Tuberculosis: Common Questions and Answers.

Approximately 10 million people worldwide were infected with tuberculosis (TB) in 2019, resulting in 1.4 million deaths. In the United States that same year, there were nearly 9,000 reported cases of TB disease and up to 13 million people were living with latent TB infection (LTBI), which is an asymptomatic, noncommunicable infection caused by Mycobacterium tuberculosis. Without treatment, LTBI will progress to active TB disease in approximately 5% to 10% of affected people. Individuals with symptoms of TB disease warrant testing. The U.S. Preventive Services Task Force recommends testing individuals at increased risk of LTBI with an interferon-gamma release assay or tuberculin skin testing. Because the incidence of LTBI in health care professionals is similar to that of the general population, periodic retesting is not recommended. After a positive test result, chest radiography should be performed and, in patients with suspected pulmonary TB disease, sputum collected for diagnosis. Both suspected and confirmed cases of LTBI and TB disease must be reported to local or state health departments. Preferred treatment regimens for LTBI include isoniazid in combination with rifapentine or rifampin, or rifampin alone for a duration of three and four months, respectively. Treatment of drug-susceptible TB disease includes an eight-week intensive phase with four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol), followed by a continuation phase lasting 18 weeks or more, with two drugs based on susceptibility testing results. Consultation with a TB expert is necessary if there is suspicion or confirmation of drug-resistant TB.

Spontaneously Resolving Joint Inflammation Is Characterised by Metabolic Agility of Fibroblast-Like Synoviocytes.

Fibroblast-like synoviocytes (FLS) play an important role in maintaining joint homeostasis and orchestrating local inflammatory processes. When activated during injury or inflammation, FLS undergo transiently increased bioenergetic and biosynthetic demand. We aimed to identify metabolic changes which occur early in inflammatory disease pathogenesis which might support sustained cellular activation in persistent inflammation. We took primary human FLS from synovial biopsies of patients with very early rheumatoid arthritis (veRA) or resolving synovitis, and compared them with uninflamed control samples from the synovium of people without arthritis. Metabotypes were compared using NMR spectroscopy-based metabolomics and correlated with serum C-reactive protein levels. We measured glycolysis and oxidative phosphorylation by Seahorse analysis and assessed mitochondrial morphology by immunofluorescence. We demonstrate differences in FLS metabolism measurable after ex vivo culture, suggesting that disease-associated metabolic changes are long-lasting. We term this phenomenon 'metabolic memory'. We identify changes in cell metabolism after acute TNFα stimulation across disease groups. When compared to FLS from patients with early rheumatoid arthritis, FLS from patients with resolving synovitis have significantly elevated mitochondrial respiratory capacity in the resting state, and less fragmented mitochondrial morphology after TNFα treatment. Our findings indicate the potential to restore cell metabotypes by modulating mitochondrial function at sites of inflammation, with implications for treatment of RA and related inflammatory conditions in which fibroblasts play a role.

Case Study of a Comprehensive Team-Based Approach to Increase Colorectal Cancer Screening.

Introduction: Colorectal cancer is the second leading cause of cancer deaths among men and women in West Virginia. In addition, 51% of all colorectal cancers diagnosed in West Virginia from 2012 to 2016 were detected at either regional (31%) or distant (20%) stages indicating a need for improved early detection. Methods: West Virginia University Cheat Lake Physicians participated in the West Virginia Program to Increase Colorectal Cancer Screening, a program of Cancer Prevention and Control at the WVU Cancer Institute. As a result, Cheat Lake Physicians assembled a team of health care professionals to implement evidence-based interventions and system changes including provider assessment and feedback, patient reminders, accurate data capture, and tracking of CRC screening tests. Results: These efforts resulted in a 15.8% increase in colorectal cancer screening rates within one year of implementation. Additionally, the clinic achieved a 66% return rate for Fecal Immunochemical Test kits, an inexpensive, stool-based colorectal cancer screening test. Implications: The utilization of a team-based approach to patient care yields positive results that can be carried over to other cancer and disease prevention efforts in primary care clinics.

Priming in response to pro-inflammatory cytokines is a feature of adult synovial but not dermal fibroblasts.

BACKGROUND: It has been hypothesized that chronic inflammatory diseases such as rheumatoid arthritis (RA) may be caused by a failure of negative feedback mechanisms. This study sought to examine negative feedback mechanisms in fibroblast-like synoviocytes (FLS), one of the most abundant cell types in the joint. We hypothesized that prior exposure of healthy FLS to an inflammatory stimulus would attenuate their responses to a second inflammatory stimulus, in the same way that negative feedback mechanisms desensitize macrophages to repeated stimulation by lipopolysaccharide. We further hypothesized that such negative feedback mechanisms would be defective in FLS derived from the joints in RA. METHODS: Synovial fibroblasts and dermal fibroblasts from non-inflamed joints and joints affected by RA and a fibroblast cell line from neonatal foreskin were stimulated twice with tumour necrosis factor (TNF) α or interleukin (IL)-1α, with a 24-h rest period between the two 24-h stimulations. Differences between response to the first and second dose of cytokine were examined by assessing secretion of inflammatory factors and intracellular signalling activity. RESULTS: FLS from both non-inflamed joints and joints affected by RA mounted an augmented response to re-stimulation. This response was site-specific, as primary dermal fibroblasts did not alter their response between doses. The fibroblast priming was also gene-specific and transient. Assessment of signalling events and nuclear localization showed prolonged activation of nuclear factor (NF)-κB during the second stimulation. CONCLUSION: This study aimed to examine mechanisms of negative regulation of inflammatory responses in FLS. Instead, we found a pro-inflammatory stromal memory in FLS obtained from both non-inflamed joints and joints affected by RA. This suggests the joint is an area at high risk of chronic inflammation, and may provide a piece in the puzzle of how chronic inflammation is established in RA.

The effects of prayer on attention resource availability and attention bias.

Two experiments were used to measure the effects of prayer, contemplation, or a control activity on attention resource capacity and attention bias. Results from a dual-task test in Experiment 1 indicated that allowing participants to pray about an issue in their lives improved subsequent task performance, but only for individuals who score highly on a measure of religiosity. Experiment 2 suggested that praying about a problem can bias attention in a word-search task. Similar effects were not observed for control activities. Thus, at least for people most likely to engage in religious behavior, praying about a problem appeared to liberate cognitive resources that are presumably otherwise consumed by worry and rumination, leaving individuals better able to process other information, and additionally to bias attention to favor detection of problem-relevant information. These effects suggest one cognitive process (attention) that may underlie how people come to perceive answers to prayers.

Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage.

BACKGROUND: We investigated two distinct synovial fibroblast populations that were located preferentially in the lining or sub-lining layers and defined by their expression of either podoplanin (PDPN) or CD248, and explored their ability to undergo self-assembly and transmigration in vivo. METHODS: Synovial fibroblasts (SF) were cultured in vitro and phenotypic changes following stimulation with interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß1 were examined. To examine the phenotype of SF in vivo, a severe combined immunodeficiency (SCID) human-mouse model of cartilage destruction was utilised. RESULTS: SF in the lining layer in rheumatoid arthritis (RA) expressed high levels of PDPN compared to the normal synovium, whereas CD248 expression was restricted to sub-lining layer cells. TNF-α or IL1 stimulation in vitro resulted in an increased expression of PDPN. In contrast, stimulation with TGF-ß1 induced CD248 expression. In the SCID human-mouse model, rheumatoid SF recapitulated the expression of PDPN and CD248. Fibroblasts adjacent to cartilage expressed PDPN, and attached to, invaded, and degraded cartilage. PDPN+ CD248- SF preceded the appearance of PDPN- CD248+ cells in contralateral implants. CONCLUSIONS: We have identified two distinct SF populations identified by expression of either PDPN or CD248 which are located within different anatomical compartments of the inflamed synovial membrane. These markers discriminate between SF subsets with distinct biological properties. As PDPN-expressing cells are associated with early fibroblast migration and cartilage erosion in vivo, we propose that PDPN-expressing cells may be an attractive therapeutic target in RA.

Impetigo: diagnosis and treatment.

Impetigo is the most common bacterial skin infection in children two to five years of age. There are two principal types: nonbullous (70% of cases) and bullous (30% of cases). Nonbullous impetigo, or impetigo contagiosa, is caused by Staphylococcus aureus or Streptococcus pyogenes, and is characterized by honey-colored crusts on the face and extremities. Impetigo primarily affects the skin or secondarily infects insect bites, eczema, or herpetic lesions. Bullous impetigo, which is caused exclusively by S. aureus, results in large, flaccid bullae and is more likely to affect intertriginous areas. Both types usually resolve within two to three weeks without scarring, and complications are rare, with the most serious being poststreptococcal glomerulonephritis. Treatment includes topical antibiotics such as mupirocin, retapamulin, and fusidic acid. Oral antibiotic therapy can be used for impetigo with large bullae or when topical therapy is impractical. Amoxicillin/clavulanate, dicloxacillin, cephalexin, clindamycin, doxycycline, minocycline, trimethoprim/sulfamethoxazole, and macrolides are options, but penicillin is not. Natural therapies such as tea tree oil; olive, garlic, and coconut oils; and Manuka honey have been anecdotally successful, but lack sufficient evidence to recommend or dismiss them as treatment options. Treatments under development include minocycline foam and Ozenoxacin, a topical quinolone. Topical disinfectants are inferior to antibiotics and should not be used. Empiric treatment considerations have changed with the increasing prevalence of antibiotic-resistant bacteria, with methicillin-resistant S. aureus, macrolide-resistant streptococcus, and mupirocin-resistant streptococcus all documented. Fusidic acid, mupirocin, and retapamulin cover methicillin-susceptible S. aureus and streptococcal infections. Clindamycin proves helpful in suspected methicillin-resistant S. aureus infections. Trimethoprim/sulfamethoxazole covers methicillin-resistant S. aureus infection, but is inadequate for streptococcal infection.

Update on latent tuberculosis infection.

Latent tuberculosis infection refers to an asymptomatic, nontransmissible infection with Mycobacterium tuberculosis, carrying a 5% to 10% lifetime risk of progressing to active disease. One-half of this risk occurs within the first two years after infection. High-risk groups include recent immigrants from high-incidence countries, health care professionals, persons living or working in institutional settings, and homeless persons. Risk factors for progression to active disease include immunodeficiency, recent exposure to tuberculosis, and chronic kidney disease requiring dialysis. Tuberculin skin testing has several limitations, including the need for multiple office visits and the potential for false-positive results in patients who have received the bacillus Calmette-Guérin vaccine or been exposed to environmental mycobacteria. Interferon-gamma release assays address these deficiencies but are limited by their cost and requirement for blood processing. Interferon-gamma release assays are preferred in immigrants exposed to bacillus Calmette-Guérin and in patients who are not likely to return for interpretation of skin test results. Tuberculin skin testing is preferred for children younger than five years. Active disease should be excluded before initiating treatment. The newest treatment option of 12 weekly doses of isoniazid and rifapentine has similar or better effectiveness than standard nine-month therapy with daily isoniazid. A four-month regimen of daily rifampin is another alternative.

Bioequivalence and safety of a novel fentanyl transdermal matrix system compared with a transdermal reservoir system.

OBJECTIVES: Fentanyl is a potent synthetic opioid used for the management of chronic pain. A newer transdermal matrix system was developed and compared with a reservoir system used in the United States. SETTING: An open-label, single-center, randomized, two-period crossover study was conducted to evaluate the bioequivalence of the transdermal matrix system to the transdermal reservoir system. Seventy-four subjects completed treatment with both the reservoir system (100 microg/h) and the matrix system (100 microg/h), each applied for 72 hours. After application of the first system, subjects completed a 9-day washout and then crossed over to receive the other system for another 72 hours. MAIN OUTCOME MEASURE: Blood samples for the determination of serum fentanyl concentrations were taken in each treatment period for up to 120 hours following application. RESULTS: The ratios of geometric means for maximum fentanyl concentration (Cmax) and area under the concentration-time curve (AUClast, and AUCinfinity) were 106 percent, 110 percent, and 110 percent, respectively. The 90% confidence intervals for the ratios of the geometric means were contained within the bioequivalence criteria of 80-125 percent. The matrix system adhered well to skin. Systemic and topical safety profiles were comparable between treatments. CONCLUSIONS: The transdermal fentanyl matrix system adhered well, was well tolerated, and produced systemic exposures of fentanyl that were bioequivalent to the reservoir system.

A perioperative education program for pediatric patients and their parents.

Preparing pediatric patients for surgery is crucial to positive patient and parent experiences. Through preoperative screening, observation, and postoperative feedback, clinical staff nurses at the Yellowstone Surgery Center (YSC) in Billings, Montana, identified a need to provide increased information to pediatric patients and their parents regarding the surgical process and postoperative expectations for recovery. The director of nursing developed a program for patients that includes preoperative education and a hands-on experience. The YSC Kids program is a customizable program that includes nine initiatives designed specifically for children. The program has been shown to successfully educate pediatric patients and their parents about the entire perioperative process, thus easing their anxiety about an unfamiliar situation.

Human papillomavirus: clinical manifestations and prevention.

Human papillomaviruses cause the most common sexually transmitted infection in the world and are responsible for nearly all cases of cervical cancer. Genital human papillomavirus infection can be divided into low-risk infections (causing genital warts) and high-risk infections (causing cervical intraepithelial neoplasia, and cervical and other cancers). Exposure to human papilloma- virus typically produces a sexually transmitted infection that may progress to a clinically apparent process, such as genital warts and cervical intraepithelial neoplasia lesions of the lower genital tract. Although most human papillomavirus infections resolve spontaneously within two years, some high-risk infections persist and are considered cancer precursors. Risk factors for persistent infection include multiple sex partners, sex at an early age, history of sexually transmitted infections, and smoking. Condom use is only partially protective against human papillomavirus infection. The two human papillomavirus vaccines are most effective if given to girls before the onset of sexual activity.

Management of keloids and hypertrophic scars.

Keloids and hypertrophic scars represent an exuberant healing response that poses a challenge for physicians. Patients at high risk of keloids are usually younger than 30 years and have darker skin. Sternal skin, shoulders and upper arms, earlobes, and cheeks are most susceptible to developing keloids and hypertrophic scars. High-risk trauma includes burns, ear piercing, and any factor that prolongs wound healing. Keloid formation often can be prevented if anticipated with immediate silicone elastomer sheeting, taping to reduce skin tension, or corticosteroid injections. Once established, however, keloids are difficult to treat, with a high recurrence rate regardless of therapy. Evidence supports silicone sheeting, pressure dressings, and corticosteroid injections as first-line treatments. Cryotherapy may be useful, but should be reserved for smaller lesions. Surgical removal of keloids poses a high recurrence risk unless combined with one or several of these standard therapies. Alternative postsurgical options for refractory scars include pulsed dye laser, radiation, and possibly imiquimod cream. Intralesional verapamil, fluorouracil, bleomycin, and interferon alfa-2b injections appear to be beneficial for treatment of established keloids. Despite the popularity of over-the-counter herb-based creams, the evidence for their use is mixed, and there is little evidence that vitamin E is helpful.

Initial results of managing severe bone loss in infected total joint arthroplasty using customized articulating spacers.

Twenty-three cases of infected total joint arthroplasty with substantial bone loss were treated with a cement spacer, which was customized intraoperatively to achieve joint stability and to allow motion. All but one of the patients were ambulatory with the spacer in place. Spacer dislocation occurred in 1 hip patient (9%) and in none of the knee patients. Articulating antibiotic-impregnated spacers with intraoperative customization is our preferred treatment of cases of infected total joint arthroplasty even in the presence of bone loss.