Philadelphia-like B-cell acute lymphoblastic Leukaemia: Disease features and outcomes in the era of immunotherapy.

Philadelphia chromosome (Ph)-like acute lymphoblastic leukaemia (ALL) is a high-risk subtype with a gene expression profile similar to Ph-positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph-like ALL, this single-centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.4%) Ph-like, 89 (33.2%) Ph-positive, and 111 (41.4%) Ph-negative. Ph-like patients were the youngest age at diagnosis (p = 0.007), most likely to have refractory disease (p < 0.001), and least likely to achieve minimal residual disease (MRD) negativity after induction (p = 0.031). Relative to Ph-negative ALL, Ph-like achieved worse event-free survival (EFS) (HR = 1.66; 95% CI 1.12-2.46; p = 0.012), whereas Ph-positive had improved EFS (HR = 0.60; 95% CI 0.38-0.93; p = 0.024) and cumulative incidence of relapse (CIR) (HR = 0.59; 95% CI 0.35-0.99; p = 0.046). Within the transplant subgroup, Ph status did not impact disease-free survival (DFS), CIR, or overall survival (OS). However, patients who received blinatumomab within 1-year pre-HSCT had improved DFS (HR = 0.43; 95% CI 0.20-0.94; p = 0.034) and CIR (HR = 0.26; 95% CI 0.09-0.75; p = 0.13). In conclusion, our data suggest that Ph-like is less likely to respond to standard induction therapy and HSCT may result in similar survival outcomes to Ph-negative ALL.

Health care utilization, prevalence, and risk factors of dry eyes after cataract surgery.

OBJECTIVE: To quantify post-cataract surgery health care utilization caused by dry eye symptoms (DES) and identify preoperative risk factors and mediators of postoperative DES. SETTING: An outpatient surgical centre in Toronto, Canada. DESIGN: Retrospective cohort study. PARTICIPANTS: Included patients had cataract surgery between April 2019 and January 2020, completed a preoperative Dry Eye Questionnaire 5 (DEQ5), and were over age 18. METHODS: Data collected included DES risk factors, prophylaxis, and intraoperative and postoperative details. DES health care utilization and prevalence were reported as percentages. Risk of DES follow-up with DES prophylaxis use, and within each DEQ5 severity group, were analyzed with χ2-square test of independence and odds ratios. Binomial logistic regression assessed for significance of multiple preoperative and intraoperative risk factors, controlling for one another. RESULTS: Of 1074 patients (46% male, mean age: 71, mean DEQ5: 5.12), 18.1% had at least one nonroutine postoperative appointment due to DES. Patients with moderate/severe DEQ5 scores were 1.843 times likelier to have postoperative DES concerns than those with no/mild scores (CI = 1.307-2.599). Preoperative DES prophylaxis did not reduce DES risk in any severity group. Higher DEQ5 score, female sex, bilateral sequential surgeries, and femtosecond laser-assisted cataract surgery had higher likelihood of postoperative DES (B = 0.054; p < 0.001; B = -0.351; p = 0.037; B = 0.695; p = 0.003; B = 0.491; p = 0.003, respectively). CONCLUSION: Nearly 1 in 5 patients had DES postcataract surgery, with 1 in 12 requiring one or more nonroutine follow-ups for DES, suggesting substantial health care burden. Current standard preoperative DES treatment may not reduce postoperative DES, and further studies are needed to elucidate why.

Combination Therapy With Asciminib and Ponatinib as a Bridge to Brexucabtagene Autoleucel and Maintenance in a Patient With Relapsed Refractory Philadelphia Positive B-Cell Acute Lymphoblastic Leukemia.

Tyrosine kinase inhibitors (TKIs) have changed the prognosis of Philadelphia-positive B-cell acute lymphoblastic leukemia (ALL); however, relapsed and refractory disease after multiple TKIs continues to be a clinical challenge. Brexucabtagene autoleucel (brexu-cel) is a novel FDA-approved therapy for relapsed and refractory ALL. Given the lengthy manufacturing time, bridging therapy is commonly employed prior to brexu-cel. Here we describe a case of a 75-year-old Hispanic male patient with relapsed/refractory Philadelphia-positive B-cell ALL with extramedullary disease involving abdominal lymph nodes and skin. He was initially treated with chemotherapy in combination with imatinib, and later received dasatinib and subsequently blinatumomab and nilotinib. As the patient progressed, he received ponatinib with low-dose salvage chemotherapy and did not show kinase domain mutation. In a final effort, a novel combination of ponatinib with asciminib was used as a bridge therapy before brexu-cel and later as maintenance therapy after brexu-cel. This novel combination was able to control disease prior to brexu-cel for 2 months and maintained remission for at least 10 months. This report shows that the novel combination of ponatinib and asciminib is tolerable and effective as a bridge and maintenance therapy after brexu-cel.

Graft Versus Host Disease Prophylaxis in Matched Donor Stem Cell Transplantation: Post-transplantation Cyclophosphamide Combinations Versus Methotrexate/Tacrolimus.

BACKGROUND: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft versus host disease (GVHD) for haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). There is limited data on the role of PTCy as GVHD prophylaxis in matched-sibling and fully matched-unrelated donor (MSD/MUD) allo-HSCT. METHODS: Our single-center retrospective study aims to compare outcomes of PTCy alone or in combination with mycophenolate mofetil and tacrolimus (PTCy/MMF/TAC) relative to methotrexate and tacrolimus (MTX/TAC). The primary endpoint of our study was GVHD-free, relapse free survival (GRFS). Secondary endpoints were overall survival (OS), disease free survival (DFS), and incidence of severe acute and chronic GVHD. We identified 74 adult patients who underwent MSD/MUD allo-HSCT at our institution from 2015 to 2023. RESULTS: Within our cohort, 33.8% (n = 25) received MTX/TAC, while 54.0% (n = 40) received PTCy/MMF/TAC, and 12.2% (n = 9) received PTCy alone. Patients receiving PTCY had the longest time to neutrophil engraftment relative to MTX/TAC (15 days vs. 12 days, P = .010). PTCy/MMF/TAC was associated with improved GRFS relative to MTX/TAC (hazard ratio [HR] = HR 0.42, 95% CI 0.19-0.93, P = .031), which persisted when controlling for age. Incidence of chronic GVHD was lower in the PTCy/MMF/TAC group compared to MTX/TAC (1-year 9.0% vs. 30.1%, HR 0.19, 95% CI 0.06-0.59, P = .005). However, OS and DFS were comparable across all groups. CONCLUSIONS: Our results demonstrate decreased rates of severe chronic GVHD resulting in improved GRFS when using PTCy/TAC/MTX as GVHD prophylaxis compared to MTX/TAC in MSD/MUD.

Micropulse Transscleral Cyclophotocoagulation in Non-Incisional Eyes with Ocular Hypertension and Primary Open-Angle Glaucoma.

Purpose: To investigate the safety and effectiveness of micropulse transscleral cyclophotocoagulation (MPTSCPC) in non-incisional eyes with ocular hypertension (OHT) and early, moderate, and severe primary open-angle glaucoma (POAG). Methods: Retrospective cohort study of eyes that underwent MPTSCPC from 2016 to 2019 at an outpatient clinic in Canada. Eyes were excluded if any incisional procedures, except cataract surgery, were performed prior to MPTSCPC treatment. Laser power ranged from 900 to 2500mW. Results: A total of 153 eyes from 93 patients were included (OHT n=22; early POAG n=46; moderate POAG n=35; severe POAG n=50). The baseline IOP was 18.37 ± 4.76mmHg in the total cohort. All cohorts experienced a significant mean IOP reduction by final follow-up (total p<0.001; OHT p=0.003; early POAG p<0.001; moderate POAG p=0.022; severe POAG p=0.015). Overall, 52.9% of eyes achieved an IOP reduction of ≥20% from baseline to final follow-up (OHT 59.1%; early POAG 58.7%; moderate POAG 45.7%; severe POAG 50.0%). There was worsening in best-corrected visual acuity in the total cohort (mean difference=0.11 ± 0.36 logMAR, p=0.11), mostly attributable to cataract progression (34.1% of phakic eyes) and ocular surface disease (7.2%). The number of topical medications and drug classes remained unchanged in the total cohort (p=0.425 and p=0.791, respectively). Twenty-two eyes (14.4%) required retreatment, which provided an additional IOP reduction of 1.26mmHg (p=0.344). By final follow-up, 8 eyes (5.2%) required escalation to incisional procedures. Conclusion: MPTSCPC is a safe and effective adjunct IOP-lowering treatment in non-incisional eyes with OHT and POAG.

Donor matters: Donor selection impact on hematopoietic stem cell transplantation outcomes in Hispanic patients with B-cell acute lymphocytic leukemia: Insights from a myeloablative HSCT study.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients. METHODOLOGY: This single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023. RESULTS: Compared to Haploidentical transplants, MSD exhibited worse cumulative incidence of relapse (CIR) (HR = 3.39; P = 0.014) and disease-free survival (DFS) (HR = 2.44; P = 0.048) whereas MUD outcomes did not differ. This effect persisted even when controlling for pre-HSCT stage and Minimal residual disease (MRD) status. In addition, Ph-like was a significant predictor of worse DFS (HR = 3.60; P=0.014) and CIR (HR = 2.97; P=0.035) on multivariate analysis. Older donor age correlated with worse GVHD-free, relapse-free survival (GRFS) in haploidentical transplants (HR = 1.05; P=0.036). CONCLUSION: Our data highlights improved outcomes with younger, haploidentical donors among Hispanic B-cell ALL patients undergoing myeloablative HSCT. This underscores the importance of donor selection in optimizing outcomes for ALL patients.

Case report: Pulse cyclophosphamide for treatment of multi-agent-refractory hepatic graft-versus-host disease.

Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality in HSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies. We present the case of a 46-year-old woman diagnosed with acute undifferentiated leukemia, who exhibited persistently elevated levels of serum total bilirubin (T.Bili), alkaline phosphatase (ALP), and liver function tests (LFTs) beginning on [day +201] post-haploidentical peripheral blood stem cell (PBSC) transplantation. The patient received fludarabine/total body irradiation (Flu/TBI) as a myeloablative conditioning regimen and post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) as GVHD prophylaxis. A liver biopsy confirmed the diagnosis of GVHD, while other possible etiologies were excluded by corresponding tests. Initial treatment with prednisone and tacrolimus, and the later addition of ruxolitinib, all showed poor response indicated by worsening T.Bili, ALP, and LFTs at the same time. Based on a multidisciplinary comprehensive assessment, we decided to administer 1,000 mg/m2 (1,600 mg) of cyclophosphamide ("pulse Cy"), which resulted in a dramatic improvement in T.Bili and transaminases starting from the very next day. A durable response to pulse cyclophosphamide was observed, as all indicators normalized ("complete response") within 55 days without relapses. The patient remains in good health with no recurrence of hepatic GVHD. To our knowledge, this is the first case in which Grade IV hepatic GVHD, refractory to multiple agents including steroids, tacrolimus, and ruxolitinib, demonstrated a complete response to pulse cyclophosphamide. The success highlights the potential therapeutic role of cyclophosphamide, a potent and cost-effective chemotherapy agent, in treating multi-agent-refractory GVHD. Large-scale clinical trials are warranted to validate its efficacy in this setting.

Feasibility of an artificial intelligence phone call for postoperative care following cataract surgery in a diverse population: two phase prospective study protocol.

INTRODUCTION: Artificial intelligence (AI) development has led to improvements in many areas of medicine. Canada has workforce pressures in delivering cataract care. A potential solution is using AI technology that can automate care delivery, increase effectiveness and decrease burdens placed on patients and the healthcare system. This study assesses the use of 'Dora', an example of an AI assistant that is able to deliver a regulated autonomous, voice-based, natural-language consultation with patients over the telephone. Dora is used in routine practice in the UK, but this study seeks to assess the safety, usability, acceptability and cost-effectiveness of using the technology in Canada. METHODS AND ANALYSIS: This is a two-phase prospective single-centred trial. An expected 250 patients will be recruited for each phase of the study. For Phase I of the study, Dora will phone patients at postoperative week 1 and for Phase II of the study, Dora will phone patients within 24hours of their cataract surgery and again at postoperative week 1. We will evaluate the agreement between Dora and a supervising clinician regarding the need for further review based on the patients' symptoms. A random sample of patients will undergo the System Usability Scale followed by an extended semi-structured interview. The primary outcome of agreement between Dora and the supervisor will be assessed using the kappa statistic. Qualitative data from the interviews will further gauge patient opinions about Dora's usability, appropriateness and level of satisfaction. ETHICS AND DISSEMINATION: Research Ethics Board William Osler Health System (ID: 22-0044) has approved this study and will be conducted by guidelines of Declaration of Helsinki. Master-linking sheet will contain the patient chart identification (ID), full name, date of birth and study ID. Results will be shared through peer-reviewed journals and presentations at conferences.

Anterior chamber cytokine production and postoperative macular edema in patients with diabetes undergoing FLACS.

PURPOSE: To evaluate the effect of femtosecond laser-assisted cataract surgery (FLACS) and manual cataract surgery (MCS) on proinflammatory cytokine expression in patients with diabetes vs nondiabetic patients. SETTING: Outpatient surgical center in Vaughan, Ontario, Canada. DESIGN: Prospective cohort study. METHODS: Patients with diabetes and nondiabetic patients undergoing noncomplicated MCS or FLACS were assigned into 4 cohorts: MCS nondiabetic (n = 30), FLACS nondiabetic (n = 42), MCS diabetic (n = 40), and FLACS diabetic (n = 40). Aqueous humor inflammatory mediator concentrations were evaluated at MCS onset and after femtosecond laser treatment. The presence of cystoid macular edema, anterior chamber (AC) inflammation, central retinal thickness, macular volume, and retinal microvascular changes (through optical coherence tomography angiography) were evaluated preoperatively and on postoperative day 1, week 1, month 1 (POM1), and month 3 (POM3). RESULTS: Patients with diabetes receiving FLACS had a higher concentration of interleukin (IL)-7, IL-13, and interferon-induced protein-10 than MCS diabetic patients; they also demonstrated higher levels of vascular endothelial growth factor and lower levels of interferon (IFN)-γ, granulocyte colony-stimulating factor, and IFN-α2 compared with MCS nondiabetic patients. Macular volume appeared to be significantly higher in MCS diabetic vs MCS non-diabetic patients at POM1 and between FLACS diabetic vs FLACS nondiabetic patients at POM3. There were no other significant differences between the cohorts for any parameter. CONCLUSIONS: FLACS use in patients with diabetes demonstrated some differences in AC cytokine expression compared with non-diabetic FLACS or diabetic patients undergoing MCS; however, there was no increase in clinical inflammatory biomarkers. FLACS seems to be a safe technique to use in patients with diabetes.

Concordance of Next-Generation Sequencing and Multiparametric Flow Cytometry Methods for Detecting Measurable Residual Disease in Adult Acute Lymphoblastic Leukemia: Optimizing Prediction of Clinical Outcomes From a Single-Center Study.

INTRODUCTION: Detection of measurable residual disease (MRD) in adults with acute lymphoblastic leukemia (ALL) is a vital biomarker in risk prediction and treatment selection. Next-generation sequencing (NGS) offers greater sensitivity relative to multiparametric flow cytometry (MFC) and may be a better predictive tool for identifying ALL patients at risk of relapse. PATIENTS AND METHODS: This single-center retrospective study compares MRD detection by NGS versus MFC in 52 adult B- and T-ALL patients treated at our institution between 2018 and 2023. Pretreatment bone marrow samples were used for assay calibration, while post-treatment MRD assessment was completed up to 4.5 months after the first complete remission (CR1) using an MRD cutoff of 10-6 for distinguishing relapse risk. RESULTS: The 2-year cumulative incidence of relapse (CIR) among patients who were MRD positive using MFC and NGS was 39.5% and 46.2%, respectively. Unlike MFC, post-CR1 MRD positivity with NGS significantly predicted CIR (HR = 9.47, P = .028). In patients who were MRD negative by MFC, low levels of MRD detected by NGS distinguished patients at high risk of relapse (HR 10.3, P = .026, 2-year CIR 51.6%). CONCLUSION: Our data suggests that assessment of post-CR1 MRD using a highly sensitive NGS assay can identify ALL patients undergoing frontline therapy at increased risk of relapse and guide the use of adjuvant therapy.

Unique challenges to diagnosing sweet syndrome following induction chemotherapy for relapsed Acute Myeloid Leukemia (AML): A case and brief-review.

Background: Sweet Syndrome (SS) is a rare inflammatory skin condition characterized by the sudden appearance of tender, erythematous or violaceous papules, plaques, and nodules typically found on the face, neck, shoulder, upper extremities, and trunk. Often, SS is difficult to diagnose because of its various non-specific manifestations, including fever, arthralgia, myalgia and ocular involvement. In most cases described in literature, cutaneous and pulmonary symptoms of SS present in a concomitant manner. Several reported cases of pulmonary SS have shown that if left untreated, acute respiratory distress syndrome can ensue and progress to fatal respiratory failure. Case report: A 58-year-old female with acute myeloid leukemia (AML) secondary to chronic lymphocytic leukemia (CLL) presented with new nodular lesions, dyspnea, and fevers. Chest X-ray revealed pulmonary infiltrates. The patient developed new facial lesions and worsening hypoxic respiratory failure. Further infectious workup was negative. She was found to have SS with pulmonary involvement and initiated on high-dose intravenous (IV) steroids with marked clinical improvement. Conclusions: Major and minor criteria for the diagnosis of lung-associated SS should be carefully evaluated, especially when a biopsy is unavailable. The following case report describes the clinical course and outcomes from treatment for this patient.

Comparison of pain perception in patients undergoing manual cataract surgery versus refractive laser-assisted cataract surgery.

OBJECTIVES: To assess pain perception in patients undergoing manual cataract surgery versus femtosecond laser-assisted cataract surgery (FLACS) and pain perception of patients receiving anaesthesia at 2 different time points during the FLACS procedure. We also aimed to assess the factors affecting pain perception in these different study groups. DESIGN: Prospective cohort comparison of patient-selected surgical approach. PARTICIPANTS: Patients undergoing delayed sequential bilateral cataract surgery at an ambulatory surgical centre in Ontario. METHODS: Patients were assigned to 3 groups: a manual cataract surgery cohort (n = 30) and 2 FLACS cohorts, those who received neurolept anaesthesia just prior to draping for phacoemulsification (FLACS standard cohort; n = 38) and those who received neurolept anaesthesia prior to the femtosecond laser part of the procedure (FLACS early cohort; n = 35). Outcome metrics included pain scores on the visual analogue scale on postoperative day 0 and at postoperative week 1. Secondary outcome measures included anxiety scores, surgeon or anaesthesiologist patient cooperation scores, ocular metrics, and perioperative systemic vitals. RESULTS: There were no significant differences in pain perception on postoperative day 0 and at postoperative week 1 among the manual cataract surgery and FLACS standard cohorts (p = 0.94 and p = 0.72, respectively) or FLACS early and FLACS standard cohorts (p = 0.76 and p = 0.67, respectively). Patients had higher pain scores during second-eye procedures than first-eye procedures. CONCLUSIONS: Cataract surgery technique or timing of anaesthesia for FLACS procedures does not affect pain perception postoperatively. Second-eye procedures are associated with higher pain scores than first-eye procedures.

Real world experience: Examining outcomes using letermovir for CMV prophylaxis in high-risk allogeneic hematopoietic stem cell patients in the setting of using T-cell depletion as GVHD prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) infection significantly impacts the morbidity and mortality of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Despite monitoring and pharmacologic prophylaxis with drugs such as valganciclovir or ganciclovir, rates of early CMV reactivation have continually persisted, contributing to increased rates of morbidity and mortality in allogeneic-HSCT patients. This study evaluates the outcomes of letermovir in preventing CMV reactivation and CMV-related complications in HSCT recipients with initiation of therapy at +21 days in high-risk patients. METHODS: We retrospectively analyzed adult patients at University of Southern California (USC) Norris Cancer Hospital who received allogeneic-HSCT from 2018 to 2020 with subsequent serial CMV monitoring and treatment. CMV reactivation was determined in patients if they had clinically significant serum CMV viremia (viremia requiring treatment) or organ involvement by day+100. Primary endpoint assessed was day+100 rates of CMV reactivation. Secondary end-points included 1-year OS, 1-year RFS, and incidence of GVHD. Descriptive statistics were used to compare characteristics between groups used in this study, with a significance level of α = 0.05. RESULTS: Between 2018 and 2020, 116 adult HSCT recipients were reviewed. 51% were male and 49% were female; donor sources consisted of 27% match related donor (MRD) 28% match-unrelated donor (MUD), and 45% haploidentical donor. Of the 116 patients, 92 were identified as high-risk for CMV reactivation. 71 patients received letermovir prophylaxis, and 21 patients received no prophylaxis. In high-risk patients, after adjusting for GVHD status and transplant type, patients that received letermovir had no statistically significant difference of having D + 100 CMV reactivation compared to patients that did not receive letermovir. 1.02 (95% CI: 0.35, 3.20) (p = 0.97). Moreover, there were no statistically significant difference observed between letermovir treatment and 1-year OS, 1-year RFS, and incidence of GVHD. CONCLUSION: Patients in the high-risk letermovir group had outcomes that were comparable to the lower risk "non-letermovir" group. There was no significant difference in CMV D + 100 reactivation between high-risk patients who did not receive letermovir compared to the patients who did. While other studies have shown that early initiation of letermovir may be associated with improved outcomes, our study shows that the use of letermovir with initiation at 21 days may not necessarily translate to improved secondary outcomes such as overall survival. Further prospective studies evaluating the time of initiating therapy and outcomes are needed.

Investigation of four-dimensional (4D) Monte Carlo dose calculation in real-time tumor tracking stereotatic body radiotherapy for lung cancers.

PURPOSE: To investigate the dosimetric variations and radiobiological impacts as a consequence of delivering treatment plans of 3D nature in 4D manner based on the 4D Monte Carlo treatment planning framework implemented on Cyberknife. METHODS AND MATERIALS: Dose distributions were optimized on reference 3D images at end of exhale phase of a 4DCT dataset for twenty-five lung cancer patients treated with 60 Gy / 3Fx or 48 Gy / 4Fx. Deformable image registrations (DIR) between individual 3DCT images to the reference 3DCT image in the 4DCT study were performed to interpolate doses calculated on multiple anatomical geometries back on to the reference geometry to compose a 4D dose distribution that included the tracking beam motion and organ deformation. The 3D and 4D dose distributions that were initially calculated with the equivalent path-length (EPL) algorithm (3DEPL dose and 4DEPL dose) were recalculated with the Monte Carlo algorithm (3DMC dose and 4DMC dose). Dosimetric variations of V60Gy / 48Gy and D99 of GTV, mean doses to the lung and the heart and maximum dose (D1 ) of the spinal cord as a consequence of tracking beam motion in deforming anatomy, dose calculation algorithm, and both were quantified by the relative change from 4DMC to 3DMC doses, from 4DMC to 4DEPL doses, and from 4DMC to 3DEPL doses, respectively. RESULTS: Comparing 4DMC to 3DEPL plans, V60Gy / 48Gy and D99 of GTV decreased considerably by 13 ± 22% (mean ± 1SD) and 9.2 ± 5.5 Gy but changes of normal tissue doses were not more than 0.5 Gy on average. The generalized equivalent uniform dose (gEUD) and tumor control probability (TCP) were reduced by 14.3 ± 8.8 Gy and 7.5 ± 5.2%, and normal tissue complication probability (NTCP) for myelopathy and pericarditis were close to zero and NTCP for radiation pneumonitis was reduced by 2.5 ± 4.1%. Comparing 4DMC to 4DEPL plans found decreased V60Gy / 48Gy and D99 by 12.3 ± 21.6% and 7.3 ± 5.3 Gy, the normal tissues doses by 0.5 Gy on average, gEUD and TCP by 13.0 ± 8.6 Gy and 7.1 ± 5.1%. Comparing 4DMC to 3DMC doses, V60Gy / 48Gy and D99 of GTV was reduced by 5.2 ± 8.8 %and 2.6 ± 3.3 Gy, and normal tissues hardly changed from 4DMC to 3DMC doses. The corresponding decreases of gEUD and TCP were 2.8 ± 4.0 Gy and 1.6 ± 2.4%. CONCLUSION: The large discrepancy between original 3DEPL plan and benchmarking 4DMC plan is predominately due to dose calculation algorithms as the tracking beam motion and organ deformation hardly influenced doses of normal tissues and moderately decreased V60Gy / 48Gy and D99 of GTV. It is worth to make a thoughtful weight of the benefits of full 4D MC dose calculation and consider 3D MC dose calculation as a compromise of 4D MC dose calculation considering the multifold computation time. This article is protected by copyright. All rights reserved.

Autologous Platelet-Rich Plasma Drops for Evaporative Dry Eye Disease from Meibomian Gland Dysfunction: A Pilot Study.

Purpose: To evaluate the effects of autologous platelet-rich plasma (PRP) drops for evaporative dry eye (EDE) disease from meibomian gland dysfunction (MGD). Methods: This is a retrospective, consecutive case series of 20 eyes of 10 patients with EDE from MGD treated with PRP drops from November 2020 to November 2021 at a single outpatient clinic in Ontario, Canada. PRP drops were prepared from whole blood using a two-step centrifugation method. Patients were instructed to instill these drops six times daily for 4 weeks. The Canadian Dry Eye Assessment (CDEA) questionnaire score, patient subjective assessment (PSA) score, first and average non-invasive break-up times (f/a NIBUT), tear meniscus height (TMH), bulbar redness (BR), and meibograph grade (MG) were measured before and after the treatment course. Results: Significant improvements in dry eye symptoms and tear film parameters were observed. Dry eye symptoms significantly improved as per the CDEA (mean difference (MD) = -5.45, 95% confidence interval (CI) = [-7.9, -3.1], p<0.001) and PSA (MD = -2.6, 95% CI = [-3.9, -1.2], p<0.001). There were significant improvements in tear film parameters including fNIBUT (MD = 3.85s, 95% CI = [1.2, 6.8], p=0.006), aNIBUT (MD = -6.81s, 95% CI = [5.7, 11.1], p<0.001) and TMH (MD = 0.08, 95% CI = [0.003, 0.2], p=0.045). There was an improvement in conjunctival injection as measured by BR (MD = -0.36, 95% CI = [-0.4, -0.15], p=0.373). Five eyes experienced a one-grade improvement in MG (p=0.453), and none experienced worsening in MG with treatment. No temporary or permanent adverse effects were noted. Conclusion: Four weeks of PRP therapy resulted in significant functional improvements in dry eye symptoms and tear film quality and quantity. Improvements in conjunctival injection and microstructural improvements in meibomian glands were also observed in some eyes. Overall, PRP is a promising treatment option for patients with EDE from MGD refractory to conventional treatments.

Comparison of Barrett Toric Calculations Using Measured and Predicted Posterior Corneal Astigmatism in Cataract Surgery Patients.

Aim: To compare residual astigmatism prediction errors across Barrett toric calculations using predicted posterior corneal astigmatism (PCA) and PCA measured using the IOL Master 700 with total keratometry (IOLM). Methods: A retrospective cohort study was undertaken on patients with corneal astigmatism and no other ocular comorbidities that underwent uneventful refractive femtosecond laser-assisted cataract surgery with toric IOL implantation between May 2019 and November 2019. Toric calculations were performed using the Barrett toric calculator and the following values: predicted PCA with anterior corneal measurements from Pentacam, IOLM standard keratometry (SK), OPD scan, and median measurements from these devices; predicted PCA with IOLM total keratometry (TK); and measured PCA with IOLM SK or IOLM TK. Residual astigmatism prediction error was calculated for each device and method of calculation at postoperative month 1 and 3 using the astigmatism double angle plot tool. Results: A total of 24 eyes, 10 with-the-rule (WTR), 10 against-the-rule (ATR) and 4 oblique astigmatism, from 24 patients were included in this study. PCA ranged from 0.00 to 0.67 D with a mean of 0.24 ± 0.15 D in all eyes. PCA was significantly greater in WTR eyes (0.32 D) compared to ATR eyes (0.16 D; p < 0.05). In ATR eyes, calculations made using IOLM SK and measured PCA had significantly lower total corneal astigmatism and toric IOL cylinder power compared to calculations made using Pentacam and IOLM TK (p < 0.05). No significant difference in mean absolute or centroid residual astigmatism prediction error was observed across devices or calculation methods. The percentage of eyes with absolute astigmatism prediction errors ≤0.5 D was not significantly different across groups. Conclusion: Barrett toric calculations using predicted PCA and PCA measured using IOLM produced comparable residual astigmatism prediction errors. The incorporation of median measurements did not significantly impact calculation accuracy.

A Night-Time Monitoring System (eNightLog) to Prevent Elderly Wandering in Hostels: A Three-Month Field Study.

Older people are increasingly dependent on others to support their daily activities due to geriatric symptoms such as dementia. Some of them stay in long-term care facilities. Elderly people with night wandering behaviour may lose their way, leading to a significant risk of injuries. The eNightLog system was developed to monitor the night-time bedside activities of older people in order to help them cope with this issue. It comprises a 3D time-of-flight near-infrared sensor and an ultra-wideband sensor for detecting human presence and to determine postures without a video camera. A threshold-based algorithm was developed to classify different activities, such as leaving the bed. The system is able to send alarm messages to caregivers if an elderly user performs undesirable activities. In this study, 17 sets of eNightLog systems were installed in an elderly hostel with 17 beds in 9 bedrooms. During the three-month field test, 26 older people with different periods of stay were included in the study. The accuracy, sensitivity and specificity of detecting non-assisted bed-leaving events was 99.8%, 100%, and 99.6%, respectively. There were only three false alarms out of 2762 bed-exiting events. Our results demonstrated that the eNightLog system is sufficiently accurate to be applied in the hostel environment. Machine learning with instance segmentation and online learning will enable the system to be used for widely different environments and people, with improvements to be made in future studies.

Unique Challenges to Diagnosing Human Herpesvirus-6 (HHV-6) Encephalitis Following Post-Hematopoietic Stem Cell Transplant: A Case and Brief Review.

A patient with an ultimate diagnosis of human herpesvirus-6 (HHV-6) encephalitis developed central nervous system (CNS) symptoms 13 days after undergoing myeloablative haploidentical allogeneic hematopoietic stem cell transplant (HSCT). Due to the patient's body habitus, magnetic resonance (MR) imaging was not obtained until the onset of retrograde amnesia on day +24. MR imaging and other clinical findings eliminated all skepticism of HHV-6 encephalitis and HHV-6 antivirals were initiated on day +28, leading to gradual recovery. This case demonstrates some of the factors that may complicate the diagnosis of post-alloHSCT HHV-6 encephalitis. Because HHV-6 encephalitis and viremia can occur without warning, a single negative study should not exclude future development, especially if CNS symptoms are present. Acute graft-versus-host disease and cord blood transplantation are both significant risk factors for HHV-6 encephalitis. Human leukocyte antigen (HLA) mismatch, engraftment complications, or certain HLA alleles have also been associated with HHV-6 encephalitis. Chromosomally integrated HHV-6 must also be ruled out to prevent inappropriate and potentially harmful administration of antivirals. Due to the severe short- and long-term sequelae of HHV-6 encephalitis, appropriate treatment should be administered as soon as possible.