Background: The treatment of keloids remains challenging. Cryosurgery and intralesional corticosteroids have been considered as the mainstream of therapy; however, the long-term use of corticosteroids has been found to be associated with serious side effects. Intralesional 5-fluorouracil (5-FU) has only been used in one study for the treatment of hypertrophic scars and keloids, mostly in combination with other treatments. The efficacy of 5-FU as an individual therapeutic agent is unknown. Objective: To evaluate the efficacy and safety of intralesional injections of 5-FU in the treatment of small keloid lesions. Methods: Twenty-four (12 male, 12 female) consecutive patients with keloids of 6 cm or less in their maximum dimension were treated with intralesional injections of 50–150 mg 5-FU per week for a maximum of 16 injections. Results: One third (8/24, 33.3%) of the patients showed more than 75% flattening of the keloid. Three out of 8 patients (with >75% flattening) required less than 16 (13, 13 and 15) injections for achieving the desired response. Overall, about half of the patients showed more than 50% flattening of the treated keloid. A correlation with the duration of keloid was found. Six (54.5%) out of 11 patients with keloids of ≤5 years duration, in contrast to only 2 (15.4%) out of 13 patients with keloids of >5 years duration showed more than 75% flattening (p < 0.05). Side effects included pain (all patients), hyperpigmentation (all patients) and ulceration (1 patient). No difference in peripheral blood count was noted before, during and after the therapy. Conclusion: Intralesional 5-FU can be safely used for the management of small keloids of shorter duration.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–driven coronavirus disease 2019 (COVID-19) has caused unprecedented human death and has seriously threatened the global economy. Early data suggest a surge in proinflammatory cytokines in patients with severe COVID-19, which has been associated with poor outcomes. We recently postulated that the inflammatory response in patients with severe COVID-19 disease is not inhibited by natural killer (NK) cells, resulting in a “cytokine storm.” Here, we assessed the NK-cell functional activity and the associated cytokines and soluble mediators in hospitalized COVID-19 patients. Significantly impaired NK-cell counts and cytolytic activity were observed in COVID-19 patients when compared with healthy controls. Also, cytokines like interleukin 12 (IL12), IL15, and IL21 that are important for NK-cell activity were not detected systematically. Serum concentrations of soluble CD25 (sCD25)/soluble IL2 receptor α (sIL2-Rα) were significantly elevated and were inversely correlated with the percentage of NK cells. Impaired NK-cell cytolytic activity together with other laboratory trends including elevated sCD25 were consistent with a hyperinflammatory state in keeping with macrophage-activation syndrome. Our findings suggest that impaired counts and cytolytic activity of NK cells are important characteristics of severe COVID-19 and can potentially facilitate strategies for immunomodulatory therapies.

AYUSH, an acronym for Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa-Rigpa and Homeopathy represents the alternative systems of medicine recognized by the Government of India. Understanding the patterns of utilization of AYUSH care has been important for various reasons including an increased focus on its mainstreaming and integration with biomedicine-based health care system. Based on a nationally representative health survey 2014, we present an analysis to understand utilization of AYUSH care across socioeconomic and demographic groups in India. Overall, 6.9% of all patients seeking outpatient care in the reference period of last two weeks have used AYUSH services without any significant differentials across rural and urban India. Importantly, public health facilities play a key role in provisioning of AYUSH care in rural areas with higher utilization in Chhattisgarh, Kerala and West Bengal. Use of AYUSH among middle-income households is lower when compared with poorer and richer households. We also find that low-income households display a greater tendency for AYUSH self-medication. AYUSH care utilization is higher among patients with chronic diseases and also for treating skin-related and musculo-skeletal ailments. Although the overall share of AYUSH prescription drugs in total medical expenditure is only about 6% but the average expenditure for drugs on AYUSH and allopathy did not differ hugely. The discussion compares our estimates and findings with other studies and also highlights major policy issues around mainstreaming of AYUSH care.

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Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD)occurs frequently when rabbit antithymocyte globulin (ATG) is used in hematopoietic cell transplant (HCT) conditioning. We retrospectively studied 554 patients undergoing ATG-conditioned myeloablative HCT. Strategies used to minimize mortality due to PTLD were either therapy of biopsy-diagnosed PTLD in the absence of EBV DNAemia monitoring (n = 266) or prompt therapy of presumed PTLD (based on clinical/radiologic signs and high EBV DNAemia, in the setting of weekly EBV DNAemia monitoring) (n = 199). Both strategies resulted in similar mortality due to PTLD (0.7% vs 1% at 2 years, P = .43) and similar overall survival (63% vs 67% at 2 years, P = .23) even though there was a trend toward higher PTLD incidence with the prompt therapy.Donor positive with recipient negative EBV (D+R−) serostatus was a risk factor for developing PTLD. Older patient age, HLA-mismatched donor, and graft-versus-host disease were not associated with increased risk of PTLD. In summary, in ATGconditioned HCT, D+R− serostatus, but not older age, mismatched donor or GVHD is a risk factor for developing PTLD. EBV DNAemia monitoring may be a weak risk factor for developing/diagnosing PTLD; the monitoring coupled with prompt therapy does not improve survival. K E Y W O R D SEpstein-Barr virus, post-transplant lymphoproliferative disorder, prompt therapy, rituximab

BackgroundDiagnosing tuberculosis (TB) in children presents considerable challenges. Upfront testing on Xpert® MTB/RIF (‘Xpert’)—a rapid molecular assay with high sensitivity and specificity—for pediatric presumptive TB patients, as recommended by India’s Revised National Tuberculosis Control Program (RNTCP), can pave the way for early TB diagnosis. As part of an ongoing project implemented by Foundation for Innovative New Diagnostics (FIND) dedicated to providing upfront free-of-cost (FOC) Xpert testing to children seeking care in the public and private sectors, a qualitative assessment was designed to understand how national guidelines on TB diagnosis and Xpert technology have been integrated into the pediatric TB care practices of different health providers.MethodsWe conducted semi-structured interviews with a sample of health providers from public and private sectors engaged in the ongoing pediatric project in 4 major cities of India. Providers were sampled from intervention data based on sector of practice, number of Xpert referrals, and TB detection rates amongst referrals. A total of 55 providers were interviewed with different levels of FOC Xpert testing uptake. Data were transcribed and analyzed inductively by a medical anthropologist using thematic content analysis and narrative analysis.ResultsIt was observed that despite guidance from RNTCP on the use of Xpert and significant efforts by FIND and state authorities to disseminate these guidelines, there was notable diversity in their implementation by different health care providers. Xpert, apart from being utilized as intended, i.e. as a first diagnostic test for children, was utilized variably–as an initial screening test (to rule out TB), confirmatory test (once TB diagnosis is established based on antibiotic trial or clinically) and/or only for drug susceptibility testing after TB diagnosis was confirmed. Most providers who used Xpert frequently reported that Xpert was an important tool for managing pediatric TB cases, by reducing the proportion of cases diagnosed only on clinical suspicion and by providing upfront information on drug resistance, which is seldom suspected in children. Despite non-standard use, these results showed that Xpert access helped raise awareness, aided in antibiotic stewardship, and reduced dependence on clinical diagnosis among those who diagnose and treat TB in children.ConclusionAccess to free and rapid Xpert testing for all presumptive pediatric TB patients has had multiple positive effects on pediatricians’ diagnosis and treatment of TB. It has important effects on speed of diagnosis, empirical treatment, and awareness of drug resistance among TB treatment naive children. In addition, our study shows that access to public sector Xpert machines may be an important way to encourage Public-Private integration and facilitate the movement of patients from the private to public sector for anti-TB treatment. Despite availability of rapid and free Xpert testing, our study showed an alarming diversity of Xpert utilization strat...

Although previous studies involving allogeneic hematopoietic cell transplantation (HCT) without in vivo T cell depletion by rabbit antithymocyte globulin (ATG) have reported a substantial survival difference between D-R- and D+R- patients, but little to no survival difference between D-R+ and D+R+ patients (D, donor; R, recipient; +, cytomegalovirus [CMV] seropositive; -, CMV seronegative), whether this applies to HCT using ATG is unknown. We studied 928 patients who underwent myeloablative HCT for hematologic malignancies in Alberta between 1999 and 2014 who received graft-versus-host disease (GVHD) prophylaxis using ATG (Thymoglobulin, 4.5 mg/kg) in addition to methotrexate and cyclosporine. D-R- and D+R- patients had similar survival (no significant difference). D-R+ patients had a substantially lower survival than D+R+ patients (41% versus 59% at 5 years; P = .001). This difference was attributed to higher nonrelapse mortality, apparently due to higher GVHD-associated mortality. Survival rates were also lower for D-R+ HLA-matched sibling transplant recipients compared with D+R+ HLA-matched unrelated donor transplant recipients (44% versus 66% at 5 years; P = .009). In conclusion, when using ATG, choosing a seronegative donor for a seronegative patient is relatively unimportant, whereas choosing a seropositive donor for a seropositive patient is important, even if this requires the use of a seropositive matched unrelated donor graft.