Glaucoma tube shunt surgery with repeat penetrating keratoplasty in an aphakic patient.

We present a complicated case of mixed mechanism glaucoma in the setting of failed corneal transplant and aphakia. The patient was a 54-year old male with HLA B27 uveitis and prior open globe injury. He was left aphakic after cataract extraction and had a subsequent corneal transplant for bullous keratopathy. Due to elevated intraocular pressure in the setting of a failed corneal graft, the decision was made to insert a pars plana tube shunt and perform repeat penetrating keratoplasty as a combined case with the glaucoma, cornea, and retina services. We illustrate the surgical steps and decision making and in this complex case.

Safety and efficacy of acalabrutinib plus bendamustine and rituximab in patients with treatment-naive or relapsed / refractory mantle cell lymphoma: phase Ib trial.

This multicenter, open-label, phase 1b study (ACE-LY-106) assessed the safety and efficacy of acalabrutinib, bendamustine, and rituximab (ABR) in treatment-naive (TN) and relapsed or refractory (R/R) mantle cell lymphoma (MCL). Patients received acalabrutinib from cycle 1 until disease progression or treatment discontinuation, bendamustine on days 1 and 2 of each cycle for up to 6 cycles, and rituximab on day 1 of each cycle for 6 cycles, continuing every other cycle from cycle 8 for 12 additional doses (TN cohort). Eighteen patients enrolled in the TN and 20 in the R/R cohort. Median duration of exposure to acalabrutinib was 34.0 and 14.6 months in the TN and R/R cohorts, respectively. No new safety risks were identified, and most adverse events (AEs) were grades 1 or 2. Thirteen patients from the TN cohort (72.2%) and 17 patients from the R/R cohort (85.0%) reported grade 3-4 AEs, most commonly neutropenia (TN: 38.9%, R/R: 50.0%). AEs leading to death were pneumonitis (n=1, TN cohort), COVID-19, and cerebrospinal meningitis (n=1 each, R/R cohort). Overall response was 94.4% and 85.0% in the TN and R/R cohorts, respectively; complete response rates were 77.8% and 70.0%, respectively. After a median follow-up of 47.6 months, median progression-free survival (PFS) and overall survival (OS) were not reached in the TN cohort. After a median follow-up of 20.4 months, median PFS was 28.6 months and OS was not reached in the R/R cohort. Results indicate that ABR was safe and efficacious, supporting further study in patients with TN MCL. ClinicalTrials.gov identifier: NCT02717624.

A global blueberry phylogeny: Evolution, diversification, and biogeography of Vaccinieae (Ericaceae).

Vaccinieae is a morphologically diverse and species-rich (∼1430 species) tribe in Ericaceae. Although the majority of diversity is tropical, Vaccinieae are best known for temperate crops (i.e., blueberries, cranberries, and lingonberries) in Vaccinium. Vaccinium itself (∼500 species) has been previously suggested as highly polyphyletic and taxonomic boundaries among many of the other genera in the tribe remain uncertain. We assessed the evolutionary history of Vaccinieae with phylogenomic analyses based on a target-enrichment dataset containing 256 low-copy nuclear loci and 210 species representing 30 of the 35 genera in the tribe and 25 of the 29 sections of Vaccinium. We conducted time-calibrated biogeographic analyses and diversification analyses to explore the area of origin and global dispersal history of the tribe. The analysis recovered a temperate North American origin for Vaccinieae approximately 30 million years ago. Tropical diversity of Vaccinieae was inferred to result from multiple, independent movements into the tropics from north-temperate ancestors. Diversification rate increases corresponded to radiation into the Andes and SE Asia. The pseudo-10-locular ovary evolved once in the tribe from the five-locular state, coinciding with the diversification of a major clade that includes most Asian Vaccinium and the group from which commercial blueberries are derived (V. sect. Cyanococcus). A reconstruction from available chromosome counts suggests that a major polyploid event predated the evolution of nearly half the diversity of Vaccinieae. The extent of polyphyly in Vaccinium documented here supports the need for a generic reclassification of the tribe.

High-grade B-cell lymphoma, not otherwise specified: CNS involvement and outcomes in a multi-institutional series.

ABSTRACT: Little is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal = 6, parenchymal = 4, and both = 1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR = 3.5) and testicular (in men) or female pelvic (in women) involvement (OR = 8.1). There was no significant difference in survival outcomes between patients with HGBL NOS with (median PFS = 4 years) or without (median PFS = 2.4 years) baseline CNS involvement (P = 0.45). The cumulative incidence of CNS recurrence at 3 years was 11%. Patients with baseline CNS involvement were at the highest risk (48.5% vs 8% for those without baseline CNS involvement) and were excluded from the risk factors analysis for CNS recurrence. The risk for CNS recurrence was significantly associated with blood or bone marrow involvement, CD5 expression, non-germinal center B-cell subtype, and "dual-expresser lymphoma" phenotype, however, high CNS IPI was not. The prognosis of relapsed HGBL NOS was poor, regardless of whether recurrence was systemic or limited to the CNS, and with currently available salvage strategies, including autologous transplantation and chimeric antigen receptor T-cell modalities, almost all patients with CNS recurrence ultimately succumbed to their disease.

Siponimod-associated cystoid macular edema without known risk factors.

Purpose: This case report highlights the importance of monitoring ocular health for patients starting on siponimod treatment, a sphingosine-1-phosphate receptor modulator, for relapsing-remitting multiple sclerosis. By showing how medication adverse events present in patients, we can revisit the current guidelines on ophthalmic evaluation recommendations. Observations: We report a 60-year-old patient who presented with unilateral blurry vision upon initiating siponimod therapy for the treatment of relapsing-remitting multiple sclerosis. Her exam findings did not show visual field defects but were significant for cystoid macular edema distorting the foveal contour. Upon stopping siponimod therapy, the patient's macular edema and symptoms resolved significantly within 7 days and completely resolved 1 month later. Conclusions and importance: This case showcases siponimod-associated cystoid macular edema in a patient without known risk factors, such as diabetes mellitus and uveitis. The patient also had the earliest reported symptom onset to date following the initiation of siponimod therapy. Current recommendations from the American Academy of Ophthalmology and FDA stress the importance of ophthalmic evaluation three to four months after treatment initiation for patients with a history of risk factors. Given our current case and its comparison with four previously reported cases, we recommend that physicians inform patients of possible ocular adverse events with siponimod therapy regardless of their past medical history and duration of treatment.

Radiology-Pathology Concordance and Prognostication of Nodal Features in pN+ Oral Cavity Cancer.

BACKGROUND AND PURPOSE: The aims of our study are to evaluate the diagnostic performance and prognostic value of radiological lymph node (LN) characteristics in pN+ oral cavity squamous carcinoma (OSCC). MATERIALS AND METHODS: pN+ OSCC treated between 2012 and 2020 were included. Preoperative imaging was reviewed by a single radiologist blinded to pathologic findings for the following nodal features: imaging-positive LN (iN+), laterality and total number, and image-identified extranodal extension (iENE). The sensitivity of iN+ for pN+ was calculated. The diagnostic performance of other nodal features was evaluated in the iN+ subgroup. The association of radiologic nodal features with overall survival (OS) was evaluated. Inter-rater kappa for radiologic nodal features was assessed in 100 randomly selected cases. RESULTS: Of 406 pN+ OSCC, 288 were iN+. The sensitivity of iN+ for pN+ was 71% overall, and improved to 89% for pN+ LN >1.5 cm. Within iN+, sensitivity/specificity for LN size (>3 cm), total LN number (>4), and ENE were 0.44/0.95, 0.57/0.84, and 0.27/0.96, respectively. Sensitivity of iENE was higher in the subset, with major (>2 mm) versus minor (≤2 mm) pENE (43% vs. 13%, p = 0.001). Reduced OS was observed in iN+ versus iN- (p = 0.006), iENE+ versus iENE- (p = 0.004), LN size >3 versus ≤3 cm (p < 0.001), and higher LN number (p < 0.001). Inter-rater kappa for iN+, laterality, total LN number, and presence of iENE were 0.71, 0.57, 0.78, and 0.69, respectively. CONCLUSION: Our study shows that despite modest sensitivity of most radiological nodal features, the specificity of image-identified nodal features is high and their prognostic values are retained in pN+ OSCC. LEVEL OF EVIDENCE: Level 3 (retrospective review comparing cases and controls) Laryngoscope, 2024.

Ulcerated CRTC1::TRIM11 cutaneous tumor with metastases.

CRTC1::TRIM11 cutaneous tumor (CTCT) is a rare skin tumor of uncertain differentiation. In the 49 reported cases, only four cases showed regional or distant metastasis, but follow-up remains limited. Herein, we present a case of metastatic CTCT with ulceration, a histological feature that has not been previously described. A 75-year-old male with a 2-month history of toe ulceration underwent a shave biopsy, which showed a dermal nodular neoplasm that was immunoreactive for SOX10 and S100, negative for Melan-A, and was initially diagnosed as melanoma. Upon pathology review at our institution, the tumor was composed of intersecting fascicles and nests of epithelioid and spindle cells. Additional immunohistochemistry revealed immunoreactivity of the tumor for MiTF and NTRK and negativity for HMB-45 and PRAME. Next-generation sequencing identified CRTC1::TRIM11 fusion, leading to a revised diagnosis of CTCT. The patient proceeded to a toe amputation and sentinel lymph node (SLN) biopsy 5 months after the shave biopsy. The amputation showed residual CTCT and a focus on lymphovascular invasion. The SLN revealed multifocal subcapsular metastases. The patient was started on adjuvant nivolumab and showed biopsy-proven recurrence in the right inguinal lymph nodes and imaging findings suspicious for pulmonary metastases 8 months after the excision. In summary, we present a case of CTCT with ulceration and lymphovascular invasion. We also provide additional evidence that a subset of CTCT behaves aggressively. The optimal surgical and medical treatments are unknown.

Evaluation of deep-learning TSE images in clinical musculoskeletal imaging.

In this study, we compared the fat-saturated (FS) and non-FS turbo spin echo (TSE) magnetic resonance imaging knee sequences reconstructed conventionally (conventional-TSE) against a deep learning-based reconstruction of accelerated TSE (DL-TSE) scans. A total of 232 conventional-TSE and DL-TSE image pairs were acquired for comparison. For each consenting patient, one of the clinically acquired conventional-TSE proton density-weighted sequences in the sagittal or coronal planes (FS and non-FS), or in the axial plane (non-FS), was repeated using a research DL-TSE sequence. The DL-TSE reconstruction resulted in an image resolution that increased by at least 45% and scan times that were up to 52% faster compared to the conventional TSE. All images were acquired on a MAGNETOM Vida 3T scanner (Siemens Healthineers AG, Erlangen, Germany). The reporting radiologists, blinded to the acquisition time, were requested to qualitatively compare the DL-TSE against the conventional-TSE reconstructions. Despite having a faster acquisition time, the DL-TSE was rated to depict smaller structures better for 139/232 (60%) cases, equivalent for 72/232 (31%) cases and worse for 21/232 (9%) cases compared to the conventional-TSE. Overall, the radiologists preferred the DL-TSE reconstruction in 124/232 (53%) cases and stated no preference, implying equivalence, for 65/232 (28%) cases. DL-TSE reconstructions enabled faster acquisition times while enhancing spatial resolution and preserving the image contrast. From these results, the DL-TSE provided added or comparable clinical value and utility in less time. DL-TSE offers the opportunity to further reduce the overall examination time and improve patient comfort with no loss in diagnostic accuracy.

An Examination into the Effects of a Nutraceutical Supplement on Cognition, Stress, Eye Health, and Skin Satisfaction in Adults with Self-Reported Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory (p = 0.037), but not for working memory (p = 0.418) or verbal learning (p = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire (p = 0.022), increased plasma brain-derived neurotrophic factor (p = 0.030), decreased plasma malondialdehyde (p = 0.040), and increased skin carotenoid concentrations (p = 0.006). However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

The link between ancient whole-genome duplications and cold adaptations in the Caryophyllaceae.

PREMISE: The Caryophyllaceae (the carnation family) have undergone multiple transitions into colder climates and convergence on cushion plant adaptation, indicating that they may provide a natural system for cold adaptation research. Previous research has suggested that putative ancient whole-genome duplications (WGDs) are correlated with niche shifts into colder climates across the Caryophyllales. Here, we explored the genomic changes potentially involved in one of these discovered shifts in the Caryophyllaceae. METHODS: We constructed a data set combining 26 newly generated transcriptomes with 45 published transcriptomes, including 11 cushion plant species across seven genera. With this data set, we inferred a dated phylogeny for the Caryophyllaceae and mapped ancient WGDs and gene duplications onto the phylogeny. We also examined functional groups enriched for gene duplications related to the climatic shift. RESULTS: The ASTRAL topology was mostly congruent with the current consensus of relationships within the family. We inferred 15 putative ancient WGDs in the family, including eight that have not been previously published. The oldest ancient WGD (ca. 64.4-56.7 million years ago), WGD1, was found to be associated with a shift into colder climates by previous research. Gene regions associated with ubiquitination were overrepresented in gene duplications retained after WGD1 and those convergently retained by cushion plants in Colobanthus and Eremogone, along with other functional annotations. CONCLUSIONS: Gene family expansions induced by ancient WGDs may have contributed to the shifts to cold climatic niches in the Caryophyllaceae. Transcriptomic data are crucial resources that help unravel heterogeneity in deep-time evolutionary patterns in plants.

Molecular determinants of Ras-mTORC2 signaling.

Recent research has identified the mechanistic Target of Rapamycin Complex 2 (mTORC2) as a conserved direct effector of Ras proteins. While previous studies suggested the involvement of the Switch I (SWI) effector domain of Ras in binding mTORC2 components, the regulation of the Ras-mTORC2 pathway is not entirely understood. In Dictyostelium, mTORC2 is selectively activated by the Ras protein RasC, and the RasC-mTORC2 pathway then mediates chemotaxis to cAMP and cellular aggregation by regulating the actin cytoskeleton and promoting cAMP signal relay. Here, we investigated the role of specific residues in RasC's SWI, C-terminal allosteric domain, and hypervariable region (HVR) related to mTORC2 activation. Interestingly, our results suggest that RasC SWI residue A31, which was previously implicated in RasC-mediated aggregation, regulates RasC's specific activation by the Aimless RasGEF. On the other hand, our investigation identified a crucial role for RasC SWI residue T36, with secondary contributions from E38 and allosteric domain residues. Finally, we found that conserved basic residues and the adjacent prenylation site in the HVR, which are crucial for RasC's membrane localization, are essential for RasC-mTORC2 pathway activation by allowing for both RasC's own cAMP-induced activation and its subsequent activation of mTORC2. Therefore, our findings revealed new determinants of RasC-mTORC2 pathway specificity in Dictyostelium, contributing to a deeper understanding of Ras signaling regulation in eukaryotic cells.

Acalabrutinib plus venetoclax and rituximab in treatment-naive mantle cell lymphoma: 2-year safety and efficacy analysis.

ABSTRACT: This phase 1b study evaluated safety and efficacy of acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive mantle cell lymphoma (TN MCL). Patients received acalabrutinib from cycle 1 until progressive disease (PD) or undue toxicity, rituximab for 6 cycles with maintenance every other cycle through cycle 24 or until PD, and venetoclax, beginning at cycle 2, for 24 cycles. Twenty-one patients were enrolled; 95.2% completed induction (6 AVR cycles) and 47.6% continued acalabrutinib maintenance. Thirteen (61.9%) patients had grade 3-4 adverse events (AEs), most commonly neutropenia (33.3%). Seven (33.3%) patients had COVID-19 infection (6 [28.6%] serious AEs and 5 [23.8%] deaths, all among unvaccinated patients). There was no grade ≥3 atrial fibrillation, ventricular tachyarrhythmias, major hemorrhages, or tumor lysis syndrome. Overall response rate (ORR) was 100% (95% CI, 83.9-100.0) with 71.4% complete response. With median follow-up of 27.8 months, median progression-free survival (PFS) and overall survival (OS) were not reached. PFS rates at 1 and 2 years were 90.5% (95% CI, 67.0-97.5) and 63.2% (95% CI, 34.7-82.0), respectively; both were 95% after censoring COVID-19 deaths. OS rates at 1 and 2 years were 95.2% (95% CI, 70.7-99.3) and 75.2% (95% CI, 50.3-88.9), respectively; both were 100% after censoring COVID-19 deaths. Overall, 87.5% of patients with available minimal residual disease (MRD) data achieved MRD negativity (10-6; next-generation sequencing) during treatment. AVR represents a chemotherapy-free regimen for TN MCL and resulted in high ORR and high rates of MRD negativity. The trial was registered at www.ClinicalTrials.gov as #NCT02717624.

Implications of Malignancy, Radiation, and Timing of Major Nasal Reconstruction.

Owing to the complex, multilayered anatomy of the nose in the central face, major nasal reconstruction can pose a significant challenge for reconstructive surgeons. It is the responsibility of reconstructive surgeons to have an understanding of the most common cutaneous malignancies and excisional techniques that may lead to complex nasal defects. The purpose of this article is to discuss these malignancies, excisional techniques, and impacts of radiation on tissue that has implications for reconstructive surgeons.

The impact of a regionally based translational cancer research collaborative in Australia using the FAIT methodology.

BACKGROUND: Translating research, achieving impact, and assessing impact are important aspirations for all research collaboratives but can prove challenging. The Hunter Cancer Research Alliance (HCRA) was funded from 2014 to 2021 to enhance capacity and productivity in cancer research in a regional centre in Australia. This study aimed to assess the impact and benefit of the HCRA to help inform future research investments of this type. METHOD: The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred methodology. FAIT incorporates three validated methodologies for assessing impact: 1) Modified Payback; 2) Economic Analysis; and 3) Narrative overview and case studies. All three FAIT methods are underpinned by a Program Logic Model. Data were collected from HCRA and the University of Newcastle administrative records, directly from HCRA members, and website searches. RESULTS: In addition to advancing knowledge and providing capacity building support to members via grants, fellowships, scholarships, training, events and targeted translation support, key impacts of HCRA-member research teams included: (i) the establishment of a regional biobank that has distributed over 13,600 samples and became largely self-sustaining; (ii) conservatively leveraging $43.8 M (s.a.$20.5 M - $160.5 M) in funding and support from the initial $9.7 M investment; (iii) contributing to clinical practice guidelines and securing a patent for identification of stem cells for endometrial cell regeneration; (iv) shifting the treatment paradigm for all tumour types that rely on nerve cell innervation, (v) development and implementation of the world's first real-time patient treatment verification system (Watchdog); (vi) inventing the effective 'EAT' psychological intervention to improve nutrition and outcomes in people experiencing radiotherapy for head and neck cancer; (vi) developing effective interventions to reduce smoking rates among priority groups, currently being rolled out to disadvantaged populations in NSW; and (vii) establishing a Consumer Advisory Panel and Consumer Engagement Committee to increase consumer involvement in research. CONCLUSION: Using FAIT methodology, we have demonstrated the significant impact and downstream benefits that can be achieved by the provision of infrastructure-type funding to regional and rural research collaboratives to help address inequities in research activity and health outcomes and demonstrates a positive return on investment.

Optimal antiseptic skin preparation agents for minimizing surgical site infection following surgery: cost and cost-effectiveness analysis.

BACKGROUND: The application of antiseptic skin agents prior to incision minimizes the rate of surgical site infection. Despite their ubiquity, the optimal skin preparation agent remains uncertain. A retrospective economic analysis was conducted to complement the results from the NEWSkin Prep trial which prospectively compared three preparation agents. METHODS: A cost and cost-effectiveness analysis was performed from a healthcare service perspective to compare chlorhexidine with 70% ethanol, and aqueous povidone-iodine, against povidone-iodine with 70% ethanol. Resource use estimates accounted for hospital admissions, readmissions associated with surgical site infection, outpatient and general practitioner attendances, visits from community nurses and therapeutic consumables. The measure of effectiveness comprised the net difference in number of patients with surgical site infections per 1000 patients. Costs were compared using a two-sample Welch's t-test. Deterministic and probabilistic sensitivity analyses were performed to evaluate the incremental cost-effectiveness ratio. RESULTS: The null hypothesis that the mean costs for the trial arms were significantly different was not rejected (Welch's t-test P value: 0.771 for chlorhexidine with 70% ethanol against povidone-iodine with 70% ethanol; and 0.955 for aqueous povidone-iodine against povidone-iodine with 70% ethanol). Based on bootstrap averages, the chlorhexidine with 70% ethanol intervention generated 8.0 fewer surgical site infections per 1000 patients and net cost savings of €151,698 (Euros) per 1000 patients compared with povidone-iodine with 70% ethanol, and aqueous povidone-iodine produced a net cost saving of €37,494 per 1000 patients but generated an additional 11.6 surgical site infections per 1000 patients compared with povidone-iodine with 70% ethanol. The comparison of chlorhexidine with 70% ethanol to povidone-iodine with 70% ethanol was sensitive to the inclusion of cost outliers, while the comparison of aqueous povidone-iodine to povidone-iodine with 70% ethanol was sensitive to the estimated cost per surgical site infection. CONCLUSION: Based on the outcomes from the NEWSkin Prep study, this economic analysis found no definitive evidence in favour of any one of the study comparators. Future model-based economic analyses of alternative skin preparations should critically address the quality of evidence and integrate the results from the NEWSkin Prep study.

High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models.

Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T cell therapies include prevention of graft-vs-host disease (GvHD) and suppression of allograft rejection. Here, we describe preclinical data supporting the ongoing first-in-human clinical study, the CaMMouflage trial (NCT05722418), evaluating CB-011 in patients with relapsed/refractory multiple myeloma. CB-011 is a hypoimmunogenic, allogeneic anti-B-cell maturation antigen (BCMA) CAR T cell therapy candidate. CB-011 cells feature 4 genomic alterations and were engineered from healthy donor-derived T cells using a Cas12a CRISPR hybrid RNA-DNA (chRDNA) genome-editing technology platform. To address allograft rejection, CAR T cells were engineered to prevent endogenous HLA class I complex expression and overexpress a single-chain polyprotein complex composed of beta-2 microglobulin (B2M) tethered to HLA-E. In addition, T-cell receptor (TCR) expression was disrupted at the TCR alpha constant locus in combination with the site-specific insertion of a humanized BCMA-specific CAR. CB-011 cells exhibited robust plasmablast cytotoxicity in vitro in a mixed lymphocyte reaction in cell cocultures derived from patients with multiple myeloma. In addition, CB-011 cells demonstrated suppressed recognition by and cytotoxicity from HLA-mismatched T cells. CB-011 cells were protected from natural killer cell-mediated cytotoxicity in vitro and in vivo due to endogenous promoter-driven expression of B2M-HLA-E. Potent antitumor efficacy, when combined with an immune-cloaking armoring strategy to dampen allograft rejection, offers optimized therapeutic potential in multiple myeloma. See related Spotlight by Caimi and Melenhorst, p. 385.

Hypertension treatment for patients receiving ibrutinib: a multicenter retrospective study.

ABSTRACT: Although Bruton tyrosine kinase inhibitors (BTKis) are generally well tolerated and less toxic than chemotherapy alternatives used to treat lymphoid malignancies, BTKis like ibrutinib have the potential to cause new or worsening hypertension (HTN). Little is known about the optimal treatment of BTKi-associated HTN. Randomly selected patients with lymphoid malignancies on a BTKi and antihypertensive drug(s) and with at least 3 months of follow-up data were sorted into 2 groups: those diagnosed with HTN before BTKi initiation (prior-HTN), and those diagnosed with HTN after BTKi initiation (de novo HTN). Generalized estimating equations assessed associations between time varying mean arterial pressures (MAPs) and individual anti-HTN drug categories. Of 196 patients included in the study, 118 had prior-HTN, and 78 developed de novo HTN. Statistically significant mean MAP reductions were observed in patients with prior-HTN who took ß blockers (BBs) with hydrochlorothiazide (HCTZ), (-5.05 mmHg; 95% confidence interval [CI], 10.0 to -0.0596; P = .047), and patients diagnosed with de novo HTN who took either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) with HCTZ (-5.47 mmHg; 95% CI, 10.9 to -0.001; P = .05). These regimens also correlated with the greatest percentages of normotensive MAPs. Treatment of HTN in patients taking a BTKi is challenging and may require multiple antihypertensives. Patients with prior-HTN appear to benefit from combination regimens with BBs and HCTZ, whereas patients with de novo HTN appear to benefit from ACEi/ARBs with HCTZ. These results should be confirmed in prospective studies.