalance

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death with a five-year survival rate of only 10%. A major feature of PDAC tumor microenvironment (TME) is desmoplasia, which are dense fibrotic and inflammatory stromal regions constituting the PDAC TME. This desmoplastic reaction results in poor intratumoral perfusion and elevated interstitial fluid pressure, creating regions with severe oxygen and nutrient deprivation. One result is a significant deficiency in unsaturated fatty acids (UFAs) because the de novo synthesis of UFAs requires molecular oxygen. Our data indicate that PDAC cells experience endoplasmic reticulum (ER) stress and trigger a subsequent unfolded protein response (UPR) under tumor-like stress, which can be mitigated by UFAs. The UPR regulates an intricate signaling network mediated by three major stress sensors: Inositol-requiring enzyme 1a (IRE1a), PKR-like ER kinase (PERK) and activating transcription factor 6a (ATF6a). UPR output can be either cytoprotective or cytotoxic depending on tumor types and the severity of stress. Our data suggest that B-I09, a selective IRE1 RNase inhibitor, impairs PDAC cell viability under stress conditions, indicating a pro-survival role for IRE1a. Previous studies showed that MYC-driven cancer cells are highly reliant on UPR pathways. Therefore, we hypothesize that the two major PDAC transcriptional subtypes “Classical” and “Basal-like” may have distinct dependencies on UPR pathways, with the Basal-like subtype being more dependent due to an enrichment of MYC gene signatures. Overall, we hypothesize that IRE1a, PERK and/or ATF6a play(s) an oncogenic role in PDAC tumorigenesis due to lipid saturation abnormalities, and the Basal-like PDAC subtype is more sensitive to inhibition of UPR pathway(s). We are evaluating the role of IRE1a, PERK and ATF6a using pharmacologic inhibition and genetic knockdown in vitro and in vivo under UFA deprived conditions. We will also evaluate PDAC intracellular and interstitial fluid lipidomics using LC-MS. In addition, we will assess whether hypoxic PDAC cells experience ER stress in vivo due to UFA deprivation using Stimulated Raman scattering (SRS) microscopy. To explore the subtype-specific dependency on the UPR pathways, we are querying a UPR gene signature in different tumor cell clusters using single cell RNA-seq datasets of patient samples. In addition, we will employ an isogenic system for PDAC subtypes and examine subtype-specific responses to UPR inhibition in vitro and in vivo. Our goal is to better understand UPR pathways in PDAC cells as a survival mechanism in response to the “lipotoxicity” induced by ER membrane saturation, with a consideration of intratumoral heterogeneity of PDAC cell subtype. Citation Format: Yanqing (Christine) Jiang, Xu Han, Michelle Burrows, Carson Poltorack, Celeste Simon, Brian Keith. Investigating unfolded protein responses in pancreatic ductal adenocarcinoma under lipid imbalance [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-027.

Evaluating the Effect of Intraoperative Near-Infrared Observation on Anastomotic Leakage After Stapled Side-to-Side Anastomosis in Colon Cancer Surgery Using Propensity Score Matching.

Recent studies have clarified that near-infrared observation using indocyanine green has the advantage of evaluating perfusion of the anastomotic site, especially in rectal cancer surgery, resulting in a reduction in anastomotic leak. The aim of this study was to evaluate the efficacy of near-infrared observation for reducing the anastomotic leak after stapled side-to-side anastomosis in colon cancer surgery. This was a retrospective propensity score case-matched study. The study was conducted at 3 institutions in the Yokohama Clinical Oncology Group. From January 2011 to December 2019, patients who underwent colon cancer surgery with stapled side-to-side anastomosis were included. The main outcome was the percentage of anastomotic leak within 30 days after surgery. A total of 1034 patients were collected. There were 532 patients who underwent near-infrared observation and 502 who did not. A total of 370 patients were matched to the near-infrared and non-near-infrared groups. In the near-infrared group, 12 patients (3.2%) were judged to have poor perfusion (4 patients) and no perfusion (8 patients), so the planned transection point was changed. There were no cases of anastomotic leak among these 12 patients. The anastomotic leak rates were 3.5% (13/370) in the non-near-infrared group and 0.8% (3/370) in the near-infrared group. The anastomotic leak and reoperation rates were significantly lower in the near-infrared group than in the non-near-infrared group (OR, 0.224; 95% CI, 0.063-0.794, p = 0.001; OR, 0.348; 95% CI, 0.124-0.977, p = 0.036). Although we reduced selection bias by performing propensity score matching, this was a retrospective study and was not randomized. This large-scale case-matched study showed that assessing perfusion by near-infrared observation significantly reduced the anastomotic leak and reoperation rates after stapled side-to-side anastomosis in colon cancer surgery and may be better suited to colo-colonic anastomosis. Video Abstract at http://links.lww.com/DCR/B513.Japanese Clinical Trials Registry: UMIN-CTR000039977. ANTECEDENTES:Estudios recientes han aclarado que la observación con infrarrojo cercano con verde de indocianina tiene la ventaja de evaluar la perfusión del sitio anastomótico, especialmente en la cirugía de cáncer de recto, lo que resulta en una reducción de la fuga anastomótica.OBJETIVO:El objetivo de este estudio fue evaluar la eficacia de la observación con infrarrojo cercano para reducir la fuga anastomótica después de una anastomosis latero-lateral con engrapadora en la cirugía de cáncer de colon.DISEÑO:Este fue un estudio retrospectivo emparejado con puntaje de propensión.AJUSTE:El estudio se llevó a cabo en tres instituciones del Grupo de Oncología Clínica de Yokohama.PACIENTES:Desde enero de 2011 hasta diciembre de 2019, se incluyeron pacientes que se sometieron a cirugía de cáncer de colon con anastomosis latero-lateral con engrapadora.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue el porcentaje de fuga anastomótica dentro de los 30 días posteriores a la cirugía.RESULTADOS:Se recogió un total de 1034 pacientes. Hubo 532 pacientes que se sometieron a observación con infrarrojo cercano y 502 que no. Un total de 370 pacientes fueron emparejados con los grupos de infrarrojo cercano y no infrarrojo cercano. En el grupo de infrarrojo cercano, se consideró que 12 casos (3,2%) tenían mala perfusión (4 casos) y ninguna perfusión (8 casos), por lo que se cambió el punto de transección planificado. No hubo casos de fuga anastomótica entre estos 12 casos. Las tasas de fuga anastomótica fueron del 3,5% (13/370) en el grupo sin infrarrojo cercano y del 0,8% (3/370) en el grupo con infrarrojo cercano. Las tasas de fuga anastomótica y de reintervención fueron significativamente menores en el grupo con infrarrojo cercano que en el grupo sin infrarrojo cercano (razón de posibilidades 0,224, intervalo de confianza del 95% 0,063-0,794, p = 0,001; razón de posibilidades 0,348, intervalo de confianza del 95% 0,124 -0,977, p = 0,036, respectivamente).LIMITACIONES:Aunque se redujo el sesgo de selección al realizar el emparejamiento por puntaje de propensión, este fue un estudio retrospectivo y no fue aleatorio.CONCLUSIÓN:Este estudio de casos emparejados a gran escala demostró que la evaluación de la perfusión mediante la observación con infrarrojo cercano redujo significativamente la fuga anastomótica y las tasas de reintervención después de la anastomosis latero-lateral con engrapadora en la cirugía de cáncer de colon y puede ser más adecuada para la anastomosis colo-colónica. Consulte Video Resumen en http://links.lww.com/DCR/B513.Registro japonés de ensayos clínicos: UMIN-CTR000039977.

Relative Adrenal Insufficiency: Crisis Averted?

Relative adrenal insufficiency (AI) is a disease process commonly associated with preterm birth and critical illness. Further, the incidence of AI is inversely proportional to gestational age. The incidence of AI is likely underreported; however, it is reported to occur in 150-280/1,000,000 live births worldwide. Functional development of the adrenal gland does not occur until after 30 weeks of gestation; however, advances made in neonatal care increase the survivability of infants born well before this period. Among infants with AI, the adrenal gland is transiently incapable of secreting physiologic levels of cortisol in response to stressors. Common and nonspecific signs include hypotension, poor perfusion, and dysregulation of fluid, electrolytes, and euglycemia. Recognition, diagnosis, and steroid therapy is critical, as inappropriately managed AI can lead to an adrenal crisis, shock, and death. Understanding the presentation and common risk factors for developing relative AI is crucial for quick diagnosis and timely management to prevent morbidity and mortality in this vulnerable population.

Supra-systemic pulmonary hypertension after complicated percutaneous mitral balloon valvuloplasty: a case report and review of literature

BackgroundThe World Symposium of Pulmonary Hypertension in 2018, updated the definition of pulmonary hypertension (PH) as mean pulmonary artery pressures (PAP) > 20 mmHg. Pulmonary venous hypertension secondary to left-heart disease, constitutes the most common cause of PH, and the determination of a co-existent pre-capillary (primary) PH becomes paramount, particularly at the moment of evaluating and managing patients with heart failure. Pulmonary artery pressures above the systemic pressures define supra-systemic PH and generally leads to frank right ventricular failure and high mortality.Case presentationWe present the perioperative management of a patient with rheumatic mitral valve disease, initially found to have severe PH due to pulmonary venous hypertension, who underwent percutaneous mitral balloon valvuloplasty complicated with mitral chordae rupture, severe mitral regurgitation and supra-systemic PH. Multiple medical therapies and an intra-aortic balloon pump were used as means of non-surgical management of this complication.ConclusionsThis case report illustrates the perioperative implications of combined pre- and post-capillary PH and supra-systemic PH, as this has not been widely discussed in previous literature. A thorough literature review of the clinical characteristics of PH, methods to determine co-existent pre- and post-capillary PH components, as well as concomitant right ventricular failure is presented. Severe PH has known detrimental effects on the hemodynamic status of patients, which can ultimately lead to a decrease in effective cardiac output and poor tissue perfusion.

EP.TU.826Using Indocyanine Green (ICG) during laparoscopic bowel resections for elective cancer patients reduces anastomotic leaks and length of stay

Abstract Introduction Anastomotic leakage (AL) after colorectal surgery is associated with significant morbidity and mortality. Poor perfusion of bowel anastomosis is a significant contributing factor. ICG is a dye administered during laparoscopic surgery to assess bowel perfusion by fluorescent imaging – the aim of this study was to determine whether its use in our centre during elective laparoscopic colorectal cancer resections led to improved patient outcomes. Method Single-centre comparative study of all patients who underwent elective colorectal laparoscopic resections for cancer January 2019- January 2021. Primary outcome investigated was AL. Secondary outcomes: in-patient length of stay, clinical suspicion of AL and post-operative ileus. Cohorts compared with χ2 test. Results 25 patients had resections with ICG, 60 without. None in ICG group, and three in non-ICG group (5%) had AL; p-value 0.29. The ICG group were less likely to have CT for suspected anastomotic leak 12% vs 23.3%, p-value 0.29; and, post-operative ileus 5.3% vs 19.6%, p-value 0.09. Statistically significant reduction in mean inpatient length of stay when ICG used (4.0 days, 95% CI 3.3-4.7) compared to when not used (6.7 days, 95% CI 5.0-8.3). Conclusion Only a small number of previous studies have compared AL rates with and without ICG, finding that its use leads to a significant reduction in AL. While sample size small, our findings supports this. Using ICG also led to a significant reduction in inpatient length of stay. ICG fluorescence angiography is now established as our normal practice for all colorectal resections as a safe, innovative, simple technology.

Anterolateral Thigh Free Flap to Cover Diabetic Foot Defect by Using Reverse Flow of Severely Calcified Dorsalis Pedis Artery

Low blood flow in the distal part of the diabetic foot aggravates the wound to an ischemic state, which eventually leads to amputation. However, major advancements in microvascular surgery have shown the ability to salvage the limb even in the presence of poor perfusion. Since a foot is constituted of a complex network of angiosomes, each separate territory of the foot is supplied by interconnected vessels. We report the successful salvage of a severe diabetic foot injury of a 72-year-old male patient with a heavily calcified dorsalis pedis artery (DPA). Although the proximal end of the DPA was clogged to prevent the flow of blood and was insufficient to use as a recipient vessel, reverse flow from the distal end was restored after removing multiple calcification fragments. As a result, a large soft-tissue defect on the third and fourth toe region was successfully covered by a contralateral anterolateral thigh free flap.

Randomized Phase II Study of DCE-MRI-Based Dose Escalation for Poor-Prognosis Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Loco-regional failure accounts for the majority of failures in loco-regionally advanced head and neck cancer (HNC). We have previously shown that poor perfusion on DCE-MRI in HNC was associated with worse LRC and OS. A prospective randomized multi-center clinical trial was designed to evaluate the role of DCE-MRI based RT dose escalation in poor prognosis HNC. <h3>Materials/Methods</h3> Eligibility included 1) AJCC 8 stage III p16+ OPSCC or 2) T3-4 or N3 p16- oropharynx/non-oropharynx HNSCC planned for definitive chemoradiation, ECOG 0-2, with concurrent weekly cisplatin 40mg/m2 or carboplatin (AUC = 2) for cisplatin ineligibility. FDG-PET and DCE-MRI were acquired at baseline and at fraction 10. BV was derived from DCE-MRI < 0.076, and ADC was evaluated per previous report; low BV/ADC maps were created within the GTV. 79 patients with > 1cc low BV/ADC persistent tumor subvolume (GTVboost) at fraction 10 were randomized to total dose of 70Gy (arm A) or 80Gy (86Gy EQD2) total dose to GTVboost subvolume (arm B). The primary endpoint of DFS and secondary endpoints including LRC and OS were compared between treatment arms using stratified log-rank tests. Acute and late toxicities were compared with Chi-squared test. EORTC QLQ30/HN35 PROs, VFSS endpoints, HPV DNA kinetics were also analyzed. <h3>Results</h3> All patients included in this analysis (N = 91) completed definitive therapy with min 12 mo and mean 32 mo follow-up. Treatment arms were balanced with respect to sex, p16+ status, smoking status, ECOG status, and chemotherapy. Mean age was higher in arm B (<i>P</i> = 0.01). Disease sites included 62% p16(+) AJCC 8 stage 3 oropharynx cancer. Randomization was stratified by GTVtotal (≥ 56cc) and GTV boost (> 10cc). Mean GTVtotal was 91cc in p16+ OPSCC and 67 cc in p16- OPSCC/non-OPSCC. Mean GTVboost was 15cc. 12 pts (7 p16+ OPSCC) were not randomized due to < 1cc persistent boostable tumor subvolume and were treated on an observation arm with LRC 83% and OS of 83% at 2 years. Treatment outcomes for randomized patients listed in Table 1. In a subgroup analysis of p16+ OPSCC patients, LRC was improved in the boost arm 93% vs 73% (2-sided <i>P</i> = 0.088). All local failures occurred within the 70Gy isodose line. Grade 3+ toxicities occurred in 53% (arm A) vs 64% (arm B) (<i>P</i> = 0.33). Feeding tube (FT) rate at 3 months was 15% (arm A) vs 27% (arm B) (<i>P</i> = .17) with no FT at 12 months post RT. There were 2 early deaths in arm B related to lingual arterial bleeding, 1 at 3 months and 1 at 12 mo post RT. <h3>Conclusion</h3> LRC improvement was numerically but not significantly improved with DCE-MRI directed boost for all randomized patients and p16+ oropharynx subgroup; DFS was not improved. Boost volume < 1cc was associated with good prognosis. Grade 3+ toxicities and 3 mo FT use were non-significantly higher in Arm B. Table 1. Outcomes according to treatment arm for randomized patients.

Serum lactic acid level predicts poor myocardial perfusion and in-hospital outcomes in patients undergoing primary percutaneous coronary intervention

Abstract Background Elevated serum lactic acid level is associated with poor outcomes in patients with critical diseases like shock. However, the clinical implication of this biomarker in patients with acute myocardial infarction remains unclear. Purpose We aimed to explore the predictive power of serum lactic acid level on admission for in-hospital outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Methods Consecutive patients undergoing pPCI with available data on serum lactid acid level were evaluated for eligbility in this retrospective cohort study. The primary outcome was all-cause death during hospitalization. Enzymatic infarct size and major adverse cardiovascular events (MACE, defined as a combination of all-cause death, recurrent myocardial infarction, and unplanned repeated revascularization) were considered secondary outcomes. Independent preditors of in-hospital death were determined by multiple logisic regression analysis. Odds ratio (OR) with 95% confidence interval (CI) was used to demonstrate the association. The predictive power of serum latictic acid level for in-hospital death was evaluated through receiver operator characteristic curve, which generated C-statictic. A combination model was further constructed by adding serum latictic acid level to the Global Registry of Acute Coronary Events (GRACE) risk score (LA-GRACE risk score). The linear dependence between serum lactic acids level and othe clinical variables was analysed using Spearman rank correlation. Results Of the 302 patients enrolled in the current analysis, 15 (5.0%) died during hospitalization. Serum lactic acid level (OR=1.657, 95% CI: 1.115 to 2.463, p=0.012)and left ventricular ejection fraction (OR=0.858, 95% CI: 0.767 to 0.959, p=0.007) were the only two independent predictors of in-hospital death. The C-statistic of serum lactic acid level for predicting in-hospital death was 0.886 (95% CI: 0.793 to 0.979). The LA-GRACE risk score improved the C-statistic of the GRACE score from 0.898 to 0.911 (p=0.294), with continuous net reclassification improvement of 0.567 (p=0.023) and integrated discrimination improvement of 0.206 (p=0.003). High serum lactic acid level was also asscoiated with larger enzymatic infarct size (p=0.002) and MACE (p=0.004). Further, it significantly correlated with white blood cell counts (r=0.264, p&amp;lt;0.001), serum creatinine level (r=0.189, p=0.001), and systolic blood pressure (r=−0.122, p=0.034). Conclusion Serum lactic acid level on admission is asscoiated with poor myocardial perfusion and in-hospital outcomes in patients with acute myocardial infarction undergoing pPCI. It may contribute to better risk stratification in these populations. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the National Program on Key Basic Research Project of China (Grant No: 2019YFC0840601 and 2014CBA02003), National Natural Science Foundation of China (Grant No: 81870267, 81970295, 81521001, 81670318 and 81570314), Grant of Shanghai Shenkang on Key Clinical Research Project (Grant No: SHDC2020CR2015A and SHDC12019104), Grant of Shanghai Science and Technology Committee (Grant No: 19MC1910300, 18411950200 and 20JC1410800), Key Medical and Health Projects of Xiamen Province (No: 3502Z20204004), Grant of Shanghai Municipal Commission of Health and Family Planning (Grant No: 2017YQ057), Grant of Zhongshan Hospital Affiliated to Fudan University (Grant No: 2018ZSLC01), VG Funding of Clinical Trials (2017-CCA-VG-036) and Merck Funding (Xinxin-merck-fund-051). ROC of lactic acid and GRACE score