Inverse-Vaccines for Rheumatoid Arthritis Re-establish Metabolic and Immunological Homeostasis in Joint Tissues.

Rheumatoid arthritis (RA) causes immunological and metabolic imbalances in tissue, exacerbating inflammation in affected joints. Changes in immunological and metabolic tissue homeostasis at different stages of RA are not well understood. Herein, the changes in the immunological and metabolic profiles in different stages in collagen induced arthritis (CIA), namely, early, intermediate, and late stage is examined. Moreover, the efficacy of the inverse-vaccine, paKG(PFK15+bc2) microparticle, to restore tissue homeostasis at different stages is also investigated. Immunological analyses of inverse-vaccine-treated group revealed a significant decrease in the activation of pro-inflammatory immune cells and remarkable increase in regulatory T-cell populations in the intermediate and late stages compared to no treatment. Also, glycolysis in the spleen is normalized in the late stages of CIA in inverse-vaccine-treated mice, which is similar to no-disease tissues. Metabolomics analyses revealed that metabolites UDP-glucuronic acid and L-Glutathione oxidized are significantly altered between treatment groups, and thus might provide new druggable targets for RA treatment. Flux metabolic modeling identified amino acid and carnitine pathways as the central pathways affected in arthritic tissue with CIA progression. Overall, this study shows that the inverse-vaccines initiate early re-establishment of homeostasis, which persists through the disease span.

Short-term outcomes in patients with center-involving diabetic macular edema after a single dose of intravitreal bevacizumab.

BACKGROUND: A significant portion of diabetic macular edema (DME) is refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. This study investigates morphological and functional outcomes to a single intravitreal bevacizumab (IVB) injection in patients with center-involving DME (ciDME) at 4-6 weeks and compares treatment responders and non-responders based on spectral domain optical coherence tomography (SD-OCT) features. METHODS: IRB approved observational, retrospective chart review of patients with ciDME, identified by ICD-10 code, who received IVB and underwent baseline and 4-6 weeks follow-up SD-OCT imaging between January 1, 2016 and January 19, 2021. Patients who had received previous treatment with anti-VEGF or intraocular steroids within 1 year were excluded. Variables included best-corrected visual acuity (BCVA), central subfield thickness (CST) and total macular volume (TMV). Eyes were classified as responders if CST reduction was greater than 10%. OCT scans were graded qualitatively by two masked graders using Imagivault software. Paired Student's t-tests, Wilcoxon signed rank tests and Chi-Square tests were used for analysis. RESULTS: A total of 334 prospective subjects were identified, and after applying exclusion criteria 52 eyes from 46 patients (mean age 64.22 ± 8.12 years, 58.7% male) were included. Mean BCVA did not significantly change with treatment, 63.9 ETDRS letters (~ 20/50) at baseline and 65.9 ETDRS letters (~ 20/50) post-treatment (p = 0.07). Mean CST decreased from 466 ± 123 µm at baseline to 402 ± 86 µm post-treatment (p < 0.001). 22 (42.3%) of eyes were categorized as responders and 30 (57.7%) as non-responders. Average change in CST from baseline in responders was -164 µm (p < 0.001) and + 9 µm in non-responders (p = 0.47). Vitreomacular adhesion (VMA) was more prevalent in non-responders (28.7% vs. 4.8%, p = 0.03). In addition, cyst location in the inner nuclear layer (INL) was present more frequently in responders (95.5% vs. 73.3%, p = 0.037) as was subretinal fluid (45.5% vs. 13.3%, p = 0.01). CONCLUSION: The short-term response to a single IVB was sub-optimal with structural but no functional improvements. Greater baseline CST, presence of INL cysts and subretinal fluid may represent factors indicative of a better treatment response.

Novel technique for esthetic root coverage with titanium prepared platelet-rich fibrin.

Leukocyte- and platelet-rich fibrin (L-PRF) can be defined as an autologous leukocyte and platelet-rich biomaterial. Unlike other platelet-rich products, this technique does not require an anticoagulant or bovine thrombin. However, it is simply centrifuged blood without any additives, which makes it possible to avoid all of the legal restrictions related to the reimplantation of blood-derived products. L-PRF is composed of a fibrin matrix polymerized in a tetramolecular structure and is involved in the joining of platelets, leukocytes, cytokines, and circulating stem cells. The use of silica- coated test tubes is arising a lot of queries about the safety of L-PRF prepared within these test tubes. So, to avoid the use of silicacoated test tubes, titanium prepared PRF has come in practice now, as titanium is biocompatible metal and has property of histoconduction. The present case report is about successful esthetic root coverage around mandibular anterior teeth with clinical attachment loss of 4-5 mm at baseline. The patient had reduced sensitivity, CAL was 1 mm, and attached gingiva covered denuded root surface after 15 days and after 3-month recall appointment.

Oxide-based catalysis: tailoring surface structures via organic ligands and related interfacial charge carrier for environmental remediation.

Hierarchical nanostructures and the effects of ligands on their structure formation were investigated. Morphological analysis showed the change in the morphology from nanospindles to hollow hexagonal nanodisks with the change in ligands. Structural analysis exhibited the formation of both hexagonal ZnO and monoclinic CuO structures in the composition. The elemental composition confirms the presence of CuO and ZnO in the composition. An ultra-fast degradation was achieved for the nanocomposites. The ZnO/CuO composite with ethylenediamine showed the best activity by degrading 98.77% of the methylene blue dye in 36 min. A possible photocatalytic mechanism is proposed.

A Multicenter, Randomized Controlled Trial of Perioperative Palliative Care Surrounding Cancer Surgery for Patients and Their Family Members (PERIOP-PC).

Background: Despite positive outcomes associated with specialist palliative care (PC) in diverse medical populations, little research has investigated specialist PC in surgical ones. Although cancer surgery is predominantly safe, operations can be extensive and unpredictable perioperative morbidity and mortality persist, particularly for patients with upper gastrointestinal (GI) cancers. Objectives and Hypotheses: Our objective is to complete a multicenter, randomized controlled trial comparing surgeon-PC co-management with surgeon-alone management among patients pursuing curative-intent surgery for upper GI cancers. We hypothesize that perioperative PC will improve patient postsurgical quality of life. This study and design are based on >8 years of engagement and research with patients, family members, and clinicians surrounding major cancer surgery and advance care planning/PC for surgical patients. Methods: Randomized controlled superiority trial with two study arms (surgeon-PC team co-management and surgeon-alone management) and five data collection points over six months. The principal investigator and analysts are blinded to randomization. Setting: Four, geographically diverse, academic tertiary care hospitals. Data collection began December 20, 2018 and continues to December 2020. Participants: Patients recruited from surgical oncology clinics who are undergoing curative-intent surgery for an upper GI cancer. Interventions: In the intervention arm, patients receive care from both their surgical team and a specialist PC team; the PC is provided before surgery, immediately after surgery, and at least monthly until three months postsurgery. Patients randomized to the usual care arm receive care from only the surgical team. Main Outcomes and Measures: Primary outcome: patient quality of life. Secondary outcomes: patient: symptom experience, spiritual distress, prognostic awareness, health care utilization, and mortality. Caregiver: quality of life, caregiver burden, spiritual distress, and prognostic awareness. Intent-to-treat analysis will be used. Ethics and Dissemination: This study has been approved by the institutional review boards of all study sites and is registered on clinicaltrials.gov (NCT03611309, First received: August 2, 2018).

Pacemakers, Deep Brain Stimulators, Cochlear Implants, and Nerve Stimulators: A Review of Common Devices Encountered in the Dermatologic Surgery Patient.

BACKGROUND: In dermatologic and procedural surgery settings, there are commonly encountered devices in patients. Safe surgical planning requires familiarity with these devices. OBJECTIVE: To review the current implanted devices in patients and recommendations for surgical planning around these devices. METHODS AND MATERIALS: A comprehensive review using PubMed and published device recommendations was performed, searching for those most relevant to dermatologic surgery. RESULTS: Devices such as pacemakers and implantable cardiac defibrillators, deep brain stimulators, cochlear implants, and various nerve stimulators are potential devices that may be encountered in patients and specific recommendations exist for each of these devices. CONCLUSION: Dermatologic surgeons' knowledge of implanted devices in patients is paramout to safe surgical procedures.

Intravascular involvement of cutaneous squamous cell carcinoma.

We present a case of a 72-year-old man who was found to have intravascular invasion during Mohs micrographic surgery (MMS) of cutaneous squamous cell carcinoma (cSCC) on the left side of the forehead. The patient was subsequently treated with adjuvant radiation without evidence of disease recurrence. We present a case review to discuss treatment options for high-risk features of cSCC with the aim to assist in treatment guidelines.

Panretinal Photocoagulation: A Review of Complications.

Panretinal photocoagulation (PRP) is a mainstay of therapy for retinal ischemic disease. The procedure involves creating thermal burns in the peripheral retina leading to tissue coagulation, the overall consequence of which is improved retinal oxygenation. While highly effective, there have been concerns historically regarding the anatomic effects and visual complications following PRP, the most common of which include choroidal effusions, exudative retinal detachments, macular edema, visual field deficits, and night vision defects. The occurrence of these complications is closely tied to laser parameters such as increased duration and power and intensive treatment in a single sitting, all of which cause increased dispersion of thermal energy within the retina and choroid. The advent of newer laser delivery systems, such as the multispot pattern laser, has greatly mitigated but not eliminated these issues. The following article reviews the most common complications following PRP treatment, including reported occurrences, inciting factors, and underlying pathophysiology.

Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch.

Mammals have evolved neurophysiologic reflexes, such as coughing and scratching, to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases, including asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies markedly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, this study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior.

Metagenomics of petroleum muck: revealing microbial diversity and depicting microbial syntrophy.

Present study attempts in revealing taxonomic and functional diversity of microorganism from petroleum muck using metagenomics approach. Using Ion Torrent Personal Genome Machine, total of 249 Mb raw data were obtained which was analysed using MG-RAST platform. The taxonomic analysis revealed predominance of Proteobacteria with Gammaproteobacteria as major class and Pseudomonas stutzeri as most abundant organism. Several enzymes involved in aliphatic and aromatic hydrocarbon degradation through both aerobic and anaerobic routes and proteins related to stress response were also present. Comparison of our metagenome with the existing metagenomes from oil-contaminated sites and wastewater treatment plant indicated uniqueness of this metagenome taxonomically and functionally. Based on these results a hypothetical community model showing survival and syntrophy of microorganisms in hydrocarbon-rich environment is proposed. Validation of the metagenome data was done in three tiers by validating major OTUs by isolating oil-degrading microbes, confirmation of key genes responsible for hydrocarbon degradation by Sanger sequencing and studying functional dynamics for degradation of the hydrocarbons by the muck meta-community using GC-MS.

Considerations for a Pediatric Biopharmaceutics Classification System (BCS): application to five drugs.

It has been advocated that biopharmaceutic risk assessment should be conducted early in pediatric product development and synchronized with the adult product development program. However, we are unaware of efforts to classify drugs into a Biopharmaceutics Classification System (BCS) framework for pediatric patients. The objective was to classify five drugs into a potential BCS. These five drugs were selected since both oral and intravenous pharmacokinetic data were available for each drug, and covered the four BCS classes in adults. Literature searches for each drug were conducted using Medline and applied to classify drugs with respect to solubility and permeability in pediatric subpopulations. Four pediatric subpopulations were considered: neonates, infants, children, and adolescents. Regarding solubility, dose numbers were calculated using a volume for each subpopulation based on body surface area (BSA) relative to 250 ml for a 1.73 m(2) adult. Dose numbers spanned a range of values, depending upon the pediatric dose formula and subpopulation. Regarding permeability, pharmacokinetic literature data required assumptions and decisions about data collection. Using a devised pediatric BCS framework, there was agreement in adult and pediatric BCS class for two drugs, azithromycin (class 3) and ciprofloxacin (class 4). There was discordance for the three drugs that have high adult permeability since all pediatric permeabilities were low: dolasetron (class 3 in pediatric), ketoprofen (class 4 in pediatric), and voriconazole (class 4 in pediatric). A main contribution of this work is the identification of critical factors required for a pediatric BCS.

An open-label study of anakinra for the treatment of moderate to severe hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by sterile abscesses and fistulae predominantly affecting the axillae and groin. Various biologic agents have been attempted for HS, but there is still no definitive treatment. OBJECTIVES: We sought to evaluate the efficacy, safety, and tolerability of anakinra in the treatment of moderate to severe HS. METHODS: Six patients with moderate to severe HS were enrolled in an open-label study with all patients receiving active treatment for 8 weeks with an additional 8 weeks of follow-up off therapy. RESULTS: The 5 patients who completed the 8-week therapy showed a significant mean decrease in their modified Sartorius score of 34.8 points. The physician and patient global assessment of overall activity showed significant reductions between baseline and 8 weeks of therapy: 45.8 points and 35.6 points, respectively. The Dermatology Life Quality Index showed a significant reduction after 8 weeks of treatment with anakinra. Functional T-cell analysis revealed that patients had increased percentages of CD3(+) T cells in lesional skin compared with nonlesional skin before therapy. LIMITATIONS: The limited number of patients and lack of control group are limitations. CONCLUSIONS: Anakinra demonstrated decreased HS disease activity by both objective and subjective measures.

Autoinflammatory diseases in dermatology: CAPS, TRAPS, HIDS, FMF, Blau, CANDLE.

Autoinflammatory diseases, including CAPS, TRAPS, HIDS, FMF, Blau, and CANDLE, have unique dermatologic presentations that can be a clue to diagnosis. Although these conditions are rare, the morbidity and mortality can be severe, and well-informed physicians can place these conditions in their differential diagnosis when familiar with the dermatologic manifestations. This review article presents a brief overview of each condition, clues to diagnosis that focus of dermatologic manifestations and clinical images, basic laboratory tests and follow-up, a brief review of treatments, and concludes with an overview for these autoinflammatory conditions and their differential diagnoses.

Methicillin-resistant Staphylococcus aureus induced reactive arthritis treated with systemic corticosteroid.

Reactive arthritis consists of the classic clinical triad of arthritis, urethritis and conjunctivitis generally occurring within 6 weeks of an infection, typically of the gastrointestinal or genitourinary systems. Staphylococcus aureus is not usually implicated in this condition. Staphylococcal septicemia, while frequently associated with arthralgia, has rarely been associated with a sterile arthritis, although it infrequently results in septic arthritis. It is important to consider reactive arthritis, rather than solely an infectious cause of joint effusions, and arthropathy in a patient with a preceding or ongoing Staphylococcal infection. We report a case of reactive arthritis, in a human leukocyte B27-positive patient, following a recurrent bacterial prostatitis caused by methicillin-resistant S aureus.

Side effects of common acne treatments.

INTRODUCTION: A variety of acne treatments exist, including topical benzoyl peroxide, topical retinoids, topical antibiotics, oral antibiotics, hormonal therapy, isotretinoin, and procedural therapies, such as light and laser therapies. Although each of these treatment modalities confer various benefits for the management of acne, it is important for healthcare providers to be aware of their potential side effects, including ones that are most common and most serious, so that these medications can be prescribed in a safe manner. AREAS COVERED: A systematic literature review was performed to identify publications discussing the side effects of the different treatment modalities used for acne vulgaris. Acne treatments reviewed included benzoyl peroxide gel, topical retinoids, topical antibiotics, oral antibiotics, hormonal therapy, isotretinoin, and light/laser treatments. EXPERT OPINION: A comprehensive overview of acne treatments' side effects is imperative for healthcare professionals and scientists working with and prescribing acne treatments. Side effects to be aware of when prescribing range from local irritation with topical treatments to systemic side effects including liver function abnormalities and teratogenic side effects. The best available options are those that address acne severity while minimizing side effects for the patient. Consequently, personalized medicine must be strongly emphasized to healthcare providers developing patients' treatment plans.