A sensitive LC-MS/MS assay to quantitate free payload Aur0101 from ADC PYX-201 in rat and monkey plasma.

Aim: Aur0101 is a cytotoxic and small-molecule microtubule depolymerizing agent, and is the payload conjugated to antibody-drug conjugate PYX-201. Developing and validating a sensitive bioanalytical method to quantitate Aur0101 was novel and crucial in preclinical PYX-201 studies. Materials & methods: Reference standard Aur0101 and its stable isotope labelled internal standard Aur0101-d8 were used in this LC-MS/MS method. Results: This sensitive assay was validated at a lower limit of quantitation of 15 pg/ml and successfully applied to support preclinical rat and monkey toxicology studies. Preclinical plasma toxicokinetic parameters were presented. Conclusion: A sensitive and robust LC-MS/MS assay was validated for Aur0101 in rat and monkey plasma.

Quantitation of total antibody (tAb) from antibody drug conjugate (ADC) PYX-201 in rat and monkey plasma using an enzyme-linked immunosorbent assay (ELISA) and its application in preclinical studies.

PYX-201 is an investigative ADC oncology drug composed of a monoclonal human immunoglobulin G (IgG) antibody targeting the extra domain B splice variant of fibronectin (EDB + FN) conjugated to an auristatin payload through a cleavable linker. Effective measurement of PYX-201 tAb is the key to ADC drug PYX-201 preclinical pharmacokinetics (PK) assessment. PYX-201 monoclonal antibody (mAb) was used as the reference standard, goat anti-human IgG polyclonal antibody (pAb) or rabbit anti-human Kappa light chain mAb was employed as the capture antibody, and mouse mAb or goat pAb anti-human IgG the crystallizable fragment (Fc) (horseradish peroxidase (HRP)) was utilized as the detection antibody in this ELISA. This assay was validated with a dynamic range 250 - 10,000 ng/mL and 250 - 6000 ng/mL in rat and monkey K2EDTA plasma, respectively. PYX-201 tAb bioanalytical ELISA assay was reported for the first time in any biological matrix. This is the first time for a bioanalytical method to be validated for a tAb from an ADC drug targeting EDB + FN in any biological matrix.

Quantification of antibody-drug conjugate PYX-201 in rat and monkey plasma via ELISA and its application in preclinical studies.

Aim: PYX-201 is a novel antibody-drug conjugate targeting the extra domain B splice variant of fibronectin in the tumor microenvironment. Accurate quantification of PYX-201 is critical for PYX-201 pharmacokinetics profiling in preclinical studies. Materials & methods: ELISA was performed using reference standard PYX-201, mouse monoclonal anti-monomethyl auristatin E antibody, mouse IgG1, mouse monoclonal anti-human IgG horseradish peroxidase and donkey anti-human IgG horseradish peroxidase. Results: This assay was validated at 50.0-10,000 ng/ml in rat dipotassium EDTA plasma and 250-10,000 ng/ml in monkey dipotassium EDTA plasma. Conclusion: This is the first time for a PYX-201 bioanalytical assay in any matrix to be reported.

Molecular basis for polysaccharide recognition and modulated ATP hydrolysis by the O antigen ABC transporter.

O antigens are ubiquitous protective extensions of lipopolysaccharides in the extracellular leaflet of the Gram-negative outer membrane. Following biosynthesis in the cytosol, the lipid-linked polysaccharide is transported to the periplasm by the WzmWzt ABC transporter. Often, O antigen secretion requires the chemical modification of its elongating terminus, which the transporter recognizes via a carbohydrate-binding domain (CBD). Here, using components from A. aeolicus, we identify the O antigen structure with methylated mannose or rhamnose as its cap. Crystal and cryo electron microscopy structures reveal how WzmWzt recognizes this cap between its carbohydrate and nucleotide-binding domains in a nucleotide-free state. ATP binding induces drastic conformational changes of its CBD, terminating interactions with the O antigen. ATPase assays and site directed mutagenesis reveal reduced hydrolytic activity upon O antigen binding, likely to facilitate polymer loading into the ABC transporter. Our results elucidate critical steps in the recognition and translocation of polysaccharides by ABC transporters.

Results of Engineering, Primary Care, Oncology Collaborative Regarding a Survey of Primary Care on a Re-Engineered Survivorship Care Plan.

Survivorship care plans (SCPs) may facilitate cancer survivorship care shared between oncologists and primary care, particularly for patients more likely to receive care across healthcare systems such as rural patients. However, limited research has addressed primary care clinicians' information or workflow needs with regard to SCPs. This study's objective was to assess primary care clinicians' perceived usefulness with a re-engineered SCP previously developed by applying engineering approaches and informed by primary care preferences. An emailed survey of primary care clinicians assessed perceived usefulness with the re-engineered SCP. Clinicians were recruited across the USA from primary care practice-based research networks (PBRNs) with high concentrations of rural practices. Over 90% of respondents (n = 111) agreed that (1) the re-engineered SCP was useful (n = 95) and (2) they would want to receive a similar SCP (n = 93). The majority demonstrated high agreement regarding the SCP's relevance, understandability, content, and ability to help provide better survivorship care. Perceived usefulness was consistent between rural and non-rural clinicians. Suggested improvements involved decreased length, addition of a bulleted list, and electronic health record integration. Results indicate that the majority of primary care clinicians perceive the re-engineered SCP as useful. However, primary care clinicians indicated continued barriers despite end-user specific alterations. Future research should investigate additional strategies to support primary care survivorship-related workload, provide essential SCP content, and improve survivorship care delivery.

Re-engineering Survivorship Care Plans to Support Primary Care Needs and Workflow: Results From an Engineering, Primary Care and Oncology Collaborative for Survivorship Health (EPOCH).

Maintaining the health of survivors requires communication, collaboration and care coordination between oncology and primary care. Primary care clinicians have been acknowledged as important recipients of survivorship care plans (SCPs); however, current SCP templates have not been evaluated for usefulness in the primary care context. We surveyed and interviewed primary care clinicians from a rural research network regarding SCP content, format and layout (phase 1), and potential use and clinical workflows around SCPs (phase 2). Based on these data, an existing SCP template was iteratively redesigned to better support survivorship care in the primary care setting. A total of 13 clinicians (9 MDs, 4 APPs) participated. Interviewees advocated for maintaining a single SCP document shared by survivors and clinicians. Changes to the SCP template included prioritizing follow-up over summary of treatment and removing or down-playing screening recommendations not impacted by cancer or cancer treatment. The re-engineered SCP was regarded as highly relevant for survivors, but clinicians noted the significant effort to "disassemble" SCPs in order to enter the information into on the receiving health record. Primary care clinicians value the information in SCPs but had important recommendations regarding content, layout, and format. Additionally, a significant effort appears to be required by recipients in order to extract SCP information for future use.

Open Tibial Fracture Complicated by Wound Botulism: A Case Study.

Botulism is a neuroparalytic disease most commonly caused by foodborne ingestion of neurotoxin types A, B, and E, and is often fatal if untreated. Clinicians should be able to recognize the classic symptoms of botulinum intoxication (12). Owing to its rarity, there are a limited number of studies evaluating the clinical care of patients with wound botulism (10). We present an infected tibial non-union with botulism who underwent a successful radical excision and bone transport. The patient tolerated the procedure well.

Increasing system-wide implementation of opioid prescribing guidelines in primary care: findings from a non-randomized stepped-wedge quality improvement project.

BACKGROUND: Clinician utilization of practice guidelines can reduce inappropriate opioid prescribing and harm in chronic non-cancer pain; yet, implementation of "opioid guidelines" is subpar. We hypothesized that a multi-component quality improvement (QI) augmentation of "routine" system-level implementation efforts would increase clinician adherence to the opioid guideline-driven policy recommendations. METHODS: Opioid policy was implemented system-wide in 26 primary care clinics. A convenience sample of 9 clinics received the QI augmentation (one-hour academic detailing; 2 online educational modules; 4-6 monthly one-hour practice facilitation sessions) in this non-randomized stepped-wedge QI project. The QI participants were volunteer clinic staff. The target patient population was adults with chronic non-cancer pain treated with long-term opioids. The outcomes included the clinic-level percentage of target patients with a current treatment agreement (primary outcome), rates of opioid-benzodiazepine co-prescribing, urine drug testing, depression and opioid misuse risk screening, and prescription drug monitoring database check; additional measures included daily morphine-equivalent dose (MED), and the percentages of all target patients and patients prescribed ≥90 mg/day MED. T-test, mixed-regression and stepped-wedge-based analyses evaluated the QI impact, with significance and effect size assessed with two-tailed p < 0.05, 95% confidence intervals and/or Cohen's d. RESULTS: Two-hundred-fifteen QI participants, a subset of clinical staff, received at least one QI component; 1255 patients in the QI and 1632 patients in the 17 comparison clinics were prescribed long-term opioids. At baseline, more QI than comparison clinic patients were screened for depression (8.1% vs 1.1%, p = 0.019) and prescribed ≥90 mg/day MED (23.0% vs 15.5%, p = 0.038). The stepped-wedge analysis did not show statistically significant changes in outcomes in the QI clinics, when accounting for the comparison clinics' trends. The Cohen's d values favored the QI clinics in all outcomes except opioid-benzodiazepine co-prescribing. Subgroup analysis showed that patients prescribed ≥90 mg/day MED in the QI compared to comparison clinics improved urine drug screening rates (38.8% vs 19.1%, p = 0.02), but not other outcomes (p ≥ 0.05). CONCLUSIONS: Augmenting routine policy implementation with targeted QI intervention, delivered to volunteer clinic staff, did not additionally improve clinic-level, opioid guideline-concordant care metrics. However, the observed effect sizes suggested this approach may be effective, especially in higher-risk patients, if broadly implemented. TRIAL REGISTRATION: Not applicable.

Enhancing system-wide implementation of opioid prescribing guidelines in primary care: protocol for a stepped-wedge quality improvement project.

BACKGROUND: Systematic implementation of guidelines for opioid therapy management in chronic non-cancer pain can reduce opioid-related harms. However, implementation of guideline-recommended practices in routine care is subpar. The goal of this quality improvement (QI) project is to assess whether a clinic-tailored QI intervention improves the implementation of a health system-wide, guideline-driven policy on opioid prescribing in primary care. This manuscript describes the protocol for this QI project. METHODS: A health system with 28 primary care clinics caring for approximately 294,000 primary care patients developed and implemented a guideline-driven policy on long-term opioid therapy in adults with opioid-treated chronic non-cancer pain (estimated N = 3980). The policy provided multiple recommendations, including the universal use of treatment agreements, urine drug testing, depression and opioid misuse risk screening, and standardized documentation of the chronic pain diagnosis and treatment plan. The project team drew upon existing guidelines, feedback from end-users, experts and health system leadership to develop a robust QI intervention, targeting clinic-level implementation of policy-directed practices. The resulting multi-pronged QI intervention included clinic-wide and individual clinician-level educational interventions. The QI intervention will augment the health system's "routine rollout" method, consisting of a single educational presentation to clinicians in group settings and a separate presentation for staff. A stepped-wedge design will enable 9 primary care clinics to receive the intervention and assessment of within-clinic and between-clinic changes in adherence to the policy items measured by clinic-level electronic health record-based measures and process measures of the experience with the intervention. DISCUSSION: Developing methods for a health system-tailored QI intervention required a multi-step process to incorporate end-user feedback and account for the needs of targeted clinic team members. Delivery of such tailored QI interventions has the potential to enhance uptake of opioid therapy management policies in primary care. Results from this study are anticipated to elucidate the relative value of such QI activities.

Menthol Cough Drops: Cause for Concern?

BACKGROUND: Over-the-counter (OTC) cough remedies are lightly regulated and their potential side effects may go unrecognized. During 2015, over 282 million cough drops were sold in the United States. A Wisconsin community clinician (RM) made clinical observations suggesting that excessive use of OTC cough drops may exacerbate rather than benefit coughs. The goal of this project was to assess whether menthol in cough drops is related to worse cough symptoms. METHODS: From April 2016 through May 2017, 5 Wisconsin primary care clinics invited adolescent and adult outpatients seeking medical care for an acute or subacute cough to take a voluntary, anonymous, 10-question cough drop use survey that included age, sex, smoking status, cough severity, cough duration, and cough drop use (including type and amount). RESULTS: Of the 548 surveys collected and analyzed, 363 (66.2%) reported using cough drops. Cough drop use was significantly associated with longer duration of cough at presentation (P < .001) but not with overall cough severity (P = .09). Of cough drop users, 269 (90%) reported consuming drops with menthol. Univariate analysis found no statistically significant differences between the menthol and nonmenthol groups for either severity (P = .65) or duration (P = .17). However, significant independent associations were found between cough severity and 1) average menthol dose per cough drop (R = 0.19; P = .007), 2) number of cough drops consumed daily (R = 0.2; P = .002) and 3) total amount of menthol consumed per day (R = 0.21; P = .001) that remained significant (P = .003) after controlling for age, sex, smoking status, season, and clinic site. CONCLUSIONS: Cough severity in some individuals may be negatively influenced by the amount of menthol consumed via cough drops. Clinicians should include cough drop use in history taking of patients with persisting cough illnesses. Further research into potential mechanisms is warranted.

Traumatic Complex Hawkins Type IV Talar Fracture: A Case Report.

Fracture-dislocations of the talus are one of the most complex injuries involving the foot and ankle. These injuries are often accompanied by additional traumatic orthopedic injuries, avascular necrosis, and infection. When approaching limb reconstruction and salvage, the overall prognosis and functionality of the limb are key factors to consider. In the present report, we draw attention to the importance of a multidisciplinary team approach for formulating a treatment plan that incorporates the talar injury and associated injuries or pathologic features. We also reviewed the published data related to avascular necrosis of the talus, open talar fracture management, and treatment outcomes.

Catalytic Mechanism of Mammalian Adenylyl Cyclase: A Computational Investigation.

Adenylyl cyclase (AC) catalyzes the synthesis of cyclic AMP, an important intracellular regulatory molecule, from ATP. We propose a catalytic mechanism for class III mammalian AC based on density functional theory calculations. We employ a model of the AC active site derived from a crystal structure of mammalian AC activated by Gα·GTP and forskolin at separate allosteric sites. We compared the calculated activation free energies for 13 possible reaction sequences involving proton transfer, nucleophilic attack, and elimination of pyrophosphate. The proposed most probable mechanism is initiated by deprotonation of 3'OH and water-mediated transfer of the 3'H to the γ-phosphate. Proton transfer is followed by changes in coordination of the two magnesium ion cofactors and changes in the conformation of ATP to enhance the role of 3'O as a nucleophile and to bring 3'O close to Pα. The subsequent phosphoryl transfer step is concerted and rate-limiting. Comparison of the enzyme-catalyzed and nonenzymatic reactions reveals that the active site residues lower the free energy barrier for both phosphoryl transfer and proton transfer and significantly shift the proton transfer equilibrium. Calculations for mutants K1065A and R1029A demonstrate that K1065 plays a significant role in shifting the proton transfer equilibrium, whereas R1029 is important for making the transition state of concerted phosphoryl transfer tight rather than loose.

Evaluating primary care providers' views on survivorship care plans generated by an electronic health record system.

PURPOSE: Survivorship care plans for cancer survivors may facilitate provider-to-provider communication. Primary care provider (PCP) perspectives on care plan provision and use are limited, especially when care plans are generated by an electronic health record (EHR) system. We sought to examine PCPs' perspectives regarding EHR-generated care plans. METHODS: PCPs (N = 160) who were members of the Wisconsin Research and Education Network listserv received a sample 10-page plan (WREN cohort). PCPs (n = 81) who had or were currently seeing survivors enrolled onto one of our survivorship clinical trials received a copy of the survivor's personalized care plan (University of Wisconsin [UW] cohort). Both cohorts received a survey after reviewing the plan. All plans were generated within an EHR. RESULTS: Forty-six and 26 PCPs participated in the WREN and UW cohorts, respectively. PCPs regarded EHR-generated plans as useful in coordinating care (88%), understanding treatments (94%), understanding treatment adverse effects (89%), and supporting clinical decisions (82%). Few felt using EHR-generated plans would disrupt clinic workflow (14%) or take too much time (11%). Most (89%) preferred receiving the plan via EHR. PCPs reported consistent provision (81%) and standard location in the medical record (89%) as key factors facilitating their use of survivorship care plans. Important facilitators of care plan use included a more abbreviated plan, ideally one to three pages (32%), and/or a plan specifically tailored to PCP use (57%). CONCLUSION: Plans were viewed as useful for coordinating care and making clinical decisions. However, PCPs desired shorter, clinician-oriented plans, accessible within an EHR and delivered and located in a standardized manner.

Complications of indwelling retrievable versus permanent inferior vena cava filters.

OBJECTIVE: Retrievable inferior vena cava (IVC) filters are appealing because they are designed for either retrieval or long-term use. However, the long-term safety of indwelling retrievable compared with permanent filters is largely unknown. This study was undertaken to compare complication rates and types associated with indwelling retrievable and permanent filters. METHODS: A retrospective review identified 1234 IVC filters (449 retrievable, 785 permanent) placed in 1225 patients from 2005 to 2010. Patients with retrievable filters removed electively were excluded, yielding 383 patients in whom retrievable filters were left in place. These patients with indwelling retrievable filters were compared with those with permanent filters with respect to demographics, comorbidities, survival, and complication rate and type. Differences in patient characteristics were tested with χ(2), Fisher exact, and Wilcox rank-sum tests. Logistic regression was used to identify predictors of complications. Because there were differences in the characteristics of the patients with indwelling retrievable filters and permanent filters, an additional propensity score analysis was performed yielding 319 patients in each group. RESULTS: Patients with indwelling retrievable filters were younger than those with permanent filters (mean age, 62 vs 75 years; P < .0001). Patients with indwelling retrievable filters had significantly more complications than those with permanent filters (9% vs 3.0%; P < .0001) after mean follow-up of 20 months (range, 0-86 months). Filter complications were categorized as thrombotic, device related, or systemic. While the most common complication type with both indwelling retrievable and permanent filters was thrombotic (4.4% vs 2.2%; P = NS), device-related complications were significantly more common with indwelling retrievable filters compared with permanent filters (3% vs 0.5%; P < .006). Propensity score analysis demonstrated that even in the matched groups, indwelling retrievable filters were associated with significantly more complications than permanent filters (9.1% vs 3.5%; P = .0035). CONCLUSIONS: Indwelling retrievable IVC filters were associated with significantly higher complication rates than permanent filters. Both thrombotic and device-related complications were more common with retrievable filters. Long-term use of retrievable filters should be avoided, especially considering the younger population in whom they are placed.

Vascularized scapular free bone graft after nonunion of a tarsal navicular stress fracture: a case report.

Nonunion of a tarsal navicular stress fracture, although relatively uncommon, is often amenable to open reduction and internal fixation. Furthermore, avascular necrosis of the navicular whether intact or occurring after fracture is rare, secondary to the adequate blood supply it receives. However, persistent nonunion after primary surgical repair in conjunction with avascular necrosis often results in limited treatment options. Thus, the purpose of the present case report is to describe the surgical approach and complications of a vascularized scapular free bone graft for augmentation of revision talonavicular and naviculocuneiform arthrodesis.

Comparative evaluation of differential laser-induced perturbation spectroscopy as a technique to discriminate emerging skin pathology.

Fluorescence spectroscopy has been widely investigated as a technique for identifying pathological tissue; however, unrelated subject-to-subject variations in spectra complicate data analysis and interpretation. We describe and evaluate a new biosensing technique, differential laser-induced perturbation spectroscopy (DLIPS), based on deep ultraviolet (UV) photochemical perturbation in combination with difference spectroscopy. This technique combines sequential fluorescence probing (pre- and post-perturbation) with sub-ablative UV perturbation and difference spectroscopy to provide a new spectral dimension, facilitating two improvements over fluorescence spectroscopy. First, the differential technique eliminates significant variations in absolute fluorescence response within subject populations. Second, UV perturbations alter the extracellular matrix (ECM), directly coupling the DLIPS response to the biological structure. Improved biosensing with DLIPS is demonstrated in vivo in a murine model of chemically induced skin lesion development. Component loading analysis of the data indicates that the DLIPS technique couples to structural proteins in the ECM. Analysis of variance shows that DLIPS has a significant response to emerging pathology as opposed to other population differences. An optimal likelihood ratio classifier for the DLIPS dataset shows that this technique holds promise for improved diagnosis of epithelial pathology. Results further indicate that DLIPS may improve diagnosis of tissue by augmenting fluorescence spectra (i.e. orthogonal sensing).

Heat treatments modify the tribological properties of nickel boron coatings.

The effects of annealing temperature on the tribological properties of electroless nickel-boron coatings have been investigated. The coatings were annealed in a tube furnace under a flow (0.0094 N m(3)/min) of oxygen gas at temperatures of 250, 400, 550, and 700 °C for 3 h. Using scanning electron microscopy, images of the annealed coatings documented changes in surface morphology. From this it was seen that the higher annealing temperatures produced marked changes, moving from the nodular structure of nickel-boron coatings to a flaked surface morphology. The chemical effect of the annealing temperature was studied via X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. The XPS data indicated that after annealing at the temperatures of 550 and 700 °C, an accumulation of boron oxide species could be seen at the surface as well as a complete loss of nickel signal. An analysis of Raman spectra collected across the surface further identified the predominant species to be boric acid. The tribological response of the coatings was studied with a pin-on-disk tribometer with 440C stainless steel balls run against the coatings in ambient air. It was seen that the as received sample and the sample annealed at 250 °C samples exhibited modest friction properties, while the 400 °C sample had increased friction due to wear debris from the ball. The 550 and 700 °C samples showed remarkably low friction coefficients between 0.06 and 0.08, attributable to the presence of boric acid. The wear tracks were analyzed using scanning white light interferometry and from this data wear rates were obtained for the coatings ranging from 10(-8) to 10(-7) mm(3)/Nm.

Results with Viabahn-assisted subintimal recanalization for TASC C and TASC D superficial femoral artery occlusive disease.

OBJECTIVES: Many investigators including TransAtlantic Inter-Society Consensus (TASC) recommend against primary endovascular treatment for severe (TASC C and D) superficial femoral artery (SFA) disease. Vein bypass is preferable but may not be appropriate due to comorbidities or lack of suitable vein. This study reviews our results with Viabahn stent graft-assisted subintimal recanalization (VASIR) for TASC C and D SFA atherosclerosis. METHODS: In all, 13 males and 14 females, mean age 72 ± 11 years underwent 28 VASIR for severe (TASC C 8 of 28, TASC D 20 of 28, and 5 of 28 no continuous infrapopliteal runoff artery) SFA disease. Indications were claudication (14 of 28 limbs), ischemic rest pain (6 of 28), and tissue loss (8 of 28). Viabahn stent graft-assisted subintimal recanalization was chosen instead of bypass due to comorbidities or lack of vein. Patients received aspirin and, if not already taking warfarin, they also received clopidogrel. Patients were examined with Ankle-brachial Index (ABI) and duplex scan at 1 month, then every 3 months after VASIR. RESULTS: Viabahn stent graft-assisted subintimal recanalization was technically successful in all. Ankle-brachial Index averaged 0.47 ± 0.17 preprocedure, 0.89 ± 0.20 postprocedure, and increased by 0.15 or more in every case. Median follow-up is 20 months. There were 3 perioperative (<30 days) and 7 later failures including revision prior to any thrombosis. One patient required amputation. Four have died, 2 with patent grafts, none from causes related to VASIR, all more than 30 days post-VASIR. Estimated 1-year primary and secondary patency were 70% ± 11% and 73% ± 10%. Failure was not significantly associated with indications, comorbidities, or runoff status. There was a clear distinction between patients with early failure and the rest of the patients. None of the 8 patients with failure in the first 8 months after surgery has a patent graft. However, of 17 grafts primarily patent at 8 months, only 2 have failed (1 thrombosed and 1 required preemptive balloon angioplasty). There was a strong trend toward better patency with 6 and 7 mm diameter compared to 5 mm diameter stent grafts. Furthermore, although warfarin was not prescribed as part of the protocol, no patient taking warfarin before and who resumed warfarin after VASIR (n=4) suffered failure. CONCLUSIONS: Despite significant early failures, we found VASIR to be durable in those who did not have early failure. Viabahn stent graft-assisted subintimal recanalization is an acceptable alternative to vein bypass in selected patients with severe SFA disease. Smaller arterial or stent graft diameter may be associated with poorer results. Warfarin may be valuable to reduce the risk of failure after VASIR.

Real-time measurement of ArF excimer laser corneal tissue ablation rates using cross-correlation of laser waveforms.

The current popularity of excimer laser refractive surgery suggests a need for continued research and refinements to further improve clinical outcomes. A fundamental limitation of current clinical systems is the lack of real-time feedback specifically addressing the laser-tissue interactions as directly related to laser ablation rates. This paper reports data to assess the feasibility of a novel approach that holds promise as a real-time feedback scheme based on comparison of the incident and reflected laser pulse waveforms, as quantified using a cross-correlation algorithm. The approach is evaluated for ablation of bovine cornea over a range of clinically relevant laser fluences. A linear relationship was observed between several cross-correlation metrics and the directly measured corneal ablation rate, yielding an average RMS predictive error of 3.9% using a 25-shot average reflected waveform. Assessment of the cross-correlation approach for single-shot ablation data revealed a brief transient corresponding to the first few laser pulses, which is attributed to a slight hydration gradient near the surface of the de-epithelialized cornea. Clinical refractive data are necessary to assess the precision of this approach for actual refractive surgery.