Disability and quality of life in individuals with postpolio syndrome

Purpose : The purpose of the study is to investigate disability and quality of life in individuals with the characteristic symptoms of postpolio syndrome. Method : Disability is assessed by means of the self-report activities of daily living instrument, and quality of life by means of Kaasa's questionnaire and the quality of life profile. Results : The 39 subjects have on average lived with polio sequelae for 52 years. Their main difficulties are with moving, lifting and carrying. This means restricted mobility, sedentary activities and a need to prioritize. Half of them feel that polio has lessened their possibilities in life, and a quarter have still not accepted the limitations polio has involved. Nevertheless the majority report a high level of psychosocial well-being, and almost a quarter say that living with polio has meant personal development and strength. We found a significant correlation between on the one hand disability with regard to ambulation, arm strength and finger strength on the self-report ADL, and on the other hand the number of negative problems on the quality of life profile (0.33-0.45). Conclusion : The latter instrument needs further testing before its validity can be determined with certainty.     

Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status

We recently reported that Swedish V_H3-21-using chronic lymphocytic leukemia (CLL) patients showed restricted immunoglobulin gene features and poor prognosis despite V_H mutation status. To investigate this further, we analyzed the V_H and V_L gene rearrangements in 90 V_H3-21⁺ patients from Sweden, Germany, Italy, United States, Finland, and Australia and correlated these data with survival and other prognostic markers. Sixty-three percent exhibited mutated V_H genes and 37% unmutated V_H genes. Fifty (56%) patients displayed a short and homologous heavy-chain CDR3, many of these with the amino acid motif DANGMDV. Also, a highly biased V2-14 use was evident in 72% of patients with a restricted light-chain CDR3, QVWDS(S/G)SDHPWV. Combined restricted heavy- and light-chain CDR3s were found in patients from all included countries. Although V_H3-21⁺ CLLs have a remarkably predominant expression, analyses of kappa deleting element indicated a conserved light-chain rearrangement order. The overall survival was poor in the V_H3-21⁺ cohort (median survival, 88 months), with no significant difference in relation to mutation status or CDR3 homology. High ZAP-70 and CD38 expression was found in both mutated and unmutated V_H3-21⁺ cases as well as a slight increase of 11q-aberrations. In summary, highly restricted B-cell receptors and worse outcome characterize V_H3-21⁺ CLLs independent of geographic origin and mutation status.      

Back pain is also improved by lumbar disc herniation surgery

Background and purpose — Indication for lumbar disc herniation (LDH) surgery is usually to relieve sciatica. We evaluated whether back pain also decreases after LDH surgery.Patients and methods — In the Swedish register for spinal surgery (SweSpine) we identified 14,097 patients aged 20–64 years, with pre- and postoperative data, who in 2000–2016 had LDH surgery. We calculated 1-year improvement on numeric rating scale (rating 0–10) in back pain (N_back) and leg pain (N_leg) and by negative binomial regression relative risk (RR) for gaining improvement exceeding minimum clinically important difference (MCID).Results — N_leg was preoperatively (mean [SD]) 6.7 (2.5) and N_back was 4.7 (2.9) (p < 0.001). Surgery reduced N_leg by mean 4.5 (95% CI 4.5–4.6) and N_back by 2.2 (CI 2.1–2.2). Mean reduction in N_leg) was 67% and in N_back 47% (p < 0.001). Among patients with preoperative pain ≥ MCID (that is, patients with significant baseline pain and with a theoretical possibility to improve above MCID), the proportion who reached improvement ≥ MCID was 79% in N_leg and 60% in N_back. RR for gaining improvement ≥ MCID in smokers compared with non-smokers was for N_leg 0.9 (CI 0.8–0.9) and ­N_back 0.9 (CI 0.8–0.9), and in patients with preoperative duration of back pain 0–3 months compared with > 24 months for N_leg 1.3 (CI 1.2–1.5) and for N_back 1.4 (CI 1.2–1.5).Interpretation — LDH surgery improves leg pain more than back pain; nevertheless, 60% of the patients with significant back pain improved ≥ MCID. Smoking and long duration of pain is associated with inferior recovery in both N_leg and N_back.

The most common indication for lumbar disc herniation (LDH) surgery is persistent sciatica that does not respond to nonoperative treatment (Blamoutier 2013). However, most patients who undergo LDH surgery also suffer from back pain (Hakkinen et al. 2003, Stromqvist et al. 2017), on a national level reported in 93% of patients having LDH surgery (Stromqvist et al. 2017). Decades ago, Mixter (1937) therefore argued that LDH extirpation should be accompanied by fusion to minimize postoperative back pain. Recent studies have opposed this view, showing that LDH surgery is not followed by increased back pain when only removing the hernia (Pearson et al. 2008, Owens et al. 2018), and in many cases even improvement of back pain seems sustainable over time.Most studies that evaluate the outcome of LDH surgery focus on the relief from sciatica and improvement in patient-reported outcome measures (PROMs) (Weber 1983, Atlas et al. 2005, Peul et al. 2007, Weinstein et al. 2008, Lurie et al. 2014). A few studies have focused on back pain or included back pain in the evaluation (Kotilainen et al. 1993, Hakkinen et al. 2003, Toyone et al. 2004, Atlas et al. 2005, Pearson et al. 2008, Owens et al. 2018). While some of these infer that back pain is improved by the LDH surgery (Hakkinen et al. 2003, Toyone et al. 2004, Pearson et al. 2008, Owens et al. 2018) others report inconclusive results (Kotilainen et al. 1993, Atlas et al. 2005). There is a lack of consensus on the expected level of back pain reduction with LDH surgery.It would also be of clinical interest to identify preoperative factors that are associated with favorable reduction of back pain following LDH surgery such as age, sex, smoking, preoperative health, and duration of pain (Nygaard et al. 2000, Jansson et al. 2005, Stromqvist et al. 2016, Wilson et al. 2016, Hareni et al. 2019).We (i) evaluated whether back pain is reduced after LDH surgery and if so, to what extent compared with the reduction in leg pain and (ii) what proportion of patients gain improvement in back and leg pain exceeding minimum clinically important difference (MCID). The secondary aim was to identify factors associated with improvement in back pain exceeding MCID.      

The allogeneic graft-versus-cancer effect

Allogeneic haematological stem cell transplantation (HSCT) has developed into immunotherapy. Donor CD4⁺, CD8⁺ and natural killer (NK) cells have been reported to mediate graft- versus -leukaemia (GVL) effects, using Fas-dependent killing and perforin degranulation to eradicate malignant cells. Cytokines, such as interleukin-2, interferon-γ and tumour necrosis factor-α potentiate the GVL effect. Post-transplant adoptive therapy of cytotoxic T-cells (CTL) against leukaemia-specific antigens, minor histocompatibility antigens, or T-cell receptor genes may constitute successful approaches to induce anti-tumour effects. Clinically, a significant GVL effect is induced by chronic rather than acute graft- versus -host disease (GVHD). An anti-tumour effect has also been reported for myeloma, lymphoma and solid tumours. Reduced intensity conditioning enables HSCT in older and disabled patients and relies on the graft- versus -tumour effect. Donor lymphocyte infusions promote the GVL effect and can be given as escalating doses with response monitored by minimal residual disease. A high CD34⁺ cell dose of peripheral blood stem cells increases GVL. There is a balance between effective immunosuppression, low incidence of GVHD and relapse. For instance, T-cell depletion of the graft increases the risk of relapse. This paper reviews the current knowledge in graft- versus -cancer effects. Future directions, such as immunotherapy using leukaemia-specific CTLs, allo-depleted T-cells and suicide gene manipulated T-cells, are presented.     

Biomarkers of liver fibrosis: prospective comparison of multimodal magnetic resonance,serum algorithms and transient elastography

Abstract

Background and aims

Accurate biomarkers for quantifying liver fibrosis are important for clinical practice and trial end-points. We compared the diagnostic performance of magnetic resonance imaging (MRI), including gadoxetate-enhanced MRI and ³¹P-MR spectroscopy, with fibrosis stage and serum fibrosis algorithms in a clinical setting. Also, in a subset of patients, MR- and transient elastography (MRE and TE) was evaluated when available.     

Muscle energy metabolism in severe chronic congestive heart failure--effect of treatment with enalapril.

By using biopsies, skeletal muscle metabolism was investigated in 22 patients with severe chronic heart failure. All the patients were in New York Heart Association functional class IV and constituted a subgroup of the previously published CONSENSUS trial. After this initial investigation of muscle metabolism in patients with chronic heart failure, the influence of the angiotensin converting enzyme inhibitor, enalapril, on skeletal muscle metabolism was studied by randomizing the patients in a double-blind manner to receive either placebo (n = 11) or enalapril (n = 11) in addition to conventional treatment. At the time of inclusion, the muscle content of energy-rich compounds, i.e. glycogen and the high energy phosphates, adenosine triphosphate (ATP) and phosphocreatine, was reduced as compared with healthy subjects and muscle lactate content tended to be higher than normal. Following study treatment, no significant changes occurred, neither within nor between the two subgroups. Thus, patients with severe chronic congestive heart failure display metabolic derangement in muscle, which, in this study, was not corrected by treatment with enalapril.     

Adrenocorticotropin and corticotropin-releasing hormone tests in preterm infants

The short ACTH test is used in evaluating the hypothalamo-pituitary-adrenal axis (HPA-axis) in preterm neonates after dexamethasone treatment. This test mainly examines primary adrenal suppression but is also used as a method to test secondary adrenal insufficiency because long-term deprivation of ACTH causes atrophy of the adrenal cortex. The CRH test, on the other hand, directly examines the function of the pituitary. We tested 18 infants in the neonatal intensive care unit with both the ACTH test and the CRH test to determine which of these two tests more reliably demonstrates HPA-axis suppression. One patient had normal responses both in the ACTH test and in the CRH test when the limit of 360 nmol/L was used as a sign of proper cortisol secretion. In four cases the patients' cortisol secretion would have been regarded as normal by the low-dose ACTH test, whereas the CRH test did not show an adequate cortisol response. In conclusion, the ACTH test did not reliably indicate HPA-axis suppression after a short (<2 weeks) course of dexamethasone therapy in this study. Therefore, whether the infant is or will be under acute stress after short glucocorticoid treatment, ensuring adequate cortisol secretion with the CRH test should be considered.