Hierarchical Nanostructures as Acoustically Manipulatable Multifunctional Agents in Dynamic Fluid Flow.

Acoustic waves provide a biocompatible and deep-tissue-penetrating tool suitable for contactless manipulation in in vivo environments. Despite the prevalence of dynamic fluids within the body, previous studies have primarily focused on static fluids, and manipulatable agents in dynamic fluids are limited to gaseous core-shell particles. However, these gas-filled particles face challenges in fast-flow manipulation, complex setups, design versatility, and practical medical imaging, underscoring the need for effective alternatives. In this study, flower-like hierarchical nanostructures (HNS) into microparticles (MPs) are incorporated, and demonstrated that various materials fabricated as HNS-MPs exhibit effective and reproducible acoustic trapping within high-velocity fluid flows. Through simulations, it is validated that the HNS-MPs are drawn to the focal point by acoustic streaming and form a trap through secondary acoustic streaming at the tips of the nanosheets comprising the HNS-MPs. Furthermore, the wide range of materials and modification options for HNS, combined with their high surface area and biocompatibility, enable them to serve as acoustically manipulatable multimodal imaging contrast agents and microrobots. They can perform intravascular multi-trap maneuvering with real-time imaging, purification of wastewater flow, and highly-loaded drug delivery. Given the diverse HNS materials developed to date, this study extends their applications to acoustofluidic and biomedical fields.

Immune Cell-Based Microrobots for Remote Magnetic Actuation, Antitumor Activity, and Medical Imaging.

Translating medical microrobots into clinics requires tracking, localization, and performing assigned medical tasks at target locations, which can only happen when appropriate design, actuation mechanisms, and medical imaging systems are integrated into a single microrobot. Despite this, these parameters are not fully considered when designing macrophage-based microrobots. This study presents living macrophage-based microrobots that combine macrophages with magnetic Janus particles coated with FePt nanofilm for magnetic steering and medical imaging and bacterial lipopolysaccharides for stimulating macrophages in a tumor-killing state. The macrophage-based microrobots combine wireless magnetic actuation, tracking with medical imaging techniques, and antitumor abilities. These microrobots are imaged under magnetic resonance imaging and optoacoustic imaging in soft-tissue-mimicking phantoms and ex vivo conditions. Magnetic actuation and real-time imaging of microrobots are demonstrated under static and physiologically relevant flow conditions using optoacoustic imaging. Further, macrophage-based microrobots are magnetically steered toward urinary bladder tumor spheroids and imaged with a handheld optoacoustic device, where the microrobots significantly reduce the viability of tumor spheroids. The proposed approach demonstrates the proof-of-concept feasibility of integrating macrophage-based microrobots into clinic imaging modalities for cancer targeting and intervention, and can also be implemented for various other medical applications.

Characteristics of Patients with Sarcoidosis with Emphasis on Acute vs. Chronic Forms-A Single Center Experience.

Sarcoidosis is a granulomatous disease of unknown etiology that can affect almost any organ. Although the acute form can have spontaneous regression, a certain number of patients can have a chronic form, which leads to an increase in mortality and a decrease in the quality of life. Considering that the risk factors are still unknown, we wanted to compare the characteristics of patients with acute and chronic forms of sarcoidosis in Serbia in order to determine significant differences between them with hopes of contributing to everyday clinical practice. A total of 2380 patients treated in our clinic were enrolled in this study. They were separated into the following two groups: 1126 patients with acute form and 1254 patients with chronic form. They were further compared by gender, smoking status, radiological status, exposition, biomarkers for sarcoidosis, organ involvement, and other comorbidities; the distribution of patients according to regions of Serbia was also noted. Statistical significance was found in radiological findings (p < 0.001), biomarkers (calcium in 24 h urine p < 0.001; chitotriosidase p = 0.001), and the affliction of organs (p < 0.001). The differences noted in this paper could help improve our understanding of this disease.

Pineal Tumor Surgery-The Choice of the Approach Related to Tumor Characteristics and Posterior Fossa Anatomy.

OBJECTIVE: This research aimed to determine whether an adequate surgical approach can be chosen based on clearly defined values of anatomical landmarks (tentorial angle) and tumor size and extension. METHODS: We conducted a retrospective analysis of patients operated on because of pineal tumors. The cohort was divided depending on the surgical approach. On preoperative magnetic resonance imaging, we measured maximal diameters, tumor volume, and tumor propagation. In the group of patients operated with the supracerebellar infratentorial approach, we also tested the correlation of tentorial angle with residual tumor. Differences among groups in resection, complications rate, and outcome were tested by the χ2 test. Finally, in both groups, the correlation of residual tumor with tumor volume, propagation, and diameters was tested using the receiver operating characteristic curve. RESULTS: In the group operated with a supracerebellar approach, total resection was achieved in 78% of the patients. The critical value of cranio-caudal diameter correlated with tumor residue was 31 mm, for lateral-lateral diameter 25 mm, for the lateral extension 14 mm, and tumor volume 12 cm3. Tentorial angle did not influence the extent of the resection. In the group operated with an occipital transtentorial approach, the critical tumor volume related to tumor residue was 9 mm3, anterior-posterior diameter 29 mm, and cranio-caudal diameter 28 mm. The extent of the resection was significantly higher in the supracerebellar group. CONCLUSIONS: In both approaches, tumors larger than 3 cm show an increased risk of subtotal resection. Except when most tumor volume is localized above the venous system, we advocate a supracerebellar corridor as an effective approach that is not limited by tentorial angle.

Influence of Achalasia on the Spirometry Flow-Volume Curve and Peak Expiratory Flow.

BACKGROUND: Achalasia is an esophageal motor disorder characterized by aperistalsis and the failure of the relaxation of the lower esophageal sphincter. We want to find out whether external compression or recurrent micro-aspiration of undigested food has a functional effect on the airway. METHODS: The aim of this research was to analyze the influence of achalasia on the peak expiratory flow and flow-volume curve. All of the 110 patients performed spirometry. RESULTS: The mean diameter of the esophagus was 5.4 ± 2.1 cm, and nine of the patients had mega-esophagus. Seven patients had a plateau in the inspiratory part of the flow-volume curve, which coincides with the patients who had mega-esophagus. The rest of the patients had a plateau in the expiration part of the curve. The existence of a plateau in the diameter of the esophagus of more than 5 cm was significant (p 0.003). Statistical significance between the existence of a plateau and a lowered PEF (PEF < 80) has been proven (p 0.001). Also, a statistical significance between the subtype and diameter of more than 4 cm has been proved. There was no significant improvement in the PEF values after operation. In total, 20.9% of patients had a spirometry abnormality finding. The frequency of the improvement in the spirometry values after surgery did not differ significantly by achalasia subtype. The improvement in FEV1 was statistically significant compared to the FVC values. CONCLUSIONS: Awareness of the influence of achalasia on the pulmonary parameters is important because low values of PEF with a plateau on the spirometry loop can lead to misdiagnosis. The recognition of various patterns of the spirometry loop may help in identifying airway obstruction caused by another non-pulmonary disease such as achalasia.

Deep venous thrombosis in patients with atresia of the inferior vena cava and right kidney hypoplasia (KILT syndrome): Systematic review of the literature.

Inferior vena cava (IVC) anomalies are uncommon congenital causes of deep vein thrombosis (DVT). KILT syndrome (kidney and IVC abnormalities with leg thrombosis) has only been described as case reports in the literature. Therefore, the characteristics, evaluation, and management of patients with KILT syndrome have not yet been standardized. This study aimed to systematically review and analyze the clinical and radiographic data and treatment of previously reported cases of KILT syndrome. In this systematic review, we performed a literature search of the PubMed, Scopus, and Web of Science databases in December 2023, with no restrictions on the publication date. After duplicate extractions, 4195 articles were screened. Case reports and case series reporting on KILT syndrome were included. In addition to previously published cases, we included a new case of a previously healthy 25-year-old man with KILT syndrome in the analysis. A total of 34 cases were therefore included in this study. The majority (76.5%) were male patients with a median age of 24 years. In most patients, unprovoked bilateral iliofemoral thrombosis was diagnosed, and 64.7% had left kidney abnormalities. Our study suggests that anomalies of the IVC should be suspected in all young patients, especially male patients, with proximal, recurrent, or idiopathic DVT. If an IVC anomaly is confirmed, the kidneys should be examined to monitor and preserve healthy kidneys in cases of KILT syndrome. The data collected from all patients emphasize the requirement of long-term anticoagulation and risk factor control. Surgical measures may be effective for treating symptomatic refractory cases.

Nanodiamond-Enhanced Magnetic Resonance Imaging.

Nanodiamonds (ND) hold great potential for diverse applications due to their biocompatibility, non-toxicity, and versatile functionalization. Direct visualization of ND by means of non-invasive imaging techniques will open new venues for labeling and tracking, offering unprecedented and unambiguous detection of labeled cells or nanodiamond-based drug carrier systems. The structural defects in diamonds, such as vacancies, can have paramagnetic properties and potentially act as contrast agents in magnetic resonance imaging (MRI). The smallest nanoscale diamond particles, detonation ND, are reported to effectively reduce longitudinal relaxation time T1 and provide signal enhancement in MRI. Using in vivo, chicken embryos, direct visualization of ND is demonstrated as a bright signal with high contrast to noise ratio. At 24 h following intravascular application marked signal enhancement is noticed in the liver and the kidneys, suggesting uptake by the phagocytic cells of the reticuloendothelial system (RES), and in vivo labeling of these cells. This is confirmed by visualization of nanodiamond-labeled macrophages as positive (bright) signal, in vitro. Macrophage cell labeling is not associated with significant increase in pro-inflammatory cytokines or marked cytotoxicity. These results indicate nanodiamond as a novel gadolinium-free contrast-enhancing agent with potential for cell labeling and tracking and over periods of time.

Clinical Impact of Patient-Prosthesis Mismatch After Aortic Valve Replacement With a Mechanical or Biological Prosthesis.

BACKGROUND: Patient-prosthesis mismatch (PPM) may impair functional capacity and survival after aortic valve replacement. This study aimed to investigate the impact of PPM on long-term survival and quality of life after mechanical and biological aortic valve replacement. METHODS: This study included 595 consecutive patients who had undergone isolated aortic valve replacement. Patients were divided into 2 groups according to prosthesis type. The baseline and operative characteristics, survival rates, complications, and quality of life of the groups with and without PPM were compared for up to 6 years. The PPM calculation was performed using the effective orifice area value provided by the manufacturer divided by the patient's body surface area. RESULTS: The moderate to severe PPM rates were 69.8% and 3.7% after biological and mechanical prosthesis implantation, respectively. Mean survival for patients in the biological group who had PPM was statistically significantly shorter (50.2 months [95% CI, 45.2-55.3]) than for patients in the biological group without PPM (60.1 months [95% CI, 55.7-64.4]; P = .04). In the mechanical prosthesis group, there was no difference in mean survival between the subgroup with PPM (66.6 months [95% CI, 58.3-74.9]) and the subgroup without PPM (64.9 months [95% CI, 62.6-67.2]; P = .50). A quality-of-life questionnaire's scores did not differ between the groups. CONCLUSION: Mismatch is common after biological valve implantation and statistically significantly affects long-term survival and quality of life. If the risk of PPM after implantation of a biological prosthesis is suspected, adopting strategies to avoid PPM at the time of surgery is warranted.

King's Sarcoidosis Questionnaire (KSQ) - Validation study in Serbian speaking population of sarcoidosis patients.

INTRODUCTION: Sarcoidosis is a multiorgan, multisystem chronic disease of unknown etiology and unpredictable course. Health status is reduced in sarcoidosis and assessing it is a difficult multitask effort due to many faces this disease might have. Recently, a new questionnaire for assessing health status in sarcoidosis was developed by a group of authors from England-King's Sarcoidosis Questionnaire (KSQ). The benefit of KSQ is the ability to develop the best care plan for the patient, as well as to differentiate the efficacy of the administered treatment. OBJECTIVE: The aim of this study was to validate the KSQ in Serbian speaking population of sarcoidosis patients. The test itself is a modular, multi-organ health status measure for patients with sarcoidosis for use in clinic and the evaluation of therapies. The correlation of KSQ with different clinical course of sarcoidosis (acute vs chronic disease) and with the clinical outcome status (COS) in sarcoidosis was also investigated. METHODS: A total of 159 biopsy positive sarcoidosis patients participated in this study. The average age of the participants was 49.67, majority was female (67.3%) and majority had only pulmonary form of sarcoidosis (71.7%). KSQ - new disease-specific health status instrument, was compared with 5 other already existing instruments already used and validated in sarcoidosis (Saint George Respiratory Questionnaire- SGRQ, Daily Activity List -DAL, Fatigue Assessment Scale- FAS, Medical Research Council dyspnea scale-MRC, Borg Dyspnea Scale and 15D as general questionnaire. RESULTS: KSQ has significant correlation with other quality of life questionnaires already used in sarcoidosis. Translated version of KSQ shows significant internal reliability, similar to the original KSQ. Serbian version of KSQ has significant correlation with different clinical course of sarcoidosis and with COS as well. The translated version of KSQ is reliable sarcoidosis specific instrument for assessing health status in these patients.

Association between affective temperaments and psychosomatic symptoms in women with Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease of thyroid gland with a shared immunological mechanism with mood disorders. Affective temperament (AT) is a biologically determined personality trait that has been linked to mood disorders. The aim of this study was to examine the association between dominant AT and levels of psychosomatic symptoms in women newly diagnosed with HT in comparison to clinically healthy subjects. METHODS: The observational cross-sectional study with nested case control study was involving 146 consecutive participants, who were divided into three groups. The two study groups consisted of women with HT (73), including 49 with hypothyroid HT and 24 with euthyroid HT, and the third group was a control group of healthy participants (73). The Serbian version of the TEMPS-A was utilized to assess AT, while the 4DSQ was used to measure psychosomatic symptoms. RESULTS: The results showed that hyperthymic AT was dominant in all examined groups. The groups with HT differed from the control group in terms of depressive and cyclothymic AT. Furthermore, the study found higher levels of psychosomatic symptoms in the group with HT compared to the control group, with significant differences in distress (p = 0.005) and somatization (p = 0.023) levels. All AT was associated with levels of psychosomatic symptoms in subjects with hypothyroid HT. In contrast, in subjects with euthyroid HT, the association was only found between depressive and cyclothymic AT with distress and depression levels, as well as between somatization and cyclothymic AT. No association was found between AT and anxiety levels in subjects with euthyroid HT. CONCLUSION: The research found differences between study groups in the association between AT and levels of psychosomatic symptoms. Further research with a larger sample size is necessary to more clearly define the associations between affective temperaments and psychosomatic symptoms in women with euthyroid and hypothyroid HT.

Achalasia Subtype Differences Based on Respiratory Symptoms and Radiographic Findings.

Three subtypes of achalasia have been defined using esophageal manometry. Several studies have reported that symptoms are experienced differently among men and women, regardless of subtype. All subtypes could have some impact on the appearance of respiratory symptoms and lung complications due to compression of the trachea or aspiration of undigested food. The aim of this research was to analyze the differences in respiratory symptoms and radiographic presentation of lung pathology depending on the diameter and achalasia types. One or more respiratory symptoms were reported in 48% of 114 patients, and all of them had two or more gastrointestinal symptoms. The symptom score (SS) is statistically significant for the prediction of subtype 1 (area under the curve = 0.318; p < 0.001, cut-off score of 6.5 had 95.2% sensitivity) and subtype 2 (area under the curve = 0.626; p = 0.020, cut-off score of 7.5 had 93.1% sensitivity). The most common type was subtype 2 (50.8%), and although only 14 patients had subtype 3, they had the largest esophageal diameter (mean 5.8 cm). The difference in esophageal diameter was significant between subtype 1 and 3 (p = 0.011), subtype 2 and subtype 3 (p = 0.011). Nine patients (6%) had mega-esophagus (four patients in type 1, three in type 2 and two in type 3). More than half of all patients (51.7%) had at least one parenchymal lung change on CT scan. Recurrent micro-aspirations led to changes in the structure of the airways and lung parenchyma such as ground glass (GGO) and nodular changes (12%) and fibrosis (14.5%), and they had higher esophageal diameters (p < 0.001). Patients with chronic lung CT changes had significantly higher esophageal diameter than with acute changes (p < 0.001). Awareness of the association of achalasia and lung disorders is important in early diagnosis and treatment. More than half (57.5%) of patients with achalasia had some clinical and/or structural pulmonary abnormalities. All three subtypes had similar respiratory symptoms, meaning they cannot be used to predict the subtype of achalasia; on the contrary, SS can predict the first two subtypes. A higher diameter of the esophagus is associated with chronic structural lung changes. Although unexpected, the pathological radiological findings and diameter were significantly different in subtype 3 patients, but those parameters cannot lead us to a specified subtype.

Pseudorabies virus hijacks DDX3X, initiating an addictive "mad itch" and immune suppression, to facilitate viral spread.

Infections with defined Herpesviruses, such as Pseudorabies virus (PRV) and Varicella zoster virus (VZV) can cause neuropathic itch, referred to as "mad itch" in multiple species. The underlying mechanisms involved in neuropathic "mad itch" are poorly understood. Here, we show that PRV infections hijack the RNA helicase DDX3X in sensory neurons to facilitate anterograde transport of the virus along axons. PRV induces re-localization of DDX3X from the cell body to the axons which ultimately leads to death of the infected sensory neurons. Inducible genetic ablation of Ddx3x in sensory neurons results in neuronal death and "mad itch" in mice. This neuropathic "mad itch" is propagated through activation of the opioid system making the animals "addicted to itch". Moreover, we show that PRV co-opts and diverts T cell development in the thymus via a sensory neuron-IL-6-hypothalamus-corticosterone stress pathway. Our data reveal how PRV, through regulation of DDX3X in sensory neurons, travels along axons and triggers neuropathic itch and immune deviations to initiate pathophysiological programs which facilitate its spread to enhance infectivity.

The usefulness of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for diagnosis and assessment of COPD severity.

BACKGROUND: Inflammation, oxidative stress and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and to assess their relationship with lung function, symptom severity scores and recent acute exacerbations. METHODS: In this observational cohort study, serum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 ratio in the peripheral blood of COPD patients with stable disease and healthy controls were determined, and their association with lung function (postbronchodilator spirometry, body plethysmography, single breath diffusion capacity for carbon monoxide), symptom severity scores (mMRC and CAT) and exacerbation history were assessed. RESULTS: COPD patients (n = 98) had significantly higher levels of serum MMP-9 and TIMP-1 and a higher MMP-9/TIMP-1 ratio than healthy controls (n = 47) (p ≤ 0.001). The areas under the receiver operating characteristic curve for MMP-9, TIMP-1 and the MMP-9/TIMP-1 ratio for COPD diagnosis were 0.974, 0.961 and 0.910, respectively (all p < 0.05). MMP-9 and the MMP-9/TIMP-1 ratio were both negatively correlated with FVC, FEV1, FEV1/FVC, VC, and IC (all p < 0.05). For MMP-9, a positive correlation was found with RV/TLC% (p = 0.005), and a positive correlation was found for the MMP-9/TIMP-1 ratio with RV% and RV/TLC% (p = 0.013 and 0.002, respectively). Patients with COPD GOLD 3 and 4 presented greater MMP-9 levels and a greater MMP-9/TIMP-1 ratio compared to GOLD 1 and 2 patients (p ≤ 0.001). No correlation between diffusion capacity for carbon monoxide and number of acute exacerbations in the previous year was found. CONCLUSIONS: COPD patients have elevated serum levels of MMP-9 and TIMP-1 and MMP-9/TIMP-1 ratio. COPD patients have an imbalance between MMP-9 and TIMP-1 in favor of a pro-proteolytic environment, which overall indicates the importance of the MMP-9/TIMP-1 ratio as a potential biomarker for COPD diagnosis and severity.

Impact of Perioperatively Administered Amino Acids, Lidocaine, and Magnesium on Inflammatory Response and Pain Associated with Abdominal Surgery: A Prospective Clinical Study.

BACKGROUND Abdominal surgery is associated with a systemic inflammatory response which facilitates postoperative complications through immune imbalance and hypercatabolism. The aim of the study was to evaluate the effect of the combined perioperative lidocaine, magnesium, and amino acids on postoperative inflammation and pain. MATERIAL AND METHODS This prospective, randomized, double-blind study included 2 groups of patients undergoing abdominal surgery: Group 1 - receiving the aforementioned substances; and Group 2 - control (undergoing conventional general anesthesia). The following parameters were evaluated intraoperatively: arterial blood pressure, end-tidal CO2 level, urine output, bispectral index, base excess, oxygen saturation, operating room temperature and body temperature (BT), opioid use, and surgery duration; and postoperatively: total leukocyte (WBC), neutrophil, lymphocyte and platelet count; fibrinogen, C-reactive protein (CRP), procalcitonin (PCT) and interleukin (IL)-6 levels; numeric rating scale (NRS) pain level, first flatus and bowel movement, and postoperative complications. The postoperative parameters were evaluated 2 h and 6 h postoperatively, as well as on postoperative days (POD) 1, 2, 3, and 5. RESULTS Group 1 showed lower counts of WBC, neutrophils, and lymphocytes and lower fibrinogen, CRP, PCT, IL-6, and BT in the first 5 POD, as well as NRS scores and time to first flatus/bowel movement. The groups did not differ significantly regarding postoperative complications. CONCLUSIONS The isolated effects of lidocaine, magnesium, and amino acids in surgery have been described previously. To the best of our knowledge, this is the first study to show the anti-inflammatory and analgesic effects of simultaneous use of these substances in abdominal surgery.

The Clinical Impact of the Extension of Acute Type A Aortic Surgery on Long-Term Outcomes: Should We Tend to Be Conservative?

Background and Objectives: Despite advances in surgical techniques, industry adjuncts, and cerebral perfusion techniques, the in-hospital mortality rate of type A acute dissection (TAAD) remains at 15-30%. This study aimed to investigate the influence of different extents of aortic resection on survival and quality of life (QoL) after long-term follow-up. Materials and Methods: A retrospective observational trial was performed, including 165 patients operated upon for TAAD. Patients were divided into two groups according to the extent of their aortic repair: the first group comprised patients who had ascending aorta replacement and the second included patients who had hemiarch or total arch replacement. The groups were compared with regard to their baseline characteristics, operative characteristics, survival, complications, and QoL during nine years of follow-up. Results: The mean follow-up time was 75.6 months (1-108 months). The mean survival in the ascending aorta repair group was 89.651 (81.242-98.061) months and was 54.801 (40.053-69.548) months in the hemiarch and arch group; the difference between the groups was significant (log-rank p < 0.001). The rate of new postoperative neurological deficits was statistically higher in the hemiarch and arch group (17.5% vs. 8.4%, p = 0.045), the most common being stroke, and was also more frequent in the hemiarch and arch group than in the ascending aorta group (with statistical significance (15.7% vs. 6.5%)). The mean SF-12 physical score from the QoL questionnaire was higher in the ascending aorta replacement group than in the hemiarch and arch group (50.1 ± 7.3 vs. 44.0 ± 11.9, p = 0.017). Additionally, the mean SF-12 mental score was higher in the ascending aorta replacement group (52.3 ± 7.3 vs. 47.1 ± 12.8, p = 0.032). Conclusions: A more aggressive approach involving aortic arch repair means a lower survival rate and lesser quality of life after long-term follow-up in comparison with the replacement of the ascending aorta. If clinically applicable, a more defensive strategy may be considered.

Outcomes of Open Surgery for Retroperitoneal Hematoma in Covid-19 Patients: Experience from a Single Centre.

Background: Spontaneous retroperitoneal hematoma is a severe and potentially fatal complication that appears in the course of anticoagulation therapy. Therapeutic doses of low molecular weight heparin (LMWH) are used for the prevention of thrombosis in patients seriously ill with Covid-19. Methods: We describe 27 (0.14%) patients with retroperitoneal hematomas who required emergency surgery out of 19108 patients with Covid-19 who were hospitalized in Batajnica COVID Hospital between March 2021 and March 2022. All the patients were on therapeutic doses of LMWH. The existence of retroperitoneal hematoma was confirmed by abdominal ultrasound and computed tomography scans. Results: Open surgery was performed on 27 patients with spontaneous retroperitoneal hematomas (12 female and 15 male). The mean age of the study population was 71.6+-11.9 years. D-dimer was significantly elevated two days before the surgery in comparison with the values on the day of surgery (p=0.011). Six patients (22.23%) survived, while 21 (77.77%) patients died. Conclusion: Bleeding in Covid-19 patients treated by LMWH is associated with an increased risk of developing retroperitoneal hematoma. Open surgery for retroperitoneal hematoma in Covid-19 patients on anticoagulation therapy is a procedure associated with a high rate of mortality.

The HUSH complex controls brain architecture and protocadherin fidelity.

The HUSH (human silencing hub) complex contains the H3K9me3 binding protein M-phase phosphoprotein 8 (MPP8) and recruits the histone methyltransferase SETDB1 as well as Microrchidia CW-type zinc finger protein 2 (MORC2). Functional and mechanistic studies of the HUSH complex have hitherto been centered around SETDB1 while the in vivo functions of MPP8 and MORC2 remain elusive. Here, we show that genetic inactivation of Mphosph8 or Morc2a in the nervous system of mice leads to increased brain size, altered brain architecture, and behavioral changes. Mechanistically, in both mouse brains and human cerebral organoids, MPP8 and MORC2 suppress the repetitive-like protocadherin gene cluster in an H3K9me3-dependent manner. Our data identify MPP8 and MORC2, previously linked to silencing of repetitive elements via the HUSH complex, as key epigenetic regulators of protocadherin expression in the nervous system and thereby brain development and neuronal individuality in mice and humans.

The correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction.

Background: The aim of this study was to examine the correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction. Methods: Between 2014 and 2022, we prospectively evaluated 81 consecutive spina bifida children with neurogenic bowel and bladder dysfunction (35 boys and 46 girls, mean age 9.5 ± 3.4 years). All patients underwent echosonographic measurement of transverse rectal diameter and urodynamic studies. Results: We found a strong negative correlation between transverse rectal diameter and maximum bladder capacity (r = -0.682, p < 0.001) and compliance (r = -0.690, p < 0.001). There was also a strong positive correlation between transverse rectal diameter and maximal detrusor pressure (r = 0.650, p < 0.001), leak point pressure (r = 0.793, p < 0.001), and PVR (r = 0.762, p < 0.001). In ROC analysis, transverse rectal diameter demonstrated good performance for distinguishing children with upper urinary tract deterioration, with an AUC of 0.857 (95% CI 0.761-0.953). A transverse rectal diameter ≥40 mm was 83.3% sensitive and 100% specific for the diagnosis of unfavorable urodynamic patterns. Conclusion: There is a correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction. Ultrasonographically assessed transverse rectal diameter of ≥40 mm may be used as a risk factor for upper urinary tract deterioration (unfavorable urodynamic findings). We suggest the transverse rectal diameter echosonographic measurement use as an integral part of the diagnostic approach in children with neurogenic bowel and bladder dysfunction, as it can help decision-making while waiting for urodynamic testing.

Reduction of transverse rectal diameter and its effect on bladder dynamics in children with spinal dysraphism.

INTRODUCTION: To examine the reduction of transverse rectal diameter and its effect on bladder dynamics in children with spinal dysraphism. METHODS: We prospectively evaluated 61 consecutive children with spinal dysraphism, 25 (41%) boys and 36 (59%) girls, aged 4 to 16 years; mean age 9.3 ± 3.8 years, who received bowel management. All children underwent echosonographic measurement of transverse rectal diameter before and after starting bowel management. Also, all the patients had undergone urodynamic studies before and after starting bowel management, with no changes in their urological treatment. RESULTS: Bowel management caused an decrease in transverse rectal diameter by 56 ± 7.2% (p < 0.001). In addition, a decrease was observed for maximal detrusor pressure by 27.8 ± 7.8% (p < 0.001), leak point pressure by 37.2 ± 4.4% (p < 0.001), and PVR by 36.7 ± 8.0 (p < 0.001). Maximum bladder capacity was significantly increased after bowel management in both non-adjusted (36.4 ± 14.8%; p < 0.001) and adjusted analysis for age (39.4 ± 14.3%, p < 0.001). Detrusor compliance was also increased by 89.2 ± 24.8% (p < 0.001). Female gender and % change of maximal detrusor pressure were significant predictors of transversal rectal diameter change in univariate as well as in multivariate analysis (OR = 10.548, 95% CI 2.309-48.180; p = 0.002 and OR = 1.121, 95% CI 1.009-1.245; p = 0.034). CONCLUSIONS: Decrease in transverse rectal diameter may be useful for bladder function and urodynamic findings in children with spinal dysraphism. Therefore, decrease in transverse rectal diameter should be a supplement to standard urotherapy.

Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia.

INTRODUCTION: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. METHODOLOGY: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. RESULTS: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. CONCLUSIONS: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB.