Cytogenetic features of infants less than 12 months of age at diagnosis of acute lymphoblastic leukemia: impact of the 11q23 breakpoint on outcome: a report of the Childrens Cancer Group

Cytogenetic analyses of pretreatment bone marrows were performed at local institutions as part of Childrens Cancer Group (CCG) protocol CCG- 107 for infants less than 1 year of age with previously untreated acute lymphoblastic leukemia (ALL). Cytogenetic analyses from 39 patients (17 males and 22 females) were accepted after review. Several unique cytogenetic features were observed. Twelve patients (31%) had a t(4;11)(q21;q23) and had a significantly shorter event-free survival (EFS) than did the other patients with adequate cytogenetic analyses (P = .009). Five additional patients had an 11q23 breakpoint, not associated with 4q21. When EFS for these 5 patients was compared with that of the t(4;11) patients, even with these small numbers there was a strong, although not significant, suggestion that the t(4;11) patients have a reduced EFS (P = .09), indicating that the specific translocation, t(4;11)(q21;q23), and not an 11q23 breakpoint per se, may be associated with the poor prognosis of these infants. Structural abnormalities were present in 27 of 28 patients with abnormal karyotypes. A new recurring abnormality, t(5;15)(p15:1;q11) or t(5;15)(p15.3;q13), was identified in 3 patients (Arthur et al, Blood 70:274a, 1987 [abstr, suppl 1]). Two females had structural abnormalities involving Xp11, a breakpoint rarely seen in ALL. Fourteen (36%) patients had a single structural abnormality, and 13 (33%) had complex karyotypes. No patients had hyperdiploidy with more than 50 chromosomes. Only normal chromosomes were observed in 11 patients (28%), and their outcome did not differ from patients with abnormal karyotypes. These cytogenetic abnormalities found in the leukemic cells of infants are clearly different from those in older children and adults, and may explain, in part, the unique biologic characteristics of infant ALL.     

Focal segmental necrotizing glomerulonephritis in rheumatoid arthritis

We report ten patients with rheumatoid arthritis (RA) who developed a focal segmental necrotizing glomerulonephritis (FSNGN) and extracapillary proliferation typical of vasculitic glomerulonephritis. Five patients also had extrarenal vasculitis. Renal presentation was with renal impairment (n = 9) (median creatinine 726 mumol/l, range 230- 1592 mumol/l), microscopic haematuria (n = 8) and proteinuria (n = 10). Nine patients were seropositive for rheumatoid factor and nine had bone erosions. Serum from four of five patients tested by indirect immunofluorescence was positive for antineutrophil cytoplasmic antibody (ANCA) with perinuclear staining. Only three patients had penicillamine or gold therapy. Treatment was with prednisolone and cyclophosphamide (six patients, two of whom were also plasma-exchanged), prednisolone and azathioprine (two patients) and prednisolone alone (two patients). There was a marked improvement in renal function in eight patients. Two patients with dialysis-dependent renal failure recovered renal function, although in one patient this was transient and she required further dialysis 4 months later. Two other patients progressed to dialysis at 3 months and 1 year respectively. Four patients died, one remains dialysis-dependent, and four continue to have good renal function at 5 year follow-up (median creatinine 148.5 mumol/l, range 120-193 mumol/l). One patient was lost to follow-up at 5 years. FSNGN should be considered in all patients with RA and renal impairment, proteinuria and/or microscopic haematuria. This diagnosis appears to be more likely in patients with clinical extrarenal vasculitis, bone erosions or who are seropositive. In these cases, an urgent renal biopsy is indicated.      

Cross-reactivity between H-2K and H-2D products. I. Evidence for extensive and reciprocal serological cross-reactivity

Serological cross-reactivity between the products of the H-2K and H-2D genes has been demonstrated by a design in which antibody was produced against determinants controlled by one locus (e .g . H-2K(k)), and then tested against the product of the opposite locus (e .g . H-2D(d)). A total of 13 out of 18 such test combinations exhibited H-2K-H-2D cross-reactivity. The presence or absence of cross-reactivity was reciprocal in most cases (i.e. antibody directed against the H-2K(k) gene product reacted with H-2(d) determinants, and antibody directed against the H-2D(d) gene product reacted with H-2K(k) determinants). An Ia-like reaction was detected with one antiserum which implied possible cross-reactivity between the products of two discrete la genes.     

Arsenic Thiolation and the Role of Sulfate-Reducing Bacteria from the Human Intestinal Tract

Background: Arsenic (As) toxicity is primarily based on its chemical speciation. Although inorganic and methylated As species are well characterized in terms of metabolism and formation in the human body, the origin of thiolated methylarsenicals is still unclear.Objectives: We sought to determine whether sulfate-reducing bacteria (SRB) from the human gut are actively involved in the thiolation of monomethylarsonic acid (MMA^V).Methods: We incubated human fecal and colon microbiota in a batch incubator and in a dynamic gut simulator with a dose of 0.5 mg MMA^V in the absence or presence of sodium molybdate, an SRB inhibitor. We monitored the conversion of MMA^V into monomethyl monothioarsonate (MMMTA^V) and other As species by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry analysis. We monitored the sulfate-reducing activity of the SRB by measuring hydrogen sulfide (H₂S) production. We used molecular analysis to determine the dominant species of SRB responsible for As thiolation.Results: In the absence of sodium molybdate, the SRB activity—primarily derived from Desulfovibrio desulfuricans (piger)—was specifically and proportionally correlated (p < 0.01) to MMA^V conversion into MMMTA^V. Inactivating the SRB with molybdate did not result in MMA^V thiolation; however, we observed that the microbiota from a dynamic gut simulator were capable of demethylating 4% of the incubated MMA^V into arsenous acid (iAs^III), the trivalent and more toxic form of arsenic acid (iAs^V).Conclusion: We found that SRB of human gastrointestinal origin, through their ability to produce H₂S, were necessary and sufficient to induce As thiolation. The toxicological consequences of this microbial As speciation change are not yet clear. However, given the efficient epithelial absorption of thiolated methylarsenicals, we conclude that the gut microbiome—and SRB activity in particular—should be incorporated into toxicokinetic analysis carried out after As exposure.Citation: DC.Rubin SS, Alava P, Zekker I, Du Laing G, Van de Wiele T. 2014. Arsenic thiolation and the role of sulfate-reducing bacteria from the human intestinal tract. Environ Health Perspect 122:817–822; http://dx.doi.org/10.1289/ehp.1307759     

BiomarCaRE: rationale and design of the European BiomarCaRE project including 300,000 participants from 13 European countries

Biomarkers are considered as tools to enhance cardiovascular risk estimation. However, the value of biomarkers on risk estimation beyond European risk scores, their comparative impact among different European regions and their role towards personalised medicine remains uncertain. Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) is an European collaborative research project with the primary objective to assess the value of established and emerging biomarkers for cardiovascular risk prediction. BiomarCaRE integrates clinical and epidemiological biomarker research and commercial enterprises throughout Europe to combine innovation in biomarker discovery for cardiovascular disease prediction with consecutive validation of biomarker effectiveness in large, well-defined primary and secondary prevention cohorts including over 300,000 participants from 13 European countries. Results from this study will contribute to improved cardiovascular risk prediction across different European populations. The present publication describes the rationale and design of the BiomarCaRE project.     

Concomitant Seminal Vesicle Invasion in pT4a Urothelial Carcinoma of the Bladder with Contiguous Prostatic Infiltration is an Adverse Prognosticator for Cancer-Specific Survival after Radical Cystectomy

Purpose

To evaluate the prognostic value of concomitant seminal vesicle invasion (cSVI) in patients with urothelial carcinoma of the bladder (UCB) and contiguous prostatic stromal infiltration in a large cystectomy series.

Methods

A total of 385 patients with UCB and contiguous prostatic infiltration comprised our study. Patients were divided in two groups according to cSVI. Median follow-up was 36 months (interquartile range 11–74); the primary end point was cancer-specific mortality. The prognostic impact of cSVI was evaluated using multivariable Cox regression analysis. The predictive accuracy was assessed by a receiver operating characteristic analysis.

Results

A total of 229 patients (59.5 %) without cSVI comprised group A, and 156 patients (40.5 %) with cSVI comprised group B. Positive lymph nodes (63 vs. 44 %, p < 0.001) and positive surgical margins (34 % vs. 14 %, p < 0.001) were more common in patients with cSVI. The 5- and 10-year cancer-specific survival rates were 41 % and 32 % (group A) and 21 and 17 % (group B) (p < 0.001). In multivariable analysis, pathological nodal stage (hazard ratio [HR] 2.19, p < 0.001), soft tissue surgical margin (HR 1.57, p = 0.010), clinical tumor stage (HR 1.46, p = 0.010), adjuvant chemotherapy (HR 0.40, p < 0.001), and cSVI (HR 1.69, p < 0.001) independently impacted cancer-specific mortality. The c-indices of the multivariable models with and without inclusion of cSVI were 0.658 (95 % confidence interval 0.60–0.71) and 0.635 (95 % confidence interval 0.58–0.69), respectively, resulting in a predictive accuracy gain of 2.3 % (p = 0.002).

Conclusions

In patients with UCB and prostatic stromal invasion, cSVI adversely affected cancer-specific survival compared to patients without cSVI. The inclusion of cSVI significantly improved the predictive accuracy of our multivariable model regarding survival.     

The diagnostic value of fine needle aspiration in parotid lumps

Mallon DH, Kostalas M, MacPherson FJ et al. The diagnostic value of fine needle aspiration in parotid lumps. Ann R Coll Surg Engl 2013; 95: 258–262 doi 10.1308/003588413X13511609958370We read with interest the article by Mallon et al and would like to make further comment. Their paper documents what is becoming increasingly clear about fine needle aspiration (FNA) in the salivary glands. In experienced hands, it is capable of a high degree of accuracy, and is quick and safe to perform. FNA performance is optimised by the use of ultrasonography guidance, presence of cytologist/cytology technician to allow repeat aspiration and use of ancillary cytology techniques. Outside specialised units, however, the performance of FNA varies widely, as demonstrated in the recent meta-analysis by Schmidt et al.¹Even in optimised circumstances, FNA remains associated with both a high rate of non-diagnostic sampling and also false negative results.¹ These perceived failings have led to investigation into alternative biopsy techniques, which may more reliably provide an accurate preoperative diagnosis, allowing informed patient consent and appropriate operative selection.Ultrasonography guided core biopsy (USCB) has been described recently in the parotid glands, and has been shown to be both highly accurate and well tolerated.² USCB obtains a core of tissue, using a small bore needle (18G or 20G) deployed via an automated biopsy device, which can be sent for immunohistochemical analysis. This enables typing and grading of tumours. Furthermore, it allows improved diagnosis of nodal hyperplasia and the differentiation of reactive node from low grade lymphoma. USCB does not appear to be associated with either the high non-diagnostic and false negative rates or the variability in performance associated with FNA.³ We would recommend that USCB should be considered the biopsy technique of choice for parotid lump diagnosis, particularly in units where FNA is undertaken in non-optimised circumstances.     

Incidence and risk factors of renal hematoma: a prospective study of 1,300 SWL treatments

Shock wave lithotripsy (SWL) is the gold standard for the treatment of upper urinary tract stones. Despite being relatively non-invasive, SWL can cause renal hematoma (RHT). The aim of this study was to determine incidence and risk factors for RHT following SWL. 857 patients were included in a prospectively maintained database. The observation period spans from 2007 to 2012. 1,324 procedures were performed due to kidney stones. Treatment protocol included power ramping and shock wave frequency of 60–90 per minute as well as an ultrasound check within 3 days of SWL for all patients. Patients with RHT were analyzed, and treatment characteristics were compared with the complete population in a non-statistical manner due to the low event count. RHTs after SWL, sized between 2.6 × 0.6 cm and 17 × 15 cm, were verified in seven patients (0.53 %). In four patients, the RHT was asymptomatic. Three patients developed pain after SWL treatment due to a RHT. In one patient surgical intervention was necessary due to a symptomatic RHT, the kidney was preserved. The risk of RHT following SWL treatment of kidney stones is about 0.5 %. Clinically relevant or symptomatic RHTs occur in 0.23 %, RHTs requiring surgical intervention are extremely rare. Older age and vascular comorbidities appear to be risk factors for the development of RHT. The technical characteristics of SWL treatment and intake of low-dose acetylsalicylic acid due to an imperative cardiologic indication do not appear to influence the risk. Prospective studies are warranted.     

Critical consciousness of public health nurses: A descriptive,comparative survey

Background

Public Health Nurses (PHN) caring for vulnerable populations amid systemic inequality must navigate complex situations, and consequently they may experience serious moral distress known to be detrimental to PHN wellbeing.

Objective

Given PHN awareness of social inequities, the study aimed to determine if PHNs were motivated to enact social change and engage in social and political action to address inequality.

Design and sample

A survey of 173 PHNs was conducted in fall 2022. The convenience sample was mainly female (96.5%), White (85%), had associate/bachelor's degrees (71.7%), and worked in governmental public health settings (70.7%).

Measure

The study employed the Short Critical Consciousness Scales’ subscales: Critical Reflection, Critical Motivation, and Critical Action.

Results

PHNs were highly motivated to address inequities (Critical Motivation = 20.83; SD = 3.16), with similarly high awareness (Critical Reflection = 17.89; SD = 5.18). However, social and political action scores were much lower (Critical Action = 7.13; SD = 2.63). A subgroup of PHNs with strong agreement regarding the impact of poverty were more likely to be younger (p = .039) and work in a community setting (p = .003); with higher scores across subscales (p < .001).

Conclusions

High critical reflection and motivation among PHNs aligned with literature. Lower Critical Action scores warrant investigation into validity for PHNs, and possible role constraints.