Off-label Use of Secukinumab: A Potential Therapeutic Option for SAPHO Syndrome

We read the recent article by Wang et al with great interest.1 The authors described a cohort of 4 patients with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome who showed substantial improvement in skin lesions, clinical conditions, and whole-body magnetic resonance imaging before and after treatment with secukinumab without concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), nonsteroidal antiinflammatory drugs (NSAIDs), or other biologics, and suggested a potential benefit of secukinumab in the treatment of SAPHO syndrome. However, there are some details that need further clarification.

Nonsteroidal antiinflammatory drugs versus tramadol in pain management following transsphenoidal surgery for pituitary adenomas: a randomized, double-blind, noninferiority trial

OBJECTIVE Opioid-minimizing or nonopioid therapy using nonsteroidal antiinflammatory drugs (NSAIDs) or tramadol has been encouraged for pain management. This study aimed to examine the noninferiority of NSAIDs to tramadol for pain management following transsphenoidal surgery for pituitary adenomas in terms of analgesic efficacy, adverse events, and rescue opioid use. METHODS This was a randomized, single-center, double-blind noninferiority trial. Patients 18–70 years old with planned transsphenoidal surgery for pituitary adenomas were randomly assigned (in a 1-to-1 ratio) to receive NSAIDs (parecoxib injection and subsequent loxoprofen tablets) or tramadol (tramadol injection and subsequent tramadol tablets). The primary outcome was pain score assessed by a visual analog scale (VAS) for 24 hours following surgery; the secondary outcomes were VAS scores for 48 and 72 hours. Other prespecified outcomes included nausea, vomiting, dizziness, upset stomach, skin rash, peptic ulcer, gastrointestinal bleeding, and pethidine use to control breakthrough pain. Noninferiority of NSAIDs to tramadol was established if the upper limit of the 95% confidence interval (CI) of the VAS score difference was < 1 point and the rate difference of adverse events and pethidine use < 5%. The superiority of NSAIDs was assessed when noninferiority was verified. All analyses were performed on an intention-to-treat basis. RESULTS Two hundred two patients were enrolled between November 1, 2020, and May 31, 2021 (101 in the NSAIDs group, 101 in the tramadol group). Baseline characteristics between groups were well balanced. Mean VAS scores for 24 hours following transsphenoidal surgery were 2.6 ± 1.8 in the NSAIDs group and 3.5 ± 2.1 in the tramadol group (−0.9 difference, 95% CI −1.5 to −0.4; p value for noninferiority < 0.001, p value for superiority < 0.001). Noninferiority and superiority were also achieved for both secondary outcomes. VAS scores improved over time in both groups. Incidences of nausea (39.6% vs 61.4%, p = 0.002), vomiting (3.0% vs 42.6%, p < 0.001), and dizziness (12.9% vs 47.5%, p < 0.001) were significantly lower, while incidence of upset stomach (9.9% vs 2.0%, p = 0.017) was slightly higher in the NSAIDs group compared with the tramadol group. The percentage of opioid use was 4.0% in the NSAIDs group and 15.8% in the tramadol group (−11.8% difference, 95% CI −19.9% to −3.7%; p value for noninferiority < 0.001, p value for superiority = 0.005). CONCLUSIONS NSAIDs significantly reduced acute pain following transsphenoidal surgery, caused few adverse events, and limited opioid use compared with tramadol.

Two-year results of clinical use of arthromedullary bypass for knee osteoarthritis

BACKGROUND: With the ineffectiveness of conservative therapy for the knee joints osteoarthritis (OA), arthroscopic debridement (AD) of the affected joints is a common method of surgical treatment. However, the results of studies indicate a low efficiency of the use of AD in gonarthrosis. In order to improve the results of the use of AD in the knee joints OA, it was proposed to use an original implant to communicate the bone marrow cavity and the cavity of the knee joint. In the immediate postoperative period, such arthromedullary bypass surgery revealed a rapid improvement in the condition of the affected joints, a decrease in the severity of symptoms, and a decrease in the need for pain relievers. AIM: To compare the results of arthroscopic surgery in patients with knee osteoarthritis without and with the use of arthromedullary bypass (AMB) of joint at 2 years after the intervention. MATERIALS AND METHODS: The results of a comparative study involving 147 patients aged 42 to 80 years with knee osteoarthritis were presented. In the control group (67 patients), only arthroscopic debridement was performed; in the study group (80 patients, 90 operations) AMB was additionally performed (10 patients on both knee joints) for the entry of an intraosseous content into the joint cavity. The results were evaluated 3, 6, 12, and 24 months after surgery, using the Lequesne algofunctional index and the WOMAC index and the need for the nonsteroidal antiinflammatory drugs (NSAID) was assessed. RESULTS: The positive dynamics of both indicators in both groups during the first 3 months of follow-up was maintained for 24 months, and their more significant changes, as well as a decrease in stiffness and the frequency of nocturnal joint pain, occurred in the study group (p 0.01). 24 months after surgery, 87% of patients in the study group refused to take regular NSAID, and 54% in the control group (p 0.01). During the AMB, the percentage of operations with unsatisfactory and moderate results decreased by 2.53.5 times, and the percentage of cases with good and excellent results was 28% higher compared to the control group (p 0.01). СONCLUSIONS: The proposed AMB of joints had a long-term beneficial effect and is promising for the treatment of patients with knee osteoarthritis who do not respond to conservative treatment. Its use can improve joint function, reduce joint pain and dependence on analgesics, and thus ease the severity of the disease in more patients.

A comparative study between the effect of Aminophylline, Neostigmine and Gabapentin on prevention of post dural puncture headache after cesarean section

Objectives Post dural puncture headache (PDPH), since it is first described by August Bier in 1898, remains a common complication in spinal anesthesia (SA). Many pharmacological agents are suggested for PDPH management as acetaminophen, caffeine, non-steroidal antiinflammatory drugs, corticosteroids, and sumatriptan. Aim The aim of this study is to compare between the prophylactic effect of each of; aminophylline, gabapentin, and neostigmine added to atropine on the occurrence of PDPH after caesarean section (CS) under SA. Subjects and Methods This prospective randomized controlled clinical study was carried out 75 pregnant female patients 20-40 y, 60-100 kg. ASA physical status II undergoing elective CS. Patients were randomly divided into 3 groups (25 patients in each); group A: received 250 mg aminophylline IV immediately after delivery of the infant, group B: received IV neostigmine 20 µg/kg added to atropine 10 µg/kg immediately after delivery of the infant and group C: received 3 capsules gabapentin 300 mg; the 1st before SA by 2 h with sip of water, the 2nd after CS by 6 h and the 3rd after 14 h from CS. Results The incidence of PDPH was lower in group A (8% vs 40% in group B and 24% in group C. The onset of PDPH was significantly delayed in group C than group A and in group C than B, but insignificant between group A and B. The duration of PDPH and total dose of analgesic requirement was significantly lower in group A than group B and C and in group B than C. Heart rate (HR) showed significant increase in group A (post aminophylline than pre) only. HR in the other groups and mean arterial blood pressure showed insignificant difference among the three groups (between pre and post administration of drugs). As regards VAS, there was no significant difference in the three groups at 3 h. There was significant difference among the three groups at 6, 12, 24, 36, 48 and 72 h. (between group A & B from 24h up to 72h, between group A & C from 6 up to 72h and between group B & C at 6 h only (delayed onset with neostigmine)). Side effects were minimal and tolerable. Conclusion Aminophylline reduced the incidence and duration of PDPH after CS under SA more than gabapentin and neostigmine with less analgesic requirement and minimal side effects. Also, neostigmine was superior than gabapentin in delaying the onset and decreasing the duration of PDPH.

Management of risk factors for gastrointestinal bleeding in patients receiving anticoagulant therapy

Direct oral anticoagulants (DOACs) are used to prevent and treat thrombosis and thromboembolic events in patients with various diseases. Despite its high efficacy and safety, DOAC therapy is accompanied by increased risk of hemorrhage, including gastrointestinal bleeding. Bleeding risk depends on individual patient profile and their risk factors. An increased risk of bleeding is associated with manifesting effect of DOACs on existing mucosal defects, active Helicobacter pylori infection. To reduce the risk of gastrointestinal bleeding in clinical practice, changing of following modifiable risk factors is required: H. pylori eradication; dose-adjusted DOAC therapy; prophylactic proton pump inhibitors (PPIs) administration to patients with HAS-BLED score ≥3, receiving dual or triple antithrombotic therapy, taking DOACs in combination with non-steroidal antiinflammatory drugs, to those with upper gastrointestinal diseases. In addition to PPIs, patients may be prescribed with rebamipide, bismuth tripotassium dicitrate, ursodeoxycholic acid. DOAC rivaroxaban (Xarelto®) has pharmacokinetic and pharmacodynamic advantages, a convenient single dosing regimen and a favorable safety profile, which provides effective protection against thrombosis and thromboembolic events in combination with low risk of gastrointestinal bleeding.

Bromodomain containing 9 (BRD9) regulates macrophage inflammatory responses by potentiating glucocorticoid receptor activity

In macrophages, homeostatic and immune signals induce distinct sets of transcriptional responses, defining cellular identity and functional states. The activity of lineage-specific and signal-induced transcription factors are regulated by chromatin accessibility and other epigenetic modulators. Glucocorticoids are potent antiinflammatory drugs; however, the mechanisms by which they selectively attenuate inflammatory genes are not yet understood. Acting through the glucocorticoid receptor (GR), glucocorticoids directly repress inflammatory responses at transcriptional and epigenetic levels in macrophages. A major unanswered question relates to the sequence of events that result in the formation of repressive regions. In this study, we identify bromodomain containing 9 (BRD9), a component of SWI/SNF chromatin remodeling complex, as a modulator of glucocorticoid responses in macrophages. Inhibition, degradation, or genetic depletion of BRD9 in bone marrow-derived macrophages significantly attenuated their responses to both liposaccharides and interferon inflammatory stimuli. Notably, BRD9-regulated genes extensively overlap with those regulated by the synthetic glucocorticoid dexamethasone. Pharmacologic inhibition of BRD9 potentiated the antiinflammatory responses of dexamethasone, while the genetic deletion of BRD9 in macrophages reduced high-fat diet-induced adipose inflammation. Mechanistically, BRD9 colocalized at a subset of GR genomic binding sites, and depletion of BRD9 enhanced GR occupancy primarily at inflammatory-related genes to potentiate GR-induced repression. Collectively, these findings establish BRD9 as a genomic antagonist of GR at inflammatory-related genes in macrophages, and reveal a potential for BRD9 inhibitors to increase the therapeutic efficacies of glucocorticoids.

Odontological Drugs and Their Action on Some Biological Organisms

Odontology is the study of teeth, of theirs diseases and treatment of these. Many odontological drugs are commonly used in dental practice. Antibiotics are indicated for the treatment of odontogenic infections, oral non-odontogenic infections, as prophylaxis against focal infection, and as prophylaxis against local infection and spread to neighboring tissues and organs. In addition to antibiotic, antifungals (drugs for classes azoles, imidazoles and polyenes), antiviral such as antimicrobial mouthwashes and nucleases inhibitors are also indicated for the treatment. These drugs prescription is almost invariably associated with the prescription of Nonsteroidal Antiinflammatory Drugs (NSAIDs), topical corticoids, local anaesthesic for odontological pain and/or Sodium Fluoride for dental caries. Odontalogical drugs act on several levels of metabolism either of microorganisms’ constitutive material (e.g. wall, membrane, cytoplasm and nuclear materials for antibiotics, antivirals, antifungals and oxidizing substances) to destroys them or of humans system cells (receptors, enzymes, hormones for painful, inflammation, local anaesthesic and dental building drugs) to inhibit or stimulate them for the best functioning.

The secret identities of TMPRSS2: Fertility factor, virus trafficker, inflammation moderator, prostate protector and tumor suppressor

The human TMPRSS2 gene is pathogenetically implicated in both coronaviral lung infection and prostate cancer, suggesting its potential as a drug target in both contexts. SARS-COV-2 spike polypeptides are primed by the host transmembrane TMPRSS2 protease, triggering virus fusion with epithelial cell membranes followed by an endocytotic internalisation process that bypasses normal endosomal activation of cathepsin-mediated innate immunity; viral co-opting of TMPRSS2 thus favors microbial survivability by attenuating host inflammatory responses. In contrast, most early hormone-dependent prostate cancers express TMPRSS2:ERG fusion genes arising from deletions that eliminate the TMPRSS2 coding region while juxtaposing its androgen-inducible promoter and the open reading frame of ERG, upregulating pro-inflammatory ERG while functionally disabling TMPRSS2. Moreover, inflammatory oxidative DNA damage selects for TMPRSS2:ERG-fused cancers, whereas patients treated with antiinflammatory drugs develop fewer of these fusion-dependent tumors. These findings imply that TMPRSS2 protects the prostate by enabling endosomal bypass of pathogens which could otherwise trigger inflammation-induced DNA damage that predisposes to TMPRSS2:ERG fusions. Hence, the high oncogenic selectability of TMPRSS2:ERG fusions may reflect a unique pro-inflammatory synergy between androgenic ERG gain-of-function and fusogenic TMPRSS2 loss-of-function, cautioning against the use of TMPRSS2-inhibitory drugs to prevent or treat early prostate cancer.

Satisfaction with analgesic therapy in patients with rheumatic diseases in real clinical practice, according to the KOMPAS study (Quality of Pain Relief in the Opinion of Patients with Arthritis and Back Pain)

Patient's satisfaction with treatment is a fundamental indicator of the quality of medical care, which is especially important for assessing the effectiveness of therapy for musculoskeletal pain in rheumatic diseases (RD).Objective: to determine satisfaction of patients with RD with pain relief therapy and to analyze the factors influencing the subjective assessment of analgesic therapy.Patients and methods. Anonymous survey of 1040 patients (age 55.8±14.0 years, 76.8% were women) with RD, rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthritis, systemic connective tissue diseases and gout, was carried out. The presence of pain and its therapy, satisfaction with treatment, and patient's opinion about the reasons of low pain relief effectiveness were assessed. The dependence of the presence of dissatisfaction with treatment on a number of demographic and clinical factors was analyzed.Results and discussion. 71.5% of patients experienced pain in one or more joint areas and/or in the back. 70.6% of patients used non-steroidal antiinflammatory drugs (NSAIDs), 1.6% – paracetamol, 40.0% – non-drug modalities and methods of alternative medicine. 15.6% of the respondents were completely satisfied with the treatment, 64.0% were partially satisfied, and 20.4% were completely dissatisfied. The main subjective reasons for the insufficient effectiveness of analgesic therapy were: fear of taking prescribed medications due to possible complications (45.4%), low effectiveness of drugs (15.7%), insufficient attention of doctors (20.3%). Male gender, body mass index >30 kg/m2 , severe pain, pain in several areas, and the diagnosis of OA were statistically significantly associated with treatment dissatisfaction. In contrast, patients with RA showed greater satisfaction with treatment.Conclusion. Most patients with RD are dissatisfied with the results of pain therapy. Educational work with patients and a personalized approach to prescribing analgesic therapy is needed.

Influence of the microbial factor in acute pericoronitis occurrence

Pericoronitis is an inflammatory disease that occurs after the eruption of the lower wisdom teeth and affects the surrounding tissues, with a complex microbial and traumatic etiology, manifested by an erythematous swelling and gum hyperemia in the retromolar area. The main goal was to determine the etiological spectrum of the microorganisms involved in acute pericoronitis and to evaluate the antibiotics, antiinflammatory drugs effect on pericoronitis treatment. The study included 30 patients (18 male, 12 female), aged between 18-45 years (27,8±8,2 years) with acute pericoronitis of the lower wisdom tooth. The study determined the severity of infection related to subjective and objective clinical symptoms (pain, swelling, congestion), the incidence of various streptococci; antibiotics resistance analysis was performed for in order to determine the sensibility and the rate between monomicrobial and polymicrobial cultures. 14 references, 4 figures.