Key Points• In SCD, recurrent vasoocclusive crisis suppresses osteogenic lineage and activates osteoclasts.• Zoledronic acid acting on both osteoclast and osteoblast compartments is a multimodal therapy to prevent SBD.Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects a large part of the SCD patient population, and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in a humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment, with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL), and osteoclast recruitment (Rank) with upregulation of IL-6 as proresorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). To interfere with the development of SBD, zoledronic acid (Zol), a potent inhibitor of osteoclast activity/ osteoclastogenesis and promoter of osteogenic lineage, was used in H/R-exposed mice. Zol markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc), and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared with either normoxic or single-H/R-episode SCD mice. Zol used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment, and increased osteoclast activity resulted from local hypoxia, oxidative stress, and the release of proresorptive cytokine such as IL-6. Zol might act on both the osteoclast and osteoblast compartments as multimodal therapy to prevent SBD. (Blood. 2015;126(20):2320-2328 IntroductionSickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, which affects approximately 75 000 individuals in the United States and almost 20 000 to 25 000 individuals in Europe, this latter mainly related to the immigration fluxes from endemic areas such as Sub-Saharan Africa to European countries.1-3 Studies of the global burden of disease have pointed out the invalidating impact of SCD on patient quality of life.2 This requires the development of new therapeutic options to treat sickle cell-related acute and chronic complications.SCD is caused by a point mutation in the b-globin gene resulting in the synthesis of pathologic hemoglobin S (HbS). HbS displays peculiar biochemical characteristics, polymerizing when deoxygenated with associated reduction in cell ion and water content (cell dehydration), increased red cell density, and further acceleration of HbS polymerization. [4][5][6] Pathophysiologic studies have shown that dense, dehydrated red cells play a central role in acute and chronic clinical manifestations of ...

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Intracranial subdural hematoma following spinal anesthesia is an infrequent occurrence in the obstetric population. Nevertheless, it is a potentially life-threatening complication. In the majority of the cases, the first clinical symptom associated with intracranial subdural bleeding is severe headache, but the clinical course may have different presentations. In this report, we describe the case of a 38-year-old woman with an acute intracranial subdural hematoma shortly after spinal anesthesia for cesarean section. Early recognition of symptoms of neurologic impairment led to an emergency craniotomy for hematoma evacuation with good recovery of neurologic functions. The possibility of subdural hematoma should be considered in any patient complaining of severe persistent headache following regional anesthesia, unrelieved by conservative measures. Only early diagnosis and an appropriate treatment may avoid death or irreversible neurologic damage.

BackgroundMuscular fatigue and injury are frequently observed in critically ill COVID-19 patients. The aim of this study was to determine whether different muscle adipose tissue depots are associated with mortality and muscle damage in patients affected by COVID-19 admitted to the ICU.MethodsCT images were obtained in 153 ICU patients with COVID-19 (121 males and 32 females). Height, weight, body mass index (BMI), C-reactive protein, Creatine PhosphoKinase (CPK), muscle density, and intermuscular adipose tissue (IMAT) were measured.ResultsParticipants in the highest tertile of IMAT/muscle had the shorter 28-day survival from ICU admission as compared to subjects in the first tertile. Estimates derived from the Cox proportional hazard models, after adjustment for age, sex, and BMI, confirmed the results of the survival analysis (HR 3.94, 95% CI: 1.03–15.09). Participants in the lowest tertile of muscle density had the shorter survival at 28 days from ICU admission as compared to subjects in the highest tertile (HR 3.27, 95% CI: 1.18–4.61), but the relationship was no longer significant when age was included in the model. Subjects in the second muscle density tertile did not show an increased risk.Participants in the highest tertile of IMAT/muscle and those in the lowest tertile of muscle density showed both significantly higher CPK adjusted for weight values as evaluated during the first 8 days of hospitalization.ConclusionOur data seem to suggest that higher levels of IMAT/muscle and low muscle density are both associated with higher risk of ICU mortality and muscle injury as evaluated with CPK level.

Hemiplegic shoulder pain is the most common pain condition after stroke. Suprascapular nerve block is an effective treatment for shoulder pain. The aim of this pilot study was to evaluate the effects of suprascapular nerve block on pain intensity, spasticity, shoulder passive range of motion, and quality of life in long-term chronic stroke patients with hemiplegic shoulder pain. Ten chronic stroke patients (over 2 years from onset) with hemiplegic shoulder pain graded ≥30 mm on the Visual Analogue Scale underwent suprascapular nerve block injection with 1 mL of 40 mg/mL methylprednisolone and 10 mL 0.5% bupivacaine hydrochloride. Main outcome was the Visual Analogue Scale evaluated before and after nerve block at 1 h, 1 week, and 1 month. Secondary outcomes were the modified Ashworth scale and the shoulder elevation, abduction, and external rotation passive range of motion evaluated before the nerve block and after 1 h as well as the American Chronic Pain Association Quality of Life Scale evaluated before and after nerve block at 1 month. The Visual Analogue Scale significantly improved after nerve block at 1 h (P = 0.005) and 1 week (P = 0.011). Significant improvements were found at 1 h after nerve block in the modified Ashworth scale (P = 0.014) and the passive range of motion of shoulder abduction (P = 0.026), flexion (P = 0.007), and external rotation (P = 0.017). The American Chronic Pain Association Quality of Life Scale significantly improved at 1 month after nerve block (P = 0.046). Our findings support the use of suprascapular nerve block for treating hemiplegic shoulder pain in long-term chronic stroke patients.

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.

Long-term opioid therapy may be associated with analgesic efficacy and also predictable adverse events, including cardiovascular and pulmonary events, gastrointestinal disorders, endocrinological harms, psychological problems, impairment of driving ability, and risk of abuse. These effects of opioids are mostly due to the wide expression of the mu receptor. Tapentadol, a centrally acting analgesic, is the first agent of a new class of drugs (MOR-NRI), since it combines two mechanisms of action, namely µ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. Noteworthy, MOR activation with tapentadol is markedly lower compared with that exerted by classical opioids, thus likely resulting in fewer opioid-related adverse effects. In this review, we discuss current safety data on tapentadol, with a focus on some specific events, risk of abuse, and driving ability, a well-accepted proxy of the ability of taking critical decisions.