A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction.

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.

Highly BBB-permeable nanomedicine reverses neuroapoptosis and neuroinflammation to treat Alzheimer's disease.

The prevalence of Alzheimer's disease (AD) is increasing globally due to population aging. However, effective clinical treatment strategies for AD still remain elusive. The mechanisms underlying AD onset and the interplay between its pathological factors have so far been unclear. Evidence indicates that AD progression is ultimately driven by neuronal loss, which in turn is caused by neuroapoptosis and neuroinflammation. Therefore, the inhibition of neuroapoptosis and neuroinflammation could be a useful anti-AD strategy. Nonetheless, the delivery of active drug agents into the brain parenchyma is hindered by the blood-brain barrier (BBB). To address this challenge, we fabricated a black phosphorus nanosheet (BP)-based methylene blue (MB) delivery system (BP-MB) for AD therapy. After confirming the successful preparation of BP-MB, we proved that its BBB-crossing ability was enhanced under near-infrared light irradiation. In vitro pharmacodynamics analysis revealed that BP and MB could synergistically scavenge excessive reactive oxygen species (ROS) in okadaic acid (OA)-treated PC12 cells and lipopolysaccharide (LPS)-treated BV2 cells, thus efficiently reversing neuroapoptosis and neuroinflammation. To study in vivo pharmacodynamics, we established a mouse model of AD mice, and behavioral tests confirmed that BP-MB treatment could successfully improve cognitive function in these animals. Notably, the results of pathological evaluation were consistent with those of the in vitro assays. The findings demonstrated that BP-MB could scavenge excessive ROS and inhibit Tau hyperphosphorylation, thereby alleviating downstream neuroapoptosis and regulating the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Overall, this study highlights the therapeutic potential of a smart nanomedicine with the capability of reversing neuroapoptosis and neuroinflammation for AD treatment.

Postoperative laboratory testing in the era of outpatient total joint arthroplasty: Targeted patient selection and associated cost savings.

Background: With the advent of outpatient total joint arthroplasty (TJA), the days of routinely drawing postoperative labs (complete blood counts [CBCs] and metabolic panels [CMPs/BMPs]) to monitor for complications are behind us. However, there does exist a subset of at-risk patients that may benefit from diligent postoperative monitoring, though the circumstances under which labs should be ordered remains unclear and subject to surgeon discretion. A systematic review of the literature was therefore conducted to evaluate the utility of postoperative laboratory testing, approaches to targeted patient selection and associated cost-savings. Methods: The PubMed, MEDLINE, EBSCOhost, and Google Scholar electronic databases were searched on August 17, 2023, to identify all studies published since January 1, 2000, that evaluated the role of postoperative lab testing in TJA. (PROSPERO study protocol registration: CRD42023437334). Articles were included if a full-text English manuscript was available and the study assessed the utility of routine postoperative labs in TJA. 19 studies were included comprising 34,166 procedures. The mean Methodological index for Nonrandomized Studies score was 18.2 ± 1.5. Results: Abnormal postoperative lab results were common and infrequently required clinical intervention. Among several identified risk factors for patients that may benefit from postoperative laboratory monitoring, preoperative lab values proved excellent discriminators of transfusion requirement and metabolite-associated intervention. Selective testing demonstrated the ability to generate substantial cost-savings. Conclusion: Routine postoperative laboratory testing offers little clinical utility and produces unnecessary expenditures. Preoperative lab values offer the greatest predictive utility for postoperative transfusion requirement and metabolite-associated clinical intervention, with a preoperative hemoglobin threshold of 111.5 g/L offering an area under the curve (AUC) of 0.93 for predicting postoperative transfusion. Further investigations are needed for metabolic panel predictive models and should incorporate preoperative lab values. The refinement of such models can enable targeted patient selection to avoid unnecessary labs and generate substantial cost savings without compromising patient safety.

Quantification of T-Cell Receptor Excision Circles (TRECs).

Aging is a natural process that compromises the immune system's functionality increasing the risk of infectious, tumors, and autoimmune diseases. The thymus involution is an age-dependent process characterized by decreased cellularity, peripheral lymphocyte infiltration into the perivascular space, and expansion of adipose tissue. All those modifications hamper the functionality of the organ and lead to a decline of naïve T-cell production with a shrinking of the T-cell repertoire. Thymus atrophy is described in several disorders including autoimmune diseases. The quantification of T-cell receptor excision circles (TRECs) in recent thymus emigrants is a standard procedure to investigate the thymic function. In this chapter, we discuss the methodology used to quantify this molecule in peripheral blood mononuclear cells and isolated CD4+ and CD8+ T cells.

Global Metabolomics Using LC-MS for Clinical Applications.

Metabolomics can be used for a multitude of purposes, including monitoring of treatment effects and for increasing the knowledge of the pathophysiology of a wide range of diseases. Global (commonly referred to as "untargeted") metabolomics is hypothesis-generating and provides the opportunity to discover new biomarkers. Being versatile and having a high degree of selectivity and sensitivity, liquid chromatography-mass spectrometry (LC-MS) is the most common technique applied for metabolomics. We here present our global metabolomics LC-electrospray ionization-MS/MS method. The sample preparation procedures for plasma, serum, dried blood spots, urine, and cerebrospinal fluid are simple and nonspecific to reduce the risk of analyte loss. The method is based on reversed-phase chromatography using a diphenyl column. The high-resolution Q Exactive Orbitrap MS with data-dependent acquisition provides MS/MS spectra of a wide range of analytes. Our method covers a large part of the metabolome regarding hydrophobicity and compound class.

Quantitative Blood Serum IVDr NMR Spectroscopy in Clinical Metabolomics of Cancer, Neurodegeneration, and Internal Medicine.

Despite more than two decades of metabolomics having joined the "omics" scenery, to date only a few novel blood metabolite biomarkers have found their way into the clinic. This is changing now by massive large-scale population metabolic phenotyping for both healthy and disease cohorts. Here, nuclear magnetic resonance (NMR) spectroscopy is a method of choice, as typical blood serum markers can be easily quantified and by knowledge of precise reference concentrations, more and more NMR-amenable biomarkers are established, moving NMR from research to clinical application. Besides customized approaches, to date two major commercial platforms have evolved based on either 600 MHz (14.1 Tesla) or 500 MHz (11.7 Tesla) high-field NMR systems. This chapter provides an introduction into the field of quantitative in vitro diagnostics research (IVDr) NMR at 600 MHz and its application within clinical research of cancer, neurodegeneration, and internal medicine.

Nanotechnology approaches to drug delivery for the treatment of ischemic stroke.

Ischemic stroke is a major global public health concern that lacks effective treatment options. A significant challenge lies in delivering therapeutic agents to the brain due to the restrictive nature of the blood-brain barrier (BBB). The BBB's selectivity hampers the delivery of therapeutically relevant quantities of agents to the brain, resulting in a lack of FDA-approved pharmacotherapies for stroke. In this article, we review therapeutic agents that have been evaluated in clinical trials or are currently undergoing clinical trials. Subsequently, we survey strategies for synthesizing and engineering nanoparticles (NPs) for drug delivery to the ischemic brain. We then provide insights into the potential clinical translation of nanomedicine, offering a perspective on its transformative role in advancing stroke treatment strategies. In summary, existing literature suggests that drug delivery represents a major barrier for clinical translation of stroke pharmacotherapies. While nanotechnology has shown significant promise in addressing this challenge, further advancements aimed at improving delivery efficiency and simplifying formulations are necessary for successful clinical translation.

Night-time blood pressure dipping, but not 24-h blood pressure level, is linked to increased 24-h ocular volume slope

ABSTRACT Purpose: This study investigated the relationship between blood pressure and intraocular pressure in treatmentnaive, non-glaucoma patients with different blood pressure statuses, focusing on the 24-h ocular volume and nocturnal blood pressure decline. Methods: Treatment-naive, non-glaucoma patients undergoing hypertension evaluation were enrolled as study participants. Simultaneous 24-h ambulatory blood pressure measurement and 24-h ocular volume recording with a contact lens sensor. We also compared ocular volume curve parameters between normotensive and hypertensive patients, as well as between those with and without nocturnal blood pressure decline. Results: A total of 21 patients, including 7 normotensive and 14 treatment-naive hypertensive individuals, were included in the study. of them, 11 were dippers and 10 were non-dippers. No significant difference in the 24-h ocular volume slope was observed between the hypertensive and normotensive patients (p=0.284). However, dippers had a significantly higher 24-h ocular volume slope (p=0.004) and nocturnal contact lens sensor output (p=0.041) than non-dippers. Conclusion: Nocturnal blood pressure decline, rather than the blood pressure level, is associated with the increased 24-h ocular volume slope and nocturnal ocular volume. Further studies are required to determine whether the acceleration of glaucoma progression in dippers is primarily due to low blood pressure, high intraocular pressure, or a combination of both.

Prevalencia y caracterización de la anemia en cirugía electiva en un Hospital Universitario

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Introduction: Anemia is a highly prevalent disorder. Preoperative anemia is associated with higher mortality, more complications, longer hospital stays, and higher healthcare costs. Red blood cell transfusion (RBC) does not improve these outcomes. The World Health Organization recommends implementing Patient Blood Management (PBM) programmes, as they can improve these clinical outcomes, reduce unnecessary RBC transfusions, and save costs. Despite compelling evidence, the implementation of these measures has yet to be effectively achieved. The objective of this study is to conduct a situational analysis to raise awareness about this issue and encourage the implementation of these measures. Methodology: An observational, longitudinal, retrospective cohort study was conducted at a single center. All patients undergoing elective surgery from 01/01/2022 to 01/04/2022 at the Hospital de Clínicas were included. Exclusion criteria: absence of a complete blood count in the three months prior to surgery and refusal to participate in the study. Results: A total of 329 surgeries were analyzed. 52 out of 100 procedures were performed on patients with anemia. A statistically significant association was found between preoperative anemia and receiving RBC transfusion during hospitalization. OR 11.746 (4.518 - 30.540). Anemia and RBC transfusions significantly prolonged hospital stay. Length of hospitalization based on patient condition: No anemia: 10.1 ± 1.1 days, with anemia: 27.2 ± 2.3 days. Value of p < 0.001. Non-transfused: 14.5 ± 1.3 days, transfused: 41.8 ± 4.4 days. Value of p < 0.001. Only 49 (28.6%) of the 171 patients with anemia had iron metabolism assessed before surgery. Among the 140 patients with Hb < 12 g/dL undergoing surgeries with non-insignificant bleeding, only 4 received specific treatment to optimize Hb. A total of 185 units of red blood cells (RBC) were administered during hospitalization. 49 to unstable patients (intraoperative or acute hemorrhage) and 136 to stable patients. From the analysis of the latter group, 42.5% of the patients received 3 or more RBC units. The average pre-transfusion hemoglobin was 7.0 ± 0.1. A statistically significant association was found between receiving RBC units and dying during hospitalization. OR 17.182 (3.360 - 87.872). Conclusiones: A situational analysis was conducted, revealing a high prevalence of preoperative anemia, scarce study and treatment of anemia before surgeries, and an excessive amount of blood transfusions received by some patients. This work establishes the need to implement Patient Blood Management programs to reduce the prevalence of preoperative anemia and improve our transfusion practices. It also sets a comparative framework to evaluate the progress of these measures and indicates possible indicators to assess the benefits of their implementation.

Introdução : A anemia é um distúrbio altamente prevalente. A anemia pré-operatória está associada a maior mortalidade, mais complicações, tempo prolongado de internação e maiores custos de saúde. A transfusão de glóbulos vermelhos (TGV) não melhora esses resultados. A Organização Mundial da Saúde recomenda a implementação de medidas de Gerenciamento de Sangue do Paciente (GSP), pois permitem melhorar esses resultados clínicos, reduzir TGV desnecessárias e economizar custos. Apesar da evidência contundente, a implementação dessas medidas ainda está aquém de ser efetivada. O objetivo deste trabalho é realizar uma análise da situação para conscientizar sobre o problema e incentivar a implementação dessas medidas. Metodologia: Foi realizado um estudo observacional, longitudinal, retrospectivo de coorte histórica, unicêntrico. Foram incluídos todos os pacientes submetidos a cirurgias de coordenação de 01/01/2022 a 01/04/2022 no Hospital de Clínicas. Critérios de exclusão: ausência de hemograma nos três meses anteriores à cirurgia e recusa em participar do estudo. Resultados: Foram analisadas um total de 329 cirurgias. 52 a cada 100 procedimentos foram realizados em pacientes com anemia. Foi encontrada uma associação estatisticamente significativa entre a anemia pré-operatória e a recepção de TGR durante a internação. OR 11,746 (4,518 - 30,540). A anemia e as TGR prolongaram significativamente a internação hospitalar. Dias de internação em função da condição do paciente: Sem anemia: 10,1 ± 1,1 dias, com anemia: 27,2 ± 2,3 dias. Valor p < 0,001. Não transfundidos: 14,5 ± 1,3 dias, transfundidos: 41,8 ± 4,4 dias. Valor p < 0,001. Apenas 49 (28,6%) dos 171 pacientes com anemia tinham metabolismo do ferro antes da cirurgia. Dos 140 pacientes com Hb < 12 mg/dL submetidos a cirurgias com sangramento não insignificante, 4 receberam tratamento específico para otimizar a Hb. Foram administradas um total de 185 unidades de glóbulos vermelhos (UGV) durante a internação. 49 em pacientes instáveis (intraoperatório ou hemorragia aguda) e 136 em pacientes estáveis. Da análise desses últimos, 42,5% dos pacientes receberam 3 ou mais UGV. A hemoglobina pré-transfusional média foi de 7,0 ± 0,1. Foi encontrada uma associação estatisticamente significativa entre receber UGV e falecer durante a internação. OR 17,182 (3,360 - 87,872). Conclusões: Foi realizado uma análise da situação na qual foi observada uma elevada prevalência de anemia pré-operatória, um estudo e tratamento escasso da anemia antes das cirurgias e uma quantidade excessiva de UGV recebidas por alguns pacientes. Este trabalho estabelece a necessidade de implementar programas de Gerenciamento de Sangue do Paciente para reduzir a prevalência de anemia pré-operatória e melhorar nossas práticas transfusionais. Além disso, estabelece um quadro comparativo para avaliar o progresso dessas medidas e aponta possíveis indicadores para avaliar os benefícios de sua implementação.

Metabolomics and quantitative analysis to determine differences in the geographical origins and species of Chinese dragon's blood.

Objective: The aim of this study was to comprehensively analyze the differences in Chinese dragon's blood (CDB), specifically Dracaena cochinchinensis and Dracaena cambodiana, from different geographical origins. Methods: Metabolomic analysis of CDB was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A reliable ultrahigh-performance liquid chromatography method with a photodiode array detector (UHPLC-PDA) was developed and applied for the quantitative analysis of 12 phenolic compounds in 51 batches of samples. Results: A total of 1394 metabolites were detected, of which 467 were identified as differentially accumulated metabolites. Multivariate analysis revealed that both origin and species had an effect on the composition of CDB, with greater variation between species. 19 phenolic compounds were selected as quality markers to distinguish D. cochinchinensis (Hdsp) from D. cambodiana (Hdca), and oppositin and spinoflavanone a were identified as quality markers to discriminate D. cochinchinensis samples from Hainan (Hdsp) and Guangxi Provinces (Gdc). Quantitative analysis indicated that four phenolic compounds, including loureirin D, 4H-1-benzopyran-4-one,2,3-dihydro-3,5,7-trihydroxy-3-[(4-methoxyphenyl)methyl]-,(R)-, loureirin B, and pterostilbene, showed significant differences between Gdc and Hdsp. Additionally, five phenolic compounds, namely resveratrol, loureirin D, pinostilbene, 4H-1-benzopyran-4-one,2,3-dihydro-3,5,7-trihydroxy-3-[(4-methoxyphenyl)methyl]-, (R)-, and loureirin B, exhibited significant differences between Hdsp and Hdca. Conclusion: There are significant differences in the quality of CDB from different geographical origins and species, which lays the foundation for the in-depth development and utilization of different sources of CDB.

Platelet and white blood cell counts correlate with leptin and body mass index in Japanese adolescents.

Obesity is associated with mild chronic inflammation, frequently observed along with increased platelet and white blood cell (WBC) levels in adults. We aimed to clarify the relationship between peripheral blood cell count, body mass index standard deviation score (BMI-SDS), and adipocytokine levels in obese adolescents. Participants included 31 patients with obesity (age: 13.1 ± 3.1 yr) and 28 normal-weight controls (age: 13.3 ± 1.9 yr). Obesity was defined as a percentage of overweight ≥ 20%; patients with type 2 diabetes were excluded. As sex differences were observed in blood cell counts, the analysis was performed after adjusting for sex differences. The obese group has significantly higher WBC, red blood cell, and platelet counts, as well as high serum leptin levels and Homeostasis Model Assessment of insulin resistance (HOMA-IR) scores compared with those of the control group. In all participants, BMI-SDS significantly correlated with WBC and platelet counts. Platelet count correlated with serum leptin and glucose levels, whereas WBC count correlated with serum leptin, insulin, HOMA-IR, and glucose levels. Statistical analysis showed that serum leptin level significantly influenced the platelet count and HOMA-IR score affected WBC count. Increased platelet and WBC counts in adolescents with obesity may increase the risk of thrombosis.

Advancing life: innovative approaches to enhance survival in sickle cell anemia patients.

Sickle cell anemia (SCA) is a severe genetic disorder characterized by the production of abnormal hemoglobin S, leading to the formation of sickle-shaped red blood cells that cause chronic anemia, pain, and organ damage. This review explores recent innovative strategies aimed at improving survival rates and quality of life for SCA patients. Genetic therapies, particularly gene editing with CRISPR-Cas9 and gene therapy using lentiviral vectors, have shown significant potential in correcting the genetic defects responsible for SCA. Clinical trials demonstrate that these approaches can reduce sickle cell crises and minimize the need for blood transfusions by enabling the production of healthy red blood cells. Novel pharmacological treatments such as voxelotor, crizanlizumab, and L-glutamine provide additional mechanisms to prevent hemoglobin polymerization, reduce vaso-occlusive episodes, and decrease oxidative stress, respectively. These therapies offer new hope for patients, particularly those who do not respond adequately to existing treatments. Improved blood transfusion protocols, including automated red cell exchange and advanced donor-matching techniques, have enhanced the safety and efficacy of transfusions, reducing complications like alloimmunization. Comprehensive care models, integrating multidisciplinary care teams, patient education, and telemedicine, have further contributed to better disease management. By providing holistic care that addresses both medical and psychosocial needs, these models improve patient adherence to treatment and overall health outcomes. This review highlights the importance of these innovative strategies and calls for continued research and development to sustain and expand these advancements in SCA care.

Segmental vitiligo distribution follows the underlying arterial blood supply territory: a hypothesis based on anatomo-clinical, pathological and physio-pathological studies.

Background: Segmental vitiligo (SV) is a subset of vitiligo typically characterized by its unilateral distribution. The pathogenesis of SV remains unclear, and until now the two main patterns proposed for SV have lacked biological support. This calls for a new approach. Objectives: Use data obtained from anatomo-clinical, pathological, and physio-pathological studies to formulate a new hypothesis on segmental vitiligo distribution and its pathogenesis. Methods: Using transparent templates of local arterial blood supply, we evaluated anatomical correspondence (AC) in 140 SV lesions according to the number of SV lesions that fit within the corresponding arterial blood-supply areas. SV lesions were graded as 1 (moderate: AC < 50%), 2 (good: AC > 50%), or 3 (excellent: AC of all lesions). To support this anatomical investigation, we searched for complementary assessments according to the activity of SV lesions. Arterial and periarterial network impairment and inflammatory infiltration were histologically studied using nerve growth factor (NGF) and CD4 and CD8 monoclonal antibodies. Increased blood flow of the underlying arteries was also investigated using thermography and ultrasonography. Results: We recruited 140 patients with a sex ratio of 0.8 and mean age 26.13 years. Localizations: head and neck 84.28%; trunk 6.42%; upper limb 5%; genital areas 2.14%; lower limb 1.42%. The AC of each SV lesion with the underlying artery blood supply territory was rated as 72% excellent; 16% good; and 12% moderate. Histologically (40 patients), we found some periarterial network impairments. Thermal asymmetry was significantly associated with active SV (p < 0.001). Conclusion: We hypothesized that SV distribution corresponds to the underlying artery blood-supply territory.

Utilizing Multifaceted Approaches to Target Drug Delivery in the Brain: From Nanoparticles to Biological Therapies.

The blood-brain barrier (BBB) poses an important obstacle to treating neurological disorders because it limits the entry of therapeutic agents into the central nervous system (CNS). Surmounting this barrier is crucial for delivering drugs effectively and targeting precise areas of the brain affected by conditions like Parkinson's disease, Alzheimer's disease, and brain tumors. This review examines the diverse strategies employed to enhance brain targeting, including nanotechnology, viral vectors, and biological therapies. Nanoparticles, liposomes, and dendrimers offer promising approaches for encapsulating drugs and facilitating their transport across the BBB. Viral vectors, such as adeno-associated viruses, demonstrate high transfection efficiency for gene therapy applications in CNS diseases. Biological therapies, including stem cell transplantation and neuromodulation techniques, can potentially restore normal cellular function and treat genetic disorders. Challenges such as BBB permeability, safety concerns, and regulatory considerations are discussed, along with future perspectives on precision medicine, noninvasive delivery methods, and biomarker discovery. By addressing these challenges and embracing innovative approaches, the field of brain drug targeting aims to transfer the way that neurological illness is treated and improve patient outcomes.

Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study.

Aim and background: Corticosteroids are recommended for use in adult patients with septic shock requiring vasopressors for blood pressure maintenance. However, this predisposes them to hyperglycemia, which is associated with a poor outcome. This prospective randomized study compares the effect of continuous infusion with bolus hydrocortisone on blood glucose levels in septic shock. Materials and methods: Forty adult patients with sepsis and septic shock requiring vasopressor support were randomly allocated to either group C (continuous infusion of hydrocortisone 200 mg/day) or group B (intermittent bolus dose of hydrocortisone 50 mg IV 6 hourly). Blood glucose level (primary objective), number of hyperglycemic and hypoglycemic episodes, daily insulin requirement, shock reversal incidence, time to shock reversal, and nursing workload required to maintain blood glucose within the target range (82-180 mg/dL) were compared. Results: The mean blood glucose level was comparable in the two groups (136.5 ± 22.08 mg/dL in group C vs 135.85 ± 19.06 mg/dL in group B; p = 0.921). The number of hyperglycemic and hypoglycemic episodes (p = 1.000 each), insulin requirement/day (p = 1.000), and nursing workload (p = 0.751) were also comparable among groups. Shock reversal was seen in 7/20 (35%) patients in continuous group and 12/20 (60%) patients in bolus group (p = 0.113). Time to shock reversal (p = 0.917) and duration of ICU stay (p = 0.751) were also statistically comparable. Conclusion: Both the regimes of hydrocortisone, continuous infusion, and bolus dose, have comparable effects on blood glucose levels in patients with septic shock.The study was registered prospectively with ctri.nic.in (Ref. No. CTRI/2021/01/030342; registered on 8/1/2021). How to cite this article: Salhotra R, Sharahudeen A, Tyagi A, Rautela RS, Kemprai R. Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study. Indian J Crit Care Med 2024;28(9):837-841.

Vitamin D concentration in the blood of women with twin pregnancies and in the umbilical cord blood of newborns in relation to environmental factors.

Background: There is a huge gap in the knowledge of the body's nutrient resources in women with multiple gestations. Due to the increased demand hypothesis and taking into account common vitamin D deficits in women with singleton pregnancies, this issue should also be investigated in twin pregnancies. This study evaluated blood vitamin D concentration in women with twin pregnancies and in the umbilical cord blood of their newborns as well as analyzed environmental factors that may affect the level of this nutrient. Methods: The study included 56 women with twin pregnancies. Venous blood samples were collected from the women before delivery and umbilical cord blood at delivery to determine the total 25(OH)D concentration. The women were interviewed by a dietitian to collect data on their diet and lifestyle. Results: The average maternal 25(OH)D concentrations were 38.4 ± 11.0 ng/mL vs. 23.7 ± 6.1 ng/mL determined in the umbilical cord blood of the newborns. The concentration of 25(OH)D in the umbilical cord blood was strongly correlated with the concentration in the mother (p < 0.001). Vitamin D deficiency was found in 7% of women and 21% of newborns. Factors increasing the risk of too low 25(OH)D concentration in the mothers were age below 27 years (p = 0.002) and short duration of pregnancy (p = 0.011). In newborns, the risk factors included low maternal concentrations (p < 0.001) and delivery before 36 weeks of gestation (p = 0.008). The mean cord blood 25(OH)D levels were almost identical in both twins and amounted to 24.0 ± 6.1 ng/mL in the first-born and 23.4 ± 6.1 ng/mL in the second-born infant. Vitamin D supplementation was declared by 98% of the women, with 85% taking ≤2,000 IU vitamin D daily. Conclusion: Only a small percentage of women with twin pregnancies presented with vitamin D deficiency, which was probably related to the widespread supplementation of this nutrient. It can therefore be assumed that a dose of 2,000 IU vitamin D currently recommended for pregnant women may also be appropriate for twin gestations, although further research is required to validate this finding.

Blood trauma in veno-venous extracorporeal membrane oxygenation: low pump pressures and low circuit resistance matter.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become standard of care in patients with the most severe forms of acute respiratory distress syndrome. However, hemolysis and bleeding are one of the most frequent side effects, affecting mortality. Despite the widespread use of VV ECMO, current protocols lack detailed, in-vivo data-based recommendations for safe ECMO pump operating conditions. This study aims to comprehensively analyze the impact of VV ECMO pump operating conditions on hemolysis by combining in-silico modeling and clinical data analysis. METHODS: We combined data from 580 patients treated with VV ECMO in conjunction with numerical predictions of hemolysis using computational fluid dynamics and reduced order modeling of the Rotaflow (Getinge) and DP3 (Xenios) pumps. Blood trauma parameters across 94,779 pump operating points were associated with numerical predictions of shear induced hemolysis. RESULTS: Minimal hemolysis was observed at low pump pressures and low circuit resistance across all flow rates, whereas high pump pressures and circuit resistance consistently precipitated substantial hemolysis, irrespective of flow rate. However, the lower the flow rate, the more pronounced the influence of circuit resistance on hemolysis became. Numerical models validated against clinical data demonstrated a strong association (Spearman's r = 0.8) between simulated and observed hemolysis, irrespective of the pump type. CONCLUSIONS: Integrating in-silico predictions with clinical data provided a novel approach in understanding and potentially reducing blood trauma in VV ECMO. This study further demonstrated that a key factor in lowering side effects of ECMO support is the maintenance of low circuit resistance, including oxygenators with the lowest possible resistance, the shortest feasible circuit tubing, and cannulae with an optimal diameter.

Association of intra-operative red blood cell transfusion on the systemic immune index and recovery in patients undergoing cesarean section: a large propensity score-matched study.

BACKGROUND: Post-partum hemorrhage (PPH) is a leading cause of maternal death worldwide. However, the effect of blood transfusion in patients undergoing cesarean section remains unclear. MATERIALS AND METHODS: The analysis was based on the retrospective evaluation of the pre- and post-operative data for 1231 patients who underwent a cesarean section at our hospital between January 2016 and June 2020. Patients were classified into the blood transfusion group (BT) and the no blood transfusion group (NBT) based on their intra-operative blood transfusion status. RESULTS: After propensity score matching, 322 patients were included in both groups and between-group differences in length of hospital stay (LOS), perioperative systemic inflammation indicators, and post-operative complications were evaluated. The LOS was longer in the BT (median, 6.6 days) than the NBT (median, 4.2 days) group (P = 0.026). The post-operative complication rate was higher for the BT than NBT group, as follows: vomiting, 3.2% vs. 4.9%, P = 0.032; fever, 5.41% vs. 2.24%, P = 0.032; wound complications, 15.44% vs. 10.45%, P = 0.028; and intestinal obstructions, 5.88% vs. 2.75%, P = 0.034. Systemic inflammation indicators increased significantly, from the pre-operative baseline, for both groups at post-operative day (POD) 1 and POD3. On multivariate analysis, intra-operative blood transfusion was associated with a longer LOS (hazard ratio, 1.52; 95% confidence interval, 1.07-2.25). CONCLUSION: Intraoperative blood transfusion for cesarean section was associated with increased levels of systemic inflammation indicators, higher post-operative complication rates, and prolonged hospital stay.

A novel model using leukocytes to differentiating mild autonomous cortisol secretion and non-functioning adrenal adenoma.

BACKGROUND: Mild autonomous cortisol secretion (MACS) accounts for a significant proportion of adrenal incidentaloma. Current endocrinological screening tests for MACS are complex, particularly in areas with limited medical resources. This study aimed to develop a diagnostic tool based on leukocyte-related parameters to differentiate between MACS and non-functioning adrenal adenoma (NFA). METHODS: Inthis retrospective case-control study, propensity score-matching was used to select 567 patients from a cohort of 1108 patients (201 MACS, 907 NFA). External validation cohort included 52MACS and 48 NFA from two hospitals, which did not overlap with the modeling cohort patients. Leukocyte-related parameters were evaluated, and the diagnostic efficacy of each parameter was assessed by calculating Youden's J index (J) and the area under the curve (AUC). The study population was divided into training and testing samples using a 10-fold cross-validation method. Machine learning (ML) and classification and regression tree (CART) model were established. RESULTS: After propensity score matching, 567 patients were enrolled, including 197 MACS and 370 NFA. With the exception of basophil percentage, all other parameters differed significantly between the two groups. Lymphocyte count, lymphocyte percentage, eosinophils count, eosinophils percentage, and basophil percentage were lower in the MACS group compared to the NFA group. Eosinophils percentage demonstrated the highest AUC (0.650), with a sensitivity of 51.3% and specificity of 73.2%. The ML model, based on multiple parameters,exhibited better performance in diagnosing MACS (sensitivity 76%, specificity 77.4%, and AUC 0.818). A clinically usable CART model achieved an AUC of 0.872, with a sensitivity of 95% and a specificity of 75.7%.  In the validation cohort, the prediction accuracy of the ML model and the CART model were 0.784 and 0.798, respectively. CONCLUSION: TheCART diagnostic model, constructed based on leukocyte-related parameters, could assist clinicians in distinguishing between MACS and NFA.