Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Brightness Strategies toward NIR-II Emissive Conjugated Materials: Molecular Design, Application, and Future Prospects.

Recent advances have been made in second near-infrared (NIR-II) fluorescence bioimaging and many related applications because of its advantages of deep penetration, high resolution, minimal invasiveness, and good dynamic visualization. To achieve high-performance NIR-II fluorescence bioimaging, various materials and probes with bright NIR-II emission have been extensively explored in the past few years. Among these NIR-II emissive materials, conjugated polymers and conjugated small molecules have attracted wide interest due to their native biosafety and tunable optical performance. This review summarizes the brightness strategies available for NIR-II emissive conjugated materials and highlights the recent developments in NIR-II fluorescence bioimaging. A concise, detailed overview of the molecular design and regulatory approaches is provided in terms of their high brightness, long wavelengths, and superior imaging performance. Then, various typical cases in which bright conjugated materials are used as NIR-II probes are introduced by providing step-by-step examples. Finally, the current problems and challenges associated with accessing NIR-II emissive conjugated materials for bright NIR-II fluorescence bioimaging are briefly discussed, and the significance and future prospects of these materials are proposed to offer helpful guidance for the development of NIR-II emissive materials.

Characteristics and treatment for severe postpartum haemorrhage in different midwifery hospitals in one district of Beijing in China: an institution-based, retrospective cohort study.

OBJECTIVE: To identify the characteristics and treatment approaches for patients with severe postpartum haemorrhage (SPPH) in various midwifery institutions in one district in Beijing, especially those without identifiable antenatal PPH high-risk factors, to improve regional SPPH rescue capacity. DESIGN: Retrospective cohort study. SETTING: This study was conducted at 9 tertiary-level hospitals and 10 secondary-level hospitals in Haidian district of Beijing from January 2019 to December 2022. PARTICIPANTS: The major inclusion criterion was SPPH with blood loss ≥1500 mL or needing a packed blood product transfusion ≥1000 mL within 24 hours after birth. A total of 324 mothers with SPPH were reported to the Regional Obstetric Quality Control Office from 19 midwifery hospitals. OUTCOME MEASURES: The pregnancy characteristics collected included age at delivery, gestational weeks at delivery, height, parity, delivery mode, antenatal PPH high-risk factors, aetiology of PPH, bleeding amount, PPH complications, transfusion volume and PPH management. SPPH characteristics were compared between two levels of midwifery hospitals and their association with antenatal PPH high-risk factors was determined. RESULTS: SPPH was observed in 324 mothers out of 106 697 mothers in the 4 years. There were 74.4% and 23.9% cases of SPPH without detectable antenatal PPH high-risk factors in secondary and tertiary midwifery hospitals, respectively. Primary uterine atony was the leading cause of SPPH in secondary midwifery hospitals, whereas placental-associated disorders were the leading causes in tertiary institutions. Rates of red blood cell transfusion over 10 units, unscheduled returns to the operating room and adverse PPH complications were higher in patients without antenatal PPH high-risk factors. Secondary hospitals had significantly higher rates of trauma compared with tertiary institutions. CONCLUSION: Examining SPPH cases at various institutional levels offers a more comprehensive view of regional SPPH management and enhances targeted training in this area.

Unveiling the hidden impact: Subclinical hypercortisolism and its subtle influence on bone health.

In recent years, advancements in imaging technologies have led to an increased detection rate of adrenal incidentalomas (AI), with age demonstrating a significant correlation with their incidence. Among the various forms of functional adrenal incidentalomas, subclinical hypercortisolism (SH) stands out as a predominant subtype. Despite the absence of typical symptoms associated with Cushing's syndrome, both domestic and international research consistently establishes a robust link between SH and diverse metabolic irregularities, including hypertension, lipid metabolism disorders, glucose metabolism abnormalities, and disruptions in bone metabolism. Individuals with SH face an elevated risk of cardiovascular events and mortality, highlighting the clinical significance of addressing this condition. Prolonged exposure to elevated cortisol levels poses a significant threat to bone health, contributing to bone loss, alterations in bone microstructure, and an increased susceptibility to fractures. However, comprehensive reviews addressing bone metabolism changes and associated mechanisms in SH patients are currently lacking. Furthermore, the profound impact of concurrent SH on the overall health of the elderly cannot be overstated. A comprehensive understanding of the skeletal health status in elderly individuals with concomitant SH is imperative. This article aims to fill this gap by offering a detailed review of bone metabolism changes and associated mechanisms in SH patients arising from AI. Additionally, it provides a forward-looking perspective on research concerning skeletal health in elderly individuals with concurrent SH.

Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

Gradient-Janus Wires for Simultaneous Fogwater Harvesting and Electricity Generation.

A Gradient-Janus wire (GJW) with a diameter of 0.3 mm has been fabricated on a large scale through liquid confined modification, enabling the opposite conical wetting phenomenon along the same orientation of the GJW, characterized by an increasing superhydrophilic region and a decreasing hydrophobic region. This property allows the GJW to exhibit controllable water hovering, transport, and pinning during fog harvesting, i.e., at a large tilting angle α of 60° (mass increased with decreased α), the GJW can hover 0.6 mg of harvested fogwater in 30 s, can transport 3 mg of fogwater along the gradient in 30 s at α = 4° (with maximal mass reaching up to 4.3 mg at α = -10°), and finally, pin the water droplet at the end of the GJW. Such ability generates an effective torque that serves as the driving force for rotation. We designed a GJWs-wheel by radially arranging 60 GJWs together, resulting in an extremely lightweight structure weighing only 1.9 g. The cumulative torque generated during fog harvesting activates the rotation of the GJWs-wheel. When loaded with a coil within a magnetic field, electricity is generated as output power peaks at around 0.25 µW while maintaining a high water harvesting efficiency averaging approximately 38 ± 2.12 mg/min. This finding is significant as it provides valuable insights into designing materials capable of efficiently harnessing both energy and water resources.

The Role of MXene Surface Terminations on Peptide Transportation in Nanopore Sensing.

Nanopores with two-dimensional materials have various advantages in sensing, but the fast translocation of molecules hinders their scale-up applications. In this work, we investigate the influence of -F, -O, and -OH surface terminations on the translocation of peptides through MXene nanopores. We find that the longest dwell time always occurs when peptides pass through the Ti3C2O2 nanopores. This elongated dwell time is induced by the strongest interaction between peptides and the Ti3C2O2 membrane, in which the van der Waals interactions dominate. Compared to the other two MXene nanopores, the braking effect is indicated during the whole translocation process, which evidence the advantage of Ti3C2O2 in nanopore sensing. Our work demonstrates that membrane surface chemistry has a great influence on the translocation of peptides, which can be introduced in the design of nanopores for a better performance.

Designer "Quasi-Benzyne": The Spontaneous Reduction of Ortho-Diiodotetrafluorobenzene on Water Microdroplets.

It has been widely shown that water microdroplets have a plethora of unique properties that are highly distinct from those of bulk water, among which an especially intriguing one is the strong reducing power as a result of the electrons spontaneously generated at the air-water interface. In this study, we take advantage of the reducing power of water microdroplets to reduce ortho-diiodotetrafluorobenzene (o-C6F4I2) into a C6F4I2•- radical anion. Photoelectron spectroscopy and density functional theory computations reveal that the excess electron in C6F4I2•- occupies the I-C1-C2-I linkage, which elongates the C-I bonds but surprisingly shortens the C1-C2 bond, making the bond order higher than a double bond, similar to the benzyne molecule, so we named it "quasi-benzyne". The C6F4I2•- anion was further successfully utilized in a Diels-Alder reaction, a typical reaction for benzyne. This study provides a good example of strategically utilizing the spontaneous properties of water microdroplets and generating an especially exotic anion, and we anticipate that microdroplet chemistry can be an avenue rich in opportunities for new catalyst-free organic reactions.

Assessment and clinical utility of metagenomic next-generation sequencing for suspected lower respiratory tract infections.

OBJECTIVES: This study aims to compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) to traditional diagnostic methods in patients with lower respiratory tract infections (LRTIs), elucidate the etiological spectrum of these infections, and explore the impact of mNGS on guiding antimicrobial therapy. METHODS: We retrospectively analyzed data from 128 patients admitted to the Respiratory Department of Anqing 116 Hospital between July 2022 and July 2023. All patients had undergone both mNGS and conventional microbiological techniques (CMT) for LRTI diagnosis. We assessed the diagnostic performance of these methods and examined the influence of mNGS on antimicrobial decision-making. RESULTS: Overall, mNGS demonstrated superior sensitivity (96.8%) and accuracy (96.8%) compared to CMT. For Mycobacterium tuberculosis detection, the accuracy and sensitivity of mNGS was 88.8% and 77.6%, which was lower than the 94.7% sensitivity of the T-spot test and the 79.6% sensitivity of CMT. In fungal pathogen detection, mNGS showed excellent sensitivity (90.5%), specificity (86.7%), and accuracy (88.0%). Bacteria were the predominant pathogens detected (75.34%), with Mycobacterium tuberculosis (41.74%), Streptococcus pneumoniae (21.74%), and Haemophilus influenzae (16.52%) being most prevalent. Bacterial infections were most common (62.10%), followed by fungal and mixed infections (17.74%). Of the 118 patients whose treatment regimens were adjusted based on mNGS results, 102 (86.5%) improved, 7 (5.9%) did not respond favorably, and follow-up was lost for 9 patients (7.6%). CONCLUSIONS: mNGS offers rapid and precise pathogen detection for patients with suspected LRTIs and shows considerable promise in diagnosing Mycobacterium tuberculosis and fungal infections. By broadening the pathogen spectrum and identifying polymicrobial infections, mNGS can significantly inform and refine antibiotic therapy.

Optimized wideband and compact multifunctional photonic device based on Sb2S3 phase change material.

In this paper, a 1 × 2 photonic switch is designed based on a silicon-on-insulator (SOI) platform combined with the phase change material (PCM), Sb2S3, assisted by the direct binary search (DBS) algorithm. The designed photonic switch exhibits an impressive operating bandwidth ranging from 1450 to 1650 nm. The device has an insertion loss (IL) from 0.44 dB to 0.70 dB (of less than 0.7 dB) and cross talk (CT) from -26 dB to -20 dB (of less than -20 dB) over an operating bandwidth of 200 nm, especially an IL of 0.52 dB and CT of -24 dB at 1550 nm. Notably, the device is highly compact, with footprints of merely 3 × 4 µm2. Furthermore, we have extended the device's functionality for multifunctional operation in the C-band that can serve as both a 1 × 2 photonic switch and a 3 dB photonic power splitter. In the photonic switch mode, the device demonstrates an IL of 0.7 dB and a CT of -13.5 dB. In addition, when operating as a 3 dB photonic power splitter, the IL is less than 0.5 dB.

Housing debt and depressive symptoms: evidence from the China family panel studies.

BACKGROUND: There is limited evidence on the association between housing debt and depressive symptoms in China. This study aimed to examine the impact of housing debt on depressive symptoms and explore the heterogeneous impacts arising from two sources of housing debt and two types of housing demands. METHODS: Using data from the 2016 and 2018 China Family Panel Studies (CFPS), this study included 25,232 Chinese individuals. Depressive symptoms were assessed using the eight-item Center for Epidemiological Studies Depression Scale (CES-D8). Housing debt was measured by dummy variables, indicating whether an individual had housing debt, and continuous variables, which were the logarithm of the total amount of housing debt. The two-way fixed effects model was used to examine the relationship. RESULTS: Housing debt had a significant positive impact on depressive symptoms in China. Individuals with housing debt had a 0.176-point higher depressive symptom score than those without housing debt. A 10% increase in the total amount of housing debt led to a 0.16-point increase in depressive symptoms. Non-bank housing loans significantly increased the level of depressive symptoms with a larger coefficient (coef = 0.289), while the impact of bank housing loans was small and not statistically significant. In terms of the types of housing demands, a positive impact was observed only among individuals who had only one property meeting their housing consumption demands. CONCLUSIONS: This study found a significant positive impact of housing debt on depressive symptoms, primarily driven by non-bank housing loans. Furthermore, housing debt increased the depressive symptoms among individuals with consumption demands, while those with investment demands did not show a significant impact. Government interventions should prioritize easing formal financial constraints and providing support for individuals with housing consumption demands.

The timing of minimally invasive surgery for prenatally diagnosed choledochal cysts.

OBJECTIVE: There are no clear evidence-based recommendations concerning when patients with prenatally diagnosed choledochal cysts (CCs) should undergo surgery. This study was primarily designed to explore the proper timing of minimally invasive surgery for prenatally diagnosed CC patients. METHODS: Seventy-three patients with prenatally diagnosed CC were enrolled in this study and divided into 4 subgroups according to age at surgery (15 patients in the < 1 month group, 27 in the 1-2 months group, 14 in the 2-3 months group and 17 in the > 3 months group). Eighty-five healthy infants were recruited and divided into 4 age groups (29 in the < 1 month group, 20 in the 1-2 month group, 19 in the 2-3 month group and 17 in the > 3 month group). Preoperative data were collected and compared between CC patients and healthy controls in 4 age groups. Additionally, 73 patients were divided into laparoscopic and open groups to compare postoperative recovery indices and the occurrence of complications to determine the safety and feasibility of laparoscopic CC application in neonates and young infants. RESULTS: Twenty-one of 73 (28.8%) patients who were prenatally diagnosed with CCs experienced various clinical symptoms, and 15 of 21 (71.4%) patients experienced clinical symptoms less than 2 months after birth. No differences were found in alanine transaminase (ALT), aspartate transaminase (AST) or aspartate transaminase (APRI) levels between CC patients and controls at ≤ 1 month or 1-2 months of age (all p > 0.05), while higher levels were found in CC patients at 2-3 months or > 3 months of age (all p < 0.05). ALT, AST and DBIL levels 1 week after surgery were significantly lower than those before surgery in CC patients who underwent laparoscopic CC excision at > 2 months of age, while DBIL levels 1 week after surgery were also significantly lower than those before surgery in patients who underwent CC excision at ≤ 2 months of age. The initial oral feeding time in the laparoscopic surgery group was significantly earlier than that in the open surgery group for both CC patients who underwent CC excision at ≤ 2 months of age and those > 2 months of age (all p < 0.05). No differences were found in the rates of anastomotic leakage or stricture formation between the laparoscopic and open surgery groups at ≤ 2 months or > 2 months of age. CONCLUSION: Most clinical symptoms attributed to CC occur less than 2 months after birth, while liver function and liver fibrosis may deteriorate after 2 months of age in patients with prenatally diagnosed CC. Laparoscopic surgery for CC in newborns and young infants (either less than or more than 2 months old) is safe and feasible and can shorten the initial oral feeding time without increasing complications such as postoperative anastomotic leakage or stricture. Thus, performing laparoscopic CC excisions within 2 months after birth in patients with prenatally diagnosed CC may be appropriate.

Comparison of three frailty scales for prediction of prolonged postoperative ileus following major abdominal surgery in elderly patients: a prospective cohort study.

BACKGROUND: To determine whether frailty can predict prolonged postoperative ileus (PPOI) in older abdominal surgical patients; and to compare predictive ability of the FRAIL scale, the five-point modified frailty index (mFI-5) and Groningen Frailty Indicator (GFI) for PPOI. METHODS: Patients (aged ≥ 65 years) undergoing major abdominal surgery at our institution between April 2022 to January 2023 were prospectively enrolled. Frailty was evaluated with FRAIL, mFI-5 and GFI before operation. Data on demographics, comorbidities, perioperative management, postoperative recovery of bowel function and PPOI occurrence were collected. RESULTS: The incidence of frailty assessed with FRAIL, mFI-5 and GFI was 18.2%, 38.4% and 32.5% in a total of 203 patients, respectively. Ninety-five (46.8%) patients experienced PPOI. Time to first soft diet intake was longer in patients with frailty assessed by the three scales than that in patients without frailty. Frailty diagnosed by mFI-5 [Odds ratio (OR) 3.230, 95% confidence interval (CI) 1.572-6.638, P = 0.001] or GFI (OR 2.627, 95% CI 1.307-5.281, P = 0.007) was related to a higher risk of PPOI. Both mFI-5 [Area under curve (AUC) 0.653, 95% CI 0.577-0.730] and GFI (OR 2.627, 95% CI 1.307-5.281, P = 0.007) had insufficient accuracy for the prediction of PPOI in patients undergoing major abdominal surgery. CONCLUSIONS: Elderly patients diagnosed as frail on the mFI-5 or GFI are at an increased risk of PPOI after major abdominal surgery. However, neither mFI-5 nor GFI can accurately identify individuals who will develop PPOI. TRIAL REGISTRATION: This study was registered in Chinese Clinical Trial Registry (No. ChiCTR2200058178). The date of first registration, 31/03/2022, https://www.chictr.org.cn/ .

A deep learning-based method for the prediction of temporal lobe injury in patients with nasopharyngeal carcinoma.

PURPOSE: To establish a deep learning-based model to predict radiotherapy-induced temporal lobe injury (TLI). MATERIALS AND METHODS: Spatial features of dose distribution within the temporal lobe were extracted using both the three-dimensional convolution (C3D) network and the dosiomics method. The Minimal Redundancy-Maximal-Relevance (mRMR) method was employed to rank the extracted features and select the most relevant ones. Four machine learning (ML) classifiers, including logistic regression (LR), k-nearest neighbors (kNN), support vector machines (SVM) and random forest (RF), were used to establish prediction models. Nested sampling and hyperparameter tuning methods were applied to train and validate the prediction models. For comparison, a prediction model base on the conventional D0.5cc of the temporal lobe obtained from dose volume (DV) histogram was established. The area under the receiver operating characteristic (ROC) curve (AUC) was utilized to compare the predictive performance of the different models. RESULTS: A total of 127 nasopharyngeal carcinoma (NPC) patients were included in the study. In the model based on C3D deep learning features, the highest AUC value of 0.843 was achieved with 5 features. For the dosiomics features model, the highest AUC value of 0.715 was attained with 1 feature. Both of these models demonstrated superior performance compared to the prediction model based on DV parameters, which yielded an AUC of 0.695. CONCLUSION: The prediction model utilizing C3D deep learning features outperformed models based on dosiomics features or traditional parameters in predicting the onset of TLI. This approach holds promise for predicting radiation-induced toxicities and guide individualized radiotherapy.

Coupling hyperspectral imaging with machine learning algorithms for detecting polyethylene (PE) and polyamide (PA) in soils.

Soil, particularly in agricultural regions, has been recognized as one of the significant reservoirs for the emerging contaminant of MPs. Therefore, developing a rapid and efficient method is critical for their identification in soil. Here, we coupled HSI systems [i.e., VNIR (400-1000 nm), InGaAs (800-1600 nm), and MCT (1000-2500 nm)] with machine learning algorithms to distinguish soils spiked with white PE and PA (average size of 50 and 300 µm, respectively). The soil-normalized SWIR spectra unveiled significant spectral differences not only between control soil and pure MPs (i.e., PE 100% and PA 100%) but also among five soil-MPs mixtures (i.e., PE 1.6%, PE 6.9%, PA 5.0%, and PA 11.3%). This was primarily attributable to the 1st-3rd overtones and combination bands of C-H groups in MPs. Feature reductions visually demonstrated the separability of seven sample types by SWIR and the inseparability of five soil-MPs mixtures by VNIR. The detection models achieved higher accuracies using InGaAs (92-100%) and MCT (97-100%) compared to VNIR (44-87%), classifying 7 sample types. Our study indicated the feasibility of InGaAs and MCT HSI systems in detecting PE (as low as 1.6%) and PA (as low as 5.0%) in soil. SYNOPSIS: One of two SWIR HSI systems (i.e., InGaAs and MCT) with a sample imaging surface area of 3.6 mm² per grid cell was sufficient for detecting PE (as low as 1.6%) and PA (as low as 5.0%) in soils without the digestion and separation procedures.

Non-contact wide-field viewing system-assisted scleral buckling surgery for retinal detachment in silicone oil-filled eyes.

AIM: To evaluate scleral buckling (SB) surgery using a non-contact wide-field viewing system and 23-gauge intraocular illumination for the treatment of rhegmatogenous retinal detachment in silicone oil (SO)-filled eyes. METHODS: Totally 9 patients (9 eyes) with retinal detachment in SO-filled eyes were retrospectively analyzed. All patients underwent non-contact wide-field viewing system-assisted buckling surgery with 23-gauge intraocular illumination. SO was removed at an appropriate time based on recovery. The patients were followed up for at least 3mo after SO removal. Retinal reattachment, complications, visual acuity and intraocular pressure (IOP) before and after surgery were observed. RESULTS: Patients were followed up for a mean of 8.22mo (3-22mo) after SO removal. All patients had retinal reattachment. At the final follow-up, visual acuity showed improvement for 8 patients, and no change for 1 patient. The IOP was high in 3 patients before surgery, but it stabilized after treatment; it was not affected in the other patients. None of the patients had infections, hemorrhage, anterior ischemia, or any other complication. CONCLUSION: This new non-contact wide-field viewing system-assisted SB surgery with 23-gauge intraocular illumination is effective and safe for retinal detachment in SO-filled eyes.

Cardiovascular Risk in Patients With Treated Isolated Diastolic Hypertension and Isolated Low Diastolic Blood Pressure.

BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.

Haploidentical hematopoietic stem cell transplantation with busulfan, cyclophosphamide, and fludarabine conditioning for X-linked adrenal cerebral leukodystrophy.

OBJECTIVE: We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD). METHODS: A retrospective analysis of transplantation data from 29 cases of ALD, treated between December 2014 and April 2022, was conducted. Neurologic function scores (NFS) were assessed. The conditioning regimen was busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg, and fludarabine 90 mg/m2 (BFC). Graft-versus-host disease prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil, and short course of methotrexate. RESULTS: Among the 29 cases, 14 cases (NFS = 0) were asymptomatic, and 15 (NFS ≥ 1) were symptomatic. The median age at SCT was 8 years (range: 4-16 years); the median follow-up time was 1058 days (range: 398-3092 days); 28 cases were father donors and 1 case was a grandfather donor. Hematopoietic reconstitution was successful in all patients, and all of them achieved complete donor chimerism at the time of engraftment. The leading cause of death was still primary disease progression (n = 4). Survival free of major functional disabilities was 100% in asymptomatic patients versus 66.67% in the symptomatic group (p = .018). CONCLUSION: BFC regimen used in haploidentical SCT was administered safely without major transplant-related complications even in symptomatic patients, and neurological symptoms were stabilized after SCT.

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial.

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Evaluations of Weathering of Polar and Nonpolar Petroleum Components in a Simulated Freshwater-Oil Spill by Orbitrap and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

The comprehensive chemical characterization of crude oil is important for the evaluation of the transformation and fate of components in the environment. Molecular-level speciation of naphthenic acid fraction compounds (NAFCs) was investigated in a mesoscale spill tank using both negative-ion electrospray ionization (ESI) Orbitrap mass spectrometry (MS) and positive-ion atmospheric pressure photoionization Fourier transform ion cyclotron resonance mass spectrometry (APPI-FT-ICR-MS). Both ionization techniques are coupled to high-resolution mass spectrometric detectors (ESI: Orbitrap MS; APPI: FT-ICR-MS at 9.4 T), enabling insight into the behavior and fate of petrogenic compounds during a simulated freshwater crude oil spill. Negative-ion ESI Orbitrap-MS reveals that oxygen-containing (Ox) classes are detected early in the spill, whereby species with more oxygen per molecule evolve later in the simulated spill. The O2-containing species gradually decreased in relative abundance, while O3 and O4 species increased in relative abundance throughout the simulated spill, which could correspond to a relative degree of oxygen incorporation. Nonpolar speciation by positive-ion APPI 9.4 T FT-ICR-MS allowed for the identification of water-soluble nonpolar and less polar acidic species. Molecular-level graphical representation of elemental compositions derived from simulated spill water-soluble and oil-soluble species suggest that biological activity is the primary degradation mechanism and that biodegradation was the dominant mechanism based on the negative-ion ESI Orbitrap-MS results.