Case report: Sequential inotuzumab, blinatumomab, and chemotherapy with concurrent donor lymphocyte infusions induce complete remission in relapsed pre-B acute lymphoblastic leukemia.

This case report presents the successful management of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia in a 54-year-old male post-allogeneic hematopoietic cell transplantation. The combinatorial approach of sequential antibody treatment (Inotuzumab [InO] and Blinatumomab [Blina]) combined with three donor lymphocyte infusions (DLI) applications and cytoreductive chemotherapy-induced sustained complete molecular remission as documented at the last follow-up 30 months later. This case highlights the feasibility and potential synergistic efficacy of a Blina/DLI regimen and supports the hypothesis that T-cell engagers could enhance the DLI effect. Furthermore, the co-administration of InO, Blina, DLI, and cytoreductive chemotherapy was proven to be feasible without severe adverse events.

Supplemental greenhouse lighting increased the water use efficiency, crop growth, and cutting production in Cannabis sativa.

The expanding cannabis production sector faces economic challenges, intensified by freshwater scarcity in the main US production areas. Greenhouse cultivation harnesses sunlight to reduce production costs, yet the impact of greenhouse light levels on crucial production components, such as plant growth, branching, and water use efficiency (WUE), remains poorly understood. This study aimed to assess the effects of combined sunlight and supplemental lighting on the crop's main production components and leaf gas exchange of Cannabis sativa 'Suver Haze' in the vegetative stage. Within a greenhouse, LED lighting provided at intensities of ~150, 300, 500, and 700 µmol m-2 s-1 (18-hour photoperiod), combined with solar radiation, resulted in average daily light integrals of 17.9, 29.8, 39.5, and 51.8 mol m-2 d-1. Increasing light levels linearly increased biomass, leaf area, and the number of branches per plant and square meter, with respective rates of 0.26 g, 32.5 cm2, and 0.41 branches per mole of additional light. As anticipated, crop evapotranspiration increased by 1.8-fold with the increase in light intensity yet crop WUE improved by 1.6-fold when comparing the lowest and highest light treatments. Moreover, water requirements per unit of plant biomass decreased from 0.37 to 0.24 liters per gram when lighting increased from ~18 to 52 mol m-2 d-1, marking a 35% reduction in evapotranspiration. These results were supported by increments in leaf photosynthesis and WUE with light enhancement. Furthermore, our findings indicate that even 52 mol m-2 d-1 of supplemental lighting did not saturate any of the crop responses to light and can be economically viable for cannabis nurseries. In conclusion, light supplementation strongly enhanced photosynthesis and plant growth while increasing WUE. Additionally, a comprehensive discussion highlights the shared physiological mechanisms governing WUE in diverse plant species and their potential for water conservation under enhanced lighting conditions.

The graft versus leukemia effect: donor lymphocyte infusions and cellular therapy.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many hematologic malignancies as well as non-malignant conditions. Part of the curative basis underlying HSCT for hematologic malignancies relies upon induction of the graft versus leukemia (GVL) effect in which donor immune cells recognize and eliminate residual malignant cells within the recipient, thereby maintaining remission. GVL is a clinically evident phenomenon; however, specific cell types responsible for inducing this effect and molecular mechanisms involved remain largely undefined. One of the best examples of GVL is observed after donor lymphocyte infusions (DLI), an established therapy for relapsed disease or incipient/anticipated relapse. DLI involves infusion of peripheral blood lymphocytes from the original HSCT donor into the recipient. Sustained remission can be observed in 20-80% of patients treated with DLI depending upon the underlying disease and the intrinsic burden of targeted cells. In this review, we will discuss current knowledge about mechanisms of GVL after DLI, experimental strategies for augmenting GVL by manipulation of DLI (e.g. neoantigen vaccination, specific cell type selection/depletion) and research outlook for improving DLI and cellular immunotherapies for hematologic malignancies through better molecular definition of the GVL effect.

The Energy Requirement for Supplemental Greenhouse Lighting Can Be Reduced by Considering 'Excess' Light from the Previous Day.

The sunlight greenhouse crops receive varies and is often insufficient for consistent year-round growth in greenhouses. Supplemental lighting is commonly applied in winter, but this practice has a significant energy cost, accounting for 10-30% of operating expenses and impacting greenhouse profitability. Greenhouse lights are traditionally adjusted based on sunlight intensity to meet crops' daily light requirements. However, if plants can withstand lower daily light integrals (DLI) after a sunny day without reducing the growth, there is potential to reduce the energy required for supplemental lighting and increase the profit. To determine whether excess light received one day can be 'carried over' to the next, we grew oakleaf lettuce (Lactuca sativa 'Green Salad Bowl' and 'Red Salad Bowl') under six lighting regimes inside a vertical farm. Plants in all treatments received an average DLI of 15 mol·m-2·d-1, but DLIs alternated from day-to-day (15/15, 17.5/12.5, 20/10, 22.5/7.5, 25/5, and 27.5/2.5 mol·m-2·d-1), resulting in DLI fluctuations from 0 to 25 mol·m-2·d-1. Plants had similar leaf area (~800 cm2/plant) and dry weight (~1.8 g/plant) when grown with DLI fluctuations from 0 to 15 mol·m-2·d-1, while higher DLI fluctuation reduced growth. To confirm this DLI "carrying-over" effect on plants grown under sunlight with supplemental light, we conducted a second study in a greenhouse with 'Green Salad Bowl' lettuce. In this study, plants were grown with five different DLI fluctuations (15/15, 16.75/13.25, 18.5/11.5, 20.25/9.75, and 22/8 mol·m-2·d-1), ranging from 0 to 14 mol·m-2·d-1, while maintaining an average DLI of 15 mol·m-2·d-1 in all the treatments. We observed similar leaf area (~750 cm2/plant) and dry weight (~1.8 g/plant) in lettuce plants grown with DLI fluctuations from 0 to 10.5 mol·m-2·d-1. Higher DLI fluctuations reduced growth. Hence, carrying excess light from a sunny to an overcast day is possible within limits. Our study concluded that the DLI requirement can be reduced by approximately 5.25 mol·m-2·d-1 on the day following a sunny day. By analyzing historical weather data from five US locations, we quantified the potential annual energy savings from incorporating this 'carrying-over DLI' concept. This approach resulted in annual energy savings of approximately 75-190 MWh/ha in greenhouse lettuce production. Such reductions in supplemental lighting energy will enhance the profitability and sustainability of the greenhouse industry.

Remission of relapsed/refractory classical Hodgkin lymphoma induced by brentuximab vedotin and pembrolizumab combination after allogeneic hematopoietic stem cell transplantation: a case report.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with highly chemorefractory Hodgkin lymphoma (HL). The CD30-targeting antibody-drug conjugate Brentuximab-Vedotin (BV) and programmed cell death protein-1 (PD-1) blocking agents have demonstrated clinical activity with durable responses in relapsed/refractory (r/r) HL. However, patients with a history of allo-HSCT were frequently excluded from clinical trials due to concerns about the risk of graft-versus-host disease (GVHD). We report the clinical history of a patient with refractory classical HL who underwent two allo-HSCTs (first from matched unrelated and second from haploidentical donor) after relapsing on BV and nivolumab and for whom durable remission was finally obtained using BV-pembrolizumab combination for relapse after haploidentical HSCT. Such treatment was associated with the onset of GVHD after only two cycles which led to treatment discontinuation. However, the side effects were rapidly controlled, and after 2 years of follow-up, the patient is still in remission. Our data support the feasibility and efficacy of combining PD-1 blockade with BV to enhance the graft-versus-lymphoma effect after allo-HSCT.

Perioperative outcomes of ileorectal anastomosis - an analysis of 823 patients.

AIM: Ileorectal anastomosis (IRA) following total abdominal colectomy (TAC) allows for resortation of bowel continuity but prior studies have reported rates of anastomotic leak (AL) to be as high as 23%. We aimed to report rates of AL and complications in a large cohort of patients undergoing IRA. We hypothesized that AL rates were lower than previously reported and that selective use of diverting loop ileostomy (DLI) is associated with decreased AL rates. METHOD: Patients undergoing TAC or end-ileostomy reversal with IRA, with or without DLI, between 1980 and 2021 were identified from a prospectively maintained institutional database and retrospectively analysed. Redo IRA cases were excluded. Short-term (30-day) surgical outcomes were collected using our database. AL was defined using a combination of imaging and, in the case of return to the operating room, intraoperative findings. RESULTS: Of 823 patients in the study cohort, DLI was performed in 27% and performed more frequently for constipation and inflammatory bowel disease. The overall AL rate was 3% (1% and 4% in those with and without DLI, respectively) and diversion was found to be protective against leak (OR 0.28, 95% CI 0.08-0.94, p = 0.04). However, patients undergoing diversion had a higher overall rate of postoperative complications (51% vs. 36%, p < 0.001) including superficial wound infection, urinary tract infection, dehydration, blood transfusion and portomesenteric venous thrombosis (all p < 0.04). CONCLUSION: Our study represents the largest series of patients undergoing IRA reported to date and demonstrates an AL rate of 3%. While IRA appears to be a viable surgical option for diverse indications, our study underscores the importance of careful patient selection and thoughtful consideration of staging the anastomosis and temporary faecal diversion when necessary.

Risk factors and survival analysis of human leukocyte antigen loss in relapsed acute myeloid leukaemia/myelodysplastic syndrome patients after allogeneic haematopoietic stem cell transplantation.

To investigate the clinical characteristics and risk factors of specific human leukocyte antigen loss (HLA loss) in relapsed acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT), and compare the responses of patients with HLA loss relapse with those without HLA loss (non-HLA loss) to different treatment regimens. Clinical data of traceable patients with AML/MDS after myeloablative allo-HSCT in our centre between January 2010 and June 2021, who experienced disease relapse after the transplantation, were collected. The patients were divided into the HLA loss relapse group and the non-HLA loss relapsed group based on HLA loss gene test findings by next-generation sequencing. The patients' median overall survival (OS) after the relapse were compared, and univariate and multivariate analyses were performed using the Kaplan-Meier survival curve and Cox proportional hazard model to explore the responses to different treatments after relapse. A total of 2359 patients were selected. Retrospective HLA gene loss gene detection was performed for the deoxyribonucleic acid in 179 relapsed patients, including 47 patients in the HLA loss group (27.2%), 126 patients in the non-HLA loss group (72.8%) and 6 patients were excluded due to a lack of confirmed results. There was no significant statistical difference in the baseline characteristics of patients between the two groups, but as to transplantation-related characteristics, the donor-recipient relationship and HLA mismatched loci were statistically different between the two groups (both p < 0.001). Multivariate Cox analysis showed that more HLA mismatched loci ≥3 (HR = 3.66; 95% CI: 1.61-8.31; p = 0.002), time (≤6 months) from HSCT to relapse (HR = 7.92; 95% CI: 3.35-18.74; p < 0.001) and donor chimerism (CD3) in bone marrow at relapse (HR = 1.02; 95% CI: 1.00-1.03; p = 0.036) were independent factors affecting HLA loss relapse. The ratio of negative conversion of FLT3-ITD or CEBPA mutation was significantly lower in patients with post-transplantation HLA loss relapse than in the non-HLA loss group (0.0% vs. 45.5%, p = 0.003; 0.0% vs. 80.0%, p = 0.035), with none of the patients with FLT3-ITD or CEBPA mutation turned negative in the HLA loss group. The number of gene mutations turned negative when relapse in the non-HLA loss group was remarkably higher than that in the HLA loss group (p = 0.001). Using donor lymphocyte infusion (DLI) could not prolong OS for the HLA loss group (p = 0.42). Nevertheless, second transplantation had a significant positive impact on OS in the HLA loss group (p = 0.017), although only five patients in the HLA loss group underwent second transplantation. However, patients in the non-HLA loss group using DLI had a relatively longer OS time than those without DLI (p = 0.017). Second transplantation could also prolong OS in the non-HLA loss group, but the effect was not as significant as in the HLA loss group (p = 0.053). In summary, HLA loss detection is essential for patients with recurrence after transplantation, especially for those with more HLA mismatched loci and non-sibling donor. Furthermore, the detection of HLA loss has a guiding role in choosing subsequent therapy when relapsed, as secondary transplantation is more suitable than DLI for those with HLA loss.

Trimethoprim-sulfamethoxazole-induced lung injury: a case report.

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. While cutaneous adverse drug reactions associated with TMP-SMX are commonly recognized, lung toxicity induced by TMP-SMX is an unusual condition, with scattered reports of hypersensitivity pneumonitis, acute fibrinous organizing pneumonia, interstitial lung disease and acute respiratory distress syndrome. Reports of TMP-SMX-associated drug-induced lung injury (DLI) are rare in the pediatric population and its pathogenesis is not well understood. Diagnosis of DLI remains a challenge, given the wide range of clinical presentations that overlap with other conditions and the lack of diagnostic tests. In this report, we describe a case of TMP-SMX-induced lung injury in an eight-year-old child. Case Description: An eight-year-old girl presented in respiratory failure with acute symptoms of shortness of breath, fever, maculopapular rash and vomiting. This was associated with pneumonitis, pneumothorax, pneumomediastinum and subcutaneous emphysema on imaging. She had been on 25 days of TMP-SMX for treatment of Group D Salmonella bacteremia and osteomyelitis that was diagnosed prior to this current presentation. TMP-SMX was discontinued on admission due to concerns of possible drug reaction. Extensive infective, autoimmune and immunologic workup did not reveal the cause of the respiratory failure. Considering the absence of an alternative explanation for her clinical presentation and similarities in clinical courses to other reported cases, she was eventually diagnosed with TMP-SMX-associated DLI. She received a course of corticosteroids with subsequent clinical improvement and was weaned off home oxygen therapy a few months after her discharge from the hospital. Conclusions: Diagnosis of DLI can be challenging. The early identification of DLI and discontinuation of culprit drug is essential in its management. Further understanding of the underlying pathophysiology and risk factors for TMP-SMX-associated DLI is required.

The study of the cerebrovascular reserve in patients with diabetes or the combined diabetes and cerebral infarction / 中国糖尿病杂志

Objective To assess the association of cerebrovascular reserve(CVR) with diabetes(DM)、hypertensive atherosclerotic lacunar infarction(HALI),hypertension(HT) and diabetic lacunar infarction(DLI) by means of transcranial Doppler ultrasonography (TCD) with breath-holding maneuver.Methods The breath-holding index (BHI), which was the percentage increase in middle cerebral artery(MCA) blood flow velocity as index of CVR assessment,was detected during breath-holding by TCD and breath-holding technique in 30 diabetic patients,30 hypertensive atherosclerotic lacunar infarction patients,30 hypertension patients and 30 diabetic lacunar infarction patients. Results There was significant difference in the ascending rates of Vm and BHI between diabetic group and diabetic lacunar infarction group,diabete lacunar infarction group and hypertensive atherosclerotic lacunar infarction group,hypertension group and diabetic group (all P<0.05). Conclusions Diabetes can more significantly impair CVR than hypertension. Diabetic lacunar infarction can more significantly impair CVR than diabetes. Diabetic lacunar infarction can more significantly impair CVR than hypertensive atherosclerotic lacunar infarction .

The clinical study of using DLI+IL-2 after Mixed-HSCT in acute myelogenous leukemia / 中国医师进修杂志

Objective To approach curative effect of using DLI +IL-2 as immunobiotherapy after Mixed-HSCT in acute myelogenous leukemia.MethodAfter times of chemotherapy,8 cases of patients with acute myelogenous leukemia received Mixed-HSCT,then were treated with DLI +IL-2 for 2-7 times.Observed clinical effect for 1 to 5 years.Result DFS in 8 cases of patients with acute myelogenous leukemia received Mixed-HSCT and treated with DLI +IL-2 for 2-7 times were 62.5%.There were no GVHD.Conclusion Immuno-biotherapy with DLI +IL-2 after Mixed-HSCT in patients of acute myelogenous leukemia may be a method to increase DFS efficiently.

A Case of DNA Chimerism Analysis as a Marker of Donor Lymphocyte Infusion / 대한혈액학회지

Donor lymphocyte infusion (DLI) has some benefit effects as graft-versus-leukemia effect, reducing the relapse of leukemia and inducing of a complete remission. But it has also a graft-versus-host-disease (GVHD) effect. So it is required a proper marker test when DLI is performing. The DNA chimerism analysis can be a marker test in DLI. Variable number of tandem repeats (VNTR) are highly polymorphic DNA markers in the human genomic DNA and used as primers of DNA chimerism analysis. A 43-year-old male who had been diagnosed acute myelogenous leukemia was transplanted with allogeneic peripheral blood stem cells. The initial chimerism analysis showed complete chimerism but it changed to mixed chimerism after 7 months of transplantation. We predicted the relapse of leukemia and performed DLI. The patient could obtain the complete chimerism after DLI. We report a case of chimerism analysis which was useful to predict the relapse of leukemia and perform the DLI.