Isolated asymptomatic masseter muscle metastasis as first sign of metastatic disease in a patient with known melanoma

AbstractA 65-year-old woman diagnosed with a nodular melanoma on the right shoulder had a PET/CT scan 13 months later demonstrating a FDG-avid mass in the left masseter muscle, which was asymptomatic and not clinically evident. Pathologic analysis confirmed metastasis of melanoma. Further subcutaneous, intramuscular and bone metastases developed and the patient was treated with surgery and immunotherapy. The patient is in complete-remission with no evident metastases seen on PET/CT 2.5 years after treatment with adoptive cell therapy using tumor-infiltrating lymphocytes (TIL therapy). Asymptomatic skeletal muscle metastases identified with PET/CT can have therapeutic and prognostic implications and a PET/CT scan should be performed as a true whole-body scan

CD25 Appears Non Essential for Human Peripheral Treg Maintenance In Vivo

Background: IL-2 has been reported to be critical for peripheral T reg survival in mouse models. Here, we examined T reg maintenance in a series of paediatric liver transplant recipients who received basiliximab, a therapeutic anti-CD25 monoclonal antibody. Methodology/Principal Findings: FoxP3 + CD4 T cells were analyzed by flow cytometry before liver grafting and more than 9 months later. We found that in vivo CD25 blockade did not lead to Treg depletion: the proportion of FoxP3 + cells among CD4 T cells and the level of FoxP3 expression were both unchanged. IL-2Rb expression was enhanced in FoxP3 + cells both before and after basiliximab treatment, while the level of IL-2Rc expression was similar in Tregs and non-Tregs. No significant change in the weak or absent expression of IL-7Ra and IL-15Ra expression on FoxP3 + cells was observed. Although the proportion of FoxP3 + cells among CD4 T cells did not vary, food allergies occurred more rapidly after liver grafting in patients who received basiliximab, raising questions as to T reg functionality in vivo in the absence of functional CD25. Conclusions: CD25 appears non essential for human Treg peripheral maintenance in vivo. However, our results rais

Resting Regulatory CD4 T Cells: A Site of HIV Persistence in Patients on Long-Term Effective Antiretroviral Therapy

BACKGROUND: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barrier to curing the infection. Cell quiescence, by favouring HIV latency, reduces the risk of recognition and cell destruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and then virus latency, but these approaches have not eradicated the virus. CD4+CD25+ regulatory T cells (Tregs) are a CD4+ T-cell subset with particular activation properties. We investigated the role of these cells in virus persistence in patients on long-term HAART. METHODOLOGY/PRINCIPAL FINDINGS: We found evidence of infection of resting Tregs (HLADR(-)CD69(-)CD25(hi)FoxP3+CD4+ T cells) purified from patients on prolonged HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since Tregs from patients on prolonged HAART showed hyporesponsiveness to cell activation and inhibition of HIV-specific cytotoxic T lymphocyte-related functions upon activation, therapeutics targeting cell quiescence to induce virus expression may not be appropriate for purging the Treg reservoir. CONCLUSIONS: Our results identify Tregs as a particular compartment within the latent reservoir that may require a specific approach for its purging

Improved Survival of HIV-1-Infected Patients with Progressive Multifocal Leukoencephalopathy Receiving Early 5-Drug Combination Antiretroviral Therapy

Progressive multifocal leukoencephalopathy (PML), a rare devastating demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely immunocompromised patients, most of whom have advanced-stage HIV infection. Despite combination antiretroviral therapy (cART), 50% of patients die within 6 months of PML onset. We conducted a multicenter, open-label pilot trial evaluating the survival benefit of a five-drug cART designed to accelerate HIV replication decay and JCV-specific immune recovery.All the patients received an optimized cART with three or more drugs for 12 months, plus the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was the one-year survival rate. A total of 28 patients were enrolled. At entry, median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4. The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93). At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12, 81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell increment was 105 per microliter. In univariate analysis, higher total and naive CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with better survival. JCV-specific functional memory CD4+ T-cell responses, based on a proliferation assay, were detected in 4% of patients at baseline and 43% at M12 (P = 0.008).The early use of five-drug cART after PML diagnosis appears to improve survival. This is associated with recovery of anti-JCV T-cell responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors for death.ClinicalTrials.gov NCT00120367

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Current management of the gastrointestinal complications of systemic sclerosis.

Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation

Physical conditions during uplift of metamorphic terranes, as recorded by fluid inclusions

The pressure and temperature conditions through which five metamorphic terranes may have passed during uplift have been estimated using the measured compositions and densities of fluids in fluid inclusions, the rupture strength of quartz, and the minimum temperature (~380° C) of CO2-H2O miscibility in natural solutions. The pressures and temperatures of final mineral equilibration are taken as starting points. For four localities, thermal gradients of approximately 27, 33, 54 and 66° C/km existed at some stage during uplift after the rocks had cooled below 380° C. For a fifth locality, a gradient of about 43° C/km existed prior to cooling below 380° C. The P-T path during uplift in four localities was convex towards the temperature axis.Les conditions de température et de pression réalisées pendant la remontée de cinq régions métamorphiques ont été estimées à partir des déterminations de composition et de densité des fluides piégés dans les inclusions, des contraintes de rupture du quartz et de la température minimale (~380° C) de miscibilité de H2O et CO2 dans les solutions naturelles. Les pressions et températures d'équilibre ultime entre minéraux ont été prises comme conditions métamorphiques initiales. Dans quatre localités, les gradients thermiques d'environ 27, 33, 54 et 66° C/km caractérisent cette remontée après que les roches aient déjà été refroidies en dessous de 380° C. Dans une cinquième localité, un gradient d'à peu près 43° C/km existait avant que la série atteigne 380° C. Dans quatre localités le gradient d'ensemble est convexe vers l'axe des températures.Hollister Lincoln S., Burruss Robert C., Henry David L., Hendel Eva-Marie. Physical conditions during uplift of metamorphic terranes, as recorded by fluid inclusions. In: Bulletin de Minéralogie, volume 102, 5-6, 1979. Minéraux et minerais