Height-based formulas for predicting intravascular length of tunnelled neck central venous catheter in paediatric population.

INTRODUCTION: Central venous catheter (CVC) placement is commonly performed in children. We aim to develop simple formulas to predict CVC intravascular length to minimise radiation exposure associated with the procedure. METHODS: 124 paediatric patients who received tunnelled neck CVCs and subsequent CT thorax at Hong Kong Children's Hospital from January 2020 to July 2022 were reviewed retrospectively. Formula development cohorts were subdivided by insertion sites-9 right external jugular vein (REJV), 41 right internal jugular vein (RIJV), 14 left external jugular vein (LEJV), 10 left internal jugular vein (LIJV). Using measurements from CT by two radiologists, formulas predicting the CVC intravascular length based on height and insertion sites were developed using a linear regression model. These formulas were tested with validation cohorts (10 randomly selected cases in REJV and RIJV groups respectively). Validation cohorts were not available for LEJV and LIJV groups due to small sample sizes. RESULT: The goodness-of-fit (R^2) of all formulas are above 0.8. In the validation cohorts, the REJV formula was predictive of intravascular CVC length within 1 cm in 70% of CVC with mean absolute difference of 0.63 cm (SD 0.48 cm), and the RIJV formula was predictive of intravascular CVC length within 1 cm in 80% of CVC with mean absolute difference of 0.67 cm (SD 0.53 cm). CONCLUSION: Intravascular CVC length can be estimated using simple formulas based on height and insertion sites. Further prospective validation of the LEJV and LIJV formulas is needed.

Cancer-testis antigen GAGE-1 expression and serum immunoreactivity in hepatocellular carcinoma.

AIM: To explore the use of cancer-testis antigen G antigen 1 (GAGE-1) in the diagnosis and potential therapeutic targeting of hepatocellular carcinoma (HCC), we measured the expression of GAGE-1 protein levels in HCC tissues and its serum immunoreactivity in HCC patients. MATERIALS AND METHODS: We detected the expression of GAGE-1 protein in HCC by immunohistochemistry (IHC). We then analyzed the clinical significance of GAGE-1 expression in HCC with respect to clinicopathological parameters. We observed positive anti-GAGE-1 antibody reactivity in HCC patient serum, liver cirrhosis patients (LC), hepatitis B patients (HB), and normal human individuals (NHS) by enzyme-linked immunosorbent assay. RESULTS: The IHC results showed that the positive rates of GAGE-1 protein expression in cancer tissues and adjacent tissues were 43.3% (26/60) and 5% (3/60), respectively. The expression level of GAGE-1 protein in HCC tissues was significantly higher than that in tumor-adjacent tissues (P < 0.05). Positive GAGE-1 protein expression was not correlated with clinicopathological parameters (P > 0.05). Positive serum anti-GAGE-1 antibody reactivity in HCC patients, LC, HB, and NHS was 23.33% (14/59), 13.1% (8/61), 3.3% (2/60), and 3.4% (2/59), respectively. The frequency of anti-GAGE-1 antibody-positive sera in HCC patients and LC was significantly different than that in HB and NHS (P < 0.01), but no significant differences were found between HCC patients and LC (P = 0.485) or between HB and NHS (P = 0.410). Positive anti-GAGE-1 antibody reactivity was not correlated with clinicopathological parameters (P > 0.05). CONCLUSION: These data illustrate that the GAGE-1 protein exhibits moderate cancer-restricted pattern of expression and immunogenicity, laying the foundation for the application of GAGE-1 in immunotherapy and for the diagnosis of HCC.

Physiological effects of tetracycline antibiotic pollutants on non-target aquatic Microcystis aeruginosa.

This study aimed to evaluate the aquatic toxicity of three typical tetracycline antibiotics, including tetracycline, oxytetracycline, and chlortetracycline, on the cyanobacterium Microcystis aeruginosa. The cell density, chlorophyll a content, protein content, and enzymatic antioxidant activities were determined. The results showed that the cell growth was significantly inhibited by the three compounds at a low concentration. The chlorophyll a and protein content decreased significantly after exposure to 0.05 mg L(-1) of each compound for 9 d. When exposed to 0.2-1 mg L(-1) of tetracycline, the superoxide dismutase (SOD) activity increased, but peroxidase (POD) and catalase (CAT) activities decreased. In contrast, when exposed to oxytetracycline and chlortetracycline at different concentrations ranging from 0.2 to 1 mg L(-1) and from 0.01 to 0.05 mg L(-1), the SOD activity decreased, but the POD and CAT activities increased. These findings indicate that tetracycline antibiotics influence cell growth and protein synthesis, and they also induce oxidative stress in M. aeruginosa at environmentally similar concentrations. Thus, this study may provide further insights into the toxic effects of tetracycline antibiotics and the controlled use of antibiotics.

Voiding urosonography with second-generation ultrasound contrast versus micturating cystourethrography in the diagnosis of vesicoureteric reflux.

Vesicoureteric reflux has been associated with paediatric urinary tract infection. Fluoroscopic micturating cystourethrography (MCU) has been the gold standard of diagnostic test for decades; however, it has been criticized owing to its lower detection rate and radiation dose to children. Therefore, new radiation-free reflux imaging modalities have been developed, in which ultrasound-based contrast-enhanced voiding urosonography (ceVUS) is a good example. However, ultrasonography has been considered as an operator-dependent examination. Therefore, our study aimed to examine the inter-observer agreement of this sonographic technique, which has not been evaluated before. Moreover, the second-generation ultrasound contrast SonoVue has been recently marketed, and the data on its efficacy on intravesical use in ceVUS is relatively scarce. Thus, we also aimed to investigate the diagnostic performance and safety profile of SonoVue-enhanced VUS in the diagnosis of vesicoureteric reflux. Our prospective comparative study compared the diagnostic performance of ceVUS with MCU in young children presenting with first episode of urinary tract infection. We performed sequential ceVUS and MCU examinations in 31 patients (62 pelvi-ureter units). Perfect inter-observer agreement (Cohen's kappa statistics = 1.0, p < 0.001) was achieved in ceVUS, suggesting its good reliability in reflux detection and grading. Using MCU as reference, ceVUS had 100 % sensitivity and 84 % specificity and carried higher reflux detection rate than MCU (p < 0.001). There was no complication encountered. Conclusion: Voiding urosonography is a reliable, sensitive, safe and radiation-free modality in the investigation of vesicoureteric reflux in children. It should be incorporated in the diagnostic algorithm in paediatric urinary tract infection.

Abnormal voiding parameters in children with severe idiopathic constipation.

OBJECTIVE: It is suggested that idiopathic constipation may associate with abnormal voiding parameters. In this study, we investigate the voiding parameters in children with constipation. METHODS: Since 2010, seventeen consecutive children (12 boys, 5 girls) aged 5-17 (median = 14) with significant constipation according to Rome III criteria and who were not responding to conventional treatment (diet, laxatives & bowel training) for over 6 months were recruited. The rectal diameter (RD) was measured by transpubic ultrasonography (USG), RD >3.5 cm was considered as dilated. Each patient had uroflow measurement and bladder USG done to measure the maximal flow rate (Vmax), voided volume (VV), and post-void residual urine (PVR). Abnormal voiding parameters were defined as Vmax <12 ml/sec, VV <65 or >150% of age-adjusted expected bladder capacity (EBC) and/or PVR >20 ml. RESULTS: Rectal diameter ranged from 1.7 to 8.2 cm (median = 3 cm) and was abnormally dilated in eight children. Vmax was normal in all children (median = 23.7 ml/sec). Voided volume ranged from 30 to 289% of EBC and was abnormal in six children (35.5%). Post-void residual urine varied from 0 to 85 ml and was abnormal in six (35.5 %) children. Three children (17.6 %) had both abnormal VV and PVR. On the whole, the prevalence of abnormal voiding parameters in constipated children was 52.9 %. Mean RD in normal and abnormal parameters groups was 2.8 and 4.7 cm, respectively. Rectal dilation was associated with abnormal voiding parameters (p = 0.015). CONCLUSION: Abnormal voiding parameters including voided volume and post-void residual urine are prevalent in constipated children. Dilated rectum is associated with abnormal voiding parameters.

Scrotal antegradesclerotherapy demonstrates anatomical variations on venous drainage in paediatric, adolescent and young adult varicoceles.

AIM OF THE STUDY: Anatomical variations on venous drainage in varicoceles are under-reported. We report our experience in scrotal antegrade sclerotherapy (SAS) for adolescent varicoceles. METHODS: Since 2011, 15 consecutive boys with left varicoceles were recruited. Under general anaesthesia, a 5-mm transverse incision was made at scrotal neck, testicular vein was cannulated at pampiniform plexus with venogram performed. Foam sclerosant by mixing sodium tetradecyl sulphate (STS), Lipiodol(®) and air was slowly injected under fluoroscopy. Postoperatively the patients were followed-up for varicocele grading, testicular size, and complications. MAIN RESULTS: Median age at operation was 14 (10-19) years. 80 % had grade three varicoceles, 33.3 % had smaller left testis before operation. Intra-operative venogram showed three different anatomical variations. Group I: eleven patients (73.3 %) had single distinct internal spermatic vein; Group II: two patients demonstrated duplication of internal spermatic vein draining into left renal vein; Group III: two patients had pampiniform plexus draining to iliac and/or paraspinal veins. SAS was performed in Group I and II patients. Sclerosant volume injected ranged from 1.5 to 4.5 ml. In Group III patients, surgical ligation of testicular veins was performed rather than SAS to avoid uncontrolled systemic sclerosant spillage. Mean length of stay was 1.13 day. One patient with scrotal haematoma and one other with minor wound dehiscence were managed conservatively. Mean follow-up period was 10.9 (1-22) months. Thirteen patients (86.7 %) achieved varicocele grading ≤ 1. There was no postoperative testicular atrophy, hydrocele and epididymo-orchitis. CONCLUSION: Scrotal antegrade sclerotherapy using STS foam is a safe and effective treatment for adolescent varicoceles. Anatomical variations on venous drainage in varicoceles are common.

Natural selection in the water: freshwater invasion and adaptation by water colour in the Amazonian pufferfish.

Natural selection and ecological adaptation are ultimately responsible for much of the origin of biodiversity. Yet, the identification of divergent natural selection has been hindered by the spatial complexity of natural systems, the difficulty in identifying genes under selection and their relationship to environment, and the confounding genomic effects of time. Here, we employed genome scans, population genetics and sequence-based phylogeographic methods to identify divergent natural selection on population boundaries in a freshwater invader, the Amazonian pufferfish, Colomesus asellus. We sampled extensively across markedly different hydrochemical settings in the Amazon Basin and use 'water colour' to test for ecological isolation. We distinguish the relative contribution of natural selection across hydrochemical gradients from biogeographic history in the origin and maintenance of population boundaries within a single species and across a complex ecosystem. We show that spatially distinct population structure generated by multiple forces (i.e. water colour and vicariant biogeographic history) can be identified if the confounding effects of genetic drift have not accumulated between selective populations. Our findings have repercussions for studies aimed at identifying engines of biodiversity and assessing their temporal progression in understudied and ecologically complex tropical ecosystems.

Molecular composition of an antigen-specific, Ly-1 T suppressor inducer factor. One molecule binds antigen and is I-J-; another is I-J+, does not bind antigen, and imparts an Igh-variable region-linked restriction.

Immunized Ly-1+2-T cells (Ly-1 cells) make an antigen-specific soluble suppressor product (Lyl-1 TsiF) that will induce Ly-2+ cells to express suppressive activity but only if the Ly-2+ and the Ly-1 producer cell share genetic polymorphisms that are linked to the Igh locus and in particular that part where the Igh-V (or VH) is encoded. Ly-1 TsiF can be separated into entities, one binds antigen and does not express I-J determinants, and the other is I-J+ and does not bind antigen. Neither of these "subfactors" has biological activity, but a 50:50 mixture of them reconstitutes biological activity that expresses the antigen specificity of the antigen-binding molecule. Any of the three heterologous erythrocytes (antigens) studied can be used for immunization to produce the I-J+ nonantigen-binding factor, i.e., the I-J+ moiety makes no contribution to the factor's specificity. It does, however, determine the intact factor's Igh-V linked restriction. Thus, the antigen combining site of the factor is irrelevant to the factor's Igh-V restriction but crucial for its specificity. The I-J+ molecule does not bind antigen nor influence the factor's antigen specificity but expresses the Igh-V polymorphism (or anti-Igh-V polymorphism) that is required for the transmission of an inductive signal to the factor's Ly-2+ acceptor cell.

A molecular basis for MHC class II--associated autoimmunity.

Class II major histocompatibility (MHC) molecules have an immunoregulatory role. These cell-surface glycoproteins present fragments of protein antigens (or peptides) to thymus-derived lymphocytes (T cells). Nucleotide sequence polymorphism in the genes that encode the class II MHC products determines the specificity of the immune response and is correlated with the development of autoimmune diseases. This study identifies certain class II polymorphic amino acid residues that are strongly associated with susceptibility to insulin-dependent diabetes mellitus, rheumatoid arthritis, and pemphigus vulgaris. These findings implicate particular class II MHC isotypes in susceptibility to each disease and suggest new prophylactic and therapeutic strategies.

Multiple description coding with prediction compensation.

A new multiple description coding paradigm is proposed by combining the time-domain lapped transform, block level source splitting, linear prediction, and prediction residual encoding. The method provides effective redundancy control and fully utilizes the source correlation. The joint optimization of all system components and the asymptotic performance analysis are presented. Image coding results demonstrate the superior performance of the proposed method, especially at low redundancies.

Lactose drives Enterococcus expansion to promote graft-versus-host disease.

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Detailed analysis of cytomegalovirus (CMV)-specific T cells expanded for adoptive immunotherapy of CMV infection following allogeneic stem cell transplantation for malignant disease.

BACKGROUND: Cytomegalovirus (CMV) infection and its treatment causes significant morbidity following allogeneic stem cell transplantation (SCT) for malignancies. We studied the phenotype, function and growth kinetics of CMV pp65 antigen (Ag)-specific T cells expanded in a short-term culture for adoptive therapy. METHODS: Peripheral blood mononuclear cells (PBMC) from CMV-seropositive donors were cultured in various conditions with CMV pp65((495-503)) peptide to determine the most effective method for generating CMV-specific T cells. CMV-expanded cultures were tested for frequency, phenotype and functionality using peptide-MHC tetramer analysis, cytokine flow cytometry and cytolytic assays. A patient undergoing allogeneic SCT was administered CMV pp65-specific T cells generated from the donor based on these data, and recipient PBMC were analyzed following T-cell infusion. RESULTS: CMV pp65-specific T cells were consistently generated from CMV-seropositive donors at high frequencies (20-40% of CD8+ T cells), secreted interferon-gamma (IFN-gamma) in response to CMV peptide and had lytic activity against CMV peptide-expressing targets. Cultured CMV-specific T cells were infused into a SCT recipient without toxicity. DISCUSSION: Stimulating donor PBMC to generate functional, Ag-specific T cells for infusion into SCT recipients was accomplished consistently using readily available technology. We observed no toxicity in one patient receiving T cells and were able to monitor infused cells. These findings support further study of this approach as a prophylaxis against the risk of infection in patients receiving allogeneic transplantation from CMV-seropositive donors.

Haploidentical hematopoietic cell transplantation.

Haploidentical hematopoietic stem cell transplantation (HSCT) provides an opportunity for nearly all patients to benefit from HCT when a HLA genotypically matched sibling is not available. Initial results with the use of mismatched allografts led to limited enthusiasm due to GVHD and infectious complications resulting in unacceptable treatment-related morbidity and mortality. Recent advances with effective T-cell depletion, the use of 'megadoses' of stem cells, better antimicrobial therapy and reduced intensity conditioning has significantly decreased the early transplant-related mortality and GVHD. These modifications also enabled robust and prompt engraftment and led to enhancing the therapeutic benefits of haploidentical transplantation. However, the cardinal problems related to delayed immune reconstitution causing post-transplant infectious complications and relapse remain, limiting the efficacy of haploidentical transplant. Preliminary data have demonstrated the great potential in the use of adoptive cellular immunity and selective allodepletion in rapidly reconstituting immunity without GVHD. The encouraging reports from haploidentical transplant using noninherited maternal antigen (NIMA)-mismatched donors or natural killer (NK) alloreactive donors may greatly increase the donor availability and open a way to more appropriate donor selection in HLA-haploidentical HSCT. Future challenges remain in determining the safest approach for haploidentical transplant with minimal risk of GVHD, while preserving effective GVL activity and promoting prompt immune reconstitution.

Outcomes of a second non-myeloablative allogeneic stem cell transplantation following graft rejection.

Following initial graft rejection, a second attempt at allogeneic immunotherapy is often contemplated, but data on the success is limited. We therefore report on 11 patients with hematologic malignancies, renal cell cancer or marrow failure who underwent a second reduced-intensity regimen for primary or secondary graft failure. Nine of the 11 patients initially engrafted with the second attempt including two of four who used the same donor. One of the patients engrafted after the third attempt using a different donor and conditioning regimen. There were two treatment-related deaths. Four patients died from progressive disease 1-9 months after the second transplant. Two patients are still in recovery phase less than 1 year from the second transplant. Long-term remission is possible and three patients are alive in complete remission.

High-dose BCNU/Melphalan conditioning regimen before autologous stem cell transplantation in newly diagnosed multiple myeloma.

Single-agent high-dose melphalan (HDM, 200 mg/m2) has been the most commonly used conditioning regimen prior to autologous stem cell transplant, since its introduction in 1992. We used a more aggressive alkylator-based conditioning regimen in an attempt to overcome early relapse and combat drug resistance. We present a retrospective comparison and long-term follow-up of newly diagnosed patients with multiple myeloma (MM) treated with induction followed by either high-dose carmustine (BCNU) and HDM, or HDM alone, both followed by autologous stem cell transplant (ASCT). Between 1997 and 2002, 104 patients were treated with BCNU/HDM; from 2001 to 2008, 103 patients were treated with HDM alone. Median follow-up of survivors was 78 and 68 months for the BCNU/HDM and HDM groups, respectively. The median PFS was significantly increased with the BCNU/HDM regimen (40.4 vs 20.5 months, P<0.001). Median overall survival was increased with the BCNU/HDM regimen when compared with HDM alone (88.4 vs 67.2 months, P=0.07), but the difference was not statistically significant. Transplant-related mortality was similar in both groups (2.9% with BCNU and HDM vs 3.9% with HDM alone). Our findings suggest that the BCNU/HDM preparative regimen should be investigated further and potentially compared in a prospective randomized manner with HDM alone.

Graft versus host disease following allogeneic bone marrow transplantation.

Graft versus host disease is a major barrier in allogeneic bone marrow transplantation. The associated morbidity and mortality need to be understood and prevented if possible, as the potential indications for bone marrow transplantation continue to broaden. Areas of investigation include the cellular effector arm as well as the cytokines associated with the expression of the disease.

Regulating regulatory T cells.

Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress activation of other immune cells and thereby maintain immune system homeostasis, self-tolerance as well as control excessive response to foreign antigens. The mere concept of Tregs was the subject of significant controversy among immunologists for many years owing to the paucity of reliable markers for defining these cells and the ambiguity of the nature and molecular basis of suppressive phenomena. However, recent advances in the molecular characterization of this cell population have firmly established their existence and their vital role in the vertebrate immune system. Of interest, accumulating evidence from both humans and experimental animal models has implicated the involvement of Tregs in the development of graft-versus-host disease (GVHD). The demonstration that Tregs could separate GVHD from graft-versus-tumor (GVT) activity suggests that their immunosuppressive potential could be manipulated to reduce GVHD without detrimental consequence on GVT effect. Although a variety of T lymphocytes with suppressive capabilities have been reported, the two best-characterized subsets are the naturally arising, intrathymic-generated Tregs (natural Tregs) and the peripherally generated, inducible Tregs (inducible Tregs). This review summarizes our current knowledge of the generation, function and regulation of these two populations of Tregs during an immune response. Their role in the development of GVHD and their therapeutic potential for the prevention and treatment of GVHD will also be described.

Cognitive problems following hematopoietic stem cell transplant: relationships with sleep, depression and fatigue.

Cognitive problems are a significant, persistent concern for patients undergoing hematopoietic stem cell transplant (HSCT). Sleep is important for many cognitive tasks; however, the relationship between sleep and cognitive problems for HSCT patients is unknown. This study examined the relationship between sleep and cognitive problems for HSCT patients from pre to post transplant. Patients undergoing HSCT (N=138) completed questionnaires at pre-transplant and during the 12 months following transplant. Questionnaires assessed sleep and cognitive problems as well as commonly co-occurring symptoms: depressive symptoms, fatigue and pain. Post hoc analyses examined the relationship of specific sleep problems with cognitive problems. Sleep problems covaried with cognitive problems even after controlling for depressive symptoms, fatigue and pain. Depressive symptoms and fatigue were also uniquely related to cognitive problems. Post hoc analyses suggest that sleep somnolence, shortness of breath, snoring and perceptions of inadequate sleep may contribute to the association found between sleep and cognitive problems. Findings suggest that sleep problems are associated with and may contribute to cognitive problems for HSCT patients. However, sleep problems are rarely screened for or discussed during clinic visits. Assessing and treating specific sleep problems in addition to depressive symptoms and fatigue may have implications for improving cognitive problems for HSCT patients.

Retroperitoneal fibrosis following treatment for Hodgkin's disease.

With improvement and refinement of therapy, the majority of Hodgkin's disease patients are alive and free of disease at 5 years. As these patients continue to be observed, a variety of late complications have been reported. We describe herein three patients who developed retroperitoneal fibrosis following definitive therapy for Hodgkin's disease. The incidence approaches that seen with methysergide.