Germline Cancer Testing in Unselected Patients with Gastric and Esophageal Cancers: A Multi-center Prospective Study.

BACKGROUND AND AIMS: To determine prevalence and clinical utility of pathogenic germline variants (PGV) in gastric and esophageal cancer patients using universal genetic testing approach. METHODS: We undertook a prospective study of germline sequencing using an > 80 gene next-generation sequencing platform among patients with gastric and esophageal cancers receiving care at Mayo Clinic Cancer Center between April 1, 2018, and March 31, 2020. Patients were not selected based on cancer stage, family history of cancer, ethnicity, or age. Family cascade testing was offered at no cost. RESULTS: A total of 96 patients were evaluated. Median age was 66 years, 80.2% were male, 89.6% were white. Nearly 39% of the cohort had esophageal cancer, 35.4% gastric cancer and 26% gastroesophageal junction cancers. Approximately half (52%) of the patients had metastatic disease. Pathogenic germline variants (PGV) were detected in 15.6% (n = 15) patients. The prevalence of PGV was 10.8% in esophageal cancer, 17.6% in gastric cancer and 20% in gastroesophageal cancer. Eighty percent of patients with a positive result would not have been detected by screening with standard guidelines for genetic testing. Most PGV detected included genes with high and moderate penetrance related to DNA damage response including BRCA1, BRCA2, PALB2 and ATM. CONCLUSIONS: Universal multi-gene panel testing in gastric and esophageal cancers was associated with detection of heritable mutations in 15% of patients. The majority of PGV would not be detected with current screening guidelines and are related to DNA damage response.

Significant decrease of facial cellulitis admissions during COVID-19 lockdown in France: A multicentric comparative study.

During the 2020 coronavirus pandemic, a lockdown was imposed in France during the first wave. An apparent decrease in incidence of cellulitis of odontogenic origin was noticed then. This study aimed to compare the incidence of cellulitis during this extraordinary period with the same period in 2018 and 2019, based on retrospective multicentric data. All maxillofacial surgery departments in French public hospitals were contacted. Responders were asked to include all patients admitted for the surgical drainage of a head and neck abscess of odontogenic origin during the first 2020 lockdown period, and in a similar time frame in 2018 and 2019 (control group), based on screening the French diagnostic and therapeutic classification of medical acts. We report a 44% significant nationwide decrease in the incidence of admissions for cellulitis. There were 187 patients in 2020 for 334 and 333 patients in 2018/2019 respectively. The reasons to explain this finding are hypothetical (organizational reasons leading to earlier management, patients' fear to seek for medical management, usual excess in surgical indications or concomitant decrease of non-steroidal anti-inflammatory drugs delivery). Whatever the explanation, it would be of great interest to find it out in order to improve the prevention of cellulitis.

BCI learning induces core-periphery reorganization in M/EEG multiplex brain networks.

Objective.Brain-computer interfaces (BCIs) constitute a promising tool for communication and control. However, mastering non-invasive closed-loop systems remains a learned skill that is difficult to develop for a non-negligible proportion of users. The involved learning process induces neural changes associated with a brain network reorganization that remains poorly understood.Approach.To address this inter-subject variability, we adopted a multilayer approach to integrate brain network properties from electroencephalographic and magnetoencephalographic data resulting from a four-session BCI training program followed by a group of healthy subjects. Our method gives access to the contribution of each layer to multilayer network that tends to be equal with time.Main results.We show that regardless the chosen modality, a progressive increase in the integration of somatosensory areas in theαband was paralleled by a decrease of the integration of visual processing and working memory areas in theßband. Notably, only brain network properties in multilayer network correlated with future BCI scores in theα2band: positively in somatosensory and decision-making related areas and negatively in associative areas.Significance.Our findings cast new light on neural processes underlying BCI training. Integrating multimodal brain network properties provides new information that correlates with behavioral performance and could be considered as a potential marker of BCI learning.

Increased vaccine tolerability and protection via NF-κB modulation.

Improving adjuvant responses is a promising pathway to develop vaccines against some pathogens (e.g., HIV or dengue). One challenge in adjuvant development is modulating the inflammatory response, which can cause excess side effects, while maintaining immune activation and protection. No approved adjuvants yet have the capability to independently modulate inflammation and protection. Here, we demonstrate a method to limit inflammation while retaining and often increasing the protective responses. To accomplish this goal, we combined a partial selective nuclear factor kappa B (NF-kB) inhibitor with several current adjuvants. The resulting vaccines reduce systemic inflammation and boost protective responses. In an influenza challenge model, we demonstrate that this approach enhances protection. This method was tested across a broad range of adjuvants and antigens. We anticipate these studies will lead to an alternative approach to vaccine formulation design that may prove broadly applicable to a wide range of adjuvants and vaccines.

Multicenter study on the diagnostic performance of multiframe volumetric laser endomicroscopy targets for Barrett's esophagus neoplasia with histopathology correlation.

Volumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett's esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs. In total, 191 ROIs (120 nondysplastic and 71 neoplastic) from 50 BE patients were evaluated in a random order using a web-based module. All ROIs contained histopathology correlations enabled by VLE laser marking. Assessors were blinded to endoscopic BE images and histology. ROIs were first scored as nondysplastic or neoplastic. Level of confidence was assigned to the predicted diagnosis. Outcome measures were: (i) diagnostic performance of VLE assessors for identification of BE neoplasia in all VLE ROIs, defined as accuracy, sensitivity, and specificity; (ii) diagnostic performance of VLE assessors for only high level of confidence predictions; and (iii) interobserver agreement. Accuracy, sensitivity, and specificity for BE neoplasia identification were 79% (confidence interval [CI], 75-83), 75% (CI, 71-79), and 81% (CI, 76-86), respectively. When neoplasia was identified with a high level of confidence, accuracy, sensitivity, and specificity were 88%, 83%, and 90%, respectively. The overall strength of interobserver agreement was fair (k = 0.29). VLE assessors can identify BE neoplasia with reasonable diagnostic accuracy in histopathology-correlated VLE ROIs, and accuracy is enhanced when BE neoplasia is identified with high level of confidence. Future work should focus on renewed VLE image reviewing criteria and real-time automatic assessment of VLE scans.

Impact of white-spotting alleles, including W20, on phenotype in the American Paint Horse.

The American Paint Horse Association (APHA) records pedigree and performance information for their breed, a stock-type horse valued as a working farm or ranch horse and as a pleasure horse. As the name implies, the breed is also valued for its attractive white-spotting patterns on the coat. The APHA utilizes visual inspections of photographs to determine if coat spotting exceeds threshold anatomical landmarks considered characteristic of desirable patterns. Horses with sufficient white patterning enter the 'Regular' registry, rather than the 'Solid Paint-Bred' division, providing a threshold modeled phenotype. Genetic studies previously defined sequence variants corresponding to 35 alleles for white spotting in the horse. Here, we calculate the allele frequencies for nine common white-spotting alleles in the American Paint Horse using a sample of 1054 registered animals. The APHA spotting phenotype is altered by additive interactions among spotting loci, and epistatically by the MC1R and ASIP genes controlling pigment production. The W20 allele within the KIT gene, independent of other known spotting alleles, was strongly associated with the APHA-defined white-spotting phenotype (P = 1.86 × 10-18 ), refuting reports that W20 acts only as a modifier of other underlying white-spotting patterns. The parentage of an individual horse, either American Paint or American Quarter Horse, did not alter the likelihood of its entering the APHA Regular Registry. An empirical definition of the action of these genetic loci on the APHA-defined white-spotting phenotype will allow more accurate application of genome-assisted selection for improving color production and the marketability of APHA horses.

An extremely rare case of a displaced third molar into the infratemporal fossa associated with a textiloma.

BACKGROUND: Third molar extraction is one of the most common procedures performed by oral surgeons, however with rare complications. The accidental displacement of a maxillary third molar into the infratemporal fossa (ITF) is a rare complication that can occur even with experienced surgeons. CASE PRESENTATION: We describe the case of a 17-year-old patient whose right upper third molar was accidentally pushed to the ITF associated with a cellulitis and the late discovery of a textiloma (a surgical gauze). CONCLUSIONS: Extraction of third molars is a safe surgical procedure when performed in appropriate conditions. The diagnosis of textiloma following a maxillo-facial surgery is extremely rare. It is important to take into account this possibility in order to avoid delaying treatment when it occurs.

Alveolar distraction osteogenesis of a fibula free flap in maxillary reconstruction.

In maxillary reconstruction, it is challenging to obtain satisfactory maxillary projection and to optimizate the dental implant-prosthetic rehabilitation. We report a case of sagittal distraction of a fibula free flap used to reconstruct maxilla after a ballistic trauma. Distraction began seven days after implantation of the device. The distraction protocol was 0.9mm per day during a total period of 2 months. Cone beam computed tomography acquisitions were performed at 3 months after the end of the distraction. The distractor device was removed 5 months after the end of the distraction protocol to allow bone consolidation. A satisfactory total distraction of 7mm was obtained with an esthetic variation of the projection of the upper lip and closure of the nasolabial angle.

Interpretation of volumetric laser endomicroscopy in Barrett's esophagus using image enhancement software.

Image interpretation of Barrett's esophagus (BE) with volumetric laser endomicroscopy (VLE) can be enhanced by image processing software that highlights established features using a color-graded scale (intelligent real-time image segmentation, IRIS). This study aims to provide a description of IRIS features of various gastroesophageal tissue types using histologic correlation. A database of 80 VLE laser-marked targets with histologic correlation was reviewed for various tissue types. IRIS was applied off-line to the VLE scans, laser-marked targets were identified, and feature review was performed. Squamous epithelium targets (N = 7) showed IRIS layered architecture with lack of surface hyper-reflectivity and epithelial glands. Gastric cardia targets (N = 10) showed absent layering (100%) and surface hyper-reflectivity with epithelial glands (40%). Nondysplastic BE targets (N = 39) showed surface hyper-reflectivity (64%), epithelial glands (51%), and lack of layering (74%). Targets of BE with early neoplasia (N = 24), showed surface hyper-reflectivity (96%), epithelial glands (67%), and lack of layering (96%). IRIS features that characterize each tissue type appear to mirror the nonenhanced VLE counterparts that define them.

Cross-Modal Cue Effects in Motion Processing.

The everyday environment brings to our sensory systems competing inputs from different modalities. The ability to filter these multisensory inputs in order to identify and efficiently utilize useful spatial cues is necessary to detect and process the relevant information. In the present study, we investigate how feature-based attention affects the detection of motion across sensory modalities. We were interested to determine how subjects use intramodal, cross-modal auditory, and combined audiovisual motion cues to attend to specific visual motion signals. The results showed that in most cases, both the visual and the auditory cues enhance feature-based orienting to a transparent visual motion pattern presented among distractor motion patterns. Whereas previous studies have shown cross-modal effects of spatial attention, our results demonstrate a spread of cross-modal feature-based attention cues, which have been matched for the detection threshold of the visual target. These effects were very robust in comparisons of the effects of valid vs. invalid cues, as well as in comparisons between cued and uncued valid trials. The effect of intramodal visual, cross-modal auditory, and bimodal cues also increased as a function of motion-cue salience. Our results suggest that orienting to visual motion patterns among distracters can be facilitated not only by intramodal priors, but also by feature-based cross-modal information from the auditory system.

Photon upconversion for the enhancement of microfluidic photochemical synthesis.

Photochemical transformations are greatly improved in yield by fluidic reactor technology. However, the delivery of synthetically-active light to the reactants is a challenge. Here, we use upconversion in a bio-inspired microreactor to augment the flux of critical wavelengths of light. This new technology increased of a model reaction by converting a greater portion of sunlight to photochemically-available photons.

SENSIBILIZACIÓN A AEROALERGENOS EN PACIENTES CON RINITIS Y ASMA

Las enfermedades alérgicas han aumentado en las últimas décadas en todo el mundo. El asma y la rinitis alérgica podrían representar un espectro de la misma enfermedad, cuya patogénesis puede explicarse, entre otros factores, por la sensibilización a aeroalergenos. Los aeroalergenos más frecuentemente involucrados como sensibilizantes se hallan en el polvo del interior del hogar o lugar de trabajo (indoor). Dentro de los aeroalergenos indoor, los dermatophagoides son los más prevalentes. Este estudio demuestra que la prevalencia de sensibilidad a aeroalergenos indoor, en pacientes con rinitis y asma, es coincidente con la bibliografía. Es un área a investigar en el futuro, la prevalencia de sensibilidad a aeroalergenos outdoor

Allergic diseases have increased in recent decades worldwide. Asthma and allergic rhinitis could represent a spectrum of the same disease, whose pathogenesis can be explained, among other factors, by sensitization to aeroallergens. The aeroallergens most frequently involved as sensitizers are found in the dust inside the home or workplace (indoor). Within indoor aeroallergens, dermatophagoides are the most prevalent. This study demonstrates that the prevalence of sensitivity to indoor Aeroallergens, in patients with rhinitis and asthma, is consistent with the literature. It is an area to investigate in the future, the prevalence of sensitivity to outdoor aeroallergens.

Do recent reports about the adverse effects of proton pump inhibitors change providers' prescription practice?

Proton pump inhibitors (PPI) are utilized for a variety of indications, including treatment of gastroesophageal reflux disease, peptic ulcer disease, and prevention of gastrointestinal (GI) bleeding. Several studies have documented an increasing prevalence of inappropriate PPI use. Furthermore, recent media reports have highlighted new research data suggesting a possible association between chronic PPI use and several adverse medical outcomes, leading to frequent patient inquiries about these associations. Thus, providers face the challenge of counseling patients about the balance of risks and benefits related to PPI use. We aimed to explore providers' knowledge and attitudes toward reported adverse effects of PPI use and compare providers' prescription practices. A comprehensive, non-incentivized electronic survey was sent to all providers (residents, fellows, advanced practice providers, and consultants across 8 internal medicine specialties) at our tertiary academic medical center. The survey contained 21 questions covering provider demographics and responses to challenging clinical scenarios dealing with PPI use. Chi-square was used to compare responses from providers. The survey was distributed to 254 providers, of which 94 (24 GI and 70 non-GI) completed the survey (37% response rate). Among those 94 providers, 48 were consultants, 17 were advanced practice providers, and 29 were trainees. Non-GI providers included cardiology, pulmonary, endocrinology, family medicine, general internal medicine, hematology/oncology, and nephrology. Over half of the providers (51 [54%]) described their practice as outpatient setting, 29 (31%) providers defined their practice as a mixed setting (inpatient and outpatient), while 14 (15%) designated it as inpatient only. Nineteen (80%) GI providers and 48 (69%) non-GI providers discussed the risks and benefits with patients (P = 0.64). Fifteen (63%) GI providers and 33 (47%) non-GI providers indicated that recent reports changed their practice (P = 0.49). More GI providers (5 [21%]) lowered the dose of PPI compared with non-GI (1[1%]) (P = 0.004); 18 (26%) of non-GI and 3 (13%) of GI providers discontinued PPI and substituted it with a histamine 2 (H2) blocker (P = 0.29). A larger but nonsignificant percentage of trainees (8 [28%]) switched PPI to H2 blockers compared with consultants (8 [17%]; P = 0.39). Six (25%) of GI providers and 14 (20%) of non-GI providers were concerned about Clostridium difficile infection (P = 0.58). Twenty-four (34%) of the non-GI were worried about kidney diseases compared with 3 (13%) of the GI providers (P = 0.1). Ten (21%) consultants were concerned about risk of osteoporosis compared with 3 (10%) trainees (P = 0.38), while 8 (28%) trainees were worried about the risk of C. difficile infection compared with 10 (21%) consultants (P = 0.69). Most providers (85 [90%]) agreed that educational activities would be helpful to address these challenges. More GI providers lowered the dose of PPI compared with non-GI; non-GI providers were more likely to discontinue PPI and substitute it with an H2 blocker. Educating patients and providers about potential adverse effects of PPI is imperative.

Longitudinal outcomes of radiofrequency ablation versus surveillance endoscopy for Barrett's esophagus with low-grade dysplasia.

Radiofrequency ablation of Barrett's esophagus with low-grade dysplasia is recommended in recent American College of Gastroenterology guidelines, with endoscopic surveillance considered a reasonable alternative. Few studies have directly compared outcomes of radiofrequency ablation to surveillance and those that have are limited by short duration of follow-up. This study aims to compare the long-term effectiveness of radiofrequency ablation versus endoscopic surveillance in a large, longitudinal cohort of patients with Barrett's esophagus, and low-grade dysplasia.We conducted a retrospective analysis of patients with confirmed low-grade dysplasia at a single academic medical center from 1991 to 2014. Patients progressing to high-grade dysplasia or esophageal adenocarcinoma within one year of index LGD endoscopy were defined as missed dysplasia and excluded. Risk factors for progression were assessed via Cox proportional hazards model. Comparison of progression risk was conducted using a Kaplan-Meier analysis. Subset analyses were conducted to examine the effect of reintroducing early progressors and excluding patients diagnosed prior to the advent of ablative therapy. Of 173 total patients, 79 (45.7%) underwent radiofrequency ablation while 94 (54.3%) were untreated, with median follow up of 90 months. Seven (8.9%) patients progressed to high-grade dysplasia or adenocarcinoma despite ablation, compared with 14 (14.9%) undergoing surveillance (P = 0.44). This effect was preserved when patients diagnosed prior to the introduction of radiofrequency ablation were excluded (8.9% vs 13%, P = 0.68). Reintroduction of patients progressing within the first year of follow-up resulted in a trend toward significance for ablation versus surveillance (11.1% vs 23.8%, P = 0.053).In conclusion, progression to high-grade dysplasia or adenocarcinoma was not significantly reduced in the radiofrequency ablation cohort when compared to surveillance. Despite recent studies suggesting the superiority of radiofrequency ablation in reducing progression, diligent endoscopic surveillance may provide similar long-term outcomes.

Ptosis and vertical diplopia after ligation of ethmoidal arteries.

The treatment of epistaxis is well codified, ligation of the ethmoidal arteries being the last resort. We report the case of a 25-year-old pregnant patient, who has had a ligation of the anterior and posterior ethmoidal arteries after a persistent epistaxis. Postoperatively, she presented a complete ptosis and an impaired eye elevation without any visual acuity disorders, evoking a lesion of the upper branch of the common oculomotor nerve (third cranial nerve). The patient totally recovered after 3 months. Anatomical study shows that the upper branch of the third cranial nerve is lying very close to the optic nerve and cannot be affected by surgery without any associated damage of the optic nerve. Thus, a vascular etiology seems to be the best explanation of the complication experienced by our patient. Ligation of the posterior ethmoidal artery should be done with caution.

Comparison of Cancer Diagnoses Between the US Solid Organ Transplant Registry and Linked Central Cancer Registries.

US transplant centers are required to report cancers in transplant recipients to the transplant network. The accuracy and completeness of these data, collected in the Scientific Registry of Transplant Recipients (SRTR), are unknown. We compared diagnoses in the SRTR and 15 linked cancer registries for colorectal, liver, lung, breast, prostate and kidney cancers; melanoma; and non-Hodgkin lymphoma (NHL). Among 187 384 transplants, 9323 cancers were documented in the SRTR or cancer registries. Only 36.8% of cancers were in both, with 47.5% and 15.7% of cases additionally documented solely in cancer registries or the SRTR, respectively. Agreement between the SRTR and cancer registries varied (kappa = 0.28 for liver cancer and kappa = 0.52-0.66 for lung, prostate, kidney, colorectum, and breast cancers). Upon evaluation, some NHLs documented only in cancer registries were identified in the SRTR as another type of posttransplant lymphoproliferative disorder. Some SRTR-only cases were explained by miscoding (colorectal cancer instead of anal cancer, metastases as lung or liver cancers) or missed matches with cancer registries, partly due to recipients' outmigration from catchment areas. Estimated sensitivity for identifying cancer was 52.5% for the SRTR and 84.3% for cancer registries. In conclusion, SRTR cancer data are substantially incomplete, limiting their usefulness for surveillance and research.

Solution-Processed p-Dopant as Interlayer in Polymer Solar Cells.

We report here an original approach to dope the semiconducting polymer-metal interface in an inverted bulk-heterojunction (BHJ) organic solar cell. Solution-processed 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ), is deposited on top of a P3HT:PC61BM layer before deposition of the top electrode. Doping of P3HT by F4-TCNQ occurs after thermally induced diffusion at 100 °C of the latter into the BHJ. Diffusion and doping are evidenced by XPS and UV-vis-NIR absorption. XPS highlights the decrease in Fluorine concentration on top of the BHJ after annealing. In the same time, a charge transfer band attributed to doping is observed in the UV-vis-NIR absorption spectrum. Inverted polymer solar cells using solution-processed F4-TCNQ exhibit power conversion efficiency of nearly 3.5% after annealing. This simple and efficient approach, together with the low annealing temperature required to allow diffusion and doping, leads to standard efficiency P3HT:PC61BM polymer solar cells, which are suitable for printing on plastic flexible substrate.