Grade III-IV Research Articles

Haploidentical Stem Cell Transplantation With Dual Source of Cells and Post-Transplant Cyclophosphamide.

Dual sources of cells (DSC) with peripheral blood stem cell apheresis (PBSC) and surgical bone marrow (BM) for haploidentical hematopoietic cell transplantation (Hid-HCT) are used in China and some Asian countries. The experience of the Baltimore group for haploidentical transplant with post-transplant cyclophosphamide (PT-Cy) and reduced-intensity-conditioning (RIC) regimen used BM as a source of hematopoietic stem cells. We retrospectively analyzed 64 Hid-HCT with DSC and PT-Cy, RIC (n = 57), or myeloablative-conditioning (MAC) (n = 7), from two public health Brazilian centers, with a median follow-up of 23.3 months (6.7-45.4). The 49 malignant patients were 27/46 (58.7%) beyond the first remission or with no complete response, and three patients did not complete disease status evaluation before transplant. Eight of 62 patients (12.9%) had grade 2 or more Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI), and two patients had no HCT-CI classified. Cytomegalovirus (CMV) viremia occurred in 26 of 57 (45.6%). The cumulative incidence of 100-day grade III-IV acute GVHD was 12.3% (7/57), with a 95% confidence interval (CI) of 3.8% and 20.8%, and 2-year moderate or severe chronic GVHD was 21.1% (11/52; 95% CI, 10.1%-32.3%). The 2-year relapses were 24.5% for malignant disease (12/49; 95% CI, 12.4%-36.5%). The 2-year overall survival (OS) probability was 54.7% (35/64; 95% CI, 42.5%-66.9%). Benign diseases achieve 2-year OS in 73.3% (11/15; 95% CI, 51%-95.7%) of the patients. The HCT-CI were significant in multivariate analyses for DFS (p = 0.002) and OS in uni- and multivariate analyses (both p < 0.001). The number of CD34+ cells by apheresis collection was significant in multivariate analysis for DFS (p = 0.039). Hid-HCT using PT-Cy, DSC, and RIC is a safe option for benign and malignant diseases.

The impact of socioeconomic status on glioma survival: a retrospective analysis.

Although sociodemographic factors such as socioeconomic status (SES), travel time to health care, cohabitation status, and region of residence are observed to influence incidence and survival for several types of cancers, it is unclear whether similar effects have been observed in patients with glioma. This study investigates whether these factors affect survival for glioma patients. In this retrospective study, the Swedish National Quality Registry for Brain Tumors was used to identify 1,276 patients with glioma WHO grade I-IV for whom data were deposited between 2009 and 2013. The RISK North database, which links data from the National Cancer Quality Register with citizen demographic data from the Longitudinal Integration Database for Health Insurance and Labor Market Studies (LISA), the Total Population Registry (TPR), and the Geography Database (GD), was utilized to assess survival in patients with glioma in relation to education level, cohabitation status, travel time to regional hospitals, and region of residence. In the multivariable analysis, longer survival was observed among WHO grade III-IV glioma patients with higher education level (middle school (ref) HR: 1, high school HR: 0.81 CI [0.67-0.98], p = 0.033; university/college HR: 0.81 CI [0.66-1.00], p = 0.048). Survival was not associated with travel time, cohabitation status, or region of residence in the multivariable survival analysis. Low education level was associated with reduced survival for patients with glioma WHO grade III and IV in multivariable survival analyses, but no differences in survival were found in relation to travel time, cohabitation status, or region of residence.

Reversal of Roux-en-Y Gastric Bypass: A Multi-Centric Analysis of Indications, Techniques, and Surgical Outcomes.

Roux-en-Y gastric bypass may present long-term complications that require revisional surgery or even reversal to normal anatomy. Data on the indications, surgical technique, and outcomes of RYGB reversal remain scarce. We identified 48 cases of RYGB reversals with complete 90-day follow-up within a multi-centric international retrospective database of elective secondary bariatric surgery. The operations were performed between 2010 and 2024 in high-volume referral centers in Europe and USA. Data were collected on body weight, associated diseases, and on surgical outcomes up to 1-year postoperatively. Patients were mainly female (81.3%) with a median age of 50 years (IQR 39-56). RYGB reversal was performed 7 years (median) after primary RYGB in patients with a BMI of 23.9 kg/m2 (IQR 20-27). Half of the patients underwent at least 1 bariatric revision before the reversal. Main indications for reversal were dumping syndrome (33.3%), excessive weight loss (29.2%), marginal ulcer (14.6%), malabsorption (12.5%), and abdominal pain (10.4%). Rate of conversion to open surgery was 8.3%, and the postoperative complications during the first year reached 50%, including 31.3% Clavien-Dindo grade I-II, 16.7% grade III-IV complications, and one death. At 1 year, the mean BMI of the cohort increased by 18% to 28.25 kg/m2; only 1 patient reached pre-RYGB BMI. Although RYGB is a theoretically reversible procedure, normal anatomy is re-established only in selected cases which are refractory to medical therapy and often also to revisional bariatric surgery. RYGB reversals entail high morbidity, while the extent of recurrent weight gain at 1-year post-reversal seems to allow patients to remain below the threshold of severe obesity.

Common Hereditary Variants of the APOE Gene and Posttransplant Outcome in Acute Myeloid Leukemia.

Apolipoprotein E (APOE) has multiple functions in metabolism and immunoregulation. Its common germline variants APOE2, APOE3 and APOE4 give rise to three functionally distinct gene products. Previous studies reported yin-yang roles of APOE2 and APOE4 in immunological processes, but their effects in hematopoietic stem cell transplantation (HSCT) have never been studied. We performed APOE genotyping in two contemporary cohorts of 348 and 447 patients with acute myeloid leukemia (AML) who had received allogeneic HSCT and evaluated associations of recipient and donor APOE genetic variation with posttransplant outcome. Patients who carried at least one APOE2 allele had a higher risk of posttransplant death compared to APOE4 carriers in the discovery (hazard ratio [HR] 2.09, P = .024) and validation cohorts (HR 1.96, P = .040). Detrimental APOE2 effects were driven by an increased risk of severe chronic graft-versus-host disease (GvHD; HRadj 1.85, P = .034) and non-relapse death (HRadj 1.72, P = .044). In non-APOE2 recipients, transplantation of an APOE2-positive allograft was associated with an increased incidence of grade III-IV acute GvHD (HRadj 2.82, P = .012) and severe chronic GvHD (HRadj 2.54, P = .022) compared to APOE2-negative grafts. In summary, the APOE2 allele, typically considered a longevity gene in the general population, was associated with a higher risk of acute GvHD (HRadj 2.75, P = .002), chronic GvHD (HRadj 2.57, P = .001), and posttransplant mortality (HRadj 1.79, P = .004), when present either in the host or transplanted from the donor.

Donor Regulatory T-Cell Therapy to Prevent Graft-Versus-Host Disease.

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg cell therapy manufactured from donor mobilized peripheral blood improves one-year GVHD-free relapse free survival (GRFS) after myeloablative conditioning (trial NCT01660607). We compared this study arm to a concomitant standard of care (SOC) cohort. All donor Treg cell products were successfully manufactured and administered without cryopreservation within 72 hours. Participants had a one-year incidence of acute grade III-IV GVHD of 7%, moderate to severe chronic GVHD of 11% and non-relapse mortality rate of 4.5%. The primary endpoint of significantly improved one-year GRFS was achieved at 64% evaluated against a predicted incidence of 40% (p = 0.002) with a realized incidence of 36% in the SOC comparitor. For those trial patients whow developed grade II-IV acute GVHD, 91% responded to front-line steroid therapy wheras 50% responded in the SOC comparator group. Trial participants had a reduced incidence and burden of GVHD and improved GRFS, as compared to rates common to highly variable unmanipulated donor grafts and multi-agent immune suppression.

Everolimus with or without Mycophenolate Mofetil for Graft-versus-Host Disease Prophylaxis after Hematopoietic Stem Cell Transplantation in Children with Acute Kidney Injury: A Single-Center Retrospective Analysis.

Hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute and chronic graft-versus-host disease (GVHD) are decisive determinants of successful allogeneic HSCT. The immunosuppressive agent cyclosporin A (CsA) is most often used to prevent GVHD in pediatric patients, but it is known to be nephrotoxic. Acute kidney injury (AKI) affects 21% to 84% of pediatric HSCT recipients, compromising clinical outcomes. This retrospective single-institution analysis scrutinized the practice of substituting nephrotoxic CsA with an everolimus/mycophenolate mofetil (MMF) combination as GVHD prophylaxis in 57 patients with AKI (n = 53) or central nervous system side effects due to calcineurin inhibitor (CNI) treatment (n = 4) following first allogeneic HSCT. This retrospective cohort study analyzed the clinical courses of 57 children who were switched from CNI-based GVHD prophylaxis (CsA or tacrolimus in single cases) to the everolimus/MMF combination (n = 48) or everolimus alone (n = 9) after undergoing their first allogeneic HSCT at the Charité University Medicine Berlin. Serving as a control group were 74 patients undergoing their first allogeneic HSCT during the same period who did not receive everolimus at any time post-transplantation. Patients undergoing mismatched family donor transplantation without subsequent CNI treatment for GVHD prophylaxis were excluded. Study endpoints encompassed the retention parameter course subsequent to the GVHD prophylaxis switch, overall survival (OS), and incidences of underlying disease relapse and acute and chronic GVHD in both treatment groups. Renal function improved significantly after switching from CsA to the everolimus/MMF combination. Crucially, the transition to everolimus did not adversely affect OS following HSCT (hazard ratio [HR], 1.6; 95% confidence interval [CI], 0.74 to 3.5; P = .23), especially for patients with nonmalignant diseases (HR, 1.4; 95% CI, 0.34 to 5.9; P = .64). The incidences of grade III-IV acute GVHD (HR, 1.82; 95% CI, 0.45 to 7.4; P = .40) and severe chronic GVHD (HR, 2.76; 95% CI, 0.69 to 11.0; P = .15) were comparable in patients treated with the everolimus/MMF combination and those receiving standard CsA treatment in the control group. OS in patients with malignant underlying diseases was lower in the everolimus group (HR, 2.7; 95% CI, 1.1 to 6.9; P = .03), however, event-free survival was similar in patients with an underlying malignant disease treated with either the everolimus/MMF combination or CsA (HR, 0.87; 95% CI, 0.39 to 1.9; P = .73). Renal function improved significantly in patients who switched their immunosuppression regimen from CsA to everolimus with or without MMF cotreatment after diagnosis of AKI. Patient outcomes in the everolimus group were comparable to those in the control group. This study provides compelling real-world clinical evidence to support replacing CsA with the everolimus/MMF combination in the management of AKI following HSCT in children.

Free Functional Muscle Transfer in Brachial Plexus Injury Patients With Subclavian Artery Injury Using Arteriovenous Loop Grafts.

Free functional muscle transfer (FFMT) for brachial plexus injury (BPI) requires adequate donor arterial flow for successful anastomosis. However, concomitant BPI and subclavian artery injury are not uncommon. Arteriovenous (AV) loop graft is one of the methods used to extend vessels to areas with vascular depletion. This case series aims to report the feasibility and outcomes of AV loop grafts for FFMT in BPI patients with subclavian artery injury. This longitudinal descriptive report included adult patients with BPI and concomitant subclavian artery injury. Patients with adequate intra-operative thoracoacromial and/or thoracodorsal arterial flow, sufficient for FFMT without the need for an AV loop graft, were excluded. Of the 10 initially enrolled patients, three were excluded: two for adequate intra-operative arterial flow, and one for extensive adhesions around the external jugular vein, precluding the index surgery. Seven patients, with a median age of 37 years, mostly male and injured in motorcycle accidents, were included. Four patients underwent a single-stage operation (AV loop graft and FFMT simultaneously), while three patients underwent a two-stage operation. Success rates were 100% for the single-stage operation and 33% for the two-stage operation. The two-stage operation led to increased operative time, extended hospital stays, and anastomosis mismatch challenges. Successful cases regained gracilis muscle motor power for elbow flexion, achieving grade III-IV within 13-29 months. FFMT with AV loop graft for BPI patients with subclavian artery injury is feasible and effective. Despite complex microsurgical requirements, these procedures significantly restore limb functionality when standard FFMT operations are insufficient. ClinicalTrials.gov identifier: NCT06437990.

A retrospective study of an irradiation-based conditioning regimen and chidamide maintenance therapy in T-ALL/LBL

ABSTRACT Objectives T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) are highly malignant and aggressive hematologic tumors for which there is no standard first-line treatment. Chidamide, a novel histone deacetylase inhibitor, shows great promise. We assessed the efficacy and safety of an irradiation-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and post-transplantation chidamide maintenance in patients with T-ALL/LBL. Methods We retrospectively analyzed the clinical data of six patients with T-ALL/LBL who underwent allo-HSCT with a radiotherapy-containing pretreatment regimen and post-transplant chidamide maintenance therapy. The endpoints were relapse, graft-versus-host disease (GVHD), transplant-related mortality (TRM), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results All of the patients had uneventful post-transplant hematopoietic reconstitution, and all achieved complete molecular remission within 30 days. All six patients survived, and two relapsed with a median relapse time of 828.5 (170–1335) days. The 1-year OS rate was 100%, the 2-year PFS rate was 66.7%, and the TRM rate was 0%. After transplantation, two patients developed grade I-II acute GVHD (2/6); grade III-IV acute and chronic GVHD were not observed. The most common AEs following chidamide administration were hematological AEs, which occurred to varying degrees in all patients; liver function abnormalities occurred in two patients (grade 2), and symptoms of malaise occurred in one patient (grade 1). Conclusion Chidamide maintenance therapy after T-ALL/LBL transplantation is safe, but the efficacy needs to be further investigated.

Haploidentical hematopoietic stem cell transplantation using post-transplant cyclophosphamide in patients with inborn errors of immunity: Experience in a reference center in Colombia

Inborn errors of immunity is a diverse group of rare diseases caused by over 400 genetic mutations affecting the immune system and increasing infection susceptibility, autoimmunity, and malignancy. Hematopoietic stem cell transplantation offers a curative option for some inborn errors of immunity, with haploidentical donors providing a viable alternative when identical donors are unavailable. To determine survival, usefulness of weekly chimerism monitoring, immune reconstitution, and complications in patients with inborn errors of immunity who underwent haploidentical hematopoietic stem cell transplantation at a reference center in Colombia. We conducted a retrospective and observational study of a case series of pediatric patients who underwent haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide and follow-up with weekly chimerism. Survival analysis was performed using the Kaplan-Meier method. Sixteen patients with haploidentical familial donor transplantation were included. The most frequent diagnosis was severe combined immunodeficiency (n=5). Eleven out of seventeen patients received a non-myeloablative conditioning regimen. Twelve out of sixteen patients developed acute graft-versus-host disease. Out of these, 3 corresponded to grades III-IV. Post-transplant infections affected 14 of the subjects, predominating bacterial agents. Median T-cell chimerism was greater than 80% during the follow-up. Reconstitution of B and T lymphocytes was achieved in more than 80%. Overall survival at five years was 81%. Survival at 100 days was 94%. Haploidentical hematopoietic stem cell transplantation using post-transplant cyclophosphamide is a viable alternative for inborn errors of immunity when an identical donor is unavailable. Serial chimerism monitoring is useful for graft follow-up.

Humanized anti-CD25 monoclonal antibody replaces methotrexate as acute graft-versus-host disease prophylaxis in haploidentical allogeneic haematopoietic stem cell transplantation.

Acute graft-versus-host disease (aGVHD) significantly affects quality of life and outcomes in patients post-haploidentical haematopoietic stem cell transplantation (haplo-HSCT). Methotrexate (MTX) is commonly used to prevent aGVHD but can lead to complications like delayed haematological recovery and oral mucositis (OM). This study investigates the efficacy of anti-CD25 monoclonal antibody (mAb) as a potential MTX alternative. Participants were divided into two cohorts: a single-dose group (25 mg/day anti-CD25 mAb with MTX) and a double-dose group (50 mg/day anti-CD25 mAb without MTX). The primary end-point was the cumulative incidence (CI) of severe aGVHD by day 100. The double-dose cohort demonstrated a significantly lower CI of total aGVHD (23.53% vs. 42.11%, p = 0.009) and grade 3-4 aGVHD (7.35% vs. 18.42%, p = 0.047). After inverse probability of treatment weighting adjustment, the adjusted HR of double-dose compared with single-dose cohort for total aGVHD was 0.47 (95% CI 0.26-0.86; p = 0.015), 0.42(95% CI 0.15-1.22; p = 0.110) for grade III-IV aGVHD, 0.45 (95% CI 0.26-0.77; p = 0.004) for total cGVHD and 0.36 (95% CI 0.18-0.72; p = 0.004) for the moderate to severe cGVHD. Additionally, this double-dose regimen significantly reduced the incidence of oral mucositis and demonstrated lower rates of infections and haemorrhagic cystitis. These findings suggest that a double-dose anti-CD25 mAb regimen without MTX is a promising strategy for aGVHD prophylaxis in haplo-HSCT (ChiCTR2200060184).

Mixed T-Cell Chimerism Following Hematopoietic Cell Transplantation for Non-Malignant Disorders Is Common, Facilitates Anti-Viral Immunity, and Is Not Associated with Graft Failure in Pediatric Patients.

Myeloid chimerism better reflects donor stem cell engraftment than whole-blood chimerism in assessing graft function following allogeneic hematopoietic stem cell transplant (HCT). We describe our experience with 130 patients aged younger than 18 years, treated with allogeneic HCT using bone marrow or PBSC from HLA-matched donors for non-malignant diseases, whose pre-transplant conditioning therapy included alemtuzumab and who were monitored with lineage-specific chimerism after transplant. At 6 years post-transplant, overall survival (OS) was 91.1% and event-free survival (EFS) was 81.5%, with no grade III-IV acute GvHD or chronic GVHD observed. Recipient T-cells did not contribute to graft loss. Mixed T-cell chimerism (MC) did not affect EFS, and there was no connection between T-cell chimerism and myeloid chimerism in patients with MC or graft loss. MC significantly correlated with virus infection; more children with MC were CMV seropositive than those with complete chimerism (CC). Additionally, MC was more common in patients with CMV viramia post-transplant. CD8 T-cell reconstitution was affected by viral reactivation, including CMV, with CD8 T-cell counts higher in the MC group than in the CC group. Mixed T-cell chimerism is due to autologous, virus-specific, predominantly CD8, T-cell expansion, and is protective and not deleterious to the recipient.

Modified G-CSF/ATG-Based Haploidentical Transplantation Protocol in Pediatric Primary Hemophagocytic Lymphohistiocytosis: A Long-Term Follow-Up Single-Center Experience.

Primary hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by immune dysregulation. Hematopoietic stem cell transplantation (HSCT) represents the only option for long-term cure for primary HLH. However, only around 25% of patients have a fully HLA-matched donor. In this retrospective study, we analyzed 42 pediatric patients with primary HLH who underwent haplo-SCT using the modified granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol. The conditioning regimen included 300-600mg/m2 etoposide (VP16), along with low doses of busulfan (Bu) (0.8-1.2mg/kg every 6hours on Days -8 to -6), cyclophosphamide (Cy) (10mg/kg/day on Days -4 to -3), fludarabine (Flu) (30mg/m2/day on Days -5 to -3), and ATG (8-9mg/kg total dose on Days -5 to -2) to reduce complications. All 42 patients achieved successful engraftment. Following a median follow-up period of 48.7months, 32 of the 42 patients remained alive and disease free. The 2-year overall survival (OS) rate was 78.4%, and the 5-year OS rate was 73.7%. The 2-year failure-free survival (FFS) rate was 71.3%, and the 5-year FFS rate was 66.5%. Patients who achieved complete remission at the time of HSCT showed better OS (p<0.05). The incidence of Grade III-IV acute graft-versus-host disease (GVHD) was 26.2%, and severe chronic GVHD was observed in 11.9% of patients. Thrombotic microangiopathy occurred in 13 patients, and veno-occlusive disease in two patients. This modified G-CSF/ATG-based haploidentical protocol demonstrates significant potential for pediatric patients with primary HLH, exhibiting commendable effectiveness and safety.

Improved Overall Survival with Checkpoint Inhibition and Allogeneic Transplantation in Relapsed Hodgkin Lymphoma.

Patients with relapsed classic Hodgkin lymphomas receive salvage therapy with immune checkpoint inhibitors (ICI) or chemotherapy (no-ICI). Patients responding to therapy often undergo consolidation with allogeneic blood or marrow transplantations (alloBMT). We previously reported that relapsed cHL patients treated with ICI followed by alloBMT experienced improved 3-year progression-free survival (PFS) compared to patients treated with salvage chemotherapy without ICI, followed by alloBMT. In this retrospective analysis, we report the 5-year OS, PFS, and GVHD incidence in cHL patients treated with ICI before alloBMT with post-transplantation cyclophosphamide (PTCy) GVHD prophylaxis. Among the 147 relapsed/refractory patients with cHL, 71 (48.3%) received ICIs and 76 (51.7%) received chemotherapy without ICIs (no-ICI) before alloBMT. We observed an improved 5-year estimated OS of 91% (ICI) versus 66% (no-ICI), (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.16 to 0.98; P = 0.046) and a 5-year estimated PFS of 84% (ICI) versus 53% (no-ICI) (HR, 0.4; 95% CI, 0.2 to 0.81; P = 0.011). The 12-month cumulative incidence of grade III-IV GVHD was 20% (ICI) and 7% (no-ICI) (SDHR 3.16; 95% CI, 1.13 to 8.81 p = 0.03. More frequent grade III-IV acute GVHD was likely due to the higher incidence of grade III-IV acute GVHD in the subset of patients with pre-transplant exposure to ICI and shortened duration (60 days) of immunosuppression versus patients with long immunosuppression (day 180). These data suggest that cHL patients treated with ICI and alloBMT experience improved OS and the GVHD risk can be mitigated by immunosuppression until day 180.

Analysis of treatment outcomes of extremely preterm infants in a real-world single center

To study the treatment outcomes of extremely preterm infants. A retrospective analysis was performed for the clinical data of extremely preterm infants who were admitted to the neonatal intensive care unit of the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022. The infants were divided into a non-in-hospital death group and a survival group. SPSS 29.0 was used for data analysis. A total of 422 extremely preterm infants were included, of which 155 were in the non-in-hospital death group and 267 in the survival group. The gestational age, birth weight, cesarean section rate, and proportion of mothers with premature rupture of membranes >18 hours in the non-in-hospital death group were all lower than those in the survival group (P<0.05). In contrast, the proportions of Apgar score ≤3 at 1 minute, intubation, neonatal respiratory distress syndrome, early-onset sepsis, periventricular-intraventricular hemorrhage (grades III-IV), and pneumorrhagia were higher in the non-in-hospital death group compared to the survival group (P<0.05). Low gestational age, low birth weight, the history of birth asphyxia, severe intracranial hemorrhage, and pneumorrhagia may be the main causes of non-in-hospital death in extremely preterm infants, and therefore, perinatal health care should be enhanced to reduce the onset of asphyxia and severe diseases.

Invasive Fungal Disease in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in China: A Multicenter Epidemiological Study (CAESAR 2.0).

This study (China Assessment of Antifungal Therapy in Hematological Diseases, CAESAR 2.0) aimed to provide updated epidemiological data on invasive fungal disease (IFD) in patients undergoing allogeneic stem cell transplantation (allo-HSCT). This multicenter, real-world, observational study was conducted at 12 allo-HSCT centers in China between January 2021 and December 2021. Consecutive adult patients (≥18 years) who underwent allo-HSCT with antifungal prophylaxis were included. IFD was diagnosed according to the 2019 criteria of the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG). Follow-up was completed by December 31, 2022. A total of 2015 patients were collected. mold-active antifungal prophylaxis was used in 76.08% of patients, which included mainly voriconazole (44.37%) and posaconazole (31.71%). The cumulative incidence of IFD (proven and probable) at 1 year after allo-HSCT was 6.3%. Pathogens were identified in 47.97% of IFD cases and mainly included Candida spp. (17.89%), Mucorales (13.01%), Aspergillus spp. (8.94%), and Pneumocystis jirovecii (6.5%). Multivariate analysis identified the following factors associated with IFD: disease at advanced stage (hazard ratio [HR]= 2.55; 95% confidence interval [CI]: 1.58-4.12 P<0.001), absolute neutrophil count (ANC) engraftment (≤28 days) (HR=0.37; 95% CI: 0.15-0.92 P=0.032), platelet (PLT) engraftment (≤28 days) (HR=0.41; 95% CI: 0.27-0.62 P<0.001) and acute graft-versus-host disease grade III-IV (HR=2.97; 95% CI: 1.97-4.49 P<0.001). The IFD-attributable mortality rate was 48.28%. Despite the widespread use of mold-active prophylaxis, the risk of IFD after allo-HSCT remains high. The most common pathogens are Candida spp., Mucorales, Aspergillus spp., and Pneumocystis jirovecii.

An Analysis of Percutaneous Nephrolithotomy (PCNL) Performed at the Institute of Kidney Disease, Pakistan: Stone Clearance and Complications.

Percutaneous nephrolithotomy (PCNL) is the preferred treatment for large renal stones, yet variability in outcomes arises from patient-specific factors and institutional practices. Understanding complications and predictors of success is essential to improving procedural efficacy. This study aimed to evaluate stone clearance rates, complications classified using the Clavien-Dindo system, and predictors of PCNL outcomes, with a focus on improving lower calyx stone clearance. A retrospective analysis was conducted on 422 PCNL procedures performed from July 2021 to December 2023 at the Institute of Kidney Disease, Hayatabad Medical Complex, Peshawar, Pakistan. Patient demographics, stone characteristics, and postoperative outcomes were analyzed. Stone clearance rates were calculated, and complications were categorized by severity. Associations between patient and stone characteristics and outcomes were tested using Chi-square analysis, with significance set at p < 0.05. A total of 422 PCNL cases were analyzed, with an overall stone-free rate of 75.82% (320/422). The average patient age was 45.39 ± 12.43 years, with male patients comprising 56.87% of the cohort and a mean BMI of 27.82 ± 4.21 kg/m². Hypertension (21.43%), diabetes mellitus (18.95%), and chronic kidney disease (7.11%) were notable comorbidities. Stones averaged 3.21 ± 1.13 cm in size, predominantly composed of calcium oxalate (35.55%), and were most frequently located in the upper calyx (28.44%). Postoperative outcomes revealed a 21.33% complication rate, with 16.59% classified as minor (Clavien-Dindo Grades I-II) and 4.74% as major (Grades III-IV). Follow-up data showed that 11.83% of patients had residual stone fragments, and 9.48% experienced delayed complications, primarily minor. Stone size and location significantly influenced outcomes, with clearance rates of 80.00% for 2-3 cm stones versus 65.57% for stones >3 cm (p = 0.155). Lower calyx stones had markedly reduced clearance rates (50.00%, p < 0.001) compared to upper (75.00%) and mid-calyx (70.00%) stones, while stones in multiple locations also showed poor clearance (57.69%, p = 0.001). Key predictors of complications included higher BMI and prolonged operative times, emphasizing the need for tailored approaches, technical refinements, and institutional audits to optimize outcomes for anatomically or clinically complex cases. This study highlights the high efficacy of PCNL in managing large renal stones, achieving a stone-free rate of 75.82%. However, the findings underscore the significant challenges associated with lower calyx stones and larger stone sizes, both linked to reduced clearance rates. The Clavien-Dindo classification of complications shows that while minor complications are more frequent, major complications remain a concern, especially in patients with elevated BMI or prolonged operative times. To optimize outcomes, this study recommends refining surgical techniques and adopting technological advancements to improve lower calyx clearance, implementing institutional audits to standardize practices, and personalizing treatment strategies through preoperative risk stratification. Future multicenter prospective studies are needed to validate these findings, further explore predictors of outcomes, and develop comprehensive care protocols addressing anatomical and patient-specific challenges in PCNL procedures.

Construction and validation: A nomogram model to predict recurrence after percutaneous endoscopic discectomy.

A systematic retrospective analysis of patients with lumbar disc herniation treated with percutaneous endoscopic discectomy was performed to identify key risk factors for postoperative recurrence, and a Nomogram prediction model was constructed based on them. The data of patients with lumbar disc herniation who were treated in our hospital between January 2021 and December 2023 were included in this study. Statistical tools, including univariate and multivariate logistic regression analyses, were used to accurately screen independent risk factors significantly associated with postoperative recurrence. Based on this, a nomogram prediction model was constructed to enable personalized prediction of postoperative recurrence risk. The model performance was evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve, supplemented by calibration curve and decision curve analysis, to ensure the predictive accuracy and clinical practicability of the model. 286 patients with lumbar disc herniation were included in the study, and 29 patients had a postoperative recurrence, with a recurrence rate of 10.14%. After univariate and multivariate logistic regression analyses, a total of 5 variables were identified as independent risk factors for postoperative recurrence of lumbar disc herniation: age > 60 years (OR = 2.831; 95% CI = 1.089-5.430), body mass index (BMI) > 24 kg/m2 (OR = 4.632; 95% CI = 1.183-14.337), The type of lumbar disc herniation was herniation (OR = 5.064; 95% CI = 1.198-15.364), degeneration grade III-IV (OR = 5.916; 95% CI = 1.357-16.776), and postoperative high-intensity activity (OR = 4.731; 95% CI = 1.341-14.024). The nomogram constructed in this study for postoperative recurrence of lumbar disc herniation by percutaneous endoscopic discectomy has good predictive accuracy, and this tool can effectively assist orthopedic surgeons in identifying high-risk patients with recurrence after percutaneous endoscopic discectomy, providing a scientific basis for early intervention and individualized management strategies, thus optimizing patient prognosis.

Risk factors for noninvasive ventilation failure in preterm infants at less than 30 weeks of gestation with respiratory distress syndrome.

This study aimed to identify risk factors for noninvasive ventilation (NIV) failure in <30 weeks' gestation preterm neonates and compare morbidity in patients with and without NIV failure. This study included preterm neonates <30 weeks' gestation who received NIV support for respiratory distress syndrome (RDS). Demographic and clinical characteristics were compared between infants with and without NIV failure within the first 72 hours after birth. Of 443 preterm neonates, NIV failure occurred in 101 (22.8%). Of these, initial respiratory support was nasal continuous positive airway pressure (nCPAP) in 76 infants (75.2%) and nasal intermittent positive pressure ventilation (NIPPV) or bilevel positive airway pressure (BiPAP) in 25 infants (24.8%). Gestational age, birth weight, and antenatal steroid exposure were significantly lower in patients with NIV failure. Grade III-IV intraventricular hemorrhage, moderate/severe bronchopulmonary dysplasia, and retinopathy of prematurity requiring laser photocoagulation were significantly more common in the NIV failure group. Multivariate logistic regression analysis showed that antenatal steroid therapy reduced NIV failure [odds ratio (OR): 0.53, 95% confidence interval (CI): 0.29-0.94; P = .03], while nCPAP (OR: 2.61, 95% CI: 1.53-4.48; P < .001), surfactant requirement (OR: 2.40, 95% CI: 1.36-4.25; P = .003), and ≥2 doses of surfactant need (OR: 3.57, 95% CI: 1.89-6.74; P < .001) were associated with greater NIV failure. The results of this study indicated that administering antenatal steroids and using NIPPV or BiPAP instead of nCPAP as initial respiratory support reduced the likelihood of NIV failure in preterm infants with RDS.

Risk Score for Early Prediction of In-Hospital Mortality After Aneurysmal Subarachnoid Hemorrhage: Pooled Analysis With Score Construction and Validation

Aneurysmal subarachnoid hemorrhage (aSAH) has a high complications burden, with in-hospital mortality as the most devastating outcome. We aimed to develop and validate a risk score for early prediction of in-hospital mortality after aSAH. Data from 2 university hospitals were pooled (n= 1070), with cohorts for score construction (n= 886) and external validation (n= 184). Several parameters assessable at admission were collected. Independent predictors of in-hospital mortality were used as mortality score components. Diagnostic accuracy of the novel score was compared to the Hunt and Hess Age, Intraventricular Hemorrhage, Rebleed and World Federation of Neurosurgical Societies (WFNS) scores. Overall rate of in-hospital mortality was 19% and 14.7% in construction and validation cohorts, respectively. The novel risk score (aSAH mortality score: 0-12 points) included patients' age (≤55 years: 0 points, 56-70 years: 1 point, >70 years: 2 points), aneurysm rebleeding (2points), WFNS grade (grade I-II: 0 points, grade III-IV: 2 points, grade V: 5 points), and Hijdra sum score (≤10: 0 points, 11-20: 1 point, 21-30: 2 points, >30: 3 points). In-hospital mortality rates ranged 0.6% (0 points) to 100% (12 points) in the construction cohort, and 0% (0 points) to 60% (10 points) in the validation cohort. In the receiver operating characteristic analysis, the aneurysmal subarachnoid hemorrhage mortality score (area under the curve [AUC]: 0.829 and 0.824 in the construction and validation cohorts, respectively) was superior to the Hunt and Hess Age, Intraventricular Hemorrhage, Rebleed (AUC: 0.811 and 0.813) and WFNS scores (AUC: 0.768 and 0.795). Risk of in-hospital mortality after aSAH can be predicted with high accuracy using baseline characteristics. The novel risk score showed best diagnostic performance in the construction and validation cohorts and can aid in early prognostication and treatment decisions.

Time-restricted versus standard-duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON-96 trial.

Cyclosporine A combined with mycophenolate mofetil (CsA/MMF) has become an established regimen for the prevention of graft-versus-host disease (GVHD) following non-myeloablative (NMA) allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal duration of immunosuppression (IS) has not yet been defined and overtreatment is of concern. We hypothesized that time-restricted IS with CsA/MMF would increase the proportion of patients with non-severe GVHD compared to standard-duration IS, thereby resulting in reduction of the relapse rate and improvement of progression-free survival (PFS) and overall survival (OS). In a prospective randomized, multicenter, phase III trial, patients were allocated (1:1) to standard or time-restricted IS. A total of 389 patients were randomized, of whom 369 were transplanted (184 vs. 185 patients). The primary endpoint, the proportion of patients with non-severe GVHD defined as acute GVHD grades I-II without gut involvement or chronic GVHD not requiring systemic treatment within 180 days posttransplant, was 23% after standard-duration IS versus 24% after time-restricted IS (odds ratio: 1.02; 95% confidence interval (CI) 0.63-1.66, p = 0.92). The cumulative incidence of grade III-IV acute GVHD at 6 months posttransplant was not significantly different (14% vs. 18%; p = 0.20). The two-year cumulative incidence of chronic extensive GVHD was 50% versus 46% (p = 0.62). There were no significant differences in the rates of relapse/progression, non-relapse mortality, PFS, OS, and GVHD-free, relapse-free survival. Time-restricted IS with CsA/MMF did not increase the proportion of patients with non-severe GVHD, and secondary outcomes were not different compared to standard-duration IS following NMA-matched alloHSCT.