Risk factors for complications after emergency surgery for paediatric appendicitis: a national prospective observational cohort study.

Appendicectomy is a common procedure in children with a low risk of mortality, however, complication rates and risk factors are largely unknown. This study aimed to characterise the incidence and epidemiology of postoperative complications in children undergoing appendicectomy in the UK. This multicentre prospective observational cohort study, which included children aged 1-16 y who underwent surgery for suspected appendicitis, was conducted between November 2019 and January 2022. The primary outcome was 30-day postoperative morbidity. Data collected included: patient characteristics; comorbidities; and physiological status. Multivariable regression analysis was used to identify independent risk factors for poor outcomes. Data from 2799 children recruited from 80 hospitals were analysed, of which 185 (7%) developed postoperative complications. Children from black and 'other' minority ethnic groups were at significantly higher risk of poor outcomes: OR (95%CI) 4.13 (1.87-9.08), p < 0.001 and 2.08 (1.12-3.87), p = 0.021, respectively. This finding was independent of socio-economic status and type of appendicitis found on histology. Other risk factors for complications included: ASA physical status ≥ 3 (OR (95%CI) 4.05 (1.70-9.67), p = 0.002); raised C-reactive protein (OR 95%CI 1.01 (1.00-1.01), p < 0.001); pyrexia (OR (95%CI) 1.77(1.20-2.63), p = 0.004); and peri-operative oxygen supplementation (OR (95%CI) 4.20 (1.44-12.24), p = 0.009). In the UK NHS, which is a universally accessible healthcare system, ethnicity, but not socio-economic status, was associated with an increased risk of postoperative complications in children having surgery for acute appendicitis. Further evaluations and interventions are required to address this health inequality in keeping with NHS and international priorities.

Caesarean hysterectomy for placenta praevia/accreta using an approach via the pouch of Douglas.

UNLABELLED: Placenta praevia/accreta is associated with significant maternal morbidity and mortality and is a common cause of obstetric hysterectomy. This paper describes posterior retrograde abdominal hysterectomy, a new surgical technique for caesarean hysterectomy, in 11 women with placenta percreta, increta or accreta There were no intraoperative or postoperative maternal complications, and only one fetus required admission to the neonatal unit, for prematurity. Our technique in placenta praevia/accreta allows easy identification of the vagina and early uterine devascularisation, as well as safe resection of the involved urinary bladder in women with placenta percreta showing bladder penetration. Analytical studies are needed to confirm our findings. TWEETABLE ABSTRACT: Posterior retrograde abdominal hysterectomy in women with placenta praevia/accreta may enable safer surgery.

Biological Activity of Mouse OX40L-Igg Purified With Two Novel Resins.

One of the important stimulating molecules for the function of T lymphocytes is tumor necrosis factor receptor OX40 (CD134), activated by its cognate ligand OX40L (CD134L, CD252). OX40L interactions have been proposed as a potential therapeutic target for treating infectious and non-infectious diseases. The main purpose of this study was to determine the potency of two novel resins MBI and MEP for the purification of OX40L-IgG fusion protein and the biological activities of this OX40L-IgG fusion protein. The biological activity of the OX40L-IgG purified by these resins compared with protein A sepharose resin. Mice treated with the same doses of the OX40L purified by the three resins showed a significant delay in tumor growth compared to the controls injected with PBS. Mice treated with the OX40L purified by MBI resin showed a significant delay in tumor cell (CT26) growth compared with mice injected with OX40L purified by other resins.

Evaluation of murine OX40L-murine IgG1(MM1) fusion protein on immunogenicity against L. mexicana infection in BALB/c mice.

The majority of OX40L is found on professional antigen-presenting cells (APC), the potency of OX40L to enhance the immunogenicity of potential vaccines against leishmania is not yet fully investigated. There is no report of administration of OX40L on cutaneous leishmaniasis either in therapy or prophylactic immunisation and the present study for the first time reports the effect of OX40L on L. mexicana infection. In this study, B9B8E2 cells were transfected with the murine OX40L and IgG1 plasmids, were used to produce the mOX40-mIgG1 (MM1). The therapeutic effects of MM1(mOX40L-mIgG1) was tested in a challenge experiment using L. mexicana infected BALB/c mice. Mice received two doses of MM1, on day 3 and 7 after the infection. Mice receiving MM1 generated an inflammatory reaction a few days after the injection of the OX40L, which was gradually dampened and finally disappeared 3 weeks later. There was a significant delay in the growth of developing lesions in mice receiving OX40L compared to controls injected with PBS and the size of lesions in the group receiving MM1 was significantly smaller than that of injected with either PBS. 40% of mice given MM1 remained lesion free for two months, when experiments were terminated. The results clearly indicate the high therapeutic effect of mOX40L-mIgG1 fusion protein in L. mexicana infection. The effect of OX40L on the enhancement of immunisation, needs to be further investigated for developing new vaccine strategies.

Implant-to-implant wireless networking with metamaterial textiles.

Implanted bioelectronic devices can form distributed networks capable of sensing health conditions and delivering therapy throughout the body. Current clinically-used approaches for wireless communication, however, do not support direct networking between implants because of signal losses from absorption and reflection by the body. As a result, existing examples of such networks rely on an external relay device that needs to be periodically recharged and constitutes a single point of failure. Here, we demonstrate direct implant-to-implant wireless networking at the scale of the human body using metamaterial textiles. The textiles facilitate non-radiative propagation of radio-frequency signals along the surface of the body, passively amplifying the received signal strength by more than three orders of magnitude (>30 dB) compared to without the textile. Using a porcine model, we demonstrate closed-loop control of the heart rate by wirelessly networking a loop recorder and a vagus nerve stimulator at more than 40 cm distance. Our work establishes a wireless technology to directly network body-integrated devices for precise and adaptive bioelectronic therapies.

Nerve growth factor induces the expression of chaperone protein calreticulin in human epithelial ovarian cells.

Epithelial ovarian cancer is highly angiogenic and high expression of Nerve Growth Factor (NGF), a proangiogenic protein. Calreticulin is a multifunctional protein with anti-angiogenic properties and its translocation to the tumor cell membrane promotes recognition and engulfment by dendritic cells. The aim of this work was to evaluate calreticulin expression in human normal ovaries, benign and borderline tumors, and epithelial ovarian cancer samples and to evaluate whether NGF regulates calreticulin expression in human ovarian surface epithelium and in epithelial ovarian cancer cell lines. Calreticulin mRNA and protein levels were analyzed using RT-PCR, Western blot and immunohistochemistry in 67 human ovarian samples obtained from our Institution. Calreticulin expression induced by NGF stimulation in cell lines was evaluated using RT-PCR, Western blot and immunocytochemistry. We found a significant increase of calreticulin mRNA levels in epithelial ovarian cancer samples as compared to normal ovaries, benign tumors, and borderline tumors. Calreticulin protein levels, evaluated by Western blot, were also increased in epithelial ovarian cancer with respect to benign and borderline tumors. When HOSE and A2780 cell lines were stimulated with Nerve Growth Factor, we found an increase in calreticulin protein levels compared to controls. This effect was reverted by GW441756, a TRKA specific inhibitor. These results suggest that NGF regulates calreticulin protein levels in epithelial ovarian cells through TRKA receptor activation.

Nerve growth factor stimulates cellular proliferation of human epithelial ovarian cancer.

Due to its ability to induce vascular endothelial growth factor expression and proliferation, migration, and vasculogenesis of endothelial cells, nerve growth factor (NGF) has been considered as an angiogenic factor in epithelial ovarian cancer (EOC). In this work, we evaluated the angiogenic and proliferative mRNA expression profiles of EOC and addressed the responsiveness of EOC explants to NGF stimulation. Twenty EOC samples were obtained from Obstetrics and Gynecology Department, University of Chile's Clinical Hospital. Global gene expression profiles of selected poorly differentiated serous EOC samples were obtained with DNA oligonucleotide microarrays. In addition, EOC explants were subjected to NGF stimulation and levels of p-AKT, BAX, BCL2, Ki-67, c-MYC, and FOXL2 proteins were determined by immunohistochemistry. Results showed that mRNAs coding for specific transcriptional regulators and antiapoptotic components of the NGF signaling pathway were upregulated in EOC cells. At the protein level, key members of the NGF pathway including p-AKT, BCL2/BAX, Ki-67, and c-MYC were found increased, while FOXL2 was decreased in response to NGF stimulation. These findings strongly suggest that NGF stimulates cellular proliferation of human EOC.

[Heart autotransplantation for the treatment of a rhabdomyosarcoma of the left ventricle. Report of one case]. / Autotrasplante cardiaco en el tratamiento quirúrgico de tumores cardiacos primarios. Caso clínico.

Heart autotransplantation is an exceptional surgical technique used in the treatment of uncontrolled cardiac arrhythmias and primary unresectable cardiac tumors. We report a 28-year-old male with a rhabdomyosarcoma of the left ventricle, localized in the lateral and posterior wall, which involved the mitral valve and circumflex artery. After a complete study ruling out dissemination of the tumor, the patient was operated. Surgical exploration determined the unresectability of the tumor with the heart in situ. Therefore, the heart was explanted, preserving the right atrium and coronary sinus for re-implantation. Fifty percent of the mitral valve and the circumflex artery from its origin, were resected due to tumor infiltration. The heart was reconstructed with bovine pericardium and a mechanical valve was implanted in the mitral position. Afterward, the heart was implanted again following the same sequence as in bicaval transplantation, followed by a double bypass grafting to the distal circumflex territory. The patient had no significant complications and after nine months of follow up, there was no evidence of local recurrence. In the fourth postoperative month, a subcutaneous mass in the left thigh that was considered a metastasis without histological confirmation appeared. The lesion disappeared with radio and chemotherapy.

Inhibitory Effects of Leishmania Mexicana Infection on MHC-I Expression in Bone Marrow Derived Dendritic Cells.

Background: Leishmania is a parasite causing leishmaniasis with different clinical manifestations depending on the infectious species in many countries worldwide. Although different studies have been taken place to clear the interaction of the parasite with the immune system, many aspects of immunology of leishmaniasis is remained uncertain. Methods: Bone marrow derived dendritic cells (DCs) were cultured in vitro and divided into different groups (Nottingham Trent University, Nottingham, UK). The groups were separately infected with live or autoclaved L. mexicana or loaded with Soluble Leishmania Antigen (SLA). The expression of major histocompatibility complex class I (MHC-I) molecule was checked and compared on the cultured DCs using flow cytometry. Results: Infection of L. mexicana caused a significant downregulation in expression of molecules where killed Leishmania or SLA could not induce suppression in expression of these molecules. Conclusion: L. mexicana infection results in downregulation of MHC-I expression on bone marrow-derived dendritic cells.

Wirelessly operated bioelectronic sutures for the monitoring of deep surgical wounds.

Monitoring surgical wounds post-operatively is necessary to prevent infection, dehiscence and other complications. However, the monitoring of deep surgical sites is typically limited to indirect observations or to costly radiological investigations that often fail to detect complications before they become severe. Bioelectronic sensors could provide accurate and continuous monitoring from within the body, but the form factors of existing devices are not amenable to integration with sensitive wound tissues and to wireless data transmission. Here we show that multifilament surgical sutures functionalized with a conductive polymer and incorporating pledgets with capacitive sensors operated via radiofrequency identification can be used to monitor physicochemical states of deep surgical sites. We show in live pigs that the sutures can monitor wound integrity, gastric leakage and tissue micromotions, and in rodents that the healing outcomes are equivalent to those of medical-grade sutures. Battery-free wirelessly operated bioelectronic sutures may facilitate post-surgical monitoring in a wide range of interventions.

Wireless battery-free body sensor networks using near-field-enabled clothing.

Networks of sensors placed on the skin can provide continuous measurement of human physiological signals for applications in clinical diagnostics, athletics and human-machine interfaces. Wireless and battery-free sensors are particularly desirable for reliable long-term monitoring, but current approaches for achieving this mode of operation rely on near-field technologies that require close proximity (at most a few centimetres) between each sensor and a wireless readout device. Here, we report near-field-enabled clothing capable of establishing wireless power and data connectivity between multiple distant points around the body to create a network of battery-free sensors interconnected by proximity to functional textile patterns. Using computer-controlled embroidery of conductive threads, we integrate clothing with near-field-responsive patterns that are completely fabric-based and free of fragile silicon components. We demonstrate the utility of the networked system for real-time, multi-node measurement of spinal posture as well as continuous sensing of temperature and gait during exercise.

Molecular Identification of Free-Living Amoebae (Naegleria spp., Acanthamoeba spp. and Vermamoeba spp.) Isolated from Un-improved Hot Springs, Guilan Province, Northern Iran.

BACKGROUND: This study was conducted to determine the presence and molecular identify of Acanthamoeba, Naegleria and Vermamoeba in unimproved hot springs. METHODS: From Jul to Aug 2017, 54 water samples were collected from hot springs in different parts of the Guilan Province, North Iran. For the isolation of Acanthamoeba, Naegleria and Vermamoeba approximately 500 ml of the water samples were filtered through a cellulose nitrate membrane with a pore size of 0.45 µm. The filter was transferred onto non-nutrient agar plates seeded with Gram-negative bacteria (Escherichia coli) as a food source. The morphological key of page was used to identify free-living amoebae (FLA) using an inverted microscope, PCR amplification targeting specific genes for each genus and sequencing determined frequent species and genotypes base on NCBI database. RESULTS: Fifteen of the 54 samples were positive by culture and/or PCR for Acanthamoeba and other FLA from unimproved hot springs. By sequencing the positive isolates, the strains were shown to belong to Acanthamoeba castellanii (12 case isolates belonged to T4 genotype), 4 cases of V. vermiformis, and 3 cases of N. australiensis, 2 cases of N. pagei and 1 cases of N. gruberi. CONCLUSION: Although FLA-mediated illnesses are not as high as in environmental distribution, but because of a poor prognosis, more investigations about FLA distribution in hot springs is critical. Hot spring may enhance exposure of the amoebae in individuals. Hence, more attention to unimproved hot springs is needed to prevent free-living amoebae mediated diseases.

Immunity to tumour antigens.

During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

Analog computer assisted beat-by-beat measurement of stroke volume and related variables in man.

A technique for the beat-by-beat measurement of stroke volume is described. Aortic blood velocity signals are obtained from a catheter-mounted electromagnetic velocity transducer and analysed by a purpose-built analog computer. The stroke volume is computed by integration of each period of systolic forward flow using the velocity signal as its sole input. Automatic compensation of flowmeter drift is incorporated and inappropriate triggering of integration by diastolic artefact is prevented by applying both amplitude and duration criteria for the recognition of systolic forward flow. Early diastolic reverse flow is excluded from integration. The cardiac output, mean aortic flow per beat, and interbeat interval are also computed from the velocity signal. With aortic pressure as an additional input signal the mean arterial pressure per beat and systemic vascular resistance can be computed. The computer outputs are calibrated by a manual method. Preliminary studies comparing values for the cardiac output measured by this system and the direct Fick technique have indicated an excellent correlation between the two methods.

Impact of the Gulf War on the anxiety, cortisol, and growth hormone levels of Israeli civilians.

OBJECTIVE: The authors investigated the impact of continuous and repeated stress on Israeli civilians exposed to missile attacks during the Gulf War. METHOD: Study 1 included 26 healthy volunteers aged 28-59 years. Their scores on the Hamilton Anxiety Rating Scale and levels of plasma cortisol and growth hormone (GH) were evaluated before, during, and after the war. Study 2 included 13 healthy volunteers aged 25-59 years. Their scores on the state portion of the State-Trait Anxiety Inventory and levels of cortisol and GH were measured three times daily (8:00 a.m., noon, and 6:00 p.m.) at two time points (during and after the war). RESULTS: Anxiety levels of civilians exposed to the threat of war and later to actual missile attacks were significantly higher before and during the war than afterward. Anxiety during the war reached a peak in the evening. The increase in anxiety was not accompanied by any change from basal morning cortisol and GH levels or by diurnal variations in these hormones. CONCLUSIONS: Anxiety levels during the war were similar to those 1 day before its onset, which can be explained by the nature of coping processes. During the war, anxiety levels were highest in the evening, reflecting the war routine (missile attacks occurred mostly at night). The unaltered hormone levels and their normal diurnal variations despite the subjects' persistent anxiety were probably due to adaptation of the hypothalamic-pituitary-adrenal and hypothalamic-somatotropin axes to continuous stress.

Disabled infectious single cycle-herpes simplex virus (DISC-HSV) as a vector for immunogene therapy of cancer.

Disabled infectious single cycle-herpes simplex viruses (DISC-HSV) have been shown to be safe for use in humans and may be considered efficacious as vectors for immunogene therapy in cancer. Preclinical studies show that DISC-HSV is an efficient delivery system for cytokine genes and antigens. DISC-HSV infects a high proportion of cells, resulting in rapid gene expression for at least 72 h. The DISC-HSV-mGM-CSF vector, when inoculated into tumors, induces tumor regression in a high percentage of animals, concomitant with establishing a cytotoxic T-cell response, which is MHC class I restricted and directed against peptides of known tumor antigens. The inherent properties of DISC-HSV makes it a suitable vector for consideration in human immunogene therapy trials.

Quality assurance of second opinion pathology in gynecologic oncology.

OBJECTIVE: To determine the effect of routine second review of pathologic material that was sent to Ohio State University before initiation of therapy. METHODS: All the gynecologic-oncologic histopathology review diagnoses made during a 1-year period were compared with original pathologic diagnoses. When there was a discrepant diagnosis with the second interpretation, the case was reviewed by at least two pathologists. Discrepancies were coded as no diagnostic disagreement, no diagnostic disagreement but pertinent information not included, diagnostic disagreement without clinical consequences, diagnostic disagreement with minor clinical significance, or diagnostic disagreement with major clinical significance. Proportions and confidence intervals were calculated. RESULTS: Pathology reports from 295 referred patients were reviewed. Two hundred forty-five (83.1%) showed no discrepancy. Discrepancies were found in 50 cases (16.9%). There was significant information missing in four cases (1.4%), diagnostic disagreement with no clinical significance in 22 cases (7.5%), and diagnostic disagreement with minor clinical significance in 10 cases (3.4%). In 14 cases (4.7%, 95% confidence interval 2.28, 7.12) the changes in diagnoses had major therapeutic or prognostic implications that included changes from malignant or low malignant potential to benign (seven cases), malignant to low malignant potential (three cases), change in tumor type (two cases), and assessment of invasion (two cases). The cost of reviewing 295 specimens was approximately $39,235. The cost of identifying each major discrepancy was about $2802. CONCLUSION: Routine pathology review of gynecologic-oncologic cases before definite treatment revealed notable discrepancies in diagnoses. In 4.7% of cases, the change in diagnosis had a major effect on proper treatment planning or a significant prognostic implication.

Growth pattern of the rabbit nasal bone region.

Two radiopaque implants were inserted into each left and right nasal bone in five female rabbits. Ventrodorsal cephalometric radiographs were taken at 6 and 16 weeks of age. From these radiographs, separate tracings were made on matte acetate paper of the left and right nasal bone regions including the radiopaque implants. The markers of the 16 week tracing were superposed on the markers of the 6 week tracing. The difference in the two established outlines represented the changes in size and shape in two dimensions that had occurred during the 10 week period. Our purpose was to determine the relative growth activity at several borders. The mean increase was about 6.79 mm at the proximal (posterior) border, 6.19 mm at the distal (anterior) border, 2.73 mm at the lateral border, 1.22 mm at the medial border. Thus, growth at the proximal and the distal borders was about the same and about twice that of the lateral border and about 5 times that of the medial border.