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1.
JAC Antimicrob Resist ; 6(4): dlae126, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39104770

ABSTRACT

Objectives: Viridans streptococci (VS) are opportunistic oral commensals and a common cause of bacteraemia in neutropenic patients. In this retrospective single centre cohort study, we investigated the prevalence of ceftriaxone resistance in VS (CRO-R VS) blood isolates between January 2005 and December 2022 from patients treated at a tertiary care hospital. Methods: Blood culture isolates were identified using biochemicals and mass spectrometry. Susceptibility testing was performed by Kirby-Bauer and Epsilometer tests. Demographic data, clinical outcomes and antimicrobial use were assessed through electronic medical record review. Results: Among 791 patients with VS bacteraemia, 31 (4%) had confirmed CRO-R VS bacteraemia over the 18-year period; 20/31 (65%) were patients also treated at the Fred Hutchinson Cancer Center and were the focus of this study. Of these 20 patients, 18 (90%) had a known haematologic malignancy; 14 (70%) had undergone haematopoietic cell transplant (HCT); 18 (90%) were neutropenic at the time of culture. Two (10%) patients died within 30 days of CRO-R VS bacteraemia. All the CRO-R isolates (20/20) were members of the Streptococcus mitis group, 12 were multi-drug resistant; all were susceptible to vancomycin. Most patients received vancomycin once blood cultures were positive for a Gram-positive organism. Conclusions: During the study period, the frequency of VS isolate susceptibility testing increased; however, there was no concomitant increase in the percentage of CRO-R isolates at our facility. These data are important in an era where cefepime monotherapy is often used and reinforces the importance of routine resistance testing among VS bacteraemia.

2.
Eur J Orthod ; 46(5)2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39162175

ABSTRACT

BACKGROUND: The published literature represents the fundamental basis of any academic specialty, including orthodontics. Orthodontic research outputs provide useful insight into clinical and research priorities, which can help inform future research efforts and resource outputs. In recent years, the need for more patient-reported outcomes in orthodontic research has been highlighted. OBJECTIVES: To identify the most common reported research subjects in orthodontics between 2013-23; (2) identify the main outcomes and types of study design associated with this research, including study design related to patient-reported outcomes; and (3) identify trends in this research activity based upon these findings. MATERIAL AND METHODS: A literature search was performed in a single electronic database (Scopus) to return all indexed publications with relevance to orthodontics published from 2013 to 2023. The 50 most-cited publications per year were then identified. Publication characteristics were extracted using a data collection sheet. Descriptive statistics including frequency distributions were calculated. RESULTS: A total of 14 397 publications were identified. Publications on orthodontic bonding made up 7.02% of all output, followed by materials (5.88%) and tooth movement (5.42%). Subsequent analysis of the most-cited publications per year revealed the most frequently published subjects were aligners (12.5%), orthodontic tooth movement (9.45%), and digital workflow (9.09%), and the most common study designs were in vitro (19.09%) and retrospective observational studies (15.45%). The most common outcome type was morphological features of malocclusion (26.9%). Conversely, patient-focused measures were only reported in 12.7% of studies. CONCLUSIONS: Orthodontic research outputs are dynamic but do show consistent research interest in certain subjects. There is a predilection for the reporting of clinician-focused outcomes; whilst these have some value, more efforts should be focused on conducting rigorous and robust studies that include patient-reported outcomes.


Subject(s)
Bibliometrics , Orthodontics , Patient Reported Outcome Measures , Humans , Dental Research/statistics & numerical data , Longitudinal Studies
3.
Kidney360 ; 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39178041

ABSTRACT

BACKGROUND: Despite offering several advantages to patients and healthcare systems, utilization of home dialysis modalities (HDM) remains low, particularly among racial and ethnic minorities, and those with increased sociodemographic stress. Providers' apprehension towards adverse outcomes and home dialysis failure remains a barrier to HDM referral. We investigated the relationship sociodemographic factors have on HDM use and technique failure. METHODS: We performed a retrospective cohort study of adult incident ESRD patients over a six-year period at the University of Rochester to evaluate the association between demographic factors, social deprivation index (SDI), and co-morbidity burden on HDM utilization and technique failure. Person-time incidence rates were calculated to compare outcome variables, and rates were compared using a Poisson Rate Ratio Test. A univariate Cox regression was used to examine predictors impacting technique failure. RESULTS: Of the 873 patients, 102 started dialysis with HDM, 79 patients converted to HDM, and 692 remained on in-center hemodialysis (ICHD). Age, race, and SDI scores were significantly different between patients starting on ICHD, peritoneal dialysis (PD) and home hemodialysis (HHD) with no significant difference in comorbidity burden. Black patients represented 32% of the overall cohort, but only 16% of the initial home dialysis population. Compared to those that remained on ICHD, individuals converting from ICHD to HDM were younger and had significantly different SDI scores. SDI was not associated with HDM technique failure. CONCLUSIONS: Historically underrepresented racial populations are less represented in those starting home dialysis, however there was no racial difference in the group transitioning to HDM after initiating ICHD. Social deprivation scores were higher in those on ICHD compared to PD. Neither social deprivation nor race predicted success on home therapy. These findings demonstrate a disparity in initial modality, and a disconnect between sociodemographic factors associated with home dialysis use and those predicting HDM technique failure.

4.
Br Dent J ; 237(3): 217-221, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39123030

ABSTRACT

The development of normal occlusion requires eruptive migration of teeth from their developmental position in the jaw into a functional position within the oral cavity. This process involves significant and coordinated movement in an axial direction and appropriate eruption through the gingival tissues. The mechanisms regulating these developmental events are poorly understood, and teeth retain eruptive potential throughout their lifespan. In recent years, the use of mouse models has helped to elucidate some of the underlying molecular and biological mechanisms of mammalian tooth eruption. Here, we outline our current understanding of tooth eruption mechanisms and discuss their relevance in terms of known human disorders of tooth eruption.


Subject(s)
Tooth Eruption , Tooth Eruption/physiology , Humans , Animals , Mice
6.
Transplant Cell Ther ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39179107

ABSTRACT

BACKGROUND: Recipients of cellular therapies, including hematopoietic cell transplant (HCT) and chimeric antigen receptor T-cell (CART) therapy, are at risk for poor outcomes from coronavirus disease 2019 (COVID-19). There are limited data describing outcomes among patients in the pre- and early post-cellular therapy period during the Omicron era when multiple antiviral therapeutics were widely available. OBJECTIVES: Describe COVID-19 treatment and outcomes in patients diagnosed with COVID-19 during the pre- or early post-cellular therapy period. STUDY DESIGN: This is a single-center retrospective cohort study of adult HCT and CART recipients diagnosed with COVID-19 in the pre- and early post-cellular therapy period who tested positive for COVID-19 at our cancer center between January 1, 2022 and March 1, 2023. Primary outcomes were 30-day COVID-19-related hospitalization and death. A secondary outcome was development of persistent COVID-19, defined by a positive SARS-CoV-2 polymerase chain reaction (PCR) 31-90 days after COVID-19 diagnosis. RESULTS: Among 65 patients included, 52 (80%) received at least one COVID-19 therapeutic. The most common treatment after initial COVID-19 diagnosis was nirmatrelvir/ritonavir (29%), followed by monoclonal antibody therapy (26%) and remdesivir (11%). Of the 64 patients with at least 30 days of follow-up, 8 (12%) had at least one COVID-19-related hospitalization and one patient died, though cause of death was not due to COVID-19. Of the 8 patients hospitalized for COVID-19, one had severe disease and 7 had mild or moderate infection. Persistent COVID-19 was observed in 13/65 (20%) patients, with 4 patients requiring additional antiviral therapy. Three pre-cellular therapy patients had delays in receiving cellular therapy due to persistent COVID-19. CONCLUSIONS: During the Omicron era, rates of 30-day COVID-19-related hospitalization and death were relatively low in this cohort of pre- and early post-HCT and CART recipients, the majority of whom received treatment with at least one antiviral agent. Persistent COVID-19 occurred in 1 in 5 patients in the peri-cellular therapy period and led to cellular therapy treatment delays in several patients, highlighting the need for new COVID-19 treatment strategies.

7.
Can J Ophthalmol ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39059786

ABSTRACT

OBJECTIVE: To quantify the observed decrease in orbital decompressions being performed at one tertiary care institution and to determine the rate and predictive factors of orbital decompression surgery following treatment with teprotumumab for thyroid eye disease. METHODS: Epic's SlicerDicer program was used to analyze recent trends in the overall number of thyroid eye disease (TED) patients evaluated in the oculoplastic surgery department, as well as usage trends of CPT codes 67445 (lateral orbitotomy with bone removal for decompression) and 67414 (orbitotomy with removal of bone for decompression). A retrospective chart review of active moderate-to-severe TED patients treated with teprotumumab was performed at a single tertiary care center. The main outcome measure was whether or not patients underwent bony orbital decompression surgery following treatment with teprotumumab. The SlicerDicer search demonstrated stable usage of CPT codes 67445 and 67414 from 2016 to 2019, followed by a significant decrease from 2020 to 2023, over a background of increasing numbers of TED patients evaluated in clinic. Following teprotumumab therapy, 25% of patients and 18% of orbits underwent bony decompression. Surgically decompressed patients had higher pre- and post-teprotumumab exophthalmometry measurements compared with patients who did not undergo bony decompression. Average time to decompression following conclusion or cessation of teprotumumab therapy was 12.6 months. CONCLUSION: While the number of TED patients treated at one tertiary care center has risen over recent years, the number of orbital decompression surgeries has declined. Orbital decompression, however, is still needed in select patients after treatment with teprotumumab.

8.
Case Rep Ophthalmol ; 15(1): 483-489, 2024.
Article in English | MEDLINE | ID: mdl-39015227

ABSTRACT

Introduction: Cytomegalovirus (CMV) retinitis in the setting of pediatric retinoblastoma is exceedingly unusual. Here, we present the first reported case of CMV retinitis in an enucleated eye with retinoblastoma after chemotherapy in the western hemisphere. Case Presentation: A 2-year-old Hispanic male without a family history of retinoblastoma presented with a 3-month history of right eye exotropia and squinting. Clinical examination revealed dense white vitreous opacities in the right eye. Ocular oncology evaluation unveiled an exudative retinal detachment with vitreous seeds, subretinal seeding, and a tumor emanating from the retina in the superonasal quadrant of the right eye. The patient was diagnosed with unilateral Group D retinoblastoma, and RB1 sequencing revealed a pathogenic variant with mosaicism. Treatment involved systemic chemotherapy, intravitreal chemotherapy, and cryotherapy. However, the patient developed a rhegmatogenous retinal detachment with diffuse vitreous hemorrhage and ultimately underwent right eye enucleation. Interestingly, histopathological analysis of the enucleated eye revealed concomitant CMV retinitis alongside retinoblastoma. After consultation with infectious disease, antiviral treatment was not initiated as the patient remained asymptomatic and maintained a recovered immune system. Repeat CMV PCR confirmed viral clearance. The patient received a prosthetic eye and continues to be monitored for retinoblastoma recurrence. Conclusion: Clinicians should be aware of the potential for CMV retinitis to develop in retinoblastoma patients receiving chemotherapy, which may complicate clinical decision-making and management. Timely identification of CMV retinitis in this setting may improve patient ocular outcomes and overall prognosis.

10.
Semin Ophthalmol ; 39(6): 424-428, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38842062

ABSTRACT

PURPOSE: Topical prostaglandin analogues are commonly used to treat patients with glaucoma, but may cause periocular and periorbital complications known as prostaglandin-associated periorbitopathy syndrome (PAPS). METHODS: A literature review was conducted on PAPS. Given the lack of consensus on grading PAPS, glaucoma specialists from Asia convened to evaluate current PAPS grading systems and propose additional considerations in grading PAPS. RESULTS: Existing grading systems are limited by the lack of specificity in defining grades and consideration for patients' subjective perception of symptoms. Patient-reported symptoms (e.g., via a self-assessment tool) and additional clinical assessments (e.g., exophthalmometry, lid laxity, differences between tonometry results, baseline measurements, and external ocular photographs) would be beneficial for grading PAPS systematically. CONCLUSIONS: Effective management of PAPS could be facilitated by a common clinical grading system to consistently and accurately diagnose and characterise symptoms. Further research is required to validate specific recommendations and approaches to stage and monitor PAPS.


Subject(s)
Glaucoma , Humans , Glaucoma/drug therapy , Intraocular Pressure/physiology , Intraocular Pressure/drug effects , Orbital Diseases/chemically induced , Orbital Diseases/diagnosis , Asia/epidemiology , Syndrome , Prostaglandins, Synthetic/adverse effects , Antihypertensive Agents/adverse effects
11.
bioRxiv ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38853992

ABSTRACT

Systemic inflammation has been implicated in the development and progression of neurodegenerative conditions such as cognitive impairment and dementia. Recent clinical studies indicate an association between sepsis, endothelial dysfunction, and cognitive decline. However, the investigations of the role and therapeutic potential of the cerebral microvasculature in systemic inflammation-induced cognitive dysfunction have been limited by the lack of standardized experimental models for evaluating the alterations in the cerebral microvasculature and cognition induced by the systemic inflammatory response. Herein, we validated a mouse model of endotoxemia that recapitulates key pathophysiology related to sepsis-induced cognitive dysfunction, including the induction of an acute systemic hyperinflammatory response, blood-brain barrier (BBB) leakage, neurovascular inflammation, and memory impairment after recovery from the systemic inflammatory response. In the acute phase, we identified novel molecular (e.g. upregulation of plasmalemma vesicle associated protein, a driver of endothelial permeability, and the pro-coagulant plasminogen activator inhibitor-1, PAI-1) and functional perturbations (i.e., albumin and small molecule BBB leakage) in the cerebral microvasculature along with neuroinflammation. Remarkably, small molecule BBB permeability, elevated levels of PAI-1, intra/perivascular fibrin/fibrinogen deposition and microglial activation persisted 1 month after recovery from sepsis. We also highlight molecular neuronal alterations of potential clinical relevance following systemic inflammation including changes in neurofilament phosphorylation and decreases in postsynaptic density protein 95 and brain-derived neurotrophic factor suggesting diffuse axonal injury, synapse degeneration and impaired neurotrophism. Our study serves as a standardized model to support future mechanistic studies of sepsis-associated cognitive dysfunction and to identify novel endothelial therapeutic targets for this devastating condition. SIGNIFICANCE: The limited knowledge of how systemic inflammation contributes to cognitive decline is a major obstacle to the development of novel therapies for dementia and other neurodegenerative diseases. Clinical evidence supports a role for the cerebral microvasculature in sepsis-induced neurocognitive dysfunction, but the investigation of the underlying mechanisms has been limited by the lack of standardized experimental models. Herein, we optimized a mouse model that recapitulates important pathophysiological aspects of systemic inflammation-induced cognitive decline and identified key alterations in the cerebral microvasculature associated with cognitive dysfunction. Our study provides a reliable experimental model for mechanistic studies and therapeutic discovery of the impact of systemic inflammation on cerebral microvascular function and the development and progression of cognitive impairment.

12.
Bone Marrow Transplant ; 59(8): 1049-1056, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38822141

ABSTRACT

Graft-versus-host disease is among the most common clinical complications following allogeneic hematopoietic stem cell transplantation. It causes inflammation-mediated destruction and dysfunction of various organ systems including ocular tissues in 60-90% of the patients and is termed ocular GVHD (oGVHD). In oGVHD, donor-derived T-cells recognize host antigens as foreign, resulting in immune dysregulation, inflammation and fibrosis of lacrimal glands, meibomian glands, cornea, and conjunctiva. The clinical presentation in oGVHD patients range from mild dry eye symptoms to catastrophic inflammation mediated pathological changes which can cause corneal perforation and blindness. In this review article, we provide detailed insights into the impact of mucosal barrier disruption, the afferent and efferent phases of immunological response involving activation of antigen presenting cells and T cells, respectively. We evaluate the evidence outlining the effector phase of the disease leading to cellular destruction and eventually fibrosis in patients with oGVHD. Finally, we discuss the well-established criteria for the diagnosis of oGVHD.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Graft vs Host Disease/immunology , Eye Diseases/etiology , Eye Diseases/immunology
13.
Plast Reconstr Surg ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38722563

ABSTRACT

BACKGROUND: To compare the outcomes of two types of tarsoconjunctival pedicle flaps for reconstruction of large lower eyelid defects. METHODS: Retrospective medical record review of consecutive patients who underwent centrally-based or laterally-based tarsoconjunctival pedicle transconjunctival flap for lower eyelid reconstruction for defects greater than 50% of the lid margin. Full thickness skin grafts were used for anterior lamellar reconstruction in all cases. The primary outcome measure was eyelid position, function and satisfactory cosmesis. RESULTS: Forty-three patients were identified. Twenty-six patients underwent reconstruction with a centrally-based tarsoconjunctival pedicle flap; 17 patients underwent reconstruction with a laterally-based tarsoconjunctival pedicle flap. The average size of the lid defect was 77.7% (range 50-100%) in the central group and 75% (range 50-100%) in the lateral group (p=0.604). Mean follow up time was 61.5 weeks in the central group and 46.6 weeks in the lateral group (p=0.765). After division of the flap and during follow up, 27% of the centrally based group required revisional surgery with none in the laterally based group (p=0.03). 100% of the patients with centrally based flaps required second staged division of flap, whereas only 52% of patients with a laterally based flaps underwent second staged flap division. (p<0.001). CONCLUSION: Outcome suggests that for reconstruction of large lower lid defects requiring lid sharing procedures, both centrally and lateral-based procedures have equivalent functional outcome. However, the laterally based group has less need for revisional procedures and may not need a second stage division of the flap.

14.
Article in English | MEDLINE | ID: mdl-38722772

ABSTRACT

PURPOSE: This study evaluates the efficacy of teprotumumab in reducing eyelid retraction in thyroid eye disease (TED) patients. METHODS: This retrospective study included patients with active or chronic moderate-to-severe TED who completed at least 4 cycles of teprotumumab. Patients with upper and/or lower eyelid retraction, defined as margin-to-reflex distance (MRD) 1 and/or MRD2 of more than 5 mm, in one or OU were included. The main outcome measure was a change in MRD1 and MRD2 after treatment. Changes in MRD1 and MRD2 were each analyzed for correlation (r) with changes in exophthalmolmetry. Student t test was performed for each comparison, and p values <0.05 were considered significant. RESULTS: The study included 91 patients, predominantly female (87%), with an average age of 52.02 ± 14.6 years. The mean baseline proptosis measurement was 21.8 ± 2.9 OD and 21.7 ± 3.3 OS. The average MRD1 was 5.5 ± 1.5 OD and 5.4 ± 1.7 OS, and the average MRD2 was 6.1 ± 1.1 OD and 6.2 ± 1.1 OS. The follow-up duration post-treatment was 37.5 ± 31.7 weeks. At first follow-up post-treatment, the mean change in proptosis, MRD1, and MRD2 were -2.6 ± 2.0 OD, -2.5 ± 2.1 OS, -0.8.5 ± 1.4 OD, -0.8 ± 1.0 OS, and -0.7 ± 0.9 OD, -0.8 ± 1.0 OS, respectively. Correlation analysis showed that proptosis reduction was positively correlated with MRD1 and MRD2 reduction at the first post-treatment follow-up (MRD1: r = 0.23, p value < 0.01; MRD2: r = 0.17, p = 0.03]. CONCLUSION: Teprotumumab treatment improves upper and lower eyelid retraction. The improvement in MRD correlated positively with proptosis reduction, indicating the influence of globe position on eyelid position.

15.
Article in English | MEDLINE | ID: mdl-38534072

ABSTRACT

PURPOSE: This cross-sectional prospective study measured utility values of upper eyelid dermatochalasis to quantify its impact on quality of life and assess cost-effectiveness of upper blepharoplasty. METHODS: Utility of dermatochalasis was assessed using the standard reference gamble and time trade-off methods, with dual anchor points of perfect eye function and perfect health. The utility value obtained was used to create a Markov model and run a cost-effectiveness analysis of blepharoplasty as a treatment for dermatochalasis while utilizing the societal perspective. RESULTS: One hundred three patients with dermatochalasis recruited from an urban outpatient ophthalmology clinic completed the utility survey. The authors determined utility values for dermatochalasis ranging from 0.74 to 0.92 depending on the measurement method (standard reference gamble/time trade-off) and anchor points. The cost-effectiveness analysis yielded an incremental cost-effectiveness ratio of $3,146 per quality-adjusted life year, well under the conventional willingness-to-pay threshold of $50,000 per quality-adjusted life year. Probabilistic sensitivity analysis with Monte Carlo simulation demonstrated that blepharoplasty would be cost-effective in 88.1% of cases at this willingness-to-pay threshold. CONCLUSIONS: Dermatochalasis has an impact on quality of life that is significantly associated with level of perceived functional impairment. Rising health care costs have underscored the importance of providing value-based treatment to patients, and the results of this study suggest that blepharoplasty is a cost-effective treatment option for symptomatic bilateral upper eyelid dermatochalasis.

17.
J Glaucoma ; 33(9): 709-714, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38551403

ABSTRACT

PRCIS: In the largest clinic-based study to date, our review of 588 patients presenting with glaucoma in Northern Ghana revealed 36% of these had primary angle closure glaucoma (PACG). OBJECTIVE: Glaucoma is the second leading cause of blindness worldwide. In Africa, glaucoma is an established public health problem, and PACG is not commonly discussed. Recognizing it is important because of its negative impact on visual morbidity, and also because its treatment is different from primary open angle glaucoma. In response to the observation of many PACG cases at the Northern Community Eye Hospital in Tamale, Ghana, we investigated the proportion of those attending with a first diagnosis of glaucoma who had PACG. PATIENTS AND METHODS: Using the electronic records, we identified 976 patients who attended with a first diagnosis of glaucoma between January 2021 and October 2022. Of these, 588 met the inclusion criterion of a clear glaucoma subtype diagnosis. RESULTS: Of these 316 (53.7%) had primary open angle glaucoma, 210 (35.7%) PACG, and 62 (10.5%) secondary glaucoma. Thus, over a third of presenting glaucomas had PACG. CONCLUSION: This study highlights that PACG is present in about a third of patients presenting to our clinic in North Ghana. Our study demonstrates the importance of a clear diagnostic pathway including gonioscopy in the assessment of glaucoma patients and the consideration of wider training on angle closure glaucoma diagnosis and management.


Subject(s)
Glaucoma, Angle-Closure , Intraocular Pressure , Humans , Glaucoma, Angle-Closure/diagnosis , Glaucoma, Angle-Closure/epidemiology , Ghana/epidemiology , Male , Female , Middle Aged , Aged , Intraocular Pressure/physiology , Glaucoma, Open-Angle/diagnosis , Glaucoma, Open-Angle/epidemiology , Gonioscopy , Retrospective Studies , Aged, 80 and over , Adult , Tonometry, Ocular , Prevalence , Visual Acuity/physiology
18.
Clin Infect Dis ; 79(1): 86-95, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38427848

ABSTRACT

BACKGROUND: Hematopoietic cell transplant (HCT) or chimeric antigen receptor (CAR) T-cell therapy recipients have high morbidity from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are limited data on outcomes from SARS-CoV-2 infection shortly before cellular therapy and uncertainty whether to delay therapy. METHODS: We conducted a retrospective cohort study of patients with SARS-CoV-2 infection within 90 days before HCT or CAR-T-cell therapy between January 2020 and November 2022. We characterized the kinetics of SARS-CoV-2 detection, clinical outcomes following cellular therapy, and impact on delays in cellular therapy. RESULTS: We identified 37 patients (n = 15 allogeneic HCT, n = 11 autologous HCT, n = 11 CAR-T-cell therapy) with SARS-CoV-2 infections within 90 days of cellular therapy. Most infections (73%) occurred between March and November 2022, when Omicron strains were prevalent. Most patients had asymptomatic (27%) or mild (68%) coronavirus disease 2019 (COVID-19). SARS-CoV-2 positivity lasted a median of 20.0 days (interquartile range, 12.5-26.25 days). The median time from first positive SARS-CoV-2 test to cellular therapy was 45 days (interquartile range, 37.75-70 days); 1 patient tested positive on the day of infusion. After cellular therapy, no patients had recrudescent SARS-CoV-2 infection or COVID-19-related complications. Cellular therapy delays related to SARS-CoV-2 infection occurred in 70% of patients for a median of 37 days. Delays were more common after allogeneic (73%) and autologous (91%) HCT compared to CAR-T-cell therapy (45%). CONCLUSIONS: Patients with asymptomatic or mild COVID-19 may not require prolonged delays in cellular therapy in the context of contemporary circulating variants and availability of antiviral therapies.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive , Receptors, Chimeric Antigen , SARS-CoV-2 , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , COVID-19/therapy , COVID-19/immunology , Female , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , Adult , Immunotherapy, Adoptive/methods , Aged , Receptors, Chimeric Antigen/immunology , Treatment Outcome
19.
Int J Mol Sci ; 25(4)2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38396722

ABSTRACT

Brain metastases represent a significant clinical challenge in the treatment of non-small-cell lung cancer (NSCLC), often leading to a severe decline in patient prognosis and survival. Recent advances in imaging and systemic treatments have increased the detection rates of brain metastases, yet clinical outcomes remain dismal due to the complexity of the metastatic tumor microenvironment (TME) and the lack of specific biomarkers for early detection and targeted therapy. The intricate interplay between NSCLC tumor cells and the surrounding TME in brain metastases is pivotal, influencing tumor progression, immune evasion, and response to therapy. This underscores the necessity for a deeper understanding of the molecular underpinnings of brain metastases, tumor microenvironment, and the identification of actionable biomarkers that can inform multimodal treatment approaches. The goal of this review is to synthesize current insights into the TME and elucidate molecular mechanisms in NSCLC brain metastases. Furthermore, we will explore the promising horizon of emerging biomarkers, both tissue- and liquid-based, that hold the potential to radically transform the treatment strategies and the enhancement of patient outcomes.


Subject(s)
Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Tumor Microenvironment , Biomarkers, Tumor , Brain Neoplasms/pathology
20.
J Am Coll Surg ; 239(2): 134-144, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38357984

ABSTRACT

BACKGROUND: Assigning trauma team activation (TTA) levels for trauma patients is a classification task that machine learning models can help optimize. However, performance is dependent on the "ground-truth" labels used for training. Our purpose was to investigate 2 ground truths, the Cribari matrix and the Need for Trauma Intervention (NFTI), for labeling training data. STUDY DESIGN: Data were retrospectively collected from the institutional trauma registry and electronic medical record, including all pediatric patients (age <18 years) who triggered a TTA (January 2014 to December 2021). Three ground truths were used to label training data: (1) Cribari (Injury Severity Score >15 = full activation), (2) NFTI (positive for any of 6 criteria = full activation), and (3) the union of Cribari+NFTI (either positive = full activation). RESULTS: Of 1,366 patients triaged by trained staff, 143 (10.47%) were considered undertriaged using Cribari, 210 (15.37%) using NFTI, and 273 (19.99%) using Cribari+NFTI. NFTI and Cribari+NFTI were more sensitive to undertriage in patients with penetrating mechanisms of injury (p = 0.006), specifically stab wounds (p = 0.014), compared with Cribari, but Cribari indicated overtriage in more patients who required prehospital airway management (p < 0.001), CPR (p = 0.017), and who had mean lower Glasgow Coma Scale scores on presentation (p < 0.001). The mortality rate was higher in the Cribari overtriage group (7.14%, n = 9) compared with NFTI and Cribari+NFTI (0.00%, n = 0, p = 0.005). CONCLUSIONS: To prioritize patient safety, Cribari+NFTI appears best for training a machine learning algorithm to predict the TTA level.


Subject(s)
Injury Severity Score , Triage , Wounds and Injuries , Humans , Child , Retrospective Studies , Wounds and Injuries/therapy , Wounds and Injuries/diagnosis , Wounds and Injuries/mortality , Female , Male , Child, Preschool , Adolescent , Triage/standards , Triage/methods , Machine Learning , Trauma Centers , Patient Care Team/organization & administration , Infant , Registries
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