Predicting Colonic Neoplasia Surgical Complications: A Machine Learning Approach.

BACKGROUND: A range of statistical approaches have been used to help predict outcomes associated with colectomy. The multifactorial nature of complications suggests that machine learning algorithms may be more accurate in determining postoperative outcomes by detecting nonlinear associations, which are not readily measured by traditional statistics. OBJECTIVE: The aim of this study was to investigate the utility of machine learning algorithms to predict complications in patients undergoing colectomy for colonic neoplasia. DESIGN: Retrospective analysis using decision tree, random forest, and artificial neural network classifiers to predict postoperative outcomes. SETTINGS: National Inpatient Sample database (2003-2017). PATIENTS: Adult patients who underwent elective colectomy with anastomosis for neoplasia. MAIN OUTCOME MEASURES: Performance was quantified using sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve to predict the incidence of anastomotic leak, prolonged length of stay, and inpatient mortality. RESULTS: A total of 14,935 patients (4731 laparoscopic, 10,204 open) were included. They had an average age of 67 ± 12.2 years, and 53% of patients were women. The 3 machine learning models successfully identified patients who developed the measured complications. Although differences between model performances were largely insignificant, the neural network scored highest for most outcomes: predicting anastomotic leak, area under the receiver operating characteristic curve 0.88/0.93 (open/laparoscopic, 95% CI, 0.73-0.92/0.80-0.96); prolonged length of stay, area under the receiver operating characteristic curve 0.84/0.88 (open/laparoscopic, 95% CI, 0.82-0.85/0.85-0.91); and inpatient mortality, area under the receiver operating characteristic curve 0.90/0.92 (open/laparoscopic, 95% CI, 0.85-0.96/0.86-0.98). LIMITATIONS: The patients from the National Inpatient Sample database may not be an accurate sample of the population of all patients undergoing colectomy for colonic neoplasia and does not account for specific institutional and patient factors. CONCLUSIONS: Machine learning predicted postoperative complications in patients with colonic neoplasia undergoing colectomy with good performance. Although validation using external data and optimization of data quality will be required, these machine learning tools show great promise in assisting surgeons with risk-stratification of perioperative care to improve postoperative outcomes. See Video Abstract . PREDICCIN DE LAS COMPLICACIONES QUIRRGICAS DE LA NEOPLASIA DE COLON UN ENFOQUE DE MODELO DE APRENDIZAJE AUTOMTICO: ANTECEDENTES:Se han utilizado una variedad de enfoques estadísticos para ayudar a predecir los resultados asociados con la colectomía. La naturaleza multifactorial de las complicaciones sugiere que los algoritmos de aprendizaje automático pueden ser más precisos en determinar los resultados posoperatorios al detectar asociaciones no lineales, que generalmente no se miden en las estadísticas tradicionales.OBJETIVO:El objetivo de este estudio fue investigar la utilidad de los algoritmos de aprendizaje automático para predecir complicaciones en pacientes sometidos a colectomía por neoplasia de colon.DISEÑO:Análisis retrospectivo utilizando clasificadores de árboles de decisión, bosques aleatorios y redes neuronales artificiales para predecir los resultados posoperatorios.AJUSTE:Base de datos de la Muestra Nacional de Pacientes Hospitalizados (2003-2017).PACIENTES:Pacientes adultos sometidos a colectomía electiva con anastomosis por neoplasia.INTERVENCIONES:N/A.PRINCIPALES MEDIDAS DE RESULTADO:El rendimiento se cuantificó utilizando la sensibilidad, especificidad, precisión y la característica operativa del receptor del área bajo la curva para predecir la incidencia de fuga anastomótica, duración prolongada de la estancia hospitalaria y mortalidad de los pacientes hospitalizados.RESULTADOS:Se incluyeron un total de 14.935 pacientes (4.731 laparoscópicos, 10.204 abiertos). Presentaron una edad promedio de 67 ± 12,2 años y el 53% eran mujeres. Los tres modelos de aprendizaje automático identificaron con éxito a los pacientes que desarrollaron las complicaciones medidas. Aunque las diferencias entre el rendimiento del modelo fueron en gran medida insignificantes, la red neuronal obtuvo la puntuación más alta para la mayoría de los resultados: predicción de fuga anastomótica, característica operativa del receptor del área bajo la curva 0,88/0,93 (abierta/laparoscópica, IC del 95%: 0,73-0,92/0,80-0,96); duración prolongada de la estancia hospitalaria, característica operativa del receptor del área bajo la curva 0,84/0,88 (abierta/laparoscópica, IC del 95%: 0,82-0,85/0,85-0,91); y mortalidad de pacientes hospitalizados, característica operativa del receptor del área bajo la curva 0,90/0,92 (abierto/laparoscópico, IC del 95%: 0,85-0,96/0,86-0,98).LIMITACIONES:Los pacientes de la base de datos de la Muestra Nacional de Pacientes Hospitalizados pueden no ser una muestra precisa de la población de todos los pacientes sometidos a colectomía por neoplasia de colon y no tienen en cuenta factores institucionales y específicos del paciente.CONCLUSIONES:El aprendizaje automático predijo con buen rendimiento las complicaciones postoperatorias en pacientes con neoplasia de colon sometidos a colectomía. Aunque será necesaria la validación mediante datos externos y la optimización de la calidad de los datos, estas herramientas de aprendizaje automático son muy prometedoras para ayudar a los cirujanos con la estratificación de riesgos de la atención perioperatoria para mejorar los resultados posoperatorios. (Traducción-Dr. Fidel Ruiz Healy ).

Evaluation and Management After Acute Left-Sided Colonic Diverticulitis : A Systematic Review.

BACKGROUND: The value of interventions used after acute colonic diverticulitis is unclear. PURPOSE: To evaluate postdiverticulitis colonoscopy and interventions to prevent recurrent diverticulitis. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, CINAHL, and ClinicalTrials.gov from 1 January 1990 through 16 November 2020. STUDY SELECTION: Comparative studies of interventions of interest reporting critical or important outcomes, and larger single-group studies to evaluate prevalence of colonoscopy findings and harms. DATA EXTRACTION: 6 researchers extracted study data and risk of bias. The team assessed strength of evidence. DATA SYNTHESIS: 19 studies evaluated colonoscopy. Risk for prevalent colorectal cancer (CRC) compared with the general population is unclear. Based on low-strength evidence, long-term CRC diagnosis is similar with or without colonoscopy. High-strength evidence indicates that risk for prevalent CRC is higher among patients with complicated diverticulitis and colonoscopy complications are rare. Based on high-strength evidence, mesalamine does not reduce recurrence risk (6 randomized controlled trials [RCTs]). Evidence on other nonsurgical interventions is insufficient. For patients with prior complicated or smoldering or frequently recurrent diverticulitis, elective surgery is associated with reduced recurrence (3 studies; high strength). In 19 studies, serious surgical complications were uncommon. LIMITATIONS: Few RCTs provided evidence. Heterogeneity of treatment effect was not adequately assessed. CONCLUSION: It is unclear whether patients with recent acute diverticulitis are at increased risk for prevalent CRC, but those with complicated diverticulitis are at increased risk. Mesalamine is ineffective in preventing recurrence; other nonsurgical treatments have inadequate evidence. Elective surgery reduces recurrence in patients with prior complicated or smoldering or frequently recurrent diverticulitis, but it is unclear which of these patients may benefit most. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and American College of Physicians. (PROSPERO: CRD42020151246).

Diagnostic Imaging and Medical Management of Acute Left-Sided Colonic Diverticulitis : A Systematic Review.

BACKGROUND: Clinicians need to better understand the value of computed tomography (CT) imaging and nonsurgical treatment options to manage acute left-sided colonic diverticulitis. PURPOSE: To evaluate CT imaging, outpatient treatment of uncomplicated diverticulitis, antibiotic treatment, and interventional radiology for patients with complicated diverticulitis. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, CINAHL, and ClinicalTrials.gov from 1 January 1990 through 16 November 2020. STUDY SELECTION: Existing systematic reviews of CT imaging accuracy, as well as randomized trials and adjusted nonrandomized comparative studies reporting clinical or patient-centered outcomes. DATA EXTRACTION: 6 researchers extracted study data and risk of bias, which were verified by an independent researcher. The team assessed strength of evidence across studies. DATA SYNTHESIS: Based on moderate-strength evidence, CT imaging is highly accurate for diagnosing acute diverticulitis. For patients with uncomplicated acute diverticulitis, 6 studies provide low-strength evidence that initial outpatient and inpatient management have similar risks for recurrence or elective surgery, but they provide insufficient evidence regarding other outcomes. Also, for patients with uncomplicated acute diverticulitis, 5 studies comparing antibiotics versus no antibiotics provide low-strength evidence that does not support differences in risks for treatment failure, elective surgery, recurrence, posttreatment complications, and other outcomes. Evidence is insufficient to determine choice of antibiotic regimen (7 studies) or effect of percutaneous drainage (2 studies). LIMITATIONS: The evidence base is mostly of low strength. Studies did not adequately assess heterogeneity of treatment effect. CONCLUSION: Computed tomography imaging is accurate for diagnosing acute diverticulitis. For patients with uncomplicated diverticulitis, no differences in outcomes were found between outpatient and inpatient care. Avoidance of antibiotics for uncomplicated acute diverticulitis may be safe for most patients. The evidence is too sparse for other evaluated questions. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and American College of Physicians. (PROSPERO: CRD42020151246).

Predicting Anastomotic Leak After Elective Colectomy: Utility of a Modified Frailty Index.

BACKGROUND: Anastomotic leak is the most dreaded complication following colonic resection. While patient frailty is increasingly being recognized as a risk factor for surgical morbidity and mortality, the current colorectal body of literature has not assessed the relationship between frailty and anastomotic leak. OBJECTIVE: Evaluate the relationship between patient frailty and anastomotic leak as well as patient frailty and failure to rescue in patients who experienced an anastomotic leak. DESIGN: Retrospective cohort study. SETTING: American College of Surgeons National Surgical Quality Improvement Program Database from 2015 to 2017. PATIENTS: Patients with the diagnosis of colonic neoplasia undergoing an elective colectomy during the study time period. MAIN OUTCOME MEASURE: Anastomotic leak, failure to rescue. RESULTS: A total of 30,180 elective colectomies for neoplasia were identified. The leak rate was 2.9% (n = 880). Compared to nonfrail patients, frail patients were at increased odds of anastomotic leak (frailty score = 1: OR 1.34, 95% CI 1.10-1.63; frailty score = 2: OR 1.32, 95% CI 1.04-1.68; frailty score = 3: OR = 2.41, 95% CI 1.47-3.96). After an anastomotic leak, compared to nonfrail patient, a greater proportion of frail patients experienced mortality (3.4% vs 5.9%), septic shock (16.1% vs 21.0%), myocardial infarction (1.1% vs 2.9%), and pneumonia (6.8% vs 11.8%). Furthermore, the odds of mortality, septic shock, myocardial infarction, and pneumonia increased in frail patients with higher frailty scores. LIMITATIONS: Potential misclassification bias from lack of a strict definition of anastomotic leak and retrospective design of the study. CONCLUSION: Frail patients undergoing colectomy for colonic neoplasia are at increased risk of an anastomotic leak. Furthermore, once a leak occurs, they are more vulnerable to failure to rescue. See Video Abstract at http://links.lww.com/DCR/B784. PREDICCIN DE LA FUGA ANASTOMTICA DESPUS DE UNA COLECTOMA ELECTIVA UTILIDAD DE UN NDICE DE FRAGILIDAD MODIFICADO: ANTECEDENTES:La fuga anastomótica es la complicación más temida después de la resección colónica. Si bien la fragilidad del paciente se reconoce cada vez más como un factor de riesgo de morbilidad y mortalidad quirúrgicas, la bibliografía colorrectal actual no ha evaluado la relación entre la fragilidad y la fuga anastomótica.OBJETIVO:Evaluar la relación entre la fragilidad del paciente y la fuga anastomótica, así como la fragilidad del paciente y la falta de rescate en pacientes que sufrieron una fuga anastomótica.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Base de datos del Programa Nacional de Mejora de la Calidad Quirúrgica del Colegio Estadounidense de Cirujanos de 2015 a 2017.PACIENTES:Pacientes con diagnóstico de neoplasia de colon sometidos a colectomía electiva durante el período de estudio.PRINCIPAL MEDIDA DE RESULTADO:Fuga anastomótica, falta de rescate.RESULTADOS:Se identificaron 30.180 colectomías electivas por neoplasia. La tasa de fuga fue del 2,9% (n = 880). En comparación con los pacientes no frágiles, los pacientes frágiles tenían mayores probabilidades de fuga anastomótica para (puntuación de fragilidad = 1: OR = 1,34, IC del 95%: 1,10-1,63; puntuación de fragilidad = 2: OR = 1,32, IC del 95%: 1,04- 1,68; puntuación de fragilidad = 3: OR 2,41; IC del 95%: 1,47-3,96). Después de una fuga anastomótica, en comparación con un paciente no frágil, una mayor proporción de pacientes frágiles experimentó mortalidad (3,4% frente a 5,9%), choque séptico (16,1% frente a 21,0%), infarto de miocardio (1,1% frente a 2,9%) y neumonía (6,8% vs 11,8%). Además, las probabilidades de mortalidad, choque séptico, infarto de miocardio y neumonía aumentaron en pacientes frágiles con puntuaciones de fragilidad más altas.LIMITACIONES:Posible sesgo de clasificación errónea debido a la falta de una definición estricta de fuga anastomótica, diseño retrospectivo del estudio.CONCLUSIÓN:Los pacientes frágiles sometidos a colectomía por neoplasia de colon tienen un mayor riesgo de una fuga anastomótica. Además, una vez que ocurre una fuga, son más vulnerables a fallas en el rescate. Consulte Video Resumen en http://links.lww.com/DCR/B784.

Expert Commentary on Complicated Diverticulitis.

Complicated diverticulitis encompasses a variety of clinical scenariors as outlined in the well-written and succinct review by Drs Mendez and Garcia-Henriquez. These range from acute presentations, such as abscesses and free perforations with peritonitis, to more chronic, insidious sequelae such as fistulas and strictures.The contemporary surgical management of diverticular disease has evolved considerably with better appreciation of the pathophysiology and natural history. Just as in uncomplicated diverticulitis, there has been a significant shift toward a less aggressive surgical strategy in complicated diverticulitis, aided further with improved diagnostic and interventional radiology.I would like to add a few salient points for each listed complication.

The reconstruction of skull base defects in infants using pedicled nasoseptal flap-a review of four cases.

INTRODUCTION: Benign lesions of the skull base are common in the paediatric population, and are usually congenital in aetiology. Majority of these lesions are treated transcranially exposing the patients to a number of risks. Although endoscopic endonasal surgery (EES) helps avoid many of these potential morbidities, CSF leak with its attendant complication remains a big concern. This study reports the use of the Hadad flap in the reconstruction of skull base defects in infants to prevent this problem. The study was conducted on four infants with a mean age of 7 months, who underwent repairs for CSF leaks associated with congenital lesions like meningocele or meningoencephalocele, using the Hadad flap. Of the four patients, three cases were revision cases and one was primary where the patients presented with complaints such as nasal obstruction and watery nasal discharge. Post surgery, the infants were monitored for a mean period of 23 months and no major complications or recurrent CSF drainage were observed. Minor complications that were observed include vestibulitis and crusting in the nose. The utility of the Hadad flap in the reconstruction of skull base defects in the paediatric age group has been controversial while its utility in infants has not been studied in literature so far. We report here in our series four infant patients in whom we believe that the nasal septum and the skull base will develop proportionally to each other, hence lowering the chances of a short flap and eliminating the occurrence of future complications. CONCLUSION: The nasoseptal flap is an effective and safe technique for reconstructing skull base defects in infancy. It can be concluded that this technique does not have any potential effect on septal or craniofacial growth as the flap is harvested only on one side with normal mucosal cover on the other side. There is no posterior septectomy or any form of bony or cartilaginous resection that is performed, hence avoiding any effects on bony growth. No studies have been published in literature so far and to the best of our knowledge, this is the first report describing the efficacy of the nasoseptal flap in infants.

Endonasal endoscopic skullbase surgery in children.

OBJECTIVE: The role of endonasal endoscopic approach for pathologies in the paediatric population is evolving and has still not been accepted as standard of care in neurosurgery. It represents a challenge in terms of narrow access, instrument manipulation and adequate reconstruction of defects. We have described our experience in 49 cases from a single neurosurgical unit in paediatric skull base surgeries through this approach over the last 12 years. MATERIAL AND METHODS: A case series of 59 paediatric skull base surgeries in 49 children through endoscopic endonasal route over the last 12 years is presented. The age ranges from 4 months to 18 years. Out of 49 cases, 22 cases were of craniopharyngiomas, 8 cases of pituitary adenomas, 5 cases with CSF rhinorrhea, 5 cases with meningoencephalocele, 3 cases of Rathke's cleft cysts, 2 cases of odontoidectomy and 4 miscellaneous cases viz. mucocele, hypothalamic glioma, esthesioneuroblastoma and epidermoid. CSF leaks were repaired with free graft in the initial years and by vascularized flap more recently. RESULTS: The goal of surgery was achieved in all but two cases in whom the tumour excision was unsatisfactory due to failure of the cyst wall to collapse after decompression. Extent of tumour excision was not compromised by the choice of this approach. Revision surgery for CSF leak was required in three patients. Local vascularized nasoseptal flap has been possible even in very young patients and has now become the standard for reconstruction. CONCLUSION: In spite of the challenges posed by small nostrils and ill-developed sinuses in the paediatric age group, surgery from endoscopic endonasal corridor is possible to be carried out successfully in selected cases.

Combined endoscopic approach in the management of suprasellar craniopharyngioma.

INTRODUCTION: Craniopharyngiomas are dysontogenic tumors with benign histology but aggressive behavior. The surgical challenges posed by the tumor are well recognized. Neuroendoscopy has recently contributed to its surgical management. This study focuses on our experience in managing craniopharyngiomas in recent years, highlighting the role of combined endoscopic trans-ventricular and endonasal approach. CASE SERIES: Ninety-two patients have been treated for craniopharyngioma from 2000 to 2016 by the senior author. A total of 125 procedures, microsurgical (58) and endoscopic (67), were undertaken. Combined endoscopic approach was carried out in 18 of these patients, 16 children and 2 young adults. All of these patients presented with a large cystic suprasellar mass associated with hydrocephalus. In the first instance, they were treated with a transventricular endoscopic procedure to decompress the cystic component. This was followed by an endonasal transsphenoidal procedure for excision within the next 2 to 6 days. All these patients improved after the initial cyst decompression with relief of hydrocephalus while awaiting remaining tumor removal in a more elective setting. Gross total resection could be done in 84% of these patients. Diabetes insipidus was the most common postsurgical complication seen in 61% patients in the immediate period but was persistent in only two patients at 1-year follow-up. None of the children in this group developed morbid obesity. There was one case of CSF leak requiring repair after initial surgery. Peri-operative mortality was seen in one patient secondary to ventriculitis. DISCUSSION: The patients who benefit most from the combined approach are those who present with raised intracranial pressure secondary to a large tumor with cyst causing hydrocephalus. Intraventricular endoscopic cyst drainage allows resolution of hydrocephalus with restoration of normal intracranial pressure, gives time for proper preoperative work up, and has reduced incidence of CSF leak after transnasal surgery. CONCLUSION: Combined endoscopic approach thus gives a unique opportunity to remove these lesions more radically with less morbidity.

Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy.

PURPOSE: To characterise longitudinal changes in the retinal microvasculature of type 2 diabetes mellitus (T2DM) as exemplified in a patient with proliferative diabetic retinopathy (PDR) using an adaptive optics scanning light ophthalmoscope (AOSLO). METHODS: A 35-year-old T2DM patient with PDR treated with scatter pan-retinal photocoagulation at the inferior retina 1 day prior to initial AOSLO imaging along with a 24-year-old healthy control were imaged in this study. AOSLO vascular structural and perfusion maps were acquired at four visits over a 20-week period. Capillary diameter and microaneurysm area changes were measured on the AOSLO structural maps. Imaging repeatability was established using longitudinal imaging of microvasculature in the healthy control. RESULTS: Capillary occlusion and recanalisation, capillary dilatation, resolution of local retinal haemorrhage, capillary hairpin formation, capillary bend formation, microaneurysm formation, progression and regression were documented over time in a region 2° superior to the fovea in the PDR patient. An identical microvascular network with same capillary diameter was observed in the control subject over time. CONCLUSIONS: High-resolution serial AOSLO imaging enables in vivo observation of vasculopathic changes seen in diabetes mellitus. The implications of this methodology are significant, providing the opportunity for studying the dynamics of the pathological process, as well as the possibility of identifying highly sensitive and non-invasive biomarkers of end organ damage and response to treatment.

Oral Mechanical Bowel Preparation for Colorectal Surgery: Systematic Review and Meta-Analysis.

BACKGROUND: Oral mechanical bowel preparation is often used before elective colorectal surgery to reduce postoperative complications. OBJECTIVE: The purpose of this study was to synthesize the evidence on the comparative effectiveness and safety of oral mechanical bowel preparation versus no preparation or enema. DATA SOURCES: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and CINAHL without any language restrictions (last search on September 6, 2013). We also searched the US Food and Drug Administration Web site and ClinicalTrials.gov and supplemented our searches by asking technical experts and perusing reference lists. STUDY SELECTION: We included English-language, full-text reports of randomized clinical trials and nonrandomized comparative studies of patients undergoing elective colon or rectal surgery. For adverse events we also included single-group cohort studies of at least 200 participants. INTERVENTIONS: Interventions included oral mechanical bowel preparation, oral mechanical bowel preparation plus enema, enema only, and no oral mechanical bowel preparation or enema. MAIN OUTCOME MEASURES: Anastomotic leakage, all-cause mortality, wound infection, peritonitis/intra-abdominal abscess, reoperation, surgical site infection, quality of life, length of stay, and adverse events were measured. We synthesized results across studies qualitatively and with Bayesian random-effects meta-analyses. RESULTS: A total of 18 randomized clinical trials, 7 nonrandomized comparative studies, and 6 single-group cohorts were included. In meta-analyses of randomized clinical trials, the credibility intervals of the summary OR included the null value of 1.0 for comparisons of oral mechanical bowel preparation and either no oral preparation or enema for overall mortality, anastomotic leakage, wound infection, peritonitis, surgical site infection, and reoperation. These results were robust to extensive sensitivity analyses. Evidence on adverse events was sparse. LIMITATIONS: The study was limited by weaknesses in the underlying evidence, such as incomplete reporting of relevant information, exclusion of non-English and relevant unpublished studies, and possible missed indexing of nonrandomized studies. CONCLUSIONS: Our results could not exclude modest beneficial or harmful effects of oral mechanical bowel preparation compared with no preparation or enema.

FELLOW EYE CHANGES IN PATIENTS WITH NONISCHEMIC CENTRAL RETINAL VEIN OCCLUSION: Assessment of Perfused Foveal Microvascular Density and Identification of Nonperfused Capillaries.

PURPOSE: Eyes fellow to nonischemic central retinal vein occlusion (CRVO) were examined for abnormalities, which might explain their increased risk for future occlusion, using adaptive optics scanning light ophthalmoscope fluorescein angiography. METHODS: Adaptive optics scanning light ophthalmoscope fluorescein angiography foveal microvascular densities were calculated. Nonperfused capillaries adjacent to the foveal avascular zone were identified. Spectral domain optical coherence tomography, ultrawide field fluorescein angiographies, and microperimetry were also performed. RESULTS: Ten fellow eyes of nine nonischemic CRVO and 1 nonischemic hemi-CRVO subjects and four affected eyes of three nonischemic CRVO and one nonischemic hemi-CRVO subjects were imaged. Ninety percent of fellow eyes and 100% of affected eyes demonstrated at least 1 nonperfused capillary compared with 31% of healthy eyes. Fellow eye microvascular density (35 ± 3.6 mm(-1)) was significantly higher than that of affected eyes (25 ± 5.2 mm(-1)) and significantly lower than that of healthy eyes (42 ± 4.2 mm(-1)). Compared with healthy controls, spectral domain optical coherence tomography thicknesses showed no significant difference, whereas microperimetry and 2/9 ultrawide field fluorescein angiography revealed abnormalities in fellow eyes. CONCLUSION: Fellow eye changes detectable on adaptive optics scanning light ophthalmoscope fluorescein angiography reflect subclinical pathology difficult to detect using conventional imaging technologies. These changes may help elucidate the pathogenesis of nonischemic CRVO and help identify eyes at increased risk of future occlusion.

Outer retinal structure after closed-globe blunt ocular trauma.

PURPOSE: To evaluate outer retinal structural abnormalities in patients with visual deficits after closed-globe blunt ocular trauma. METHODS: Nine subjects with visual complaints after closed-globe blunt ocular trauma were examined between 1 month after trauma and 6 years after trauma. Spectral domain optical coherence tomography was used to assess the outer retinal architecture, whereas adaptive optics scanning light ophthalmoscopy was used to analyze the photoreceptor mosaic integrity. RESULTS: Visual deficits ranged from central scotomas to decreased visual acuity. Spectral domain optical coherence tomography defects included focal foveal photoreceptor lesions, variable attenuation of the interdigitation zone, and mottling of the outer segment band, with one subject having normal outer retinal structure. Adaptive optics scanning light ophthalmoscopy revealed disruption of the photoreceptor mosaic in all subjects, variably manifesting as foveal focal discontinuities, perifoveal hyporeflective cones, and paracentral regions of selective cone loss. CONCLUSION: We observe persistent outer retinal disruption in subjects with visual complaints after closed-globe blunt ocular trauma, albeit to a variable degree. Adaptive optics scanning light ophthalmoscopy imaging allows the assessment of photoreceptor structure at a level of detail not resolvable using spectral domain optical coherence tomography or other current clinical imaging tools. Multimodal imaging seems to be useful in revealing the cause of visual complaints in patients after closed-globe blunt ocular trauma. Future studies are needed to better understand how photoreceptor structure changes longitudinally in response to various traumas.

Use of Navigation System in the Management of Deep Neck Space Infection-A Case Report.

Deep neck space infections are an ENT (Ear, Nose, Throat) emergency. Navigation system (NS) can be utilized to assist in locating the exact site of pathology and avoiding iatrogenic injury especially in paediatric patients. This manuscript explores the importance of NS in managing retro pharyngeal abscess (RPA) in an 11 month old baby. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04406-9.

Immunogenicity phase II study evaluating booster capacity of nonadjuvanted AKS-452 SARS-Cov-2 RBD Fc vaccine.

AKS-452, a subunit vaccine comprising an Fc fusion of the ancestral wild-type (WT) SARS-CoV-2 virus spike protein receptor binding domain (SP/RBD), was evaluated without adjuvant in a single cohort, non-randomized, open-labelled phase II study (NCT05124483) at a single site in The Netherlands for safety and immunogenicity. A single 90 µg subcutaneous booster dose of AKS-452 was administered to 71 adults previously primed with a registered mRNA- or adenovirus-based vaccine and evaluated for 273 days. All AEs were mild and no SAEs were attributable to AKS-452. While all subjects showed pre-existing SP/RBD binding and ACE2-inhibitory IgG titers, 60-68% responded to AKS-452 via ≥2-fold increase from days 28 to 90 and progressively decreased back to baseline by day 180 (days 28 and 90 mean fold-increases, 14.7 ± 6.3 and 8.0 ± 2.2). Similar response kinetics against RBD mutant proteins (including omicrons) were observed but with slightly reduced titers relative to WT. There was an expected strong inverse correlation between day-0 titers and the fold-increase in titers at day 28. AKS-452 enhanced neutralization potency against live virus, consistent with IgG titers. Nucleocapsid protein (Np) titers suggested infection occurred in 66% (46 of 70) of subjects, in which only 20 reported mild symptomatic COVID-19. These favorable safety and immunogenicity profiles support booster evaluation in a planned phase III universal booster study of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.

A randomized phase I/II safety and immunogenicity study of the Montanide-adjuvanted SARS-CoV-2 spike protein-RBD-Fc vaccine, AKS-452.

BACKGROUND: Previous interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study. METHODS: This phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 - 72 years) receiving AKS-452 subcutaneously at one 90 µg dose (cohort 1, 26 subjects) or two 45 µg doses 28 days apart (cohort 2, 26 subjects). Serum samples were collected at the first dose (day 0) and at days 28, 56, 90, and 180. Safety and immunogenicity endpoints were assessed, along with induction of IgG isotypes, cross-reactive immunity against viral variants, and IFN-γ T cell responses. RESULTS: All AEs were mild/moderate (grades 1 or 2), and no SAEs were attributable to AKS-452. Seroconversion rates reached 100% in both cohorts, although cohort 2 showed greater geometric mean IgG titers that were stable through day 180 and associated with enhanced potencies of SP/RBD-ACE2 binding inhibition and live virus neutralization. AKS-452-induced IgG titers strongly bound mutant SP/RBD from several SARS-CoV-2 variants (including Omicrons) that were predominantly of the favorable IgG1/3 isotype and IFN-γ-producing T cell phenotype. CONCLUSION: These favorable safety and immunogenicity profiles of the candidate vaccine as demonstrated in this phase II study are consistent with those of the phase I study (ClinicalTrials.gov: NCT04681092) and suggest that a total of 90 µg received in 2 doses may offer a greater duration of cross-reactive neutralizing titers than when given in a single dose.