Necrotizing Enterocolitis: A Current Understanding and Challenges for the Future.

This perspective reviews the definition and current understanding of necrotizing enterocolitis and evaluates a future prevention approach to this multifactorial disease. An overview of the prevention approach in general is presented, where key aspects and emerging criticisms are identified. In addition, key elements of early diagnosis and treatment are presented, together with some of their challenges and ambiguities. Moreover, it concludes with emerging questions from the global community to reach a consensus on the definition, diagnosis, and management of necrotizing enterocolitis disease.

Clinical Picture, Diagnosis, Management of NEC, and Effects of Probiotics on its Prevention: A Narrative Review.

Preterm newborns represent a population at risk of developing intestinal dysbiosis as well as being predisposed to sepsis and Necrotizing Enterocolitis. Necrotizing Enterocolitis is a condition burdened by many complications and mortality due to an alteration of the intestinal barrier, an immaturity of the immune system, and intestinal dysbiosis. Low gestational age at birth, low birth weight, and early use of antibiotics are other predisposing factors. Instead, breast milk and probiotics are protective factors in providing intestinal homeostasis and microbiome regulation. In this mini-review, we analysed the protective role of probiotics in the onset of Necrotizing Enterocolitis in preterm populations.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in low-weight patients with atrial fibrillation.

It remains unclear whether non-vitamin K antagonist oral anticoagulants (NOACs) are more effective and safer than warfarin in low-weight patients with atrial fibrillation (AF). Here, we retrospectively compared the effectiveness and safety of NOACs with those of warfarin in low-weight patients with AF. We extracted the July 2011-September 2022 data of patients with AF treated with a NOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) or warfarin at a tertiary hospital. The patients were divided into low-weight (body weight ≤ 60 kg) and non-low-weight (body weight = 60-100 kg) groups. The primary outcomes were hospitalization for ischemic stroke (IS) or systemic embolism (SE) and major bleeding, whereas the secondary outcomes were any ischemic and bleeding events. We used the inverse probability of treatment weighting to balance the baseline characteristics between the groups. In total, 5,044 patients (mean age = 73.7 years, mean CHA2DS2-VASc score = 3.0, mean HAS-BLED score = 2.3) were enrolled and divided into low-weight and non-low-weight groups-containing 1,666 (1,406 NOAC users, 260 warfarin users) and 3,378 (2,978 NOAC users, 400 warfarin users) patients, respectively. NOACs were associated with a lower risk of any bleeding event in the low-weight group (adjusted hazard ratio = 0.61, 95% confidence interval = 0.51-0.73). The between-group differences in the risks of IS/SE, any ischemic event, major bleeding, and any bleeding event were nonsignificant. Thus, the use of NOACs (specifically dabigatran or edoxaban) is associated with a lower risk of any bleeding event than warfarin use in low-weight patients with AF.

Thoracoscopic primary repair is useful for esophageal atresia with tracheoesophageal fistula in neonates with low body weight.

PURPOSE: The surgical indication of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula is under debate. The current study aimed to investigate the outcome of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula in patients weighing < 2000 g and those who underwent emergency surgery at the age of 0 day. METHODS: The surgical outcomes were compared between patients weighing < 2000 g and those weighing > 2000 g at surgery and between patients who underwent surgery at the age of 0 day and those who underwent surgery at age ≥ 1 day. RESULTS: In total, 43 patients underwent thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula. The surgical outcomes according to body weight were similar. Patients who underwent surgery at the age of 0 day were more likely to develop anastomotic leakage than those who underwent surgery at the age of ≥ 1 day (2 vs. 0 case, p = 0.02). Anastomotic leakage was treated with conservative therapy. CONCLUSION: Thoracoscopic primary repair is safe and useful for esophageal atresia with tracheoesophageal fistula even in newborns weighing < 2000 g. However, emergency surgery at the age of 0 day should be cautiously performed due to the risk of anastomotic leakage.

Peripheral blood stem cell harvesting in young children weighing less than 15 kg.

Autologous peripheral blood stem cell (PBSC) transplantation is crucial in pediatric cancer treatment, and tandem transplantation is beneficial in certain malignancies. Collecting PBSCs in small children with low body weight is challenging. We retrospectively analyzed data of pediatric cancer patients weighing <15 kg who underwent autologous PBSC harvesting in our hospital. Collections were performed in the pediatric intensive care unit over 2 or 3 consecutive days, to harvest sufficient stem cells (goal ≥2 × 106 CD34+ cells/kg per apheresate). From April 2006 to August 2021, we performed 129 collections after 50 mobilizations in 40 patients, with a median age of 1.9 (range, 0.6-5.6) years and a body weight of 11.0 (range, 6.6-14.7) kg. The median CD34+ cells in each apheresate were 4.2 (range, 0.01-40.13) × 106/kg. 78% and 56% of mobilizations achieved sufficient cell dose for single or tandem transplantation, respectively, without additional aliquoting. The preapheresis hematopoietic progenitor cell (HPC) count was highly correlated with the CD34+ cell yield in the apheresate (r = 0.555, P < 0.001). Granulocyte colony-stimulating factor alone was not effective for mobilization in children ≥2 years of age, even without radiation exposure. By combining the preapheresis HPC count ≥20/µL and the 3 significant host factors, including age <2 years, no radiation exposure and use of chemotherapy, the prediction rate of goal achievement was increased (area under the curve 0.787).

Body mass index modified the effectiveness of low dose aspirin treatment on frozen-thawed embryo transfer outcome: a propensity score-matched study.

Background: Low-dose aspirin is one of the widely used adjuvants in assisted reproductive technologies with the hope of improving the live birth rate. However, the studies regarding its effects are conflicting. The study aimed to investigate the association between aspirin administration and live birth following frozen-thawed embryo transfer (FET) in patients with different body mass index (BMI). Methods: A retrospective cohort study was performed on 11,993 patients receiving FET treatments. 644 of which received a low-dose aspirin (100 mg/day) during endometrial preparation until 10 weeks after transfer. Propensity score matching was performed to avoid selection biases and potential confounders. Results: The clinical pregnancy rate and live birth rate were similar before matching (54.4% versus 55.4%, RR: 1.02, 95%CI: 0.95-1.09, and 46.3 versus 47.8, RR: 1.03, 95%CI: 0.95-1.12 respectively). A weak association in favor of aspirin administration was found in the matched cohort (49.5% versus 55.4%, RR: 1.12, 95%CI: 1.01-1.24, and 41.9% versus 47.8%, RR: 1.14, 95%CI: 1.01-1.29 respectively). However, when stratified the patients with WHO BMI criteria, a significant increase in live birth rate associated with aspirin treatment was found only in patients with low BMI (<18.5 kg/m2) in either unmatched (46.4% versus 59.8%, RR:1.29, 95%CI:1.07-1.55) or matched cohort (44% versus 59.8%, RR: 1.36, 95%CI: 1.01-1.83) but not in patients with higher BMI categories. With the interaction analysis, less association between aspirin and live birth appeared in patients with normal BMI (Ratio of OR:0.49, 95%CI: 0.29-0.81) and high BMI (Ratio of OR:0.57, 95%CI: 0.27-1.2) compared with patients with low BMI. Conclusion: BMI may be considered when evaluating aspirin's effect in FET cycles.

Evaluation of Postoperative Outcomes After Enterostomy Closure in Low Body Weight Infants: A Multi-Center Retrospective Analysis.

BACKGROUND: The minimum weight for enterostomy closure (EC) in infants remains debated with the current acceptable cut-off of >2 kg. As enterostomy-related complications or high enterostomy output (>30cc/kg/d) may prohibit a premature infant from reaching 2 kg, additional data is needed to evaluate the safety of EC in infants <2 kg. The objective of this study was to evaluate postoperative outcomes in low body weight (<2 kg) infants undergoing EC compared to larger infants. METHODS: We performed a multi-center retrospective analysis from 1/1/2012-12/31/2022 of all infants (age <1 year) who were <4 kg at time of EC. Primary outcomes included postoperative complications and 30-day mortality. Non-parametric analysis was performed using the Kruskal-Wallis one-way analysis of variance and chi-square tests. Univariable logistic regression was performed to identify factors associated with postoperative complications. RESULTS: Of 92 infants, 15 infants (16.3%) underwent EC at <2 kg, 16 (17.4%) at 2-2.49 kg, 31 (33.7%) at 2.5-2.99 kg, and 30 (32.6%) at ≥3 kg. Infants <2 kg at time of EC exhibited higher rates of hyperbilirubinemia (P = .030), neurologic comorbidities (P = .030), and high enterostomy output (P = .041). There was no difference in postoperative complications (P = .460) or 30-day mortality (P = .460) between the <2 kg group and larger weight groups. Low body weight was not associated with an increased risk for developing a postoperative complication (OR: 1.001, 95% CI: 1.001-1.001; P = .032). CONCLUSION: Our findings suggest that EC in infants <2 kg may be safe with comparable postoperative outcomes to larger weight infants. Thus, the timing of EC should be based on the infant's physiologic status, in contrast to a predetermined minimum weight cut-off.

[Prevalence and trends of low body weight among elderly population aged 60 years and above in China in 2002-2015].

OBJECTIVE: Understand the current situation and changing trends of low body weight in elderly population aged 60 years and above. METHODS: Data was collected from 2002 Chinese Nutrition and Health Survey, 2010-2013 Chinese Nutrition and Health Surveillance and 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Multi-stage stratified cluster random sampling was used for all surveys or surveillance. In 2002, 27 778 samples of people aged 60 and over were taken from 132 monitoring sites in mainland China. In 2010-2013, 34 581 subjects were selected from 150 monitoring points in mainland China. In 2015, 59 576 subjects were selected from 302 monitoring points in mainland China. Questionnaires collected basic information such as gender, and date of birth, and information such as height and weight were collected through physical examination. RESULTS: The prevalence of low body weight in the elderly aged 60 years and above showed a downward trend from 2002 to 2015 in China(P<0.01). The prevalence of low body weight decreased from 11.67% in 2002 to 5.19% in 2015. The prevalence of low body weight among males decreased from 11.51% in 2002 to 5.21% in 2015. The prevalence of low body weight among females decreased from 11.83% in 2002 to 5.17% in 2015. The prevalence of low body weight in the elderly aged 60 years and above showed an upward trend with age. The prevalence of low body weight in urban areas decreased from 5.85% in 2002 to 3.31% in 2015. The prevalence of low body weight in rural areas decreased from 16.25% in 2002 to 6.67% in 2015. The prevalence of low body weight in seven geographic regions of China decreased from 2002 to 2015. The prevalence of low body weight was highest in the elderly population aged 60 years and above in South China(9.49%(95%CI 8.61%-10.38%)) and lowest in North China(2.55%(95%CI 2.15%-2.95%)) in 2015. CONCLUSION: The prevalence of low body weight among the elderly aged 60 years and above in China decreased from 2002 to 2015. The prevalence of low body weight increased with age. The prevalence was higher in rural areas than in urban areas, and the prevalence in South China was higher than in other geographic regions.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Low Body Weight Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

INTRODUCTION: Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m2). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients. METHODS: We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model. RESULTS: Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17-1.92), (OR 1.55, 95% CI 1.29-1.86), (OR 2.92, 95% CI 1.87-4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93-1.52). DISCUSSION: In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m2) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.

Impact of Reduced Enoxaparin Prophylactic Dosing on Bleeding and Thrombotic Risk for Low Body Weight Post-Operative Colorectal Surgery Patients.

Introduction: Colorectal surgery (CORS) patients are at the highest risk of any general surgery population for the development of post-operative venous thromboembolism (VTE) and are also at an increased risk for post-operative bleeding, especially with procedures related to early cancer stages. Low molecular weight heparin (LMWH) is recommended for VTE prophylaxis in this surgical population. Current guidelines and primary literature along with institutional protocols support dosage adjustments for obesity and impaired renal function, but literature providing optimal VTE prophylactic LMWH dosing is extremely limited for underweight, surgical patients. Objectives: The aim of this study was to evaluate both bleeding and VTE rates for hospitalized underweight colorectal surgery patients receiving post-operative VTE prophylaxis with standard enoxaparin 40 mg subcutaneously (SQ) every 24 hours versus reduced dose enoxaparin 30 mg SQ every 24 hours. Methods: This trial was a multicenter, retrospective chart review with data collected on post-operative CORS patients over a 10-year period. Patients were included if aged 18 years and older, weighed less than 50 kg, and received at least 1 dose of enoxaparin 40 mg or 30 mg post-operatively. The primary endpoint was a descriptive comparison of post-operative bleeding with use of standard enoxaparin 40 mg SQ every 24 hours compared to reduced dose enoxaparin 30 mg SQ every 24 hours for post-operative VTE prophylaxis. The secondary endpoint was the descriptive comparison of post-operative thrombotic event rates in the same population. Results: The total population investigated included 146 patients. One hundred twenty-nine (88.4%) received standard enoxaparin and 17 (11.6%) received reduced enoxaparin. Overall, 9 bleeding events (7.0%) and 2 major VTE events (1.6%) occurred, all within the standard enoxaparin group. Conclusion: Standard dose enoxaparin for post-operative VTE prophylaxis demonstrated increased bleeding and thrombotic events requiring medical and surgical intervention in comparison to reduced dose enoxaparin for low body weight CORS patients. The results of this study are hypothesis generating and continued research involving more robust systematic reviews are needed to evaluate both safety and efficacy of reduced VTE prophylaxis with LMWH in the underweight, surgical patient population.

Safety and efficacy of peripheral blood stem cells collection in healthy children and pediatric patients with thalassemia major weighing 20 kg or less.

BACKGROUND: Peripheral blood stem cell (PBSC) collection in children poses challenges due to their small size, low body weight (BW), and unique pediatric physiology, especially among children weighing 20 kg (kg) or less. METHODS: PBSC collection data of both healthy children and patients with thalassemia major (TM) weighing 20 kg or less between January 2013 and December 2020 were reviewed. Moreover, PBSCs characteristics along with various aspects of efficiency and safety between healthy donors and patients with TM were compared. RESULTS: A total of 262 PBSC procedures were performed on 255 children. Of these, 91 procedures were carried out on 85 allogeneic healthy donors, and 171 auto-backup collections were performed on 170 patients with TM to ensure PBSC availability and prevent transplantation failure. A minimum pre-apheresis hemoglobin (HGB) level of 60 g/L was discovered to be safe and feasible in patients with TM. The median CD34+ cell dose in the PBSC product during the initial apheresis procedure was higher in healthy donors compared to patients with TM (7.29 ± 5.28 × 106 cells/kg vs5.88 ± 4.23 × 106 cells/kg, P = .043). The total CD34+ cells/kg recipient weight exhibited a positive correlation with pre-apheresis monocyte counts, but a negative correlation with donor weight. Apheresis significantly reduced hematocrit and platelet counts in the allogeneic group compared to the autologous group. Patients with TM experienced a higher occurrence of bone pain related to granulocyte colony-stimulating factor treatment. Notably, no serious complications related to PBSCs mobilization, central venous catheter placement, or the apheresis procedure were observed in either group. CONCLUSIONS: PBSCs collection was both safe and effective in healthy children and pediatric patients with TM weighing 20 kg or less.

Associations between low body weight, weight loss, and medical instability in adults with eating disorders.

OBJECTIVE: The physical complications of atypical anorexia nervosa remain understudied, with most studies completed in adolescents. This study seeks to examine the impact of various weight measures as predictors of medical instability in a large cohort of adult eating disorder patients. METHODS: In this retrospective cohort study, the impact of admission body mass index (BMI), weight suppression, and recent weight loss (the rate of weight loss within the last 12 months) toward the development of medical complications of malnutrition were examined. Multivariable logistic regression assessed the association of binary clinical outcomes of interest with recent weight loss and weight suppression (adjusting for age, admission BMI, gender, and purging behaviors). Odds ratios (OR) and 99% confidence intervals were reported. RESULTS: Greater recent weight loss increased the odds of developing low prealbumin and reduced hand grip strength. A greater weight suppression was associated with increased likelihood of amenorrhea, reduced systolic blood pressure, nadir hemoglobin, and weekly weight gain upon nutritional rehabilitation. Lower admission BMI was predictive of all the medical outcomes examined, with the exception of bradycardia, and was generally the strongest predictor based on standardized coefficients. DISCUSSION: Recent weight loss and weight suppression are predictive of some of the physiologic changes of malnutrition, although low BMI is seemingly the greatest predictor for the development of these complications. These findings suggest that some patients with aggressive weight suppression and/or acute weight loss would benefit from medical stabilization, although this needs to be further defined. PUBLIC SIGNIFICANCE: In adults, low BMI seems to be a better predictor of medical complications than weight suppression or aggressive recent weight loss. In adults, greater weight suppression is associated with increased likelihood of amenorrhea, reduced systolic blood pressure, nadir hemoglobin, and weight gain upon nutritional rehabilitation.

Venous Thromboembolism Prophylaxis in Low Body Weight Critically Ill Patients.

OBJECTIVE: To compare bleeding and thromboembolic events in low body weight patients receiving reduced-dose venous thromboembolism (VTE) prophylaxis versus standard-dose VTE prophylaxis. DESIGN: Multicenter, retrospective, cohort study. SETTING: Five Ascension Health Hospitals. PATIENTS: Adult, critically ill, low body weight (≤50 kg) patients who received either reduced-dose VTE prophylaxis (n = 140) or standard-dose VTE prophylaxis (n = 279) for at least 48 h. INTERVENTION: Reduced-dose prophylaxis (enoxaparin 30 mg daily or heparin 5000 units every 12 h subcutaneously) or standard-dose prophylaxis (enoxaparin 40 mg daily, enoxaparin 30 mg every 12 h, or heparin 5000 units every 8 h subcutaneously). MEASUREMENTS AND MAIN RESULTS: A total of 419 patients were included with a mean weight of 45.1 ± 4.2 kg in the standard-dose group and 44.0 ± 5.1 kg in the reduced-dose prophylaxis group (P = .02). The primary endpoint, composite bleeding, was significantly lower in patients receiving reduced-dose prophylaxis (5% vs 12.5%, P = .02). After adjusting for confounding factors, results remained consistent demonstrating reduced composite bleeding with reduced-dose prophylaxis (odds ratio: 0.36, 95% confidence interval: 0.14-0.96). Major bleeding events occurred in 3.6% of reduced-dose patients compared with 8.6% in standard-dose patients (P = .056). Clinically relevant nonmajor bleeding (5.4% vs 2.9%, P = .24) and VTE (2.2% vs 0%, P = .08) events were similar between groups. CONCLUSIONS: A reduced-dose VTE prophylaxis strategy in low body weight, critically ill patients was associated with a lower risk of composite bleeding and similar rate of thromboembolism.

Direct Oral Anticoagulant Dosing in Patients With Atrial Fibrillation: An Asian Perspective.

Optimal dosing of direct oral anticoagulants (DOACs) for stroke prevention in "gray area" patients with atrial fibrillation (AF) remains a challenge for clinicians. In Asia, this is concerning in patients who are very elderly, have low body weight, and are at a high risk of bleeding. This review aims to summarize the dose reduction criteria for DOACs, discuss the evidence on dosing of DOACs across Asian regions, and collate opinions from authors across Asia. Nonrecommended dosing of DOACs is common in Asia, primarily due to the fear of bleeding, with the total clinical benefit of higher dosing being overlooked. The ELDERCARE-AF (Edoxaban Low-Dose for Elder Care-Atrial Fibrillation Patients) trial and real-world case studies provide some evidence on the use of low-dose DOACs in gray area patients. Opinions on dose adjustment guidance, concomitant medication adjustments, and therapeutic drug monitoring were collated. Research is needed to fill the evidence gaps on optimal DOAC doses for gray area patients.

The prevalence and risk factors of coagulopathy in pediatric patients undergoing surgery for epilepsy.

OBJECTIVE: Hematological consequences of novel antiseizure medications (ASMs) or combined therapies are rarely reported, especially in pediatric patients undergoing surgery for epilepsy. This study aimed to assess the prevalence and risk factors of coagulation dysfunction in this population and evaluate their relationship with intra- and postoperative bleeding. METHODS: Three hundred ninety children who underwent surgery for epilepsy and 104 children without epilepsy who underwent nonepilepsy surgery at the authors' center were included in the study. The authors retrospectively collected and analyzed the following clinical data: sex, age, weight, course of epilepsy, antiseizure therapy, first laboratory data after admission, and transfusion-related data. RESULTS: ASMs were responsible for the higher incidence of coagulation dysfunction in pediatric epilepsy surgery patients. Low body weight (OR 0.95, 95% CI 0.92-0.98) and valproic acid (VPA) therapy (OR 5.13, 95% CI 3.25-8.22) were the most relevant factors leading to coagulation dysfunction. The most common hematological side effects of VPA were thrombocytopenia and hypofibrinogenemia, whereas low body weight was only associated with hypofibrinogenemia. Both VPA and low body weight increased the need for intra- or postoperative transfusion (p < 0.001). CONCLUSIONS: Pediatric epilepsy surgery patients often take multiple ASMs, resulting in an increased incidence of coagulopathy. VPA levels and low body weight were found to be the main influential factors associated with an increased risk of coagulation dysfunction. Platelet and fibrinogen levels were the main indices that were affected. Both VPA and low body weight were relevant to additional surgery-related transfusion, necessitating the need for increased awareness of preoperative coagulopathy before pediatric epilepsy surgery. Clinical trial registration no.: NCT05675254 (ClinicalTrials.gov).

Assessment of bleeding risk in low-weight patients receiving prophylactic subcutaneous unfractionated heparin.

BACKGROUND: Underweight patients may be at an increased risk of bleeding while receiving venous thromboembolism (VTE) prophylaxis. Additional evidence is needed to identify patient-specific factors associated with bleeding. The objective of the study was to describe the incidence and identify risk factors associated with bleeding in low-weight (⩽ 60 kg) adult patients receiving subcutaneous unfractionated heparin (SQH) for VTE prophylaxis. METHODS: This was a single-center, retrospective, nested case-control study of low-weight patients receiving SQH for VTE prophylaxis for ⩾ 48 hours. Cases, patients with clinically relevant bleeding while receiving SQH, and controls, patients without a bleeding event, were matched in a 1:3 ratio for age, sex, primary service (surgical or medical), and time at risk of bleeding on SQH to determine factors associated with bleeding. RESULTS: A total of 3761 patients met the inclusion criteria, of which 38 cases of clinically relevant bleeding were identified. The bleeding incidence was 1% at hospital day 6 and 2.8% at hospital day 14. Most patients in this study (69%) received SQH 5000 units three times daily. ICU admission at SQH start was associated with bleeding, OR 2.97 (95% CI 1.21-7.29). CONCLUSION: Bleeding in low-weight patients on prophylactic SQH was uncommon. Patients admitted to the ICU at time of SQH start may be at a higher risk of bleeding. Further studies are needed to detect additional risk factors associated with bleeding and investigate the effects of reduced dosing in this population.

Risk of fracture according to temporal changes of low body weight changes in adults over 40 years: a nationwide population-based cohort study.

BACKGROUND: Low body weight is associated with an increased risk of fractures. However, the effect of temporal changes in the low body weight status on the risk of fracture remains unknown. This study aimed to evaluate the relationships between temporal changes in low body weight status and the risk of fractures in adults over the age of 40 years. METHODS: This study included data on adults over 40 years old who underwent two biannual consecutive general health examinations between January 1, 2007 and December 31, 2009 extracted from the National Health Insurance Database, a large nationwide population database. Fracture cases in this cohort were monitored from the time of the last health examination to the end of the designated follow-up period (from January 1, 2010 to December 31, 2018) or the participant's death. Fractures were defined as any fracture resulting in hospitalization or outpatient treatment claim after the date of general health screening. The study population was then separated into four groups based on the temporal changes in low body weight status as follows: low body weight to low body weight (L-to-L), low body weight to non-low body weight (L-to-N), non-low body weight to low body weight (N-to-L), and non-low body weight to non-low body weight (N-to-N). The hazard ratios (HRs) for new fractures, depending on weight changes over time, were calculated using Cox proportional hazard analysis. RESULTS: Adults in the L-to-L, N-to-L, and L-to-N groups had a substantially increased risk of fractures after multivariate adjustment (HR, 1.165; 95% confidence interval [CI], 1.113-1.218; HR, 1.193; 95% CI, 1.131-1.259; and HR, 1.114; 95% CI, 1.050-1.183, respectively). Although the adjusted HR was greater in participants who changed into having a low body weight, followed by those with consistently low body weight, those with low body weight remained to have an elevated risk of fracture independent of weight fluctuation. Elderly men (aged over 65 years), high blood pressure, and chronic kidney disease were significantly associated with an increase in fractures (p < 0.05). CONCLUSION: Individuals aged over 40 years with low body weight, even after regaining normal weight, had an increased risk of fracture. Moreover, having a low body weight after having a normal body weight increased the risk of fractures the most, followed by those with consistently low body weight.

Pharmacokinetic and dose-finding study of osimertinib in patients with impaired renal function and low body weight.

The safety of osimertinib is limited in patients with severe or moderate renal impairment, or low body weight. This study aimed to investigate the safety, pharmacokinetics (PK) and recommended dose (RD) of osimertinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with impaired renal function and low body weight. Thirty-one eligible patients were enrolled and allocated into four cohorts: A, normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 mL/min/1.73 m2 ) and normal body weight (≥45 kg); B, moderate renal impairment (eGFR = 30-50 mL/min/1.73 m2 ); C, low body weight (<45 kg); and D, severe renal impairment (eGFR <30 mL/min/1.73 m2 or undergoing dialysis). PK parameters and safety were evaluated with a starting dose of 80 mg osimertinib administered orally once daily in cohorts A, B, and C and 40 mg once daily in cohort D. The PK parameters in cohorts A, B, and C were found to be similar. No dose-limiting toxicity was observed, and the RD was determined to be 80 mg once daily in patients with moderate renal function and low body weight. Four serious adverse events, acneiform rash, diarrhea, QTc prolongation, and interstitial lung disease, were noted. Although the PK parameters of osimertinib were similar across all cohorts, toxicity occurred more frequently in patients with impaired renal function and low body weight. Clinicians should prescribe osimertinib with caution in NSCLC patients with impaired renal function and low body weight.

Peripheral blood stem cells collection by apheresis in very low-weight children with malignant diseases-A single center experience.

BACKGROUND: Hematopoietic stem cell transplantation is used in the treatment of children with malignant and non-malignant diseases. However, apheresis of peripheral blood stem cells (PBSC) represents a challenge in children below 10 kg. METHODS: A retrospective trial was conducted in the Cellular Therapy Department of Portuguese Oncology Institute of Porto. INCLUSION CRITERIA: children with body weight inferior to 10 kg who underwent autologous PBSC apheresis until 2021. Demographic and clinical data were collected and our institutional protocol was described. COBE Spectra apheresis system (TerumoBCT, Lakewood, Colorado) until 2012 and then Spectra Optia (TerumoBCT) were used. RESULTS: Sixteen leukocytaphereses were performed in 13 patients-nine females (69%). Mean age and weight were 13.31 months (±5.26) and 8.31 kg (±1.17), respectively. The initial CD34+ cells/µL in peripheral blood was 70.8 (±61.9). A central venous catheter (CVC) was exclusively used in all but one patient, in whom a peripheral vein was also required. In 10 procedures, both heparin and anticoagulant citrate dextrose solution-formula A (ACD-A) were used; in the remaining ones, only ACD-A was employed. The median duration of each procedure was 168 minutes (±45) and 2.96 blood volumes (±0.31) were processed. Median CD34+ cells yield per leukocytapheresis was 6.52 × 106 /kg (±9.87 × 106 ). CD34+ cell extraction rates were not significantly different between the two apheresis systems. Platelet and magnesium levels were significantly lower after collection (P < .001 and P = .009, respectively). CONCLUSIONS: Although recommendations are lacking, we have successfully and safely performed leukocytaphereses in children with body weight below 10 kg. The authors believe that a permanent and dynamic comprehensive evaluation of each child is paramount for attaining good results.