BRD2 promotes antibody class switch recombination by facilitating DNA repair in collaboration with NIPBL.

Efficient repair of DNA double-strand breaks in the Ig heavy chain gene locus is crucial for B-cell antibody class switch recombination (CSR). The regulatory dynamics of the repair pathway direct CSR preferentially through nonhomologous end joining (NHEJ) over alternative end joining (AEJ). Here, we demonstrate that the histone acetyl reader BRD2 suppresses AEJ and aberrant recombination as well as random genomic sequence capture at the CSR junctions. BRD2 deficiency impairs switch (S) region synapse, optimal DNA damage response (DDR), and increases DNA break end resection. Unlike BRD4, a similar bromodomain protein involved in NHEJ and CSR, BRD2 loss does not elevate RPA phosphorylation and R-loop formation in the S region. As BRD2 stabilizes the cohesion loader protein NIPBL in the S regions, the loss of BRD2 or NIPBL shows comparable deregulation of S-S synapsis, DDR, and DNA repair pathway choice during CSR. This finding extends beyond CSR, as NIPBL and BRD4 have been linked to Cornelia de Lange syndrome, a developmental disorder exhibiting defective NHEJ and Ig isotype switching. The interplay between these proteins sheds light on the intricate mechanisms governing DNA repair and immune system functionality.

Folic Acid-Conjugated Brush Polymers Show Enhanced Blood-Brain Barrier Crossing in Static and Dynamic In Vitro Models Toward Brain Cancer Targeting Therapy.

Over the past decades, evidence has consistently shown that treatment of central nervous system (CNS)-related disorders, including Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, and brain cancer, is limited due to the presence of the blood-brain barrier (BBB). To assist with the development of new therapeutics, it is crucial to engineer a drug delivery system that can cross the BBB efficiently and reach target cells within the brain. In this study, we present a potentially efficient strategy for targeted brain delivery through utilization of folic acid (FA)-conjugated brush polymers, that specifically target the reduced folate carrier (RFC, SLC19A1) expressed on brain endothelial cells. Here, azide (N3)-decorated brush polymers were prepared in a straightforward manner coupling a heterotelechelic α-NH2, ω-N3-poly(2-ethyl-2-oxazoline) (NH2-PEtOx-N3) to N-acylated poly(amino ester) (NPAE)-based brushes. Strain-promoted azide-alkyne cycloaddition (SPAAC) 'click chemistry' with DBCO-folic acid (FA) yielded FA-brush polymers. Interestingly, while azide functionalization of the brush polymers dramatically reduced their association to brain microvascular endothelial cells (hCMEC/D3), the introduction of FA to azide led to a substantial accumulation of the brush polymers in hCMEC/D3 cells. The ability of the polymeric brush polymers to traverse the BBB was quantitatively assessed using different in vitro BBB models including static Transwell and microfluidic platforms. FA-brush polymers showed efficient transport across hCMEC/D3 cells in a manner dependent on FA composition, whereas nonfunctionalized brush polymers exhibited limited trafficking under the same conditions. Further, cellular uptake inhibition studies suggested that the interaction and transport pathway of FA-brush polymers across BBB relies on the RFC-mediated pathways. The potential application of the developed FA-brush polymers in brain cancer delivery was also investigated in a microfluidic model of BBB-glioblastoma. Brush polymers with more FA units successfully presented an enhanced accumulation into U-87 MG glioma cells following its BBB crossing, compared to controls. These results demonstrate that FA-modified brush polymers hold a great potential for more efficient delivery of future brain therapeutics.

Angiopep-2-Functionalized Lipid Cubosomes for Blood-Brain Barrier Crossing and Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is an aggressive brain cancer with high malignancy and resistance to conventional treatments, resulting in a bleak prognosis. Nanoparticles offer a way to cross the blood-brain barrier (BBB) and deliver precise therapies to tumor sites with reduced side effects. In this study, we developed angiopep-2 (Ang2)-functionalized lipid cubosomes loaded with cisplatin (CDDP) and temozolomide (TMZ) for crossing the BBB and providing targeted glioblastoma therapy. Developed lipid cubosomes showed a particle size of around 300 nm and possessed an internal ordered inverse primitive cubic phase, a high conjugation efficiency of Ang2 to the particle surface, and an encapsulation efficiency of more than 70% of CDDP and TMZ. In vitro models, including BBB hCMEC/D3 cell tight monolayer, 3D BBB cell spheroid, and microfluidic BBB/GBM-on-a-chip models with cocultured BBB and glioblastoma cells, were employed to study the efficiency of the developed cubosomes to cross the BBB and showed that Ang2-functionalized cubosomes can penetrate the BBB more effectively. Furthermore, Ang2-functionalized cubosomes showed significantly higher uptake by U87 glioblastoma cells, with a 3-fold increase observed in the BBB/GBM-on-a-chip model as compared to that of the bare cubosomes. Additionally, the in vivo biodistribution showed that Ang2 modification could significantly enhance the brain accumulation of cubosomes in comparison to that of non-functionalized particles. Moreover, CDDP-loaded Ang2-functionalized cubosomes presented an enhanced toxic effect on U87 spheroids. These findings suggest that the developed Ang2-cubosomes are prospective for improved BBB crossing and enhanced delivery of therapeutics to glioblastoma and are worth pursuing further as a potential application of nanomedicine for GBM treatment.

Insights into Targeted and Stimulus-Responsive Nanocarriers for Brain Cancer Treatment.

Brain cancers, especially glioblastoma multiforme, are associated with poor prognosis due to the limited efficacy of current therapies. Nanomedicine has emerged as a versatile technology to treat various diseases, including cancers, and has played an indispensable role in combatting the COVID-19 pandemic as evidenced by the role that lipid nanocarrier-based vaccines have played. The tunability of nanocarrier physicochemical properties -including size, shape, surface chemistry, and drug release kinetics- has resulted in the development of a wide range of nanocarriers for brain cancer treatment. These nanocarriers can improve the pharmacokinetics of drugs, increase blood-brain barrier transfer efficiency, and specifically target brain cancer cells. These unique features would potentially allow for more efficient treatment of brain cancer with fewer side effects and better therapeutic outcomes. This review provides an overview of brain cancers, current therapeutic options, and challenges to efficient brain cancer treatment. The latest advances in nanomedicine strategies are investigated with an emphasis on targeted and stimulus-responsive nanocarriers and their potential for clinical translation.

The lived experiences of healthcare professionals working in pre-hospital emergency services in Jordan: A qualitative exploratory study.

INTRODUCTION: Globally, injuries account for 9% of all deaths, with road accidents contributing to approximately a quarter of these fatalities. A major concern is the inadequacy of pre-hospital care (emergency medical services provided before arrival at a hospital) and delays in transportation to medical facilities, identified as leading causes of preventable injury-related deaths. This study explores the experiences of emergency health professionals (EHPs) in peri-hospital services (emergency medical services provided immediately upon arrival and within the hospital setting). METHODS: A qualitative exploratory design, underpinned by Van Manen's (1990) descriptive phenomenological principles, was used. Thirty EHPs from five central and southern Jordanian emergency departments were purposefully sampled, including physicians, nurses, and paramedics from both emergency departments and pre-hospital services. RESULTS: Two primary themes emerged: (1) In Search of Clarity: The Unsettled Journey of Pre-hospital Emergency Care Providers; (2) Frustrations on the Frontline: Role Ambiguity and Emotional Exhaustion in Trauma Care, with EHPs reporting fluid and unclear roles, physical and verbal abuse, and limited authority in critical interventions. CONCLUSION: The study highlights several service lapses in peri-hospital care that negatively impact healthcare professionals, posing risks to patient safety. These findings urge decision-makers to devise actionable strategies to rectify these deficiencies, enhancing care quality and thereby decreasing injury-induced mortality and morbidity.

Death from methamphetamine intoxication in a body stuffer.

A 28-year-old man was admitted dead to the emergency department of the regional hospital. All resuscitation attempts were unsuccessful in this case. Attending officers stated that he was suspected of possessing drugs at the time of arrest and had taken them quickly to cover up. Upon arrival at the hospital, signs of violence were noted all over his body. During the autopsy, two large blue plastic packages were found in the antrum of the stomach. The first was 6.3 × 2.2 cm and had two tight knots, while the second was 7.6 x 1.7 cm and had a single knot. Both packages were irregularly shaped and contained tablet debris that was clearly leaking, as a large amount of gastric juice was present in both packages. A confirmatory forensic toxicology analysis revealed toxic concentrations of methamphetamine in the blood of the dissected case. The patient died of acute methamphetamine intoxication associated with a severe stress condition resulting from violent resistance during arrest.

A comparative evaluation of the sniffing, the simple head extension and the head hyperextension positions for laryngoscopic view and intubation difficulty in adults undergoing direct laryngoscopy.

OBJECTIVE: This work aimed to compare between the laryngoscopy positions; sniffing, simple head extension and head hyperextension positions to assess whether the laryngeal view, intubation time and intubation difficulty could improve with one of these positions than the others. DESIGN: Prospective randomized three arms clinical trial. SETTING: Operation room, the phoniatrics unit [removed for blind peer review]. PARTICIPANTS: The study included 75 cases with 25 cases in each group. Group "A" with head in the sniffing position, Group "B" with the head in simple extension position, Group "C" with head in hyperextension position. RESULTS: The three groups were compared regarding intubation time and laryngoscopic view time. Intubation time showed statistically significant difference between the three groups. Mean of sniffing group (No. = 25) was 13.19 s (± 3.35). Mean of simple extension group (No. = 25) was 11.29 s (± 3.14). Mean of Hyperextension group (No. = 25) was 14.39 s (± 4.14). Laryngoscopic view time showed statistically highly significant difference between the three groups. Mean of sniffing group (No. = 25) was 17.19 s (± 7.27). Mean of simple group (No. = 25) was 12.18 s (± 4.46). Mean of hyperextension group (No. = 25) was 17.08 s (± 6.51). CONCLUSION: Comparing the sniffing, the simple extension and the hyperextension positions, the simple extension position showed the best time regarding intubation time and laryngoscopic view time.

Variability of contribution of 1,25 (OH)2D3 (vitamin D) level to hematopoietic stem cell transplantation outcome.

BACKGROUND: The impact of vitamin D status on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) has recently been the focus of interest with a lot of controversy. In this study we aimed to evaluate the impact of pre-transplant vit. D level on the outcome of HSCT. METHODS: In this study, we evaluated the impact of vitamin D level on the risk of development of graft versus host disease (GVHD) and survival after HSCT. The study included 97 patients who received allogeneic HSCT from an identical sibling. Serum vitamin D level was measured before conditioning using ELIZA. Student t-test, Mann-Whitney U test, ANOVA F-test and Kruskal-Wallis H tests were used to determine significance of difference for quantitative data. Pearson correlation, Spearman correlation and Chi-square test were used to determine correlations and associations. Kaplan-Meier and Log rank (Mantel-Cox) tests were used for analysis of survival. P value ≤ 0.05 was considered significant. RESULTS: Vitamin D level showed a range of 18.24-84.6 with a mean of 38.14 ± 9.73 and a median of 36.26 ng/ml. Two patients had vitamin D level <20 and 17 had a level <30 ng/ml. Acute GVHD occurred in 33 (34 %) and chronic GVHD in 29 (29.9 %) patients. Vitamin D level had no impact on frequency or severity of GVHD; either did it impact survival. This might be attributable to the relatively normal level in the majority of our patients on account of the sunny weather of Egypt. This might also be a potential explanation for the inconsistency of the different studies with variable levels of vitamin D. CONCLUSIONS: The current study failed to demonstrate an impact of pre-transplant vitamin D level on the outcome of HSCT. This might be attributed to the low prevalence of vitamin D deficiency in our population on account of our almost always sunny weather. The marked variability in the level of vitamin D that is considered sufficient interferes with objective comparison between studies; a consensus on what is considered sufficient, insufficient, or deficient is essential.

Effect of alkali metals on physical and spectroscopic properties of cellulose.

A 3-unit cellulose model molecule was built and optimized using DFT B3LYP/6-31G(d,p). The electronic properties of the optimized structure of cellulose were investigated in terms of total dipole moment (TDM), HOMO-LUMO band gap (ΔE), and molecular electrostatic potential (MESP). Cellulose demonstrated a TDM of 9.106 Debye and ΔE of 7.647 eV. The hydrogen atom of the hydroxyl group of the CH2OH group of each cellulose unit was replaced by an alkali metal atom (X) such that the 3-unit cellulose once had 1X atom, then 2X, then 3X atoms, where X = Li, Na or K, both without and with 2, 4 and 6 water molecules (W), respectively, to study also the effect of hydration. Without hydration, the values of TDM decreased for all of the proposed interaction, but increased with hydration, while ΔE decreased in all interactions, confirming that interaction cellulose-alkali metal interaction, especially with hydration, resulted in more reactive structures. Mapping of HOMO-LUMO and MESP indicated significant change in the electron density distribution around cellulose under the effect of interaction with the alkali metals, both with and without hydration. The plots of projected density of states also clearly demonstrated the contribution of each alkali metal as well as water in the molecular orbitals, reflecting their effect on the electronic properties of cellulose and cellulose-alkali metals composites. The theoretical calculations were experimentally verified using FTIR and FT-Raman spectroscopy.

Genetic Polymorphism in FSCN1 rs3801004 C/G and CD44 rs353639 A/C, as Prognostic Factor in Egyptian Breast Cancer Patients.

BACKGROUND: One of the main causes of cancer-related deaths is breast cancer. Fascin-1(FSCN1) is an actin-binding protein that is present in the mesenchymal, neuronal, and endothelial cells of mammals. Patients with breast cancer have been found to have FSCN1 overexpression. CD44 is crucial for the development, invasion, and tumour spread. Therefore, we aimed to investigate the role of FSCN1&CD44 gene polymorphisms in breast cancer (BC) risk and prognosis. MATERIALS & METHODS: A total of 96 BC patients and 50 controls were included in the case-control study for risk prediction. We examined the association between The SNPs on FSCN1(rs3801004) and CD44(rs353639) and BC susceptibility and clinicopathological features using a real-time PCR in a cohort of the Egyptian population.  Results: A significant association of both SNPs on FSCN1(rs3801004)C allele and CD44(rs353639)A allele and BC susceptibility(adjusted OR=4.38,95%CI:2.6-7.4,p<0.001, and adjusted OR=4.44,95%CI:2.65-7.44,p <0.001,respectively). Moreover, CC genotype in FSCN1(rs3801004) were likely to progress to developing G2&G3 and N2&N3 and stage II & stage IV, according to the TNM staging and GG+GC genotypes increased within individuals who had a positive family history of BC. Individuals who carry at least one A allele for CD44rs353639 were likely to progress developing N2 according to the TNM in BC patients. CONCLUSIONS: These findings suggest that both SNPs on FSCN1 (rs3801004) and CD44 (rs353639) affected BC susceptibility. FSCN1 (rs3801004) genetic variants may have a significant effect on BC prognosis. However, CD44 (rs353639) affected lymph node invasions in BC patients.

DFT and QSAR studies of PTFE/ZnO/SiO2 nanocomposite.

Polytetrafluoroethylene (PTFE) is one of the most significant fluoropolymers, and one of the most recent initiatives is to increase its performance by using metal oxides (MOs). Consequently, the surface modifications of PTFE with two metal oxides (MOs), SiO2 and ZnO, individually and as a mixture of the two MOs, were modeled using density functional theory (DFT). The B3LYPL/LANL2DZ model was used in the studies conducted to follow up the changes in electronic properties. The total dipole moment (TDM) and HOMO/LUMO band gap energy (∆E) of PTFE, which were 0.000 Debye and 8.517 eV respectively, were enhanced to 13.008 Debye and 0.690 eV in the case of PTFE/4ZnO/4SiO2. Moreover, with increasing nano filler (PTFE/8ZnO/8SiO2), TDM changed to 10.605 Debye and ∆E decreased to 0.273 eV leading to further improvement in the electronic properties. The molecular electrostatic potential (MESP) and quantitative structure activity relationship (QSAR) studies revealed that surface modification of PTFE with ZnO and SiO2 increased its electrical and thermal stability. The improved PTFE/ZnO/SiO2 composite can, therefore, be used as a self-cleaning layer for astronaut suits based on the findings of relatively high mobility, minimal reactivity to the surrounding environment, and thermal stability.

Molecular and biological activities of metal oxide-modified bioactive glass.

Bioactive glass (BG) was prepared by sol-gel method following the composition 60-([Formula: see text]) SiO2.34CaO.6P2O5, where x = 10 (FeO, CuO, ZnO or GeO). Samples were then studied with FTIR. Biological activities of the studied samples were processed with antibacterial test. Model molecules for different glass compositions were built and calculated with density functional theory at B3LYP/6-31 g(d) level. Some important parameters such as total dipole moment (TDM), HOMO/LUMO band gap energy (ΔE), and molecular electrostatic potential beside infrared spectra were calculated. Modeling data indicated that P4O10 vibrational characteristics are enhanced by the addition of SiO2.CaO due to electron rush resonating along whole crystal. FTIR results confirmed that the addition of ZnO to P4O10.SiO2.CaO significantly impacted the vibrational characteristics, unlike the other alternatives CuO, FeO and GeO that caused a smaller change in spectral indexing. The obtained values of TDM and ΔE indicated that P4O10.SiO2.CaO doped with ZnO is the most reactive composition. All the prepared BG composites showed antibacterial activity against three different pathogenic bacterial strains, with ZnO-doped BG demonstrating the highest antibacterial activity, confirming the molecular modeling calculations.

HNRNPU facilitates antibody class-switch recombination through C-NHEJ promotion and R-loop suppression.

B cells generate functionally different classes of antibodies through class-switch recombination (CSR), which requires classical non-homologous end joining (C-NHEJ) to join the DNA breaks at the donor and acceptor switch (S) regions. We show that the RNA-binding protein HNRNPU promotes C-NHEJ-mediated S-S joining through the 53BP1-shieldin DNA-repair complex. Notably, HNRNPU binds to the S region RNA/DNA G-quadruplexes, contributing to regulating R-loop and single-stranded DNA (ssDNA) accumulation. HNRNPU is an intrinsically disordered protein that interacts with both C-NHEJ and R-loop complexes in an RNA-dependent manner. Strikingly, recruitment of HNRNPU and the C-NHEJ factors is highly sensitive to liquid-liquid phase separation inhibitors, suggestive of DNA-repair condensate formation. We propose that HNRNPU facilitates CSR by forming and stabilizing the C-NHEJ ribonucleoprotein complex and preventing excessive R-loop accumulation, which otherwise would cause persistent DNA breaks and aberrant DNA repair, leading to genomic instability.

Prognostic value of free air under diaphragm on chest radiographs in correlation with peritoneal soiling intraoperatively.

PURPOSE: Gastrointestinal perforation is a significant injury that originates mainly from gastrointestinal ulcers. It is associated with a high rate of morbidity and mortality. The height of the column of the air under the diaphragm can be used to estimate the amount of peritoneal soiling due to viscus perforation. This study aimed to determine the correlation between this estimate and the incidence of morbidity and mortality. METHODS: To achieve this aim, a prospective cohort study was conducted on 83 patients at Kasr al ainy hospital who, between March 2021 and March 2022, presented to the emergency department with free air under the diaphragm at chest X-ray and required surgical intervention for a perforated viscus. For each case, the amount of peritoneal soiling and the amount of air under the diaphragm as determined by a chest X-ray were recorded. RESULTS: The mean air under the diaphragm in a plain erect chest X-ray was 1.78 ± 1.92 cm, and the mean amount of peritoneal soiling was 1201.83 ± 948.99 CC. There are positive correlations between the amount of air under the diaphragm as shown on an X-ray and the size of the perforation (p = 0.034), the amount of peritoneal soiling (p = 0.003), and the mortality (p = 0.013). CONCLUSION: There was a statistically significant correlation between air under the diaphragm according to X-ray and the amount of peritoneal soiling in patients with a perforated viscus. This measure can be used as a sensitive tool to predict morbidity and mortality as more free air in the chest X-ray is associated with significant mortality. These results may enhance the decision making using sensitive and available tool of diagnosis.

In vivo fluorescence imaging: success in preclinical imaging paves the way for clinical applications.

Advances in diagnostic imaging have provided unprecedented opportunities to detect diseases at early stages and with high reliability. Diagnostic imaging is also crucial to monitoring the progress or remission of disease and thus is often the central basis of therapeutic decision-making. Currently, several diagnostic imaging modalities (computed tomography, magnetic resonance imaging, and positron emission tomography, among others) are routinely used in clinics and present their own advantages and limitations. In vivo near-infrared (NIR) fluorescence imaging has recently emerged as an attractive imaging modality combining low cost, high sensitivity, and relative safety. As a preclinical tool, it can be used to investigate disease mechanisms and for testing novel diagnostics and therapeutics prior to their clinical use. However, the limited depth of tissue penetration is a major challenge to efficient clinical use. Therefore, the current clinical use of fluorescence imaging is limited to a few applications such as image-guided surgery on tumors and retinal angiography, using FDA-approved dyes. Progress in fluorophore development and NIR imaging technologies holds promise to extend their clinical application to oncology, cardiovascular diseases, plastic surgery, and brain imaging, among others. Nanotechnology is expected to revolutionize diagnostic in vivo fluorescence imaging through targeted delivery of NIR fluorescent probes using antibody conjugation. In this review, we discuss the latest advances in in vivo fluorescence imaging technologies, NIR fluorescent probes, and current and future clinical applications.

Computational Analysis of Deleterious SNPs in NRAS to Assess Their Potential Correlation With Carcinogenesis.

The NRAS gene is a well-known oncogene that acts as a major player in carcinogenesis. Mutations in the NRAS gene have been linked to multiple types of human tumors. Therefore, the identification of the most deleterious single nucleotide polymorphisms (SNPs) in the NRAS gene is necessary to understand the key factors of tumor pathogenesis and therapy. We aimed to retrieve NRAS missense SNPs and analyze them comprehensively using sequence and structure approaches to determine the most deleterious SNPs that could increase the risk of carcinogenesis. We also adopted structural biology methods and docking tools to investigate the behavior of the filtered SNPs. After retrieving missense SNPs and analyzing them using six in silico tools, 17 mutations were found to be the most deleterious mutations in NRAS. All SNPs except S145L were found to decrease NRAS stability, and all SNPs were found on highly conserved residues and important functional domains, except R164C. In addition, all mutations except G60E and S145L showed a higher binding affinity to GTP, implicating an increase in malignancy tendency. As a consequence, all other 14 mutations were expected to increase the risk of carcinogenesis, with 5 mutations (G13R, G13C, G13V, P34R, and V152F) expected to have the highest risk. Thermodynamic stability was ensured for these SNP models through molecular dynamics simulation based on trajectory analysis. Free binding affinity toward the natural substrate, GTP, was higher for these models as compared to the native NRAS protein. The Gly13 SNP proteins depict a differential conformational state that could favor nucleotide exchange and catalytic potentiality. A further application of experimental methods with all these 14 mutations could reveal new insights into the pathogenesis and management of different types of tumors.

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine.

Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, ß-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.

Secondary Hyperparathyroidism Before and After Bariatric Surgery: a Prospective Study with 2-Year Follow-Up.

PURPOSE: Secondary hyperparathyroidism (SHPT) is linked to obesity. Bariatric surgery may be associated with calcium and vitamin D deficiencies leading to SHPT. This study aimed to detect the prevalence of SHPT before and after bariatric surgery. METHODS: This prospective study assessed the prevalence of SHPT after sleeve gastrectomy (SG, n = 38) compared to one-anastomosis gastric bypass (OAGB, n = 86). All patients were followed up for 2 years. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. RESULTS: Of the 124 patients, 71 (57.3%) were females, and 53 (42.7%) were males, with a mean age of 37.5 ± 8.8 years. Before surgery, 23 patients (18.5%) suffered from SHPT, and 40 (32.3%) had vitamin D deficiency. The prevalence of SHPT increased to 29.8% after 1 year and 36.3% after 2 years. SHPT was associated with lower levels of vitamin D and calcium and higher reduction of BMD in the hip but not in the spine. After 2 years, SHPT was associated with a significantly lower T-score in the hip. SHPT and vitamin D deficiency were significantly more common in patients subjected to OAGB compared to SG (p = 0.003, and p < 0.001, respectively). There is a strong negative correlation between vitamin D levels and parathormone levels before and after surgery. CONCLUSION: Prevalence of SHPT is high in obese patients seeking bariatric surgery, especially with lower vitamin D levels. Bariatric surgery increases the prevalence of SHPT up to 2 years. Gastric bypass is associated with a higher risk of developing SHPT compared to SG.

Combined Thoracic Spinal-Epidural Anesthesia for Laparoscopic Sleeve Gastrectomy; One Hundred Case Experience.

BACKGROUND: Obesity is a growingly impacting human health concern. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for morbid obesity. However, the general anesthesia (GA) used in this major surgery has its documented drawbacks in obese patients with high risk. On the other hand, combined thoracic spinal-epidural anesthesia (CTSEA), a modern regional anesthesia procedure, has the advantages of both spinal and epidural anesthesia but without their shortcomings. This prospective study is a case experience that assesses the feasibility of CTSEA as an anesthesia option for laparoscopic sleeve gastrectomy (LSG). METHODS: A total of 100 patients were recruited for LSG as a management procedure for morbid obesity, which was performed under CTSEA. Perioperative events, functional parameters, and patients' satisfaction scores were recorded. RESULTS: Our prospective study showed successful use of CTSEA in 99% of the patients, except for one patient (1%) in whom CTSEA was converted into GA due to severe pain and anxiety. Few adverse events occurred and were managed accordingly. The satisfaction score revealed that 94% of the patients were satisfied. CONCLUSIONS: CTSEA was a successful anesthetic alternative procedure for LSG surgery.