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.      

Dopamine D2 Modulation of Sign and Goal Tracking in Rats

In Pavlovian conditioning, sign- and goal-tracking behaviors represent different approaches towards the conditioned stimulus. These behavioral patterns have been associated with predictive or incentive properties of the conditioned stimulus, with a crucial involvement of the mesolimbic dopamine system. As it is possible that sign tracking behavior is more sensitive to dopamine modulation, we evaluated the dopamine-dependence of sign- and goal-tracking behavior. We assessed responses to both a D2 agonist and an antagonist, and tested performance in a behavioral paradigm known to activate dopamine projections and in an animal model that affects mesolimbic and mesocortical function. Sign trackers displayed a greater sensitivity to a D2 agonist and smaller prepulse inhibition of the acoustic startle response than goal trackers, suggesting a reduced inhibitory ability. In addition, a neonatal ventral hippocampal lesion resulted in the loss of incentive salience of cues in sign trackers. Overall, these data indicate that sign-tracking behavior is more heavily controlled by dopamine than goal tracking.     

Influenza Virus Infection in Nonhuman Primates

To determine whether nonhuman primates are infected with influenza viruses in nature, we conducted serologic and swab studies among macaques from several parts of the world. Our detection of influenza virus and antibodies to influenza virus raises questions about the role of nonhuman primates in the ecology of influenza.     

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.     

Human burst-forming units-erythroid need direct interaction with stem cell factor for further development

To understand the factors that regulate the early growth and development of immature erythroid progenitor cells, the burst-forming units-erythroid (BFU-E), it is necessary to have both highly purified target cells and a medium free of serum. When highly purified human blood BFU-E were cultured in a serum-free medium adequate for the growth of later erythroid progenitors, BFU-E would not grow even with the addition of recombinant human interleukin-3 (rIL-3), known to be essential for these cells. However, the addition of recombinant human stem cell factor (rSCF), which supports germ cell and pluripotential stem cell growth, stimulated BFU-E to grow equally well in serum-free as in serum-containing medium. Limiting dilution studies showed that rSCF acts directly on the BFU-E that do not require accessory cells for growth. Furthermore, rSCF was necessary for BFU-E development during the initial 7 days of culture, until these cells reached the stage of the late progenitors, the colony-forming units-erythroid (CFU-E). These studies indicate that early erythropoiesis is dependent on the direct action of SCF that not only affects early stem cells but is continually necessary for the further development of committed erythroid progenitor cells until the CFU-E stage of maturation.