Search Results (991)

Diamond–Blackfan anemia (DBA) is a rare genetic disorder affecting the bone marrow’s ability to produce red blood cells, leading to severe anemia and various physical abnormalities. Approximately 75% of DBA cases involve heterozygous mutations in ribosomal protein (RP) genes, classifying it as a ribosomopathy, with RPS19 being the most frequently mutated gene. Non-RP mutations, such as in GATA1, have also been identified. Current treatments include glucocorticosteroids, blood transfusions, and hematopoietic stem cell transplantation (HSCT), with HSCT being the only curative option, albeit with challenges like donor availability and immunological complications. Gene therapy, particularly using lentiviral vectors and CRISPR/Cas9 technology, emerges as a promising alternative. This review explores the potential of gene therapy, focusing on lentiviral vectors and CRISPR/Cas9 technology in combination with non-integrating lentiviral vectors, as a curative solution for DBA. It highlights the transformative advancements in the treatment landscape of DBA, offering hope for individuals affected by this condition. Full article

Objectives: To determine whether in a labor floor housed continuously by senior physicians the risk of adverse maternal and neonatal outcome is affected by time of delivery. Methods: This retrospective cohort study, conducted at a tertiary medical center, assessed singleton term deliveries from 1 January 2011 to 30 January 2020. Participants were categorized based on delivery timing, correlating with nursing shifts, to evaluate perinatal outcomes. The primary endpoint included adverse maternal outcomes such as emergency Cesarean section, anal sphincter injuries, blood product transfusions, and postpartum surgeries (laparotomy/laparoscopy). Secondary outcomes focused on neonatal health indicators, including low Apgar scores, ICU admissions, respiratory issues, extended hospital stays, and neurological complications. Results: 87,863 deliveries were available for analysis with equal distribution during the day. The risk of adverse composite maternal outcome was highest during the evening (aOR 1.25, 95% CI 1.18–1.32) and lowest during the night (aOR 0.94, 95% CI 0.88–0.99) compared to daytime deliveries. This difference was primarily driven by the highest rate of emergency CD in the evening. Neonatal outcomes were comparable, except for length of stay > 5 days, which was more frequent among newborns delivered during the evening and night shifts compared to the morning shift (aOR 1.19, 95% CI 1.07–1.33 and aOR 1.17, 95% CI 1.05–1.31, respectively). Conclusions: In term pregnancies, the evening shift is associated with the highest risk of adverse maternal and neonatal outcomes despite physician seniority. Full article

Uncontrollable bleeding is recognized as the leading cause of preventable death among trauma patients. Early transfusion of blood products, especially plasma replacing crystalloid and colloid solutions, has been shown to increase survival of severely injured patients. However, the requirements for cold storage and thawing processes prior to transfusion present significant logistical challenges in prehospital and remote areas, resulting in a considerable delay in receiving thawed or liquid plasma, even in hospitals. In contrast, freeze- or spray-dried plasma, which can be massively produced, stockpiled, and stored at room temperature, is easily carried and can be reconstituted for transfusion in minutes, provides a promising alternative. Drawn from history, this paper provides a review of different forms of dried plasma with a focus on in vitro characterization of hemostatic properties, to assess the effects of the drying process, storage conditions in dry form and after reconstitution, their distinct safety and/or efficacy profiles currently in different phases of development, and to discuss the current expectations of these products in the context of recent preclinical and clinical trials. Future research directions are presented as well. Full article

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO incompatible. Immuno-hematologic investigations allow to estimate donor/recipient ABO mismatch and anti-A/B isohemagglutinin (IHA) titration in the pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can occur post HSCT. Some preventive measures take into consideration either decision-making algorithms based on the recipient’s IHA titration or clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Product manipulation through red blood cell (RBC) and/or plasma depletion can also be taken into account. Currently, the best approach in the management of ABO-incompatible transplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHA titration are not standardized. A transfusion strategy must consider both the donor’s and recipient’s blood group systems until the RBC engraftment catches on and ABO conversion (forward and reverse typing) is confirmed on two consecutive and independent samples. Therefore, ABO incompatibility in HSCT represents a demanding immuno-hematologic challenge and requires all necessary preventive measures, including the appropriate selection of ABO blood components for transfusion. Full article

Introduction: Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients. Aims: Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted. Methods: All blood donations were screened in pools of 12–24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X − 1) where available. Results: Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01–2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, p < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X − 1). Two donors were HEV IgG-positive in the X − 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection. Conclusion: The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed. Full article

In recent years, clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) protein have emerged as a revolutionary gene editing tool to treat inherited disorders affecting different organ systems, such as blood and muscles. Both hematological and neuromuscular genetic disorders benefit from genome editing approaches but face different challenges in their clinical translation. The ability of CRISPR/Cas9 technologies to modify hematopoietic stem cells ex vivo has greatly accelerated the development of genetic therapies for blood disorders. In the last decade, many clinical trials were initiated and are now delivering encouraging results. The recent FDA approval of Casgevy, the first CRISPR/Cas9-based drug for severe sickle cell disease and transfusion-dependent β-thalassemia, represents a significant milestone in the field and highlights the great potential of this technology. Similar preclinical efforts are currently expanding CRISPR therapies to other hematologic disorders such as primary immunodeficiencies. In the neuromuscular field, the versatility of CRISPR/Cas9 has been instrumental for the generation of new cellular and animal models of Duchenne muscular dystrophy (DMD), offering innovative platforms to speed up preclinical development of therapeutic solutions. Several corrective interventions have been proposed to genetically restore dystrophin production using the CRISPR toolbox and have demonstrated promising results in different DMD animal models. Although these advances represent a significant step forward to the clinical translation of CRISPR/Cas9 therapies to DMD, there are still many hurdles to overcome, such as in vivo delivery methods associated with high viral vector doses, together with safety and immunological concerns. Collectively, the results obtained in the hematological and neuromuscular fields emphasize the transformative impact of CRISPR/Cas9 for patients affected by these debilitating conditions. As each field suffers from different and specific challenges, the clinical translation of CRISPR therapies may progress differentially depending on the genetic disorder. Ongoing investigations and clinical trials will address risks and limitations of these therapies, including long-term efficacy, potential genotoxicity, and adverse immune reactions. This review provides insights into the diverse applications of CRISPR-based technologies in both preclinical and clinical settings for monogenic blood disorders and muscular dystrophy and compare advances in both fields while highlighting current trends, difficulties, and challenges to overcome. Full article

Background/Objectives: Blood loss can be a serious complication in patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Various methods are used by surgeons to achieve hemostatic control in these patients. Complications are associated with perioperative blood loss. In this systematic review, we examined the efficacy of using bone wax to control bleeding in patients undergoing THA and TKA. Methods: The PRISMA model was used to systematically identify and aggregate articles for this study. The PubMed and EMBASE databases were used to search individual studies that examined the use of bone wax in THA or TKA. After applying the search term “bone wax”, 2478 articles were initially identified. After inclusion and exclusion criteria were applied, three articles were aggregated for this systematic review. Results: The use of bone wax in THA and TKA decreased blood loss in patients undergoing these operations. Postoperative blood loss following surgery was lower in the bone wax groups compared to the control groups as well. Patients in the bone wax groups also required fewer blood transfusions than those who did not receive bone wax. Conclusions: Bone wax appears to be another modality that can be used by physicians to maintain hemostatic control in THA or TKA patients. Reduced blood loss and transfusion rates in surgery can increase patient outcomes. More studies are needed to examine the efficacy of bone wax in comparison with other hemostatic tools. Full article

Background: Laparoscopic cholecystectomy is associated with a high safety profile. This study seeks to quantify the incidence of blood transfusion in both the elective and emergency settings, examine related patient outcomes, and investigate selection criteria for pre-operative Group and Save (G&S) sampling. Methods: A prospective multi-centre observational study was conducted to investigate patients undergoing either elective or emergency laparoscopic cholecystectomy in the UK between January 2020 and May 2021. Multivariate logistical regression models were used to identify patient factors associated with the risk of transfusion and explore outcomes linked to pre-operative G&S sampling. Results: This study comprised 959 patients, with 631 (65.8%) undergoing elective cholecystectomy and 328 (34.2%) undergoing emergency surgery. The median age was 48 years (range: 35–59), with 724 (75.5%) of the patients being female. Only five patients (0.5%) required blood transfusions, receiving an average of three units, with the first unit administered approximately six hours post-operatively. Among these cases, three patients (60%) had underlying haematological conditions. In adjusted models, male gender was significantly associated with the need for a blood transfusion (OR 11.31, p = 0.013), while the presence of a pre-operative Group and Save sample did not demonstrate any positive impact on patient outcomes. Conclusions: The incidence of blood transfusion following laparoscopic cholecystectomy is very low. Male gender and haematological conditions may present as independent risk factors. Pre-operative G&S sampling did not yield any positive impact on patient outcomes and could be safely excluded in both elective and emergency cases, although certain population subsets will warrant further consideration. Full article

Background: The use of wetting solutions (WSs) during high-volume liposuction is standard; however, the optimal amount of WS and its components and their effect on postoperative complications are unclear. We evaluated the effect of a WS and its components, calculated according to ideal body weight (IBW), on postoperative complications. Methods: High-volume liposuction with a WS containing 0.5 g of lidocaine and 0.5 mg of epinephrine in each liter was performed in 192 patients. Patients who received ≤90 mL/kg of WS were designated as group I and those who received >90 mL/kg of WS as group II. Postoperative complications and adverse events that occurred until discharge were recorded. Results: The mean total amount of epinephrine in the WS was significantly higher for group II (3.5 mg; range, 3.0–4.0 mg) than for group I (2.0 mg; range, 1.8–2.5 mg; p < 0.001), as was the mean total amount of lidocaine (3.5 g [range, 3.5–4.3 g] vs. 2.0 g [range, 1.8–2.5 g], respectively; p < 0.001). No major cardiac or pulmonary complications occurred in either group. Administration of >90 mL/kg of WS increased the median risk of postoperative nausea 5.3-fold (range, 1.8- to 15.6-fold), that of hypertension 4.9-fold (range, 1.1- to 17.7-fold), and that of hypothermia 4.2-fold (range, 1.1- to 18.5-fold). The two groups had similar postoperative pain scores and blood transfusion rates. Conclusions: The risks of postoperative nausea, vomiting, hypothermia, and hypertension may increase in patients who receive >90 mL/kg of WS calculated according to IBW during high-volume liposuction. Full article

Background/Objectives: The IWATE criteria are well-established as a helpful tool to preoperatively estimate the difficulty and perioperative outcome of laparoscopic liver resections. We evaluated the relationship between the IWATE criteria and the perioperative outcomes in robotic-assisted liver resections (RARLs). Methods: We retrospectively analyzed the data of 58 patients who underwent robotic-assisted liver surgery at our center between July 2019 and April 2023. The operative difficulty of every patient was graded according to the IWATE criteria and compared to the perioperative outcome. Results: The median operation time was 236.5 min (range 37–671 min), and the median length of stay was 6 days (range 3–37 min). The majority had no complications (65.5%; n = 38), 18 (31.0%) patients suffered from mild complications (CD ≤ 3A) and 2 patients (3.4%) suffered from relevant complications (CD ≥ 3B). We observed no deaths within 30 postoperative days. The surgery time, postoperative ICU stay and perioperative blood transfusions increased significantly with a higher difficulty level (p = < 0.001; p < 0.001; p = 0.016). The length of stay, conversion to open surgery (n = 2) and complication rate were not significantly linked to the resulting IWATE group. Conclusions: The IWATE criteria can be implemented in robotic-assisted liver surgery and can be helpful in preoperatively estimating the difficulty of robotic liver resections. Whether there is a “robotic effect” in minimally invasive liver resections has to be further clarified. The IWATE criteria can help to develop curricula for robotic training. Full article

Background/Aims: The massive transfusion protocol (MTP) can improve the outcomes of trauma patients with hemorrhagic shock and some patients with non-traumatic hemorrhagic shock. However, no information is available regarding whether MTP can improve the outcomes of acute variceal bleeding (AVB). This study aimed to determine the effects of MTP on the outcomes of patients with AVB. Methods: Consecutive patients (n = 218) with AVB who did not have current malignancy and visited the emergency room between July 2014 and June 2022 were analyzed. 42-day mortality and failure to control the bleeding were compared between patients with and without MTP activation. Additionally, propensity-score matching was conducted. Results: The amount of blood product transfused was higher in the MTP group. The 42-day mortality rate (42.1% vs. 1.5%, p < 0.001) and the rate of failure to control bleeding (36.8% vs. 0.5%, p < 0.001) were significantly higher in those who received blood transfusions by MTP. MTP was an independent factor associated with 42-day mortality in the multivariable-adjusted analysis (HR 21.05; 95% CI 3.07–144.21, p = 0.002, HR 24.04; 95% CI 3.41–169.31, p = 0.001). The MTP group showed consistently higher 42-day mortality and failure to control bleeding in all subgroup analyses, stratified by systolic blood pressure, hemoglobin level, and the model for end-stage liver disease score. The MTP group also showed higher 42-day mortality (42.9% vs. 0%, p = 0.001) and failure to control bleeding (42.9% vs. 0%, p = 0.001) in a propensity score-matched analysis (n = 52). Conclusions: MTP was associated with poor outcomes in patients with AVB. Further studies are needed to see whether MTP can be an option for patients with massive AVB. Full article

The complex epidemiology of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV) patients in West Mexico remains poorly understood. Thus, this study aimed to investigate the HCV prevalence, HCV-associated risk factors, and HCV genotypes/subtypes and assess their impacts on liver fibrosis in 294 HIV patients (median age: 38 years; 88.1% male). HCV RNA was extracted and amplified by PCR. Hepatic fibrosis was assessed using three noninvasive methods: transient elastography (TE), the aspartate aminotransferase (AST)-to-platelets ratio index score (APRI), and the fibrosis-4 score (FIB4). Patients with liver stiffness of ≥9.3 Kpa were considered to have advanced liver fibrosis. HCV genotypes/subtypes were determined by line probe assay (LiPA) or Sanger sequencing. The prevalence of HIV/HCV infection was 36.4% and was associated with injection drug use (odds ratio (OR) = 13.2; 95% confidence interval (CI) = 5.9–33.6; p < 0.001), imprisonment (OR = 3.0; 95% CI = 1.7–5.4; p < 0.001), the onset of sexual life (OR = 2.6; 95% CI = 1.5–4.5; p < 0.001), blood transfusion (OR = 2.5; 95% CI = 1.5–4.2; p = 0.001), tattooing (OR = 2.4; 95% CI = 1.4–3.9; p = 0.001), being a sex worker (OR = 2.3; 95% CI = 1.0–5.4; p = 0.046), and surgery (OR = 1.7; 95% CI = 1.0–2.7; p = 0.042). The HCV subtype distribution was 68.2% for 1a, 15.2% for 3a, 10.6% for 1b, 3.0% for 2b, 1.5% for 2a, and 1.5% for 4a. The advanced liver fibrosis prevalence was highest in patients with HIV/HCV co-infection (47.7%), especially in those with HCV subtype 1a. CD4+ counts, albumin, direct bilirubin, and indirect bilirubin were associated with liver fibrosis. In conclusion, HCV infection had a significant impact on the liver health of Mexican HIV patients, highlighting the need for targeted preventive strategies in this population. Full article

Objective: To compare the perioperative outcomes of supine and prone percutaneous nephrolithotomy (PCNL). Methods: A retrospective search of a tertiary medical center database yielded 517 patients who underwent supine (n = 91) or prone (n = 426) PCNL between September 2015 and July 2020. Data on demographics, baseline clinical parameters, and stone burden were included as predictors in a logistic regression model, generating a set of propensity scores. Seventy patients after supine PCNL were propensity score-matched 1:1 with patients after prone PCNL and compared for operative time, perioperative complications, system complexity, and stone-free rate. Results: We found that the operative time was significantly shorter in the supine PCNL group than in the prone PCNL group (85.5 ± 25.2 min vs. 96.4 ± 25.8 min, respectively; p = 0.012). The majority of both groups had low-grade (I–II) complexity systems (85.6% and 88.6%, respectively), with no significant difference among all grade groups (p = 0.749). There were no significant differences between the supine and prone PCNL groups in terms of the overall perioperative complication rate (8.6% vs. 4.3%, respectively; p = 0.301) or stone-free rate (74.3 vs. 65.7%, respectively; p = 0.356), while the rate of blood transfusion was significantly higher in the supine group (p = 0.023). Conclusions: In our study, we used propensity score matching to compare patients who underwent PCNL in the supine or prone position, adjusting for selection bias. Supine PCNL was associated with a shorter operative time but a higher blood transfusion rate, with no differences in the overall complication and stone-free rates. Full article

Background. Minimally invasive surgery for the treatment of locally advanced gastric cancer (AGC) is debated. The aim of this study was to execute a comprehensive assessment of principal surgical treatments for resectable distal gastric cancer. Methods. Systematic review and randomized controlled trials (RCTs) network meta-analysis. Open (Op-DG), laparoscopic-assisted (LapAs-DG), totally laparoscopic (Lap-DG), and robotic distal gastrectomy (Rob-DG) were compared. Pooled effect-size measures were the risk ratio (RR), the weighted mean difference (WMD), and the 95% credible intervals (CrIs). Results. Ten RCTs (3823 patients) were included. Overall, 1012 (26.5%) underwent Lap-DG, 902 (23.6%) LapAs-DG, 1768 (46.2%) Op-DG, and 141 (3.7%) Rob-DG. Anastomotic leak, severe complications (Clavien–Dindo > 3), and in-hospital mortality were comparable. No differences were observed for reoperation rate, pulmonary complications, postoperative bleeding requiring transfusion, surgical-site infection, cardiovascular complications, number of harvested lymph nodes, and tumor-free resection margins. Compared to Op-DG, Lap-DG and LapAs-DG showed a significantly reduced intraoperative blood loss with a trend toward shorter time to first flatus and reduced length of stay. Conclusions. LapAs-DG, Lap-DG, and Rob-DG performed in referral centers by dedicated surgeons have comparable short-term outcomes to Op-DG for locally AGC. Full article

Background and Objectives: Placenta accreta spectrum (PAS) disorders are placental conditions associated with significant maternal morbidity and mortality. While antenatal vaginal bleeding in the setting of PAS is common, the implications of this on overall outcomes remain unknown. Our primary objective was to identify the implications of antenatal vaginal bleeding in the setting of suspected PAS on both maternal and fetal outcomes. Materials and Methods: We performed a case-control study of patients referred to our PAS center of excellence delivered by cesarean hysterectomy from 2012 to 2022. Subsequently, antenatal vaginal bleeding episodes were quantified, and components of maternal morbidity were assessed. A maternal composite of surgical morbidity was utilized, comprised of blood loss ≥ 2 L, transfusion ≥ 4 units of blood, intensive care unit (ICU) admission, and post-operative length of stay ≥ 4 days. Results: During the time period, 135 cases of confirmed PAS were managed by cesarean hysterectomy. A total of 61/135 (45.2%) had at least one episode of bleeding antenatally, and 36 (59%) of these had two or more bleeding episodes. Increasing episodes of antenatal vaginal bleeding were associated with emergent delivery (p < 0.01), delivery at an earlier gestational age (35 vs. 34 vs. 33 weeks, p < 0.01), and increased composite maternal morbidity (76, 84, and 94%, p = 0.03). Conclusions: Antenatal vaginal bleeding in the setting of PAS is associated with increased emergent deliveries, earlier gestational ages, and maternal composite morbidity. This important antenatal event may aid in not only counseling patients but also in the coordination of multidisciplinary teams caring for these complex patients. Full article