Prognostic impact of the simple L-index and absolute lymphocyte count early after allogeneic hematopoietic stem cell transplantation.

BACKGROUND AIMS: The L-index, designed as a quantitative parameter to simultaneously assess the duration and severity of lymphopenia, and absolute lymphocyte count (ALC) have a prognostic impact after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, discrepancies have been reported in the impact of ALC, and limited information is currently available on the L-index. METHODS: To search for a better clinical tool, the authors retrospectively compared the simple L-index at 30 days (sL-index(30)), which aims to make the original L-index more compact, and ALC at 30 days (ALC(30)) after allo-HSCT in 217 patients who underwent allo-HSCT at the authors' institutions. RESULTS: Median sL-index(30) was 11 712 (range, 4419-18 511) and median ALC(30) was 404 (range, 0-3754). In a multivariate analysis, higher sL-index(30) was associated with a significantly higher cumulative incidence of relapse (CIR) (hazard ratio [HR], 1.01, 95% confidence interval [CI], 1.00-1.02, P = 0.02 for every increase of 100 in sL-index(30)) as well as non-relapse mortality (NRM) (HR, 1.02, 95% CI, 1.00-1.03, P = 0.01 for every increase of 100 in sL-index(30)). Although higher ALC(30) was associated with significantly lower CIR (HR, 0.94, 95% CI, 0.89-1.00, P = 0.04 for every increase of 100/µL in ALC(30)), it was not extracted as an independent risk factor for NRM (HR, 0.96, 95% CI, 0.88-1.05, P = 0.39). Higher sL-index(30) was associated with a slightly higher rate of grade 3-4 acute graft-versus-host disease (GVHD) (HR, 1.02, 95% CI, 1.00-1.04, P = 0.12 for every increase of 100 in sL-index(30)) but not chronic GVHD (HR, 1.00, 95% CI, 0.99-1.01, P = 0.63). ALC(30) was not associated with rates of grade 3-4 acute GVHD (HR, 1.02, 95% CI, 0.88-1.17, P = 0.81) or chronic GVHD (HR, 1.02, 95% CI, 0.98-1.06, P = 0.34). In a receiver operating characteristic curve, the cutoff values of sL-index(30) and ALC(30) for CIR were 9000 and 500, respectively, and the cutoff value of sL-index(30) for NRM was 12 000. CONCLUSIONS: sL-index(30) is a promising tool that may be applied to various survival outcomes. A large-scale prospective study is needed to clarify whether medical interventions based on sL-index(30) values will improve the clinical prognosis of patients.

First dorsal interosseous muscle transfer to restore opposition of the new thumb after index pollicization: anatomical description of an original technique and case report.

Index pollicization in severe thumb hypoplasia or aplasia in children or for the reconstruction of a mutilated thumb in adults is a rare and technically demanding procedure. Weakness of the new thumb is routinely reported after index pollicization. An inappropriate position of the first dorsal interosseous muscle (FDIM) can partly explain this strength deficit. Here, we report an original anatomical study on FDIM transfer for reanimation of the new thumb's opposition function and its clinical application. An anatomical study was carried out on three upper limbs from fresh, non-embalmed adult cadavers. We demonstrated the feasibility of an FDIM transfer pedicled on the proper FDIM artery and the deep branch of the ulnar nerve. The proximal FDIM insertions were sutured to the lateral border of the flexor retinaculum to recreate the superficial thenar musculature. This procedure was performed on a 52-year-old man who was referred to us with swelling on his hand. We discovered a myxoid inflammatory fibroblastic sarcoma of the thumb that required proximal thumb amputation while preserving the base of the first metacarpal. To our knowledge, this is the first description of FDIM pedicled flap transfer during an index pollicization procedure among an adult population. However, in severe thumb hypoplasia or aplasia cases, this procedure is limited by the size and anatomical variations of the neurovascular structures among a population affected by radial longitudinal deficiency.

Assessing health-related quality-of-life in patients with symptomatic obstructive hypertrophic cardiomyopathy: EQ-5D-based utilities in the EXPLORER-HCM trial.

AIMS: To assess the effects of mavacamten on health-related quality-of-life (HRQoL) in symptomatic obstructive hypertrophic cardiomyopathy (HCM) and estimate health utilities by New York Heart Association (NYHA) functional class. MATERIALS AND METHODS: Patients with symptomatic obstructive HCM were randomized to 30 weeks of mavacamten or to placebo treatment, with or without beta-blocker or calcium channel blocker monotherapy, in EXPLORER-HCM (ClinicalTrials.gov identifier: NCT03470545). Health utility was measured using the EuroQoL 5-dimension 5-level (EQ-5D-5L) index score with the US value set. The 30-week changes in EQ-5D-5L index score and EuroQoL visual analog scale (EQ-VAS) score were compared between the two arms using linear regression, and the proportions of patients with a meaningful improvement were compared using logistic regression. The meaningful change thresholds were estimated using both distribution- and anchor-based approaches. Mean utilities by NYHA class were estimated for each arm using a generalized estimating equation. RESULTS: Compared with placebo (N = 89), patients receiving mavacamten (N = 96) had significantly greater 30-week improvement in EQ-5D-5L index score (mavacamten = 0.084; placebo = 0.009; adjusted difference = 0.073 [95% confidence interval = 0.027-0.118]) and EQ-VAS score (mavacamten = 8.5; placebo = 0.7; adjusted difference = 7.5 [95% confidence interval = 1.8-13.2]), and a significantly higher proportion of these patients showed meaningful improvement in EQ-5D-5L index score and EQ-VAS score. Both outcomes were correlated with the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS) and HCM Symptom Questionnaire Shortness-of-Breath (HCMSQ SoB) subscore, two patient-reported anchor variables. Additionally, mean utilities significantly decreased with higher NYHA functional class (values for NYHA class I, II, and III/IV - mavacamten = 0.950, 0.866, and 0.708; placebo = 0.952, 0.850, and 0.704). CONCLUSIONS: Compared with placebo, mavacamten significantly improved EQ-5D-5L index score and EQ-VAS score - and thus HRQoL - among patients with symptomatic obstructive HCM. Patients with a higher NYHA functional class had a lower health utility value.

Assessing responsiveness of the EQ-5D-3L, the Oxford Hip Score, and the Oxford Knee Score in the NHS patient-reported outcome measures.

BACKGROUND: The degree to which a validated instrument is able to detect clinically significant change over time is an important issue for the better management of hip or knee replacement surgery. This study examines the internal responsiveness of the EQ-5D-3L, the Oxford Hip Score (OHS), and the Oxford Knee Score (OKS) by various methods. Data from NHS patient-reported outcome measures (PROMs) linked to the Hospital Episodes Statistics (HES) dataset (2009-2015) was analysed for patients who underwent primary hip surgery (N = 181,424) and primary knee surgery (N = 191,379). METHODS: Paired data-specific univariate responsiveness was investigated using the standardized response mean (SRM), the standardized effect size (SES), and the responsiveness index (RI). Multivariate responsiveness was furthermore examined using the defined capacity of benefit score (i.e. paired data-specific MCID), adjusting baseline covariates such as age, gender, and comorbidities in the Box-Cox regression models. The observed and predicted percentages of patient improvement were examined both as a whole and by the patients' self-assessed transition level. RESULTS: The results showed that both the OHS and the OKS demonstrated great univariate and multivariate responsiveness. The percentages of the observed (predicted) total improvement were high: 51 (54)% in the OHS and 73 (58)% in OKS. The OHS and the OKS showed distinctive differences in improvement by the 3-level transition, i.e. a little better vs. about the same vs. a little worse. The univariate responsiveness of the EQ-5D-3L showed moderate effects in total by Cohen's thresholds. The percentages of improvement in the EQ-5D-3L were moderate: 44 (48)% in the hip and 42 (44)% for the knee replacement population. CONCLUSIONS: Distinctive percentage differences in patients' perception of improvement were observed when the paired data-specific capacity of benefit score was applied to examine responsiveness. This is useful in clinical practice as rationale for access to surgery at the individual-patient level. This study shows the importance of analytic methods and instruments for investigation of the health status in hip and/or knee replacement surgery. The study finding also supports the idea of using a generic measure along with the disease-specific instruments in terms of cross-validation.

EQ-5D-5L Bulgarian population norms.

OBJECTIVES: The present study aimed to provide normative data for the EQ-5D-5L questionnaire in Bulgaria, based on a nationally representative sample. METHODS: Random sampling was used. In September 2018, a total of 1005 respondents (aged 18-89 years) completed the self-administered paper-based EQ-5D-5L questionnaire, including a visual analogue scale (EQ VAS). Health state utility index scores were derived using the directly measured Polish value set. RESULTS: The study sample was representative of the general Bulgarian population in terms of age, sex, geographical region, educational level, social and professional status. Mean EQ-5D-5L and EQ VAS values decreased from 0.986 and 89.7 (age group 18-24 years) to 0.789 and 53.6 (age group ≥ 75 years), respectively. Perfect health (the "11,111" health state) was reported by half of the population (50.1%), more often by men than women (55.8% vs 44.9%). The most frequently reported complaints characterised pain/discomfort dimension (39.1%), followed by anxiety/depression (34.5%). Although the least commonly reported health limitations concerned the self-care dimension, their frequency (13.6%) was the highest among the seventeen identified EQ-5D-5L population norm studies. The mean severity index score for the whole study sample was 6.96. EQ-5D-5L index was higher in respondents from lower age groups and with a higher average income per household member. CONCLUSIONS: Bulgarian population norms, which were developed for the descriptive part of the EQ-5D-5L and EQ VAS, can be used as reference values. The availability of such normative data should encourage the use of the EQ-5D-5L questionnaire in health-related quality-of-life studies in Bulgaria.

Prospective validation of the L-index reflecting both the intensity and duration of lymphopenia and its detailed evaluation using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation.

We prospectively validated the previously reported L-index, which reflects both the intensity and duration of lymphopenia, and further evaluated it using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation (HSCT) (n = 30). The L-index was defined as the area over the lymphocyte curve during lymphopenia (<700/µl), and calculated from the start of conditioning to day30 (L-index(30)) and day100 (L-index(100)). The lymphocyte subset including CD3, CD4, CD8, CD19 and CD56 was analyzed before and at 14, 21, 28, 42, 56, 70, and 84 days after HSCT. Cytomegalovirus (CMV) antigenemia was detected as >3 cells/2 slides by the C10/11 method in 21 cases (CMV-AG ≥3 group) at a median of 34 days. L-index(30) was significantly higher in the CMV-AG ≥3 group than in the CMV-AG <3 group (median 20,358 vs 17,235, P = .028). Recovery of the CD4+ and CD56+ cell counts between days 14 and 28 after HSCT was impaired in the CMV-AG ≥3 group. Regarding graft-versus-host disease (GVHD), grade II-IV acute GVHD was identified in 14 patients (GVHD group) at a median of 31 days. L-index(30) was significantly lower in the GVHD group (median 19,048 vs 22,256, P = .043). Recovery of CD3+ cells including both CD4+ and CD8+ cells between days 14 and 28 tended to be better in the GVHD group. In conclusion, L-index(30) was significantly associated with CMV reactivation and grade II-IV acute GVHD, but its clinical significance seemed to differ according to the results of a lymphocyte subset analysis.

Evaluation of L-index interference limits on Roche cobas c502 and c702 immunoturbidimetric assays using endogenously lipemic specimens and intralipid spiking.

OBJECTIVES: Specimen lipemia is a primary concern with turbidimetric and nephelometric assays due the potential interference caused by light scattering or absorption. The purpose of this study was to evaluate lipemic interference thresholds across seven FDA-cleared assays using patient specimens with varying degrees of endogenous lipemia pre- and post-ultracentrifugation (UC) and with Intralipid spiking. METHODS: Using an IRB-approved protocol, residual human serum specimens (n=42; L-indices, 1-1769; H-index ≤85; I-index ≤2) were obtained. Baseline and post-UC testing was conducted across assays on cobas c502 and c702 instruments (Roche Diagnostics; Indianapolis, IN). Serum indices and triglyceride (TRIG) concentrations were also measured pre- and post-UC. Intralipid spiking studies with human AB serum were also conducted. Lipoprotein subfraction analysis (Lipoprint; Quantimetrix; Redondo Beach, CA) was performed on three additional patient specimens with elevated TRIG post-UC to determine which TRIG-containing lipoprotein fraction(s) remain. RESULTS: Several assays showed L-index thresholds derived from endogenously lipemic specimens that were below previously defined limits from the package inserts (PIs) [new (prior)]: AAT 400 (500); CERU 100 (200); HAPTO 450 (600); TRSF 250 (500). L-index limits derived from Intralipid spiking were generally higher than those listed in PIs. UC did not adversely impact results in non-lipemic or lipemic specimens. UC was effective at clearing lipemic interference, although persistence of residual VLDL was often observed. CONCLUSIONS: This study provides an analysis of L-index thresholds for seven immunoturbidimetric assays. Due to the variety of human lipoproteins, limits defined using endogenously lipemic patient specimens may be different from those derived from spiking studies using Intralipid.

Development of a cadaveric training model for pollicization of the index finger.

There are currently no surgical models for learning index finger pollicization. This led us to develop and evaluate a cadaveric model for index finger pollicization. Ten hands from fresh cadavers were used. In each case, we evaluated all the surgical steps, the appearance of the web space, the new thumb's position, and the model's advantages and disadvantages. Flap coverage was insufficient due to poor skin condition in 3 cases and the commissure was too short in 3 cases. The dissection and tendon transfer steps were performed correctly in 9 cases. In one case, the interosseous transfer was too proximal. The new thumb was positioned correctly in 6 cases, too proximally in 3 cases, and was insufficiently rotated in one case. Our model reproduces the haptic characteristics of the surgical procedure and is valuable for dissection and flap coverage training.

ARE HEALTH VISITORS' OBSERVATIONS OF EARLY PARENT-INFANT INTERACTIONS RELIABLE? A CROSS-SECTIONAL DESIGN.

Health visitors need competences to promote healthy early parent-infant relationships. The aims of this study were to explore whether there are differences between groups of health visitors with and without additional parenting program education in terms of their knowledge of infant-parent interaction and their observation and assessment skills of such interactions. The cross-sectional study included 36 health visitors' certified Marte Meo therapists and 85 health visitors without additional parenting program education. Health visitors' observation skills were measured assessing five video-recorded mother-infant interactions. A questionnaire was used to measure their intention, self-efficacy, and knowledge. More certified Marte Meo therapists than health visitors without additional parenting program education reported a significantly higher mean level of knowledge of the early relationship, 6.42 (95% CI; 6.18-6.66) versus 5.05 (95% CI; 4.86-6.10), p = .04; and more certified Marte Meo therapists than health visitors without additional parenting program education reported a higher mean level of knowledge of infant self-regulation, 2.44 (95% CI; 2.18-2.71) versus 1.83 (95% CI; 1.62-2.03), p < .001. In the latter group, 54% (95% CI; 0.43-0.64) reported a significantly higher need for further education versus 22% (95% CI; 0.11-0.39), p = .001. Compared to health visitors without any parenting program education, health visitors certified as Marte Meo therapists reported a significantly higher frequency of correct assessment of mothers' sensitivity in two of five video-recordings, with 77.78% (95% CI; 0.61-0.87) compared to 45.88% (95% CI; 0.35-0.57) in Video 3, p = .001, and 69.44% (95% CI; 0.52-0.82) compared to 49.41% (95% CI; 0.39-0.60) in Video 4, p = .04, respectively. The results of the present study support the use of video-based education of health visitors to increase their knowledge of and skills in assessing parent-infant interactions. Randomized controlled trials are needed to determine whether the improved level of health visitors' knowledge and observation skills may be assigned to participation in the Marte Meo education program.

Active extensor indicis proprius extension strength after its use as a tendon transfer: 19 cases.

Complications following extensor indicis proprius (EIP) tendon transfer are loss of strength, independence and mobility in the index finger in extension. The main goal of this study was to measure the index finger's independent and dependent extension strength after a tendon transfer. Secondary goals were to determine if the index finger retained the ability to extend independently after the transfer and to evaluate second metacarpophalangeal (MCP) joint mobility. Our study consisted of 19 patients in whom the EIP tendon had been divided proximally to the extensor hood. The EIP tendon was retrieved through a proximal approach at the distal radius level and rerouted towards a recipient tendon. At an average follow-up of 41 months, the average independent extension strength was 5.6N versus 11N on the contralateral side and the dependent strength was 10.9N versus 20N. No patient complained of a loss of extension strength and all had retained independent active extension on the operated index finger. The second MCP joint on the operated side had an independent extension lag of 15.3° compared to the contralateral healthy side and a dependent extension lag of 0.2°. Two patients were impaired in their daily activities when moving the operated index finger. Our results show that EIP harvesting for tendon transfer leads to decreased independent and dependent strength as well as decreased active extension of the second MCP joint. However, the functional impact was negligible and should not compromise the use of the EIP as a tendon transfer. LEVEL OF EVIDENCE: III.

Impact of D-index and L-index on pulmonary infection in induction chemotherapy for acute lymphoblastic leukemia and lymphoblastic lymphoma.

OBJECTIVES: The D-index and the L-index, calculated as the area over the neutrophil and lymphocyte curves, respectively, reflect both the intensity and duration of cytopenia. We, retrospectively, investigated the impact of these indexes on pulmonary infection (PI) in induction chemotherapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). METHODS: We included 92 patients (ALL 83, LBL 9) from two institutions. We calculated the D-index and cumulative D-index until the development of PI (c-D-index), which enables real-time risk assessment for infection. We also calculated the L-index (35), defined as the area over the lymphocyte curve during lymphopenia (<700/µl) until day 35 and the cumulative-L-index until the development of PI (c-L-index). RESULTS: Eight patients developed PI on day 20 (median). Two patients were strongly suspected to have bacterial pneumonia, and the others were suspected to have pulmonary fungal infection. The D-index and the L-index (35) in patients with PI were higher than those in patients without PI (7230 ± 4734 vs. 4519 ± 3416, P = 0.041 and 15 458 ± 5243 vs. 8920 ± 5901, P = 0.018), while the c-D-index and the c-L-index were not significantly different. Although the c-L-index did not have predictive value for PI, c-D-index, when treated as a dichotomous variable with a cutoff value of 5589 as determined by a receiver operating characteristic curve analysis, showed a significant difference between two groups (P = 0.045). This association became clearer when we focused on suspected pulmonary fungal infection. DISCUSSION AND CONCLUSION: In induction chemotherapy for ALL/LBL, c-D-index with a cutoff value of 5589 might have predictive value for the development of PI.