Quantification and Predictors of Visual Field Variability in Healthy, Glaucoma Suspect, and Glaucomatous Eyes Using SITA-Faster.

PURPOSE: The newly released Swedish Interactive Thresholding Algorithm (SITA)-Faster (SFR) has significantly shorter testing durations compared with older SITA algorithms, but its variability is uncertain. This study quantified and established threshold limits of test-retest variability across the 24-2 test grid using SFR. DESIGN: Cross-sectional study with prospective longitudinal arm. PARTICIPANTS: 1426 eyes of 787 patients with healthy, suspected glaucoma, or manifest glaucoma eyes from hospital- and university- eye clinics. METHODS: Two SFR tests per eye at a baseline visit and at two follow-up visits. MAIN OUTCOME MEASURES: Pointwise variability measured by test-retest difference in pointwise sensitivity between tests one and two, mean global variability (test-retest variance) measured by average of pointwise variability for each participant, global sensitivity, and reliability indices of each eye. RESULTS: Of the 1426 eyes, 540 eyes (37.9%) had a diagnosis of glaucoma, 753 eyes (52.8%) were suspected of having glaucoma, and the remaining 133 eyes (9.3%) were healthy. Of 74 152 pointwise sensitivities obtained, the mean test-retest difference was 2.17 ± 2.9 dB, whereas the mean test-retest variance for each participant was 2.17 ± 1.2 dB. Pointwise and global variability increased with worsening threshold sensitivity and (MD), respectively, and was greater for peripheral compared with central test locations. In the longitudinal cohort, no significant difference in mean test-retest variance was found across the 3 visits (mean variability, 2.10 dB vs. 2.16 dB vs. 2.16 dB at visits F0 vs. F1 vs. F2; P = 0.53, repeated-measures analysis of variance). Baseline MD (-0.19 dB; 95% CI, -0.22 to 0.16 dB; P < 0.0001) and abnormally high sensitivity on glaucoma hemifield test (1.14 dB; 95% CI, 0.78-1.51 dB; P < 0.0001) were significantly associated with increased variability. Finally, test-retest MD showed minimal change around the recommended 15% false-positive cutoff threshold. CONCLUSIONS: The variability of SFR increases with worsening threshold sensitivity, is stable over time, and is greater for peripheral compared with central test locations. Worse baseline MD and abnormally high sensitivity are significant predictors of increased variability. A cutoff of 15% in false-positive results may be inappropriate as a threshold for judging test reliability in SFR. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Frontloading visual field tests detect earlier mean deviation progression when applied to real-world-derived early-stage glaucoma data.

PURPOSE: To examine the diagnostic accuracy of performing two (frontloaded) versus one (clinical standard) visual field (VF) test per visit for detecting the progression of early glaucoma in data derived from clinical populations. METHODS: A computer simulation model was used to follow the VFs of 10,000 glaucoma patients (derived from two cohorts: Heijl et al., Swedish cohort; and Chauhan et al., Canadian Glaucoma Study [CGS]) over a 10-year period to identify patients whose mean deviation (MD) progression was detected. Core data (baseline MD and progression rates) were extracted from two studies in clinical cohorts of glaucoma, which were modulated using SITA-Faster variability characteristics from previous work. Additional variables included follow-up intervals (six-monthly or yearly) and rates of perimetric data loss for any reason (0%, 15% and 30%). The main outcome measures were the proportions of progressors detected. RESULTS: When the Swedish cohort was reviewed six-monthly, the frontloaded strategy detected more progressors compared to the non-frontloaded method up to years 8, 9 and 10 of follow-up for 0%, 15% and 30% data loss conditions. The time required to detect 50% of cases was 1.0-1.5 years less for frontloading compared to non-frontloading. At 4 years, frontloading increased detection by 26.7%, 28.7% and 32.4% for 0%, 15% and 30% data loss conditions, respectively. Where both techniques detected progression, frontloading detected progressors earlier compared to the non-frontloaded strategy (78.5%-81.5% and by 1.0-1.3 years when reviewed six-monthly; 81%-82.9% and by 1.2-2.1 years when reviewed yearly). Accordingly, these patients had less severe MD scores (six-monthly review: 0.63-1.67 dB 'saved'; yearly review: 1.10-2.87 dB). The differences increased with higher rates of data loss. Similar tendencies were noted when applied to the CGS cohort. CONCLUSIONS: Frontloaded VFs applied to clinical distributions of MD and progression led to earlier detection of early glaucoma progression.

Rationale and Trial Protocol for a Double-Blinded Randomized Controlled Trial to assess the Impact of a Concomitant Crural Repair during Laparoscopic Sleeve Gastrectomy in Patients with a Lax Gastroesophageal Junction without Frank Hiatal Hernia (REPAIR trial protocol).

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is associated with postoperative gastroesophageal reflux disease (GERD) and erosive esophagitis (EE). The role of crural repair during LSG is still controversial. The preoperative laxity of the gastroesophageal junction (GEJ), graded by the Hill's classification, is more predictive for postoperative GERD and EE after LSG than the presence of a hiatal hernia seen on endoscopy. Thus, the authors hypothesize that a concomitant crural repair in a specific subgroup of patients with a lax GEJ (Hill's III) may reduce the incidence of postoperative GERD and EE. METHODS: A double-blinded, randomized controlled trial of patients with Hill's III GEJ undergoing LSG will be randomized to a concomitant crural repair (experimental) versus LSG alone (control). Primary outcome measures will be presence of EE at 1-year. Secondary outcome measures will include proton pump inhibitor use, postoperative complications, operative time, blood loss, quality of life, GERD and gastrointestinal symptoms. CONCLUSION: Conflicting crural repair results may be explained by differences in preoperative GEJ laxity. Patients with a frank hiatal hernia and patulous GEJ (Hill's IV) have a very high, while patients with an apposed GEJ (Hill's I, Hill's II) have a low incidence of postoperative GERD and EE respectively. Thus, the authors hypothesize that patients with a lax GEJ without frank hiatal hernia (Hill's III), might benefit from a crural repair. This study results can potentially highlight the clinical importance of preoperative endoscopic evaluation of the GEJ in all patients planned for LSG, to determine which subgroup patients may benefit from a crural repair. (Clinicaltrials.gov: NCT05330910, Registered 15-April-2022).

Skin and Bone: Intact Fish Skin to Reconstruct Traumatic Orbital Floor and Wall Defects.

Orbital reconstruction following orbital trauma, tissue sacrifice from cancer resection, or other tissue loss poses a unique challenge for surgeons. Factors to consider include the patient's systemic health status, potential for adjuvant radiation, final composition, and strength of the graft, infection risk, graft rejection, status of visual function, and cosmetic outcome. In settings where a permanent artificial implant is avoided due to exposure or infection risk, potential tissue utilized includes xenografts, allografts, and autografts-each with variable benefits and drawbacks, depending on the surgical goals of the repair. We describe a case of orbital reconstruction after a gunshot wound to the left orbit using tri-layer Kerecis (decellularized intact North-Atlantic cod fish skin) with excellent globe position and maintenance of ocular motility.

Physical Activity Trends Among Adults in a National Mobile Health Program: A Population-Based Cohort Study of 411,528 Adults.

Physical inactivity is a global public health challenge, and effective, large-scale interventions are needed. We examined the effectiveness of a population-wide mobile health (mHealth) intervention in Singapore, National Steps Challenge Season 3 (NSC3) and 2 booster challenges (Personal Pledge and Corporate Challenge). The study includes 411,528 participants. We used regression discontinuity design and difference-in-difference with fixed-effects regression to examine the association of NSC3 and the additional booster challenges on daily step counts. Participants tended to be female (58.5%), with an average age of 41.5 years (standard deviation, 13.9) and body mass index (weight (kg)/height (m)2) of 23.8 (standard deviation, 4.5). We observed that NSC3 was associated with a mean increase of 1,437 steps (95% confidence interval (CI): 1,408, 1,467) per day. Enrollments in Personal Pledge and Corporate Challenge were associated with additional mean increases of 1,172 (95% CI: 1,123, 1,222) and 896 (95% CI: 862, 930) steps per day, respectively. For NSC3, the associated mean increase in the step counts across different sex and age groups varied, with greater increases for female participants and those in the oldest age group. We provide real-world evidence suggesting that NSC3 was associated with improvements in participants' step counts. Results suggest NSC3 is an effective and appealing population-wide mHealth physical activity intervention.

Evaluation of the Consistency of Glaucomatous Visual Field Defects Using a Clustered SITA-Faster Protocol.

PURPOSE: Frontloading SITA-Faster (SFR) visual fields (2 tests per eye on the same visit) has been shown to provide repeatable perimetric data at minimal time cost. This study reports the outcomes of using frontloaded SFR in the evaluation of pointwise visual field (VF) defects in a cohort of patients with glaucoma when transitioned from SITA-Standard (SS). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: A total of 144 eyes of 91 patients with confirmed or suspected glaucoma who had an SS test on a previous visit. METHODS: Two SFR tests (T1, T2) per eye on the same visit. MAIN OUTCOME MEASURES: Global sensitivity, reliability indices, and pointwise deviation map probability scores from the pattern deviation grid of each patient were compared across the 3 sequential tests to evaluate the consistency of VF defects. RESULTS: The mean age was 68.6 years, and 79.2% of patients had a diagnosis of glaucoma. There was no significant difference in mean deviation (MD) across the 3 tests (-5.83 decibels [dB], -5.28 dB, and -5.71 dB in SS, SFR1, and SFR2, respectively, repeated-measures analysis of variance [ANOVA], P = 0.48). The frontloaded SFR tests provided repeatable VFs that confirmed existing pointwise data on the SS in 4661 (62.3%) locations, reversed an SS defect in 614 (8.2%) locations, and demonstrated a new repeatable defect in 406 (5.4%) locations of the pattern deviation grid. A new defect of at least 3 contiguous points was identified in 20.1% of eyes. The non-repeatable points on the 2 SFR tests displayed no significant difference in the distribution of defect/nondefect points based on test order or peripheral versus central locations. There was no significant difference in the rate of obtaining at least 1 reliable test result between SS and the frontloaded SFR T1 and T2 (P = 0.77). Test duration significantly decreased from SS to SFR1/2 (379 vs. 160 vs. 158 seconds, P < 0.0001). CONCLUSIONS: Frontloading SFR tests can provide repeatable data for the evaluation of the consistency of pattern deviation defects in glaucoma, with no observable decline in performance from test fatigue. This is achieved at equivalent duration and reliability as a single SS test. Frontloading SFR may be helpful in increasing testing frequency/quantity to meet recommended guidelines for progression analysis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Pepsin in saliva for the diagnosis of erosive esophagitis post-sleeve gastrectomy: a prospective observational study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become the preferred bariatric procedure in many countries. However, new onset erosive esophagitis (EE) is a major shortcoming. Current recommendation is esophago-gastro-duodenoscopy (EGD) should be performed routinely at 1 year and subsequently every 2-3 years to enable the early detection of Barrett's or esophageal adenocarcinoma. This would put significant strains on resources and costs of bariatric program. Our study assesses the association between and diagnostic value of salivary pepsin concentration and endoscopically proven EE in post-LSG patients as a surrogate for EGD. METHODS: Twenty patients on routine post-LSG endoscopy between June and September 2022 were recruited for this correlational pilot study. Under supervision, fasting and post-prandial saliva sample was collected and analyzed by Peptest lateral flow device. EGD examinations were performed, and patients completed a validated 25-item QoLRAD questionnaire. RESULTS: We found a significant correlation between positive endoscopy findings of EE and salivary pepsin concentrations. The normal group had a lower mean fasting pepsin level (13.13 ng/mL ± 18.97) versus the EE-group (90.55 ng/mL ± 81.28, p = 0.009) and lower mean post-prandial pepsin level (30.50 ng/mL ± 57.72) versus the EE-group (135.09 ng/mL ± 130.17, p = 0.02). The predictive probabilities from the binary regression of fasting and post-prandial pepsin concentrations yield AUC of 0.955 ± 0.044 (95% CI 0.868 to 1.000, p < 0.001). CONCLUSION: Our study distinctively identified salivary pepsin to have excellent sensitivity and negative predictive value in EE, potentially useful to preclude the need for post-LSG EGD in asymptomatic patients with low salivary pepsin.

Cost-savings of short stay sleeve gastrectomy and walk-in hydration clinic versus conventional inpatient care.

OBJECTIVE: We aim to evaluate the cost-saving of the short stay ward (SSW) versus conventional inpatient care following sleeve gastrectomy (LSG). We also compared the readmission rates pre- and post-inception of the intravenous hydration clinic and analyzed the cost-savings. METHODS: Patients who underwent LSG between December 2021 to March 2022 with SSW care were compared with standard inpatient care. Total costs were analyzed using univariate analysis. With a separate cohort of patients, 30-day readmission rates in the 12-months preceding and following implementation of the IV hydration clinic and associated cost-savings were evaluated. RESULTS: After matching on the propensity score to within ± 0.1, 20-subjects pairs were retained. The total cost per SSW-subject was significantly lower at $13,647.81 compared to $15,565.27 for conventional inpatient care (p = 0.0302). Lower average ward charges ($667.76 vs $1371.34, p < 0.0001), lower average daily treatment fee per case ($235.68 vs $836.54, p < 0.0001), and lower average laboratory investigation fee ($612.31 vs $797.21, p < 0.0001) accounted for the difference in costs between the groups. Thirty-day readmission rate reduced from 8.9 to 1.8% after implementation of the hydration clinic (p < 0.01) with decreased 30-day readmission cost (S$96,955.57 vs. S$5910.27, p < 0.01). CONCLUSION: SSW for LSG is cost-effective and should be preferred to inpatient management. Walk-in hydration clinics significantly reduced readmission rates and result in tremendous cost-savings.

Prenatal diagnosis of hypoplastic left heart syndrome on ultrasound using artificial intelligence: How does performance compare to a current screening programme?

BACKGROUND: Artificial intelligence (AI) has the potential to improve prenatal detection of congenital heart disease. We analysed the performance of the current national screening programme in detecting hypoplastic left heart syndrome (HLHS) to compare with our own AI model. METHODS: Current screening programme performance was calculated from local and national sources. AI models were trained using four-chamber ultrasound views of the fetal heart, using a ResNet classifier. RESULTS: Estimated current fetal screening programme sensitivity and specificity for HLHS were 94.3% and 99.985%, respectively. Depending on calibration, AI models to detect HLHS were either highly sensitive (sensitivity 100%, specificity 94.0%) or highly specific (sensitivity 93.3%, specificity 100%). Our analysis suggests that our highly sensitive model would generate 45,134 screen positive results for a gain of 14 additional HLHS cases. Our highly specific model would be associated with two fewer detected HLHS cases, and 118 fewer false positives. CONCLUSION: If used independently, our AI model performance is slightly worse than the performance level of the current screening programme in detecting HLHS, and this performance is likely to deteriorate further when used prospectively. This demonstrates that collaboration between humans and AI will be key for effective future clinical use.

Five-year corneal cross-linking outcomes: A Save Sight Keratoconus Registry Study.

BACKGROUND: We aimed to determine the long-term outcomes of epithelium-off cross-linking (CXL) in keratoconus patients. METHODS: An observational registry study from 41 centres across 5 countries was carried out. Primary outcomes included the mean change in visual acuity (VA), Kmax, K2, and thinnest corneal thickness (TCT) at 1-5 years. Secondary outcomes included the percentage of eyes with worsening, stable and improving outcomes. RESULTS: There were 976 eyes of 794 patients with 1-year of complete follow-up, 501 eyes with 2-years, 355 with 3-years, 235 with 4-years and 162 with 5-years. There was a significant improvement in mean VA from baseline by 3.7 logMAR letters (p < 0.001) in year 1, and 6.9 (p < 0.001) in year 5. Mean Kmax decreased by 1.2 dioptres (D; p < 0.01) in year 1. During subsequent years the Kmax flattening appeared sustained but this was not statistically significant. K2 flattened significantly from baseline in year 1 and then remained stable. At 1 year, 4.1% patients were poor responders to CXL in terms of VA, losing ≥15 letters. The proportion of the poor responders remained unchanged: 4.9% at 5-years. The proportion of poor responders in terms of Kmax remained similar: 5.9% steepening by ≥2D at 1-year and 7.5% at 5-years. The proportion of K2 poor responders remained stable with 4.7% steepening by ≥2D at 1-year and 5.8% at 5-years. CONCLUSIONS: Cross-linking is effective at stabilising keratoconus up to 5 years in most patients. However, a small proportion of eyes failed to stabilise and had reduced vision.

Methicillin-resistant Staphylococcus aureus-associated orbital cellulitis: a case series.

PURPOSE: In recent years, methicillin-resistant Staphylococcus aureus (MRSA) orbital cellulitis (OC) has drawn increasing clinical and public health concern. We present a case series of MRSA OC encountered at four Australian tertiary institutions. METHODS: A multi-centre retrospective case series investigating MRSA OC in Australia from 2013 to 2022. Patients of all ages were included. RESULTS: Nine cases of culture-positive non-multi-resistant MRSA (nmMRSA) OC were identified at four tertiary institutions across Australia (7 male, 2 female). Mean age was 17.1 ± 16.7 years (range 13-days to 53-years), of which one was 13 days old, and all were immunocompetent. Eight (88.9%) patients had paranasal sinus disease, and seven (77.8%) had a subperiosteal abscess. Four (44.4%) had intracranial extension, including one (11.1%) case which was also complicated by superior sagittal sinus thrombosis. Empirical antibiotics, such as intravenous (IV) cefotaxime alone or IV ceftriaxone and flucloxacillin, were commenced. Following identification of nmMRSA, targeted therapy consisting of vancomycin and/or clindamycin was added. Nine (100%) patients underwent surgical intervention. Average hospital admission was 13.7 ± 6.9 days (range 3-25 days), with two patients requiring intensive care unit (ICU) admission due to complications related to their orbital infection. All patients had favourable prognosis, with preserved visual acuity and extraocular movements, following an average follow-up period of 4.6 months (range 2-9 months). CONCLUSION: NMMRSA OC can follow an aggressive clinical course causing severe orbital and intracranial complications across a wide demographic. However, early recognition, initiation of targeted antibiotics and surgical intervention when required can effectively manage these complications and achieve favourable visual outcomes.

Expert Consensus on the Use of Teprotumumab for the Management of Thyroid Eye Disease Using a Modified-Delphi Approach.

BACKGROUND: Teprotumumab is the first treatment for thyroid eye disease (TED), a debilitating autoinflammatory condition, approved by the Food and Drug Administration in the United States, which reduces proptosis and improves quality of life. In the absence of guidelines, clinical recommendations were developed for using teprotumumab in patients with TED in the United States. METHODS: A 3-round modified-Delphi panel was conducted between October 2020 and February 2021 with experts in the management of patients with TED. Key areas regarding the use of teprotumumab were investigated, including eligible patient populations, concomitant treatments, and assessment of response and adverse events. This used 2 survey rounds via an online questionnaire, where statements were scored using 9-point Likert scales. Statements with conflict were included in the third round, involving a consensus meeting via videoconference. RESULTS: Consensus was obtained for all statements (n = 75); of which, 56% were revised to enable agreement of the group. The consensus meeting provided agreement regarding which populations should receive teprotumumab therapy, including all adult patients with TED with a clinical activity score of ≥4. Treatment with teprotumumab can also be considered for TED patients displaying the following characteristics: a CAS of <3, lid retraction of ≥2, and mild or early optic neuropathy with close clinical observation. Further recommendations included suitability of treatment for those beyond 16 months following the initial diagnosis of TED, low CAS concomitant treatment with steroids in some cases, retreatment for those who have relapses, and finally a recommendation to continue therapy for all 8 infusions despite the lack of response by the fourth infusion. CONCLUSIONS: This work constitutes the first consensus on guidelines for the use of teprotumumab. The modified Delphi approach involved physicians with significant experience with the clinical use of teprotumumab, and recommendations were based on current evidence.

Do Orbital Implants Differ in Complication Rates: A Retrospective Study of 88 Patients, and an Argument for Cost-Effective Practices in the Face of Rising Health Care Costs.

Operative repair of orbital fractures utilizes implants constructed of a plethora of materials that vary in cost. Surgeon preference as well as fracture complexity may dictate the implant chosen. In this study, we retrospectively compared the complication rates of the four most common types of implants utilized at our institution. We found no significant difference in complication rates in our sample of 88 patients. Additionally, the least expensive implant was as effective as the most expensive implant in addressing isolated orbital blowout fractures. This situation is not unique to the field of oculoplastics. As evidenced from published literature in other areas of surgery, from orthopaedics to orthodontics, cheaper alternatives often afford similar outcomes as more expensive options. We herein argue that a cost-effective approach should be considered while still allowing for high quality of care, in the face of rising health care costs and health disparities in America.

Systematic Review and Meta-Analysis of Prophylactic Transarterial Embolization for High-Risk Bleeding Peptic Ulcer Disease.

The present systematic review determined the role of transarterial embolization (TAE) as a prophylactic treatment in bleeding peptic ulcers after initial successful endoscopic hemostasis. PubMed and Ovid Medline databases were searched from inception until July 2019 for studies that included patients deemed high-risk based on Forrest Classification, Rockall score ≥ 5, or endoscopic evaluation in addition to those who underwent prophylactic TAE after initial successful endoscopic hemostasis. Meta-analysis was performed to compare patients who underwent endoscopic therapy (ET) and TAE with those who underwent ET alone. The primary outcomes measured included rates of rebleeding, reintervention, and 30-day mortality. Secondary outcome measures evaluated length of hospitalization, technical success rates, and complications associated with TAE. Of 916 publications, 5 were eligible for inclusion; 310 patients with high-risk peptic ulcer bleeding underwent prophylactic TAE, and 255 were compared against a control group of 580 patients that underwent standard treatment with ET alone. Patients who underwent ET with TAE had lower 30-day rebleeding rates (odds ratio [OR], 0.35; 95% confidence interval [CI] 0.15-0.85; P = .02; I2 = 50%). The ET with TAE group had a lower 30-day mortality rate (OR, 0.28; 95% CI, 0.10-0.83; P = .02; I2 = 58%). There was no difference in pooled reintervention rates (OR, 0.68; 95% CI, 0.43-1.08; P = .10; I2 = 0%) and length of hospitalization (mean difference, -0.32; 95% CI, -1.88 to 1.24; P = .69; I2 = 0%). Technical success rate of prophylactic TAE was 90.5% (95% CI, 83.09-97.98; I2 = 75.9%). Pooled proportion of overall complication rate was 0.18% (95% CI, 0.00-1.28; I2 = 0%). Prophylactic TAE has lower rebleeding and mortality with a good success rate and low complications. Prophylactic TAE after primary ET may be recommended for selected patients with high-risk bleeding ulcers; however, further studies should be performed to establish this as a routine tool in patients with bleeding peptic ulcer disease.

Natural orifice transluminal endoscopic one-anastomosis gastric bypass: a feasibility study using porcine model.

INTRODUCTION: Endoscopic bariatric therapies (EBT) are emerging as effective therapies in the management of overweight patient with or without metabolic syndrome. Unfortunately most procedures only restrict the gastric volume without altering the underlying metabolism which is seen in surgical patients. The aim of this study was to investigate the feasibility and limitations of a natural orifice trans-luminal endoscopic surgery (NOTES) one anastomosis gastric bypass (OAGB). METHODS: NOTES OAGB was performed in three porcine models. The steps of the procedure can be divide as follows: (1) Endoscopic sleeve gastroplasty. (2) Trans-gastric access to peritoneal cavity. (3) Identification of a loop of jejunum. (4) Introduction of the jejunal loop into the stomach. (5) Creation of the gastro-jejunostomy with lumen-apposing metal stent (LAMS). (6) Closure of gastric pylorus with overstitch system. RESULTS: All the animals underwent successful NOTES of OAGB. The mean weight for the animals was 34.3 kg (32-37 kg). The mean procedure time was 250 min (300 min for first animal and 180 min for third animal). The average bypassed bilio-pancreatic limb was 98 cm (range 65-130 cm). CONCLUSIONS: This study has provided proof-of-principle in a preclinical model that a NOTES approach can be used to perform OAGB and, therefore, merits additional evaluation and consideration.

Fight bacteria with bacteria: Bacterial membrane vesicles as vaccines and delivery nanocarriers against bacterial infections.

Bacterial membrane vesicles (MVs) are particles secreted by bacteria with diameter of 20-400 nm. The pathogen-associated molecular patterns (PAMPs) present on the surface of MVs are capable of activating human immune system, leading to non-specific immune response and specific immune response. Due to the immunostimulatory properties and proteoliposome nanostructures, MVs have been increasingly explored as vaccines or delivery systems for the prevention and treatment of bacterial infections. Herein, the recent progresses of MVs for antibacterial applications are reviewed to provide an overview of MVs vaccines and MVs-related delivery systems. In addition, the safety issues of bacterial MVs are discussed to demonstrate their potential for clinical translation. In the end of this review, the challenges of bacterial MVs as vaccines and delivery systems for clinical applications are highlighted with the purpose of predicting future research directions in this field.

Platinum-based regimens versus cetuximab in definitive chemoradiation for human papillomavirus-unrelated head and neck cancer.

For patients ineligible for cisplatin with definitive radiotherapy (CP-CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), concurrent cetuximab (C225-RT) is a popular substitute. Carboplatin-based chemoradiation (CB-CRT) is another option; however, relative efficacies of CP-CRT, CB-CRT and C225-RT are unclear, particularly in the human papillomavirus (HPV)-unrelated population. We identified 316 patients with stage III-IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225-RT (N = 61), CB-CRT (N = 74) or CP-CRT (N = 181). Kaplan-Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3-year cumulative incidences for CP-CRT, CB-CRT and C225-RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan-Meier estimates for 3 year OS were: CP-CRT: 71%; CB-CRT: 59% and C225-RT: 54%; p = 0.0094. CP-CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203-0.557, p < 0.01) and CB-CRT (HR 0.279; 95% CI 0.141-0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP-CRT (HR 0.548; 95% CI 0.355-0.845, p < 0.01) and CB-CRT (HR 0.549; 95% CI 0.334-0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB-CRT group compared to C225-RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB-CRT group compared to C225-RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB-CRT is an effective alternative to CP-CRT in HPV-unrelated LA-HNSCC with superior locoregional control and OS compared to C225-RT.

Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non-alcoholic fatty liver disease (NAFLD). We investigated the associations between serum and faecal BAs, gut microbiome and fibrosis in patients with and without NAFLD and examined the impact of diet and alcohol consumption on these relationships. METHODS: Adult patients (n = 122) underwent liver biopsy and BAs characterization by high-performance liquid chromatography/mass spectrometry. Gut microbiome composition was analysed using next-generation 16S rRNA sequencing. Diet and alcohol intake were determined by 3-day food diary. RESULTS: Serum and faecal BA concentrations increased progressively among non-NAFLD controls (n = 55), NAFLD patients with no/mild fibrosis (F0-2, n = 58) and NAFLD with advanced fibrosis (F3/4, n = 9). Progressive increases in serum BAs were driven by primary conjugated BAs including glycocholic acid [GCA] and secondary conjugated BAs. In contrast, faecal BA increase was driven by secondary unconjugated BAs (predominately deoxycholic acid [DCA]). Serum GCA levels and faecal DCA levels correlated with the abundance of Bacteroidaceae and Lachnospiraceae, and stool secondary BAs with an unclassifiable family of the order Bacteroidales (Bacteroidales;other). These bacterial taxa were also associated with advanced fibrosis. Modest alcohol consumption was positively correlated with faecal DCA levels and relative abundance of Lachnospiracaea and Bacteroidales;other. CONCLUSIONS: Higher serum and faecal BA levels are associated with advanced fibrosis in NAFLD. Specific gut bacteria link alterations in BA profiles and advanced fibrosis, and may be influenced by low-level alcohol consumption.

Motion compensation using principal component analysis and projection onto dipole fields for abdominal magnetic resonance thermometry.

PURPOSE: High intensity focused ultrasound (HIFU) has the potential to locally and non-invasively treat cancer with fewer side effects than alternative therapies. However, motion and tissue heterogeneity in the abdomen can compromise the HIFU focus and confound current thermometry methods. METHODS: The proposed thermometry method combines principal component analysis (PCA), as a multi-baseline technique, and projection onto dipole fields (PDF), as a near-referenceless method. PCA forgoes tracking tools by projecting incoming images onto a subspace spanning the motion history. PDF is subsequently used to synthesize the naturally feasible components of the residual phase using a magnetic dipole model. This leaves only the phase shifts that are induced by HIFU. RESULTS: With in vivo measurements, in porcine and human kidneys, the mean pixel-wise temperature SD was 0.86 ± 0.41°C in selected regions of interest (ROIs) across all data sets, without any user-interaction or supplementary tracking tools. This is an improvement over a benchmark hybrid method, which scored 1.36 ± 1.20°C on the same data. Uncorrected subtraction of the data yielded a score of 3.02 ± 2.87°C. CONCLUSION: The PCA-PDF hybrid method achieves superior artifact correction by exploiting the motion history and intrinsic magnetic susceptibility of the underlying tissue.

Clinical Registries in Ophthalmology.

TOPIC: Clinical registries in ophthalmology. CLINICAL RELEVANCE: In recent years, advancements in digital technology and increasing use of electronic medical records in health systems have led to the dramatic growth in large clinical data sets. Clinical data registries are organized systems that collect data on patients diagnosed with a disease or condition or who undergo a certain procedure. METHODS: A search of the PUBMED database was conducted in January 2018 for clinical registries in ophthalmology. RESULTS: Ninety-seven clinical eye registries were found, with significant growth in numbers in the last 4 decades. The most common conditions captured were blindness or low vision, corneal transplantation, glaucoma, and cataract surgery. Most registries originate in the European region, North America, and Australia. Nine registries had multinational coverage, whereas 48 were national registries. As the numbers and scope of clinical registries have expanded, valuable observational data have been used to study real-world clinical outcomes in healthcare quality measurement and improvement and to develop new guidelines and standards. Pertinent areas of its use include studying treatments and outcomes in cataract surgery, corneal transplantation, and macular degeneration. CONCLUSIONS: The use of clinical registries for quality improvement and research has grown significantly in the last few decades, and this trend will continue as information technology infrastructures develop.