Lack of Routine Postoperative Labs Not Associated With Complications in Pediatric Perforated Appendicitis.

INTRODUCTION: Postoperative (postop) management of pediatric perforated appendicitis varies significantly, and postop intra-abdominal abscesses (IAA) remain a significant issue. Between 2019 and 2020, our standardized protocol included routine postop labs after an appendectomy for perforated appendicitis. However, given the lack of predictive utility of these routine labs, we discontinued this practice in 2021. We hypothesize that discontinuing routine postop labs will not be associated with an increase in complication rates after an appendectomy for pediatric perforated appendicitis. METHODS: A single-institution, retrospective review of all pediatric appendectomies for perforated appendicitis from January 2019 to December 2021 was conducted at University Hospitals Rainbow Babies and Children's Hospital in Cleveland, Ohio. Data were collected on rate of complications (IAA development, re-admissions, bowel obstructions, superficial surgical site infections, intensive care unit transfers, Clostridium difficile infections, allergic reactions, and transfusions), postop imaging, postop interventions, and length of stay. Statistical analysis was completed using Fisher's exact test and Mann-Whitney U-test. RESULTS: A total of 109 patients (2019-2020 n = 61, 2021 n = 48) were included in the study. All 61 patients from 2019 to 2020 had postop labs compared to only eight patients in 2021. There was no statistically significant difference between the two groups in overall complication rates, but there was a decrease in IAAs reported in 2021 (P = 0.03). There were no statistically significant differences in other complications, postop imaging usage, or postop interventions. The median length of stay was 4.5 d in 2021 compared to 6.0 d in 2019-2020 (P = 0.009). CONCLUSIONS: Discontinuing routine postop labs is not associated with an increase in overall complications rates. Further studies are needed to determine whether routine postop labs can be safely removed in pediatric patients with perforated appendicitis, which would reduce patient discomfort and care costs.

Intraoperative pharmacologic opioid minimisation strategies and patient-centred outcomes after surgery: a scoping review.

BACKGROUND: Postoperative patient-centred outcome measures are essential to capture the patient's experience after surgery. Although a large number of pharmacologic opioid minimisation strategies (i.e. opioid alternatives) are used for patients undergoing surgery, it remains unclear which strategies are most promising in terms of patient-centred outcome improvements. This scoping review had two main objectives: (1) to map and describe evidence from clinical trials assessing the patient-centred effectiveness of pharmacologic intraoperative opioid minimisation strategies in adult surgical patients, and (2) to identify promising pharmacologic opioid minimisation strategies. METHODS: We searched MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases from inception to February 2023. We included trials investigating the use of opioid minimisation strategies in adult surgical patients and reporting at least one patient-centred outcome. Study screening and data extraction were conducted independently by at least two reviewers. RESULTS: Of 24,842 citations screened for eligibility, 2803 trials assessed the effectiveness of intraoperative opioid minimisation strategies. Of these, 457 trials (67,060 participants) met eligibility criteria, reporting at least one patient-centred outcome. In the 107 trials that included a patient-centred primary outcome, patient wellbeing was the most frequently used domain (55 trials). Based on aggregate findings, dexmedetomidine, systemic lidocaine, and COX-2 inhibitors were promising strategies, while paracetamol, ketamine, and gabapentinoids were less promising. Almost half of the trials (253 trials) did not report a protocol or registration number. CONCLUSIONS: Researchers should prioritise and include patient-centred outcomes in the assessment of opioid minimisation strategy effectiveness. We identified three potentially promising pharmacologic intraoperative opioid minimisation strategies that should be further assessed through systematic reviews and multicentre trials. Findings from our scoping review may be influenced by selective outcome reporting bias. STUDY REGISTRATION: OSF - https://osf.io/7kea3.

Lifestyle changes in atrial fibrillation management and intervention.

Atrial fibrillation (AF) is one of the most common arrhythmias in adults, and its continued rise in the United States is complicated by the increased incidence and prevalence of several AF risk factors, such as obesity, physical inactivity, hypertension, obstructive sleep apnea, diabetes mellitus, coronary artery disease, and alcohol, tobacco, or caffeine use. Lifestyle and risk factor modification has been proposed as an additional pillar of AF therapy, added to rhythm control, rate control, and anticoagulation, to reduce AF burden and risk. Although emerging evidence largely supports the integration of lifestyle and risk factor management in clinical practice, randomized clinical trials investigating the long-term sustainability and reproducibility of these benefits remain sparse. The purpose of this review is to discuss potentially reversible risk factors on AF, share evidence for the impact on AF by modification of these risk factors, and then provide an overview of the effects of reversing or managing these risk factors on the success of various AF management strategies, such as antithrombotic, rate control, and rhythm control therapies.

Trends and outcomes associated with intravascular ultrasound use during femoropopliteal revascularization in the Vascular Quality Initiative.

OBJECTIVE: Intravascular ultrasound (IVUS) use in lower extremity interventions is growing in popularity owing to its imaging in the axial plane, superior detail in imaging lesion characteristics, and its enhanced ability to delineate lesion severity and extent compared with catheter angiograms. However, there are conflicting data regarding whether IVUS affects outcomes. The purpose of this study was to assess the effect associated with IVUS implementation in femoropopliteal interventions. METHODS: This retrospective cohort study used Vascular Quality Initiative data. Patients undergoing an index endovascular femoropopliteal revascularization from 2016 to 2021 were included. Patients were differentiated by whether or not IVUS was used to assess the femoropopliteal segment during intervention (no IVUS, IVUS). Propensity score matching, based on preoperative demographics and measures of disease severity was used. Primary outcomes were major amputation-free survival (AFS), femoropopliteal reintervention-free survival (RFS), and primarily patent survival (PPS) at 12 months. RESULTS: IVUS use grew steadily throughout the study period, comprising 0.6% of interventions in 2016 and increasing to 8.2% of interventions by 2021; growth was most dramatic in ambulatory surgical center or office-based laboratory settings where IVUS use grew from 4.4% to 43% to 47% of interventions. In unmatched cohorts, patients receiving interventions using IVUS tended to have lower prevalence of multiple cardiovascular comorbidities (eg, congestive heart failure, hypertension, diabetes, and dialysis dependence) and presented more often with claudication and less often with chronic limb-threatening ischemia (CLTI). Intraoperatively, IVUS was used more often in complex femoropopliteal lesions (Transatlantic Intersociety grade D vs A), and more often in conjunction with stenting and/or atherectomy. IVUS use was associated with improved AFS, but similar RFS and PPS at 12 months. However, in multivariable analysis IVUS was not associated with any of the primary outcomes independently; rather, all outcomes were influenced primarily by CLTI, dialysis dependence, and prior major amputation status; technical outcomes (ie, RFS and PPS loss) were further driven by complexity of lesion (worse in Transatlantic Intersociety grade D vs A lesions) and treatment setting (ie, ambulatory surgical center or office-based laboratory setting associated with increased hazard for RFS and PPS loss). CONCLUSIONS: IVUS implementation in femoropopliteal interventions is growing, with rapid adoption among interventions in ambulatory surgical centers and office-based laboratories. IVUS was not associated with an effect on technical outcomes at 12 months; improvement in major AFS was observed; however, multivariable analysis suggests this finding may be an effect of confounding by multiple factors highly associated with IVUS use, namely, in patients with lower prevalence of CLTI, dialysis dependence, and prior major amputations, thus conveying baseline lower risk for major amputation and death.

Design of Polymeric Carriers for Intracellular Peptide Delivery in Oncology Applications.

In recent decades, peptides, which can possess high potency, excellent selectivity, and low toxicity, have emerged as promising therapeutics for cancer applications. Combined with an improved understanding of tumor biology and immuno-oncology, peptides have demonstrated robust antitumor efficacy in preclinical tumor models. However, the translation of peptides with intracellular targets into clinical therapies has been severely hindered by limitations in their intrinsic structure, such as low systemic stability, rapid clearance, and poor membrane permeability, that impede intracellular delivery. In this Review, we summarize recent advances in polymer-mediated intracellular delivery of peptides for cancer therapy, including both therapeutic peptides and peptide antigens. We highlight strategies to engineer polymeric materials to increase peptide delivery efficiency, especially cytosolic delivery, which plays a crucial role in potentiating peptide-based therapies. Finally, we discuss future opportunities for peptides in cancer treatment, with an emphasis on the design of polymer nanocarriers for optimized peptide delivery.

SCORe: SARS-CoV-2 Omicron Variant RBD-Binding DNA Aptamer for Multiplexed Rapid Detection and Pseudovirus Neutralization.

During the COVID-19 (coronavirus disease 2019) pandemic, several SARS-CoV-2 variants of concern emerged, including the Omicron variant, which has enhanced infectivity and immune invasion. Many antibodies and aptamers that bind the spike (S) of previous strains of SARS-CoV-2 either do not bind or bind with low affinity to Omicron S. In this study, we report a high-affinity SARS-CoV-2 Omicron RBD-binding aptamer (SCORe) that binds Omicron BA.1 and BA.2 RBD with nanomolar KD1. We employ aptamers SCORe.50 and SNAP4.74 in a multiplexed lateral flow assay (LFA) to distinguish between Omicron and wild-type S at concentrations as low as 100 pM. Finally, we show that SCORe.50 and its dimerized form SCOReD can neutralize Omicron S-pseudotyped virus infection of ACE2-overexpressing cells by >70%. SCORe therefore has potential applications in COVID-19 rapid diagnostics as well as in viral neutralization.

Aptamer Sandwich Lateral Flow Assay (AptaFlow) for Antibody-Free SARS-CoV-2 Detection.

The COVID-19 pandemic is among the greatest health and socioeconomic crises in recent history. Although COVID-19 vaccines are being distributed, there remains a need for rapid testing to limit viral spread from infected individuals. We previously identified the SARS-CoV-2 spike protein N-terminal domain (NTD) binding DNA aptamer 1 (SNAP1) for detection of SARS-CoV-2 virus by aptamer-antibody sandwich enzyme-linked immunoassay (ELISA) and lateral flow assay (LFA). In this work, we identify a new aptamer that also binds at the NTD, named SARS-CoV-2 spike protein NTD-binding DNA aptamer 4 (SNAP4). SNAP4 binds with high affinity (<30 nM) for the SARS-CoV-2 spike protein, a 2-fold improvement over SNAP1. Furthermore, we utilized both SNAP1 and SNAP4 in an aptamer sandwich LFA (AptaFlow), which detected SARS-CoV-2 UV-inactivated virus at concentrations as low as 106 copies/mL. AptaFlow costs <$1 per test to produce, provides results in <1 h, and detects SARS-CoV-2 at concentrations that indicate higher viral loads and a high probability of contagious transmission. AptaFlow is a potential approach for a low-cost, convenient antigen test to aid the control of the COVID-19 pandemic.

Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer.

Circulating tumor cells (CTCs) play a fundamental role in cancer progression. However, in mice, limited blood volume and the rarity of CTCs in the bloodstream preclude longitudinal, in-depth studies of these cells using existing liquid biopsy techniques. Here, we present an optofluidic system that continuously collects fluorescently labeled CTCs from a genetically engineered mouse model (GEMM) for several hours per day over multiple days or weeks. The system is based on a microfluidic cell sorting chip connected serially to an unanesthetized mouse via an implanted arteriovenous shunt. Pneumatically controlled microfluidic valves capture CTCs as they flow through the device, and CTC-depleted blood is returned back to the mouse via the shunt. To demonstrate the utility of our system, we profile CTCs isolated longitudinally from animals over 4 days of treatment with the BET inhibitor JQ1 using single-cell RNA sequencing (scRNA-Seq) and show that our approach eliminates potential biases driven by intermouse heterogeneity that can occur when CTCs are collected across different mice. The CTC isolation and sorting technology presented here provides a research tool to help reveal details of how CTCs evolve over time, allowing studies to credential changes in CTCs as biomarkers of drug response and facilitating future studies to understand the role of CTCs in metastasis.

Discovery and Characterization of Spike N-Terminal Domain-Binding Aptamers for Rapid SARS-CoV-2 Detection.

The coronavirus disease 2019 (COVID-19) pandemic has devastated families and disrupted healthcare, economies and societies across the globe. Molecular recognition agents that are specific for distinct viral proteins are critical components for rapid diagnostics and targeted therapeutics. In this work, we demonstrate the selection of novel DNA aptamers that bind to the SARS-CoV-2 spike glycoprotein with high specificity and affinity (<80 nM). Through binding assays and high resolution cryo-EM, we demonstrate that SNAP1 (SARS-CoV-2 spike protein N-terminal domain-binding aptamer 1) binds to the S N-terminal domain. We applied SNAP1 in lateral flow assays (LFAs) and ELISAs to detect UV-inactivated SARS-CoV-2 at concentrations as low as 5×105  copies mL-1 . SNAP1 is therefore a promising molecular tool for SARS-CoV-2 diagnostics.

Strategies to conserve salbutamol pressurized metered-dose inhaler stock levels amid COVID-19 drug shortage.

Essential inhaler medications for patients with respiratory diseases are backordered due to the coronavirus disease of 2019 (COVID-19). In hospitals, there has been a drastic increase in the use of salbutamol pressurized metered-dose inhalers (pMDIs), as well as salbutamol Diskus, leading to a decline in availability and causing interruptions in the supply chain. Patients with asthma are at higher risk of respiratory complications if they are infected with COVID-19. Salbutamol, a short-acting ß-agonist (SABA), could be a life-saving medication during critical conditions. Other short-acting muscarinic antagonists (SAMAs), such as ipratropium pMDI, and combinations of SABA/SAMA, such as Combivent Respimat, are also starting to have supply issues. With the ongoing pandemic, hospitals need to consider conservation strategies to facilitate resource-efficient salbutamol delivery and reduce their waste. In this current opinion, we demonstrate several strategies for avoiding pMDI wastage that can be adopted in both the hospital and community settings. These strategies include reprocessing used or expired pMDIs, using intravenous salbutamol and other short acting inhalers when available, and prescribing maintenance inhalers to prevent over usage of salbutamol pMDIs. We also highlight the important role of physicians and pharmacists in optimizing medication therapies to ensure adequate supplies.

Cytosolic delivery of siRNA by ultra-high affinity dsRNA binding proteins.

Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity. Despite concerns that excessively strong siRNA binding could prevent the discharge of siRNA from its carrier, higher affinity continually led to stronger silencing. We found that this improvement was due to both increased uptake of siRNA into the cell and improved pharmacodynamics inside the cell. Mathematical modeling predicted the existence of an affinity optimum that maximizes silencing, after which siRNA sequestration decreases potency. Our study characterizing the affinity dependence of silencing suggests that siRNA-carrier affinity can significantly affect the intracellular fate of siRNA and may serve as a handle for improving the efficiency of delivery. The two-agent delivery system presented here possesses notable biophysical properties and potency, and provide a platform for the cytosolic delivery of nucleic acids.

Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor.

AIMS: Endothelial-derived epoxyeicosatrienoic acids may regulate vascular tone and are metabolized by soluble epoxide hydrolase enzymes (sEH). GSK2256294 is a potent and selective sEH inhibitor that was tested in two phase I studies. METHODS: Single escalating doses of GSK2256294 2-20 mg or placebo were administered in a randomized crossover design to healthy male subjects or obese smokers. Once daily doses of 6 or 18 mg or placebo were administered for 14 days to obese smokers. Data were collected on safety, pharmacokinetics, sEH enzyme inhibition and blood biomarkers. Single doses of GSK2256294 10 mg were also administered to healthy younger males or healthy elderly males and females with and without food. Data on safety, pharmacokinetics and biliary metabolites were collected. RESULTS: GSK2256294 was well-tolerated with no serious adverse events (AEs) attributable to the drug. The most frequent AEs were headache and contact dermatitis. Plasma concentrations of GSK2256294 increased with single doses, with a half-life averaging 25-43 h. There was no significant effect of age, food or gender on pharmacokinetic parameters. Inhibition of sEH enzyme activity was dose-dependent, from an average of 41.9% on 2 mg (95% confidence interval [CI] -51.8, 77.7) to 99.8% on 20 mg (95% CI 99.3, 100.0) and sustained for up to 24 h. There were no significant changes in serum VEGF or plasma fibrinogen. CONCLUSIONS: GSK2256294 was well-tolerated and demonstrated sustained inhibition of sEH enzyme activity. These data support further investigation in patients with endothelial dysfunction or abnormal tissue repair, such as diabetes, wound healing or COPD.

Aptamers 101: aptamer discovery and in vitro applications in biosensors and separations.

Aptamers are single-stranded nucleic acids that bind and recognize targets much like antibodies. Recently, aptamers have garnered increased interest due to their unique properties, including inexpensive production, simple chemical modification, and long-term stability. At the same time, aptamers possess similar binding affinity and specificity as their protein counterpart. In this review, we discuss the aptamer discovery process as well as aptamer applications to biosensors and separations. In the discovery section, we describe the major steps of the library selection process for aptamers, called systematic evolution of ligands by exponential enrichment (SELEX). We highlight common approaches and emerging strategies in SELEX, from starting library selection to aptamer-target binding characterization. In the applications section, we first evaluate recently developed aptamer biosensors for SARS-CoV-2 virus detection, including electrochemical aptamer-based sensors and lateral flow assays. Then we discuss aptamer-based separations for partitioning different molecules or cell types, especially for purifying T cell subsets for therapeutic applications. Overall, aptamers are promising biomolecular tools and the aptamer field is primed for expansion in biosensing and cell separation.

Lack of the human choline transporter-like protein SLC44A2 causes hearing impairment and a rare red blood phenotype.

Blood phenotypes are defined by the presence or absence of specific blood group antigens at the red blood cell (RBC) surface, due to genetic polymorphisms among individuals. The recent development of genomic and proteomic approaches enabled the characterization of several enigmatic antigens. The choline transporter-like protein CTL2 encoded by the SLC44A2 gene plays an important role in platelet aggregation and neutrophil activation. By investigating alloantibodies to a high-prevalence antigen of unknown specificity, found in patients with a rare blood type, we showed that SLC44A2 is also expressed in RBCs and carries a new blood group system. Furthermore, we identified three siblings homozygous for a large deletion in SLC44A2, resulting in complete SLC44A2 deficiency. Interestingly, the first-ever reported SLC44A2-deficient individuals suffer from progressive hearing impairment, recurrent arterial aneurysms, and epilepsy. Furthermore, SLC44A2null individuals showed no significant platelet aggregation changes and do not suffer from any apparent hematological disorders. Overall, our findings confirm the function of SLC44A2 in hearing preservation and provide new insights into the possible role of this protein in maintaining cerebrovascular homeostasis.

Is fresh-frozen plasma clinically effective? An update of a systematic review of randomized controlled trials.

BACKGROUND: The clinical use of frozen plasma (FP) continues to increase, both in prophylactic and in therapeutic settings. In 2004, a systematic review of all published randomized controlled trials (RCTs) revealed a lack of evidence that supported the efficacy of FP use. This is an update that includes all new RCTs published since the original review. STUDY DESIGN AND METHODS: Trials involving transfusion of FP up to July 2011 were identified from searches of MEDLINE, EMBASE, CINAHL, The Cochrane Library, and the UKBTS/SRI Transfusion Evidence Library. Methodologic quality was assessed. The primary outcome measure was the effect of FP on survival. RESULTS: Twenty-one new trials were eligible for inclusion. These covered prophylactic and therapeutic FP use in liver disease, in cardiac surgery, for warfarin anticoagulation reversal, for thrombotic thrombocytopenic purpura treatment, for plasmapheresis, and in other settings, including burns, shock, and head injury. The largest number of recent RCTs were conducted in cardiac surgery; meta-analysis showed no significant difference for FP use for the outcome of 24-hours postoperative blood loss (weighted mean difference, -35.24 mL; 95% confidence interval, -84.16 to 13.68 mL). Overall, there was no significant benefit for FP use across all the clinical conditions. Only two of the 21 trials fulfilled all the criteria for quality assessment. CONCLUSION: Combined with the 2004 review, 80 RCTs have investigated FP with no consistent evidence of significant benefit for prophylactic and therapeutic use across a range of indications evaluated. There has been little improvement in the overall methodologic quality of RCTs conducted in the past few years.

Student Pharmacists Self-Perceived Confidence in Communication Skills With Healthcare Practitioners Before and After a Seminar Course.

INTRODUCTION: Competent pharmacy practice requires the ability to critically evaluate the medical literature and communicate pharmacotherapy information and recommendations to healthcare practitioners. Given the limited research on how these skills are taught, a seminar course in the third year of the pharmacy curriculum was designed to strengthen these skills and abilities. METHODS: This was a prospective, pre- and post-cohort survey design. Students were informed of the study's intent with participation being voluntary and not affecting their course grade. Students received the same survey at the beginning and end of the semester. The 20-question survey assessed self-perceived confidence in the domains of communication and literature evaluation using a 5-point, Likert-type Strongly Disagree-Strongly Agree Scale. Demographic information and students' previous pharmacy work and internship experience were collected as a part of the survey. Descriptive statistics and Student's t-test were used to assess the research question and comparisons of student demographics. RESULTS: Sixty-eight of a possible 91 students (75% response rate) completed both the pre- and post-survey. There was no statistically significant differences between any of the measured demographics. Overall, students slightly agreed they were confident in their communication and literature evaluation skills in the pre-course evaluation, with communicating drug interactions as the least confident area. Post-course, students were significantly more confident in all but 5 of 20 measured areas. CONCLUSION: The Seminar course resulted in a positive change in students' perception of confidence to communicate with healthcare professionals and ability to evaluate drug literature.

Simultaneous imaging of redox states in dystrophic neurites and microglia at Aß plaques indicate lysosome accumulation not microglia correlate with increased oxidative stress.

The inter-relationship between microglia dynamics and oxidative stress (Ox-stress) in dystrophic neurites (DNs) at Alzheimer's Disease (AD) plaques may contribute to the pathological changes in neurons. We developed new in vivo imaging strategies to combine EGFP expression in microglia with neuronal expression of genetically encoded ratiometric redox sensors (rogRFP2 or roGFP1), and immunohistochemistry to investigate how microglia influence Ox-stress at amyloid plaques in 5xFAD AD mice. By simultaneously imaging microglia morphology and neuronal Ox-stress over time in vivo and in fixed brains we found that microglia preferentially enwrapped DNs exhibiting the greatest degree of Ox-stress. After microglia were partially depleted with the CSF1 receptor antagonist PLX3397, Ox-stress in DNs increased in a manner that was inversely correlated to the extent of coverage of the adjacent Aß plaques by the remaining microglia. These data suggest that microglia do not create Ox-stress at Aß plaques but instead create protective barriers around Aß plaques possibly reducing the spread of Aß. Intracranial injection of Aß was sufficient to induce neuronal Ox-stress suggesting it to be the initial trigger of Ox-stress generation. Although Ox-stress is increased in DNs, neuronal survival is enhanced following microglia depletion indicating complex and multifactorial roles of microglia with both neurotoxic and neuroprotective components. Increased Ox-stress of DNs was correlated with higher LAMP1 and ubiquitin immunoreactivity supporting proposed mechanistic links between lysosomal accumulation in DNs and their intrinsic generation of Ox-stress. Our results suggest protective as well as neurotoxic roles for microglia at plaques and that the generation of Ox-stress of DNs could intrinsically be generated via lysosomal disruption rather than by microglia. In Brief: Simultaneous imaging of microglia and neuronal Ox-stress revealed a double-edged role for microglia in 5xFAD mice. Plaque associated microglia were attracted to and enwrapped Aß plaques as well as the most highly oxidized DNs. After partial depletion of microglia, DNs were larger with greater levels of Ox-stress. Despite increased Ox-stress after microglia removal neuronal survival improved. Greater Ox-stress was correlated with increased levels of LAMP1 and ubiquitin thereby linking lysosome accumulation and Ox-stress in DNs.

Subpalpebral Antibiotic Lavage as Safe, Emergent, and Cost-Effective Management of Acute Infectious Keratitis Related to Contact Lens Overwear: Case Report and Literature Review.

PURPOSE: The aim of this study is to describe the technique of subpalpebral antibiotic lavage (SAL), which is a highly therapeutic, efficient, and cost-effective method for managing severe bacterial keratitis. METHODS: This case report describes a 26-year-old woman with severe bacterial keratitis in the right eye due to contact lens overwear, with progressive corneal thinning, a hypopyon, impending perforation, and marked visual loss to perception of light despite treatment with intensive topical antibiotics. This was managed with SAL that involves the insertion of a cannula transcutaneously into the upper conjunctival fornix to provide continuous antibiotic irrigation of the ocular surface. RESULTS: By 11 weeks after presentation, the cornea and anterior chamber appeared clinically quiescent, and visual acuity improved to 20/40 corrected in the right eye. CONCLUSIONS: Bacterial keratitis is a potentially blinding condition for which contact lens wear is an important risk factor. Most cases are successfully managed with topical medications; however, in cases of treatment failure, a second-line approach such as SAL can be sight-saving. SAL uses readily available equipment for the delivery of high concentrations of antibiotics to the ocular surface, thus increasing therapeutic efficacy and reducing nursing staff workload. Despite its advantages, the literature reveals apparent underutilization of this technique.