Validation of BIOMED-2 multiplex PCR tubes for detection of TCRB gene rearrangements in T-cell malignancies.

The BIOMED-2 Concerted Action BMH4-CT98-3936 on 'Polymerase chain reaction (PCR)-based clonality studies for early diagnosis of lymphoproliferative disorders' developed standardized PCR protocols for detection of immunoglobulin (Ig) and T-cell receptor (TCR) rearrangements, including TCR beta (TCRB). As no comparable TCRB PCR method pre-existed and only a limited number of samples was tested within the BIOMED-2 study, we initiated this study for further validation of the newly developed TCRB PCR approach by comparing PCR data with previously generated Southern blot (SB) data in a series of 66 immature (ALL) and 36 mature T-cell malignancies. In 91% of cases, concordant PCR and SB results were found. Discrepancies consisted of either failure to detect SB-detected TCRB rearrangements by PCR (6.5%) or detection of an additional non-SB defined rearrangement (2.5%). In 99% of cases (99/100), at least one clonal TCRB rearrangement was detected by PCR in the SB-positive cases. A predominance of complete Vbeta-Jbeta rearrangements was seen in TCRalphabeta(+) T-cell malignancies and CD3-negative T-ALL (100 and 90%, respectively), whereas in TCRgammadelta(+) T-ALL, more incomplete Dbeta-Jbeta TCRB rearrangements were detected (73%). Our results underline the reliability of this new TCRB PCR method and its strategic applicability in clonality diagnostics of lymphoproliferative disorders and MRD studies.     

Effects of Pulmonary Rehabilitation Including Inspiratory Muscle Training in Patients with Chronic Obstructive Pulmonary Disease after Stratification by the Degree of Static Hyperinflation

Background

Inspiratory muscle training (IMT) improves inspiratory muscle strength, exercise capacity and health status in patients with chronic obstructive pulmonary disease (COPD). However, there is no additional effect on top of comprehensive pulmonary rehabilitation (PR). It is unclear whether patients with different baseline degrees of static hyperinflation respond differentially to IMT as part of a PR program. Therefore, the aim was to study the effects of IMT as an add-on on PR after stratification for baseline degrees of static hyperinflation.

Methods

In this single center retrospective study data were extracted between June 2013 and October 2020 of COPD patients who participated in a comprehensive PR program including IMT. IMT was performed twice daily, one session consisted of 3 series of 10 breaths and training intensity was set initially at a load of approximately 50% of patients’ maximal static inspiratory mouth pressure (MIP). The primary outcome measure was MIP. Secondary outcomes were the distance achieved on the 6-min walk test (6MWD), endurance cycling exercise capacity at 75% of the peak work rate (CWRT) and disease-specific health status using the COPD assessment test.

Results

754 patients with COPD were screened for eligibility and 328 were excluded because of repeated PR programs, missing data or baseline residual volume (RV)?>?350%. In total, 426 COPD patients were categorized into RV categories 50–130% (n?=?84), 131–165% (n?=?86), 166–197% (n?=?86), 198–234% (n?=?85) and 235–349% (n?=?85). In the whole sample, MIP, endurance exercise capacity and health status improved significantly. The change in 6MWD was higher in the lowest baseline degree of static hyperinflation [+?39 (9–92) m] compared with the baseline highest degree of static hyperinflation [+?11 (??18–54) m] (p?<?0.05).

Conclusions

IMT as part of a PR program in patients with COPD with different baseline degrees improved MIP irrespective of the degree of static lung hyperinflation. Improvement in functional exercise capacity was significantly higher in the group with the lowest degree of static hyperinflation compared with the patients with the highest degree of static hyperinflation.

     

Effectiveness of Pulmonary Rehabilitation in Patients With Chronic Obstructive Pulmonary Disease With Different Degrees of Static Lung Hyperinflation

Objective

To evaluate the effect of pulmonary rehabilitation (PR) on exercise performance and quality of life in patients with chronic obstructive pulmonary disease (COPD) with different degrees of static lung hyperinflation (LH).

Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies Report of the BIOMED-2 Concerted Action BHM4 CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements is an important diagnostic tool in mature T-cell neoplasms. However, lack of standardized primers and PCR protocols has hampered comparability of data in previous clonality studies. To obtain reference values for Ig/TCR rearrangement patterns, 19 European laboratories investigated 188 T-cell malignancies belonging to five World Health Organization-defined entities. The TCR/Ig spectrum of each sample was analyzed in duplicate in two different laboratories using the standardized BIOMED-2 PCR multiplex tubes accompanied by international pathology panel review. TCR clonality was detected in 99% (143/145) of all definite cases of T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, peripheral T-cell lymphoma (unspecified) and angioimmunoblastic T-cell lymphoma (AILT), whereas nine of 43 anaplastic large cell lymphomas did not show clonal TCR rearrangements. Combined use of TCRB and TCRG genes revealed two or more clonal signals in 95% of all TCR clonal cases. Ig clonality was mostly restricted to AILT. Our study indicates that the BIOMED-2 multiplex PCR tubes provide a powerful strategy for clonality assessment in T-cell malignancies assisting the firm diagnosis of T-cell neoplasms. The detected TCR gene rearrangements can also be used as PCR targets for monitoring of minimal residual disease.     

The impact of migraine on quality of life in the general population: the GEM study

OBJECTIVE: To assess health-related quality of life (HRQOL) in migraineurs in the general population. DESIGN: Cross-sectional study within the context of a population-based study monitoring health characteristics of the Dutch adult population in two municipalities representative of the general population in the Netherlands. Migraine was assessed in a multistaged procedure that included a semistructured clinical interview by telephone. Final diagnosis met 1988 International Headache Society criteria. HRQOL was measured with the self-administered RAND 36-item Health Survey (RAND-36), including physical functioning, social functioning, role limitations, and physical perception. HRQOL of migraineurs was compared with that of nonmigraineurs. To compare and study the effect of comorbidity, the authors also identified subjects with asthma or chronic musculoskeletal pain. There were 5998 people with complete data, 620 of whom had migraine in the last year. RESULTS: Compared with nonmigraineurs, significantly more migraineurs had asthma (OR = 1.6; 95% CI 1.1, 2.4) or chronic musculoskeletal pain (OR = 1.7; 95% CI 1.5, 2.1). Migraineurs reported diminished functioning and well-being on all eight domains as compared with nonmigraineurs. HRQOL was inversely related to attack frequency (p < 0.0002). Migraineurs had a poorer HRQOL than did those reporting asthma, except for dimensions concerning physical functioning and general health perception, but they had a better HRQOL than did subjects with chronic musculoskeletal pain. Comorbidity of asthma or chronic musculoskeletal pain in migraine further reduced HRQOL. CONCLUSIONS: Migraineurs report more asthma and chronic musculoskeletal pain. Compared with nonmigraineurs and to others with chronic conditions, migraineurs report compromised physical, mental, and social functioning, particularly those with a high frequency of attack.     

Pregnancy and delivery after mid-urethral sling procedures for stress urinary incontinence: case reports and a review of literature

In this article, the effects of pregnancy and delivery on the development of stress urinary incontinence are described with special emphasis on the obstetrical management in women who wish to become pregnant or are pregnant after a preceding mid-urethral sling procedure. Three case histories and a review of literature are presented. Pregnancy after a preceding incontinence operation is rare and makes it quite difficult to formulate guidelines about delivery when a pregnancy occurs. The best advice is to postpone incontinence surgery until after the last pregnancy. There is evidence that an elective caesarean delivery protects against stress urinary incontinence in case of pregnancy after bladder neck suspension. For mid-urethral sling procedures, this evidence is not available. The presented case reports do not clearly demonstrate that caesarean delivery is necessary in case of pregnancy and delivery after a mid-urethral sling procedure. Furthermore, a second mid-urethral sling operation is a minor procedure compared to a caesarean section, and there is evidence that a second mid-urethral sling operation has the same success rate as the first procedure.     

Genome-wide scan for body composition in pigs reveals important role of imprinting

The role of imprinting in body composition was investigated in an experimental cross between Chinese Meishan pigs and commercial Dutch pigs. A whole-genome scan revealed significant evidence for five quantitative trait loci (QTL) affecting body composition, of which four were imprinted. Imprinting was tested with a statistical model that separated the expression of paternally and maternally inherited alleles. For back fat thickness, a paternally expressed QTL was found on Sus scrofa chromosome 2 (SSC2), and a Mendelian-expressed QTL was found on SSC7. In the same region of SSC7, a maternally expressed QTL affecting muscle depth was found. Chromosome 6 harbored a maternally expressed QTL on the short arm and a paternally expressed QTL on the long arm, both affecting intramuscular fat content. The individual QTL explained from 2% up to 10% of the phenotypic variance. The known homologies to human and mouse did not reveal positional candidate genes. This study demonstrates that testing for imprinting should become a standard procedure to unravel the genetic control of multifactorial traits.