Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.

BACKGROUND: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease. METHODS: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival. RESULTS: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%). CONCLUSIONS: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).

Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents.

B-cell maturation antigen (BCMA)-targeting therapies, including bispecific antibodies (BsAbs) and antibody-drug conjugates (ADCs), are promising treatments for multiple myeloma (MM), but disease may progress after their use. CARTITUDE-2 is a phase 2, multicohort study evaluating the safety and efficacy of cilta-cel, an anti-BCMA chimeric antigen receptor T therapy, in various myeloma patient populations. Patients in cohort C progressed despite treatment with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and noncellular anti-BCMA immunotherapy. A single cilta-cel infusion was given after lymphodepletion. The primary end point was minimal residual disease (MRD) negativity at 10-5. Overall, 20 patients were treated (13 ADC exposed; 7 BsAb exposed; 1 in the ADC group also had prior BsAb exposure). Sixteen (80%) were refractory to prior anti-BCMA therapy. At a median follow-up of 11.3 months (range, 0.6-16.0), 7 of 20 (35%) patients were MRD negative (7 of 10 [70.0%] in the MRD-evaluable subset). Overall response rate (95% confidence interval [CI]) was 60.0% (36.1-80.9). Median duration of response and progression-free survival (95% CI) were 11.5 (7.9-not estimable) and 9.1 (1.5-not estimable) months, respectively. The most common adverse events were hematologic. Cytokine release syndrome occurred in 12 (60%) patients (all grade 1-2); 4 had immune effector cell-associated neurotoxicity syndrome (2 had grade 3-4); none had parkinsonism. Seven (35%) patients died (3 of progressive disease, 4 of adverse events [1 treatment related, 3 unrelated]). Cilta-cel induced favorable responses in patients with relapsed/refractory MM and prior exposure to anti-BCMA treatment who had exhausted other therapies. This trial was registered at www.clinicaltrials.gov as NCT04133636.

Treatment with low-dose, single-agent belantamab mafodotin is safe and provides long-term responses in heavily pretreated multiple myeloma patients.

OBJECTIVES: To evaluate whether low-dose belantamab mafodotin (B-MAF) dosing results in lower toxicity and better overall outcome. METHODS: We retrospectively evaluated nine consecutive patients treated with low-dose (1.9 mg/kg) B-MAF. RESULTS: The median age was 70 years. Most patients were penta-refractory. Ocular toxicity was observed in 77.7%. Adverse events resulting in treatment delays were recorded in 9 out of 124 cycles being given. Overall response rate was 66% (6/9), and all responding patients achieved very good partial response or better. Within a median follow-up of 12 (range 0.5-13.8) months, median progression-free survival and overall survival were 14 (CI95% 6-22) and 20 (95%CI 0-41) months, respectively. CONCLUSION: Low-dose B-MAF regimen showed high-efficacy and low-toxicity profile.

The impact of Boric Acid tubes on quantitative urinary bacterial cultures in hospitalized patients.

INTRODUCTION: The accuracy of urine culture results can be affected by pre-analytical factors such as transport delays and storage conditions. The objectives of this study were to analyze urine collection practices and assess the impact of introducing boric acid tubes for urine collection on quantitative urinary bacterial cultures of hospitalized patients in medical wards. METHODS: A quasi-experimental pre-post study conducted in an acute care facility. In the pre-intervention phase (2020-2021), urine samples were transported without preservatives at room temperature. In 2022 (post-intervention), we transitioned to boric acid transport tubes, evaluating its effect on significant bacterial growth (≥ 105 CFU/ml). Bivariate and multivariate analyses identified predictors of culture positivity. RESULTS: Throughout the duration of the study, a total of 12,660 urine cultures were analyzed. Date and time documentation was complete for 38.3% of specimens. Culture positivity was higher with longer processing times: positivity was 21.3% (220/1034) when specimens were processed within 4 h, 28.4% (955/3364) when processed in 4-24 h, and 32.9% (137/417) when processed after 24 h (p < 0.0001). For 4-24-hour processing, positivity decreased from 30.4% (704/2317) pre-intervention to 24.0% (251/1047) post-intervention (p < 0.001), with no significant changes in < 4 or ≥ 24-hour specimens. Stratified analysis by processing time revealed that the intervention was associated with reduced positivity only in cultures processed within 4-24 h (OR 0.80, 95% CI 0.67-0.94; p = 0.008). CONCLUSION: The introduction of boric acid transport tubes predominantly influenced cultures transported within a 4-24-hour window. This presents an opportunity to improve urine tract infection diagnostic practices in healthcare settings.

Sensory disturbances in Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia, motor impairments, and psychiatric symptoms. Sensory disturbances were occasionally reported as well. The study aims to describe the sensory symptoms of the disease. METHODS: The CJD Israeli National Database was screened for patients who presented sensory symptoms throughout the disease course. Symptoms, characteristics, and distribution were reviewed and the demographic and clinical data (sex, etiologies of the disease, age of onset, disease duration, neurological exam finding, tau protein level, EEG and MRI findings) were compared with the demographics and clinical data of CJD without sensory symptoms. Then, the patients with sensory symptoms were divided into patients with symptom distribution consistent with peripheral nervous system (PNS) involvement and central nervous system (CNS) involvement. The demographics and clinical data of the 2 groups were compared. RESULTS: Eighty-four CJD patients with sensory symptoms and 645 CJD patients without sensory symptoms were included in the study. Sensory symptoms were more common in genetic E200K CJD patients (14.6% vs. 5.6% respectively, p = 0.0005) (chi-squared test). Numbness and neuropathic pain were the most common symptoms and distribution of symptoms of "stocking gloves" with decreased deep tendon reflexes suggesting peripheral neuropathy in 44% of the patients. In these patients, the classical EEG findings of Periodic Sharp Wave Complexes were less often found (58% vs. 22%, p = 0.02) (chi-squared test). CONCLUSIONS: Sensory symptoms are more common in E200K patients and often follow peripheral neuropathy distribution that suggests PNS involvement.

Dual anti-viral treatment for persistent COVID-19 in immunocompromised hemato-oncological patients is associated with a favorable prognosis and minor side effects.

In hemato-oncological patients, COVID-19 can present as a persistent infection with ongoing symptoms and viral replication over a prolonged period of time. Data are scarce on the preferred treatment options for these patients. We describe our experience with a five-day course of dual anti-viral treatment with remdesivir and nirmatrelvir/ritonavir for hemato-oncological immunocompromised patients with persistent COVID-19. Fifteen patients with a history of lymphoma, CLL, and MM were included. Eight were male, median age was 74. All patients had an immediate clinical and virological response. In 73 % of patients, PCR for SARS-CoV-2 became negative at the end of treatment and the rest had an increase in PCR cycle threshold (CT) values, with a median increase of 6 cycles. After a follow-up of three months, 60 % of patients remained in full clinical and virological remission. None required invasive mechanical ventilation or died. The side effects we observed, neutropenia, lactatemia and elevated transaminases, were mild and almost all transient in nature. We conclude that dual anti-viral treatment appears to be a valid treatment option for persistent COVID-19.

Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: A multicentre retrospective study.

Belantamab mafodotin, an immuno-conjugate targeting B-cell maturation antigen, showed single-agent activity in phase 1 and 2 studies, and was recently approved for heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients. Real-world data and long-term follow-up are scarce. We conducted a multisite retrospective study aimed to assess safety and efficacy of belantamab mafodotin monotherapy administered via the GSK expanded access compassionate care programme. One-hundred and six RRMM patients were treated with belantamab mafodotin between July 2019 and March 2021. The median age was 69.4 years. Patients were heavily pretreated with a median of six (range 2-11) prior therapy lines. Major adverse effects included ocular toxicity (keratopathy 68.4%, grade ≥3: 40.5%; blurred vision 36.8%, grade ≥3: 6.3%), thrombocytopenia (27.4%, grade ≥3: 17.9%) and infections (11.3%, grade ≥3: 7.5%). Median follow-up time was 11.9 [95% confidence interval (CI) 10.0-13.8] months. Overall response rate was 45.5%. Median progression-free survival was 4.7 (95% CI 3.5-5.9) months in the entire cohort and 8.8 (95% CI 6.6-10.9) months among responders. Median overall survival was 14.5 (95% CI 9.5-19.6) months, and not reached for responders. To conclude, in a real-world setting, belantamab mafodotin monotherapy showed efficacy comparable with the prospective clinical trials, with a tolerable toxicity profile.

Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial.

Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM). HBI0101, a novel second generation optimized anti- BCMA CAR T-cell therapy, was developed in an academic setting. We conducted a phase I dose-escalation study of HBI0101 (cohort 1: 150x106 CAR T cells, n=6; cohort 2: 450x106 CAR T cells, n=7; cohort 3: 800x106 CAR T cells, n=7) in 20 heavily pre-treated R/R MM patients. Grade 1-2 cytokine release syndrome (CRS) was reported in 18 patients (90%). Neither grade 3-4 CRS nor neurotoxicity of any grade were observed. No dose-limiting toxicities were observed in any cohort. The overall response rate (ORR), (stringent) complete response (CR/sCR), and very good partial response rates were 75%, 50%, and 25%, respectively. Response rates were dose-dependent with 85% ORR, 71% CR, and 57% minimal residual disease negativity in the high-dose cohort 3. Across all cohorts, the median overall survival (OS) was 308 days (range 25-466+), with an estimated OS of 55% as of June 27th (data cut-off). The median progression-free survival was 160 days, with 6 subjects remaining progression free at the time of data cut-off. Our findings demonstrate the manageable safety profile and efficacy of HBI0101. These encouraging data support the decentralization of CAR T production in an academic setting, ensuring sufficient CAR T supply to satisfy the increasing local demand. Clinicaltrials.gov NCT04720313.

Management and outcome of 500 multiple myeloma patients treated for first relapse outside clinical studies.

Treatment options for multiple myeloma (MM) at 1st relapse are expanding. The current study compared common 2nd line regimens administered in a real-world setting. MM patients registered in Maccabi health care services and treated with second line therapy during 2014-2020 were evaluated, analyzing factors affecting time to third line therapy (TT3T). The study included 500 MM patients, previously treated with proteasome inhibitor (PI)-based induction. Median age at second line treatment was 68.5 years (IQR: 61.6-76.4). Most patients received a triplet based induction composed of PI (n = 471, 94.2%), with (n = 71) or without IMID (n = 400), followed by second line treatment composed of lenalidomide-dexamethasone (RD) (n = 225, 45%) or lenalidomide-dexamethasone-daratumumab (RD-Dara (n = 104, 20.8%)). Multivariable analysis confirmed treatment type (RD-Dara vs. IMID) to be associated with a lower risk to progress to third line therapy; (HR = 0.5, 95% CI 0.3-0.86, p = 0.012). Within a median follow-up period of 22.5 months (intraquartile range 11.1-39.4 m), median TT3T was not reached in patients receiving RD-Dara vs. 32.4 months (95% CI 18.0-46.8 m) with IMID, 18 months (95% CI 10.4-25.6 m) with IMID-PI and 12.1 months (95% CI 5.6-18.7 m) with PI-based regimen. In contrast, PI vs. IMID-based therapy and increased body weight were associated with a higher likelihood of progression (HR = 2.56 (95% CI 1.49-4.42); HR = 1.43, (95% CI 0.96-2.14), p = 0.08). To conclude, second line therapy with RD-Dara was associated with a significantly longer TT3T compared with IMID-based regimen, longer than obtained with PI-IMID and PI-based regimens, in patients treated outside clinical studies and previously exposed to bortezomib.

Induction of labor in twin pregnancy in patients with a previous cesarean delivery.

BACKGROUND: Trial of labor after cesarean delivery (TOLAC) in twin gestations has been associated with decreased rates of successful vaginal delivery compared to singleton pregnancies, with mixed results regarding maternal and neonatal morbidity. However, induction of labor (IOL) in this unique population has not yet been fully evaluated. OBJECTIVE: To assess success rates and maternal and neonatal outcomes in women with a twin gestation and a previous cesarean delivery undergoing IOL. METHODS: A retrospective cohort study including women with a twin gestation and one previous cesarean delivery undergoing a trial of labor between the years 2009-2020. Patients requiring IOL were compared to those with a spontaneous onset of labor. RESULTS: There were 53 patients who met the inclusion criteria: 31 had a spontaneous onset of labor (58%) and 22 required an IOL. Baseline characteristics were comparable between the groups apart from a history of labor arrest which was more common in the IOL group (40.9% vs. 9.6%, P = 0.006). A successful vaginal delivery occurred in all (100%) women with a spontaneous labor compared to 81% in the IOL group (p = 0.02). Secondary outcomes were comparable. A history of no previous vaginal delivery, maternal obesity, and IOL were associated with TOLAC failure. CONCLUSIONS: IOL after cesarean delivery in twin gestation is associated with an increased risk of TOLAC failure compared to spontaneous onset of labor. However, no adverse neonatal or maternal outcomes were found. IOL in this high-risk population is feasible but patients should be counseled about the lower rate of success.

Influence of mental stress on intraocular pressure and visual field testing: is there a white coat syndrome in glaucoma?

PURPOSE: To investigate the effects of mental stress stimulus on intraocular pressure (IOP) measurement and visual field (VF) testing. METHODS: Patients with open angle glaucoma underwent a baseline IOP measurement and VF testing. Afterwards, they completed a computerized mental stress test (Stroop test) which is a known standardized method to induce mental stress. After test completion, patients underwent a second IOP measurement and VF testing. RESULTS: Seventy-two eyes of 36 patients were enrolled. Mean age was 67.0 ± 9.5 years (range 47-84 years). The mean baseline IOP was 15.0 mmHg, and after the Stroop mental stress test, IOP increased to 16.0 mm Hg (P < 0.001). There was a trend towards significant mean deviation decreased from -6.9 dB to -8.0 dB (P = 0.054, t-test) following the stress test. This difference became significant using the Wilcoxon nonparametric test (P = 0.008). Correlation was found between glaucoma severity and change in IOP (P = 0.02) and PSD (P < 0.01). CONCLUSIONS: We found a small but statistically significant increase in IOP and a trend towards deterioration of visual field mean deviation, following a short mental stress test. Patients with more severe glaucoma showed more pronounced changes. Our results suggest that mental stress could affect IOP measurement in the clinic.

Preferences for end-of-life care settings among the healthy population in Israel-Related socio-demographic variables.

OBJECTIVE: Preferences for end-of-life (EoL) care settings is of considerable interest for developing public health policy and EoL care strategies. Culture, the cause of illness, and background characteristics may impact preferences. The present study aimed to explore preferences for EoL care settings: homes, hospitals, and inpatient hospice units among the general healthy population in Israel. Possible associations between the setting preferences and socio-demographic characteristics were also examined. METHOD: A cross-sectional survey was conducted among 311 healthy adults who were recruited through a representative internet panel of the Israeli population using the Israeli census sampling method. The sex ratio was almost 1:1 with 158 women (50.8%) and 153 men (49.2%). All participants completed self-report measures using an online survey system. The questionnaires assessed sociodemographics and preferences for EoL care settings. RESULTS: This survey revealed that 52.1% of the participants expressed preference for being cared for at home rather than in an inpatient hospice unit, 40.8% expressed being cared for at home rather than in a hospital, while 36.7% had no preference regarding being cared for in hospital or in a hospice unit. Among the socio-demographic variables, only age and gender were found to be significantly associated with preferences for EoL care settings. SIGNIFICANCE OF RESULTS: The present study highlights the need to be cautious when regarding home as the preferred EoL care setting, as some individuals declared that they would prefer EoL hospice/hospital care. Age and gender should be considered when discussing and tailoring strategies regarding EoL preferences.

Factors affecting the professional functioning of health care workers during the COVID-19 pandemic: A cross-sectional study.

AIM: To examine personal and organisational factors related to professional functioning of nurses and physicians during the COVID-19 pandemic. BACKGROUND: Exposure to COVID-19-related stressors has been associated with lower self-reported professional functioning among health care workers. METHODS: A cross-sectional study among 115 hospital workers during the COVID-19 pandemic in Israel was designed to explore (a) personal professional functioning, (b) clarity of guidelines, (c) work organisation by the management, and (d) health care workers' feeling of contribution to a global effort. RESULTS: A feeling of contribution to a global effort while treating patients with COVID-19 mediated the relationships between work organisation by the management and professional functioning (ß = .05, p < .05). The clarity of guidelines for routine procedures (ß = .21, p < .05) and a feeling of ß contribution to a global effort (ß = .34, p < .01) positively predicted professional functioning of nurses and physicians during COVID-19 pandemic (R2 = .19, p < .01). CONCLUSIONS: In order to achieve optimal functioning of health care workers in an emergency, managers should provide clear guidelines and promote workers' feelings of contribution to a global effort. IMPLICATIONS FOR NURSING MANAGEMENT: The provision of clear guidelines and protocols is essential for efficient emergency management. Expressing appreciation for health care workers and providing positive feedback may improve professional functioning.

Humoral response rate and predictors of response to BNT162b2 mRNA COVID19 vaccine in patients with multiple myeloma.

Multiple myeloma (MM) patients are at excess risk for clinically significant COVID19 infection. BNT162b2 mRNA COVID19 (BNT162b2) vaccine provides effective protection against COVID19 for the general population, yet its effect in MM patients may be compromised due to disease and therapy-related factors and was not yet evaluated. This single-centre prospective study included MM patients tested for serological response 14-21 days post second vaccine. Vaccinated healthy volunteers served as controls. In all, 171 MM patients, median age 70 (38-94) were included; 159 active MM and 12 smouldering myeloma (SMM). Seropositive response rate (median titer) was 76% (91 U/ml) in active MM patients vs 98% (992 U/ml) in the 64 controls (P < 0·0001), and 100% (822 U/ml) in SMM patients. Multivariate analysis revealed older age (P = 0·009), exposure to ≥4 novel anti-myeloma drugs (P = 0·02) and hypogammaglobulinaemia (P = 0·002) were associated with lower response rates. None of the novel agents significantly decreased response rate, whereas daratumumab trended towards reduced response (P = 0·08). Adverse events occurred in 53% and 55% of the MM patients and controls, respectively, all transient grade 1-2. In conclusion, BNT162b2 vaccine was safe and provided a high seropositivity rate in MM patients, independent of treatment type. Older, hypogammaglobulinaemic and heavily pretreated patients had lower response rates.

Correlation between BNT162b2 mRNA Covid-19 vaccine-associated hypermetabolic lymphadenopathy and humoral immunity in patients with hematologic malignancy.

PURPOSE: Vaccine-associated hypermetabolic lymphadenopathy (VAHL) is frequently observed on [18F]FDG PET-CT following BNT162b2 administration. Recent data suggest a prominent B cell germinal-center (GC) response elicited by mRNA vaccines in draining lymph nodes. Thus, in this study we aimed to explore the correlation between VAHL and humoral immunity as reflected by post-vaccination serologic testing and by comparing the incidence of VAHL between lymphoma patients treated recently with B cell depleting therapy and those that were not. METHODS: A total of 137 patients with hematologic malignancy that had post-vaccination [18F]FDG PET-CT were included (All-PET group), 86 received both vaccine doses before imaging (PET-2 group). Their VAHL status and grade on imaging were recorded. Among 102 lymphoma patients, 34 (33.3%) were treated during the year prior vaccination with anti-CD20 antibody containing therapy. A subgroup of 54 patients also underwent serologic testing 2-3 weeks after the booster dose, and their anti-spike titers were recorded and graded as well. RESULTS: The overall incidence of VAHL in patients with hematologic malignancy was 31.4%. The 34 lymphoma patients treated during the year prior vaccination with anti-CD20 antibody containing therapy had significantly lower rates of VAHL comparted with all other lymphoma patients (8.8 versus 41.2% in all-PET patients, Pv < 0.01). VAHL rates were 10% in patients with negative serology, 31.3% in patients with low anti-spike titers, and 72.2% in patients with high anti-spike titers. The positive predictive values of VAHL were 90 and 93.3% in all-PET and PET-2 patients, respectively. A positive statistically significant correlation was found between VAHL and serology ranks in All-PET patients (rs = 0.530, Pv < 0.001), and stronger correlation was found in PET-2 patients (rs = 0.642, Pv < 0.001). CONCLUSION: VAHL on [18F]FDG PET-CT of patients with hematologic malignancy may reflect GC B cell proliferation and an effective humoral response elicited by BNT162b2 vaccine.

Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review.

OBJECTIVES: Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting. METHODS: A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations. RESULTS: Forty-nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma (MM). Revised Mayo score was ≥ 3 in 67%. Hematologic overall response rate was 81%, 64% achieved very good partial response (VGPR) or better. Concurrent active MM was associated with lower rates of VGPR (OR 0.19, 95% CI 0.04-0.81; P = .03) in a multi-variate analysis. Cardiac and renal responses were 74% and 73%, respectively. Median progression-free survival (PFS) was 28.4 months and median overall survival (OS) was not reached; 2-year PFS and OS were 68.6 ± 7.5% and 90.4 ± 4.6%, respectively. Hematologic response correlated with prolonged PFS and OS. Daratumumab was safe and well tolerated, no patients discontinued therapy due to toxicity. Our data was aligned with outcomes from a systematic literature review, which identified 10 case series (n = 517) and 2 clinical trials (n = 62) meeting prespecified criteria. CONCLUSIONS: Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting.

Risk of postpartum hemorrhage in multiparous women with Gaucher disease: A call for reconsidering enzyme replacement therapy in all pregnant patients.

For the last three decades, enzyme replacement therapy (ERT) for Gaucher disease (GD) has been available. We aimed to evaluate the effect of ERT on the pregnancy and obstetric outcome in a unique group of multiparous women with type 1 GD (GD1) who had pregnancies with and without ERT. The Gaucher Unit database (1987-2019) was searched for multiparous women who had pregnancies before and after the institution of ERT. Data were collected from the clinic files and study-specific questionnaires. Descriptive, correlation analysis and generalized estimating equations (GEE) were used to study the effect of ERT and confounding variables on study outcomes. We identified 19 women with 105 pregnancies, among which 26 (24.7%) terminated in first-trimester miscarriage. The risk for miscarriage was associated with the severity of GD1 genotype and phenotype, but not with ERT usage. Early postpartum hemorrhage (PPH) was reported in 16 (84%) women after 25 deliveries (31.6%, 95% CI 21.6%-43.1%). The risks of early PPH and red blood cell (RBC) transfusions were significantly lower when ERT was used during pregnancy, OR (95% CI) 0.13 (0.03-0.54) and 0.27 (0.08-0.94), respectively, compared to pregnancies without the use of ERT. Enzyme replacement therapy during pregnancy is risk reducing for early PPH and RBC transfusions in women with GD1. We suggest considering ERT for the benefit of all pregnant women with GD1, including mild GD1.

Microvascular alterations in children with optic disk drusen evaluated by optical coherence tomography angiography.

PURPOSE: To asses changes in vessel density (VD) in children with optic disk drusen (ODD) using swept source optical coherence tomography angiography (OCTA). METHODS: Cross-sectional study of 27 eyes with ODD compared with age-matched controls. Peripapillary and macular VD were measured in the superficial retinal capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC). The correlation between VD changes with alterations in retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and visual field (VF) was analyzed. RESULTS: Mean participant age was 12.5 ± 3.3 years (range, 7-18 years); 63% was females. In the patients vs. controls, median central peripapillary VD was 52.9% vs. 50.6% (p = 0.63) for SCP; 48.1% vs. 53.8% (p = 0.017) for DCP; and 17.0% vs. 28.2% (p = 0.0037) for CC, respectively. VD in the superior and nasal CC layers was significantly lower in the patients (36.3% vs. 56.2%; p < 0.001) and (60.4% vs. 70.3%, p < 0.001), respectively. No significant differences were observed for VD in the macular region. The RNFL was thinner in eyes with superficial drusen versus controls (87 vs. 111 µm; p < 0.001). No significant differences between were observed in GCL thickness (p = 0.13). Nasal SCP and nasal RNFL VD were moderately correlated (r = 0.54, p < 0.01), while mean VF deviation was strongly correlated with median SCP VD in patients with superficial drusen (r = 0.9, p = 0.03). CONCLUSION: Impaired VD was observed in the peripapillary nasal CC in patients with ODD; this impairment was associated with a decreased RNFL thickness. Nasal SCP VD and RNFL thickness were moderately correlated in patients with ODD.

Home exercise in the dart-throwing motion plane after distal radius fractures: A pilot randomized controlled trial.

INTRODUCTION: During daily functions, our wrist moves through an oblique plane, named the dart-throwing motion (DTM) plane. This plane is considered a more stable plane because the proximal carpal row remains relatively immobile. However, rehabilitation programs that incorporate exercising in the DTM plane have yet to be explored. PURPOSE OF THE STUDY: The purpose of this study was to evaluate the rehabilitation outcomes after treatment in the DTM plane compared with outcomes after treatment in the sagittal plane after distal radius fracture. STUDY DESIGN: This is a pilot randomized controlled trial. METHODS: Subjects after open reduction internal fixation were assigned into a research group (N = 12; ages 48.7 ± 7.3) and a control group (N = 12; ages 50.8 ± 15). The control group activated the wrist in the sagittal plane, whereas the research group activated the wrist in the DTM plane. Range of motion, pain levels, functional hand motor skills tests, and satisfaction from self-training exercise were measured before and after a 12-session intervention. RESULTS: The outcome measures were similar between the treatment groups. The research group reported significantly higher satisfaction rates than the control group on topics such as general satisfaction (research group: 3.4 ± 0.7, control group: 2. 5 ± 1.2, P = .030), motivation to exert oneself (research group: 2.8 ± 1.0, control group: 2.3 ± 1.2, P = .009), progressed function (research group: 3.4 ± 0.7, control group: 2.4 ± 1.1, P = .012), and self-training contribution to the daily function (research group: 3.4 ± 0.7, control group: 2.5 ± 1.2, P = .030). DISCUSSION AND CONCLUSION: Pilot results do not favor one treatment method over the other. However, exercising in the DTM plane may contribute to the satisfaction of the client and increase self-training motivation.

Components of metabolic syndrome in patients with multiple myeloma and smoldering multiple myeloma.

BACKGROUND: The prevalences of diabetes mellitus and hypertension, both of which are components of metabolic syndrome, are known to be increased among patients with multiple myeloma (MM), but remain undetermined among patients with smoldering MM (SMM). METHODS: Changes in various components of metabolic syndrome were investigated during the follow-up of patients with either MM or SMM compared to healthy controls. The data of 153 patients (105 with MM and 48 with SMM) and 138 controls were accessed from our medical center's records between 2008 and 2015. We analyzed the patients' data at diagnosis (baseline) and after 1, 3, and 5 years of follow-up. RESULTS: Patients with SMM had a significantly higher prevalence of diabetes, hypertension, and dyslipidemia at baseline compared to controls. A multivariate Cox regression analysis revealed a higher risk to develop dyslipidemia after 1, 3, and 5 years of follow-up among the SMM patients. The MM patients had a higher risk to develop diabetes after 1 year, hypertension after 5 years, and dyslipidemia after 1, 3, and 5 years of follow-up. CONCLUSIONS: These data demonstrate that patients with SMM and those with MM are more prone to develop various components of metabolic syndrome, and they stress the importance of following-up metabolic syndrome components in both groups of patients.