To our knowledge, we report the first case of sarcoid-like granulomatous reaction induced by nivolumab, a fully human IgG4 anti-programmed death 1 (PD-1) immune checkpoint inhibitor antibody. A ...57-year-old man was treated with nivolumab 3 mg/kg for 2 weeks for a desmoplastic melanoma stage III American Joint Commission on Cancer, with no BRAF , NRAS , and cKit mutations. At 10 months, although melanoma complete response was achieved, he developed sarcoid-like granulomatous reaction in the mediastinal lymph node and skin, which resumed after nivolumab arrest. Melanoma did not relapse after 12 months of follow-up. Considering the recently demonstrated role of activated PD-1/PDL-1 axis in sarcoidosis, granulomatous reaction in the patient seems to be a paradoxical reaction, but similar observations have been reported with ipilimumab, another immune checkpoint inhibitor. Sarcoid-like granulomatous reaction during immunotherapy treatment could be a manifestation of cell-mediated immunity induced by these drugs. Impact of granulomatous reaction induced by immune checkpoint inhibitor on melanoma progression is not known and requires further study. Melanoma patients treated by immunotherapy (anti-cytotoxic T-lymphocyte-associated protein-4/anti-PD-1) should be considered for developing sarcoid-like granulomatous reaction that must not be confused with tumor progression.
Introduction
Baker grade III and IV breast prosthesis capsular contractures represent a major problem for patients undergoing mammoplasties. The risk factors involved in recurrence are debated, and ...the best surgical approach for their prevention is not established. The objective was to identify these.
Materials and Methods
We carried out a retrospective study of patients operated on for capsular contracture at the Saint-Louis Hospital in Paris from 2012 to 2014. The characteristics at inclusion were compared so as to determine the risk factors of recurrence. The surgical approaches were compared between the patients with recurrence and those without at 5 years.
Results
Of the 100 patients included, 24 had a recurrence. The minimal follow-up was 5 years. No risk factors of recurrence of capsular contracture were identified. The surgical approach associated with the lowest rate of recurrence was anterior capsulectomy OR total capsulectomy = 2.36 (0.73; 8.037) OR capsulotomy = 4.33 (1.37; 14.81) (
p
< 0.040) with alteration of the volume of the implant, whether greater or less than initially OR greater volume = 0.30 (0.096; 0.83); OR smaller volume = 0.14 (0.008; 0.85) (
p
< 0.018).
Conclusion
The occurrence of capsular contracture is a major problem with prosthetic breast surgery. The main risk factors identified to date are essentially in regard to the occurrence of a first episode. No significant risk factors for recurrence were identified. The best prevention appears to be an anterior capsulectomy with reducing the volume of the implant.
Level of Evidence IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors
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. IV
Background. Invasive wound mucormycosis (IWM) is associated with an extremely poor outcome among critically ill burn patients. We describe the detection of circulating Mucorales DNA (cmDNA) for the ...early diagnosis of IWM in those patients and report the potential value of detecting cmDNA for treatment guidance. Methods. Severely ill burn patients admitted to our tertiary referral center between October 2013 and February 2016 were included. Retrospective plasma samples were tested for the presence of cmDNA by quantitative real-time polymerase chain reaction (qPCR). Patients were then prospectively screened twice a week, and liposomal amphotericin-B therapy initiated based on a positive qPCR. The primary endpoint was the time between cmDNA detection and standard diagnosis. Secondary endpoints were the time from cmDNA detection and treatment initiation and mortality. Results. Seventy-seven patients (418 samples) were included. The average age was 46 (28–60) years, abbreviated burn severity index was 8 (7–10), and simplified acute physiology score was 33 (23–46). The total body surface area was 33% (22%–52%). cmDNA was detected 11 (4.5–15) days before standard diagnosis. The in-hospital mortality was 62% for patients with IWM and 24% for those without (P = .03). The mortality due to IWM was 80% during period A and 33% during period B (P = .46). Conclusions. This study suggests that the detection of cmDNA allows earlier diagnosis of IWM in severely ill burn patients and earlier initiation of treatment. Further studies are needed to confirm the impact of earlier treatment initiation on patient outcome.
•We report and analyse all multi-resistant Acinetobacter baumannii (MR-AB) infections in patients hospitalized in a burn unit from April to November 2014 in a prospective observational study.•We ...found that among 86 patients admitted to the ward, 15 acquired MR-AB nosocomial infection with a median time of 22 days.•Risk factors for MR-AB infection were SAPS II and ABSI scores, MR-AB colonization, invasive procedures and ≥2 skin grafts.•MR-AB infection was associated with an increased risk of death and a longer hospital stay.•Surveillance cultures should be performed to identify colonized patients in whom the risk of MR-AB infection is widely increased.•As it seems difficult to limit the number of skin grafts or invasive procedures needed to manage severely burned patients, prevention of MR-AB colonization remains critical.•This study is, to our knowledge, the first prospective study on the subject, which is a great asset.
Multidrug-Resistant Acinetobacter baumannii (MR-AB) can cause outbreaks in burn units. We aimed to study the incidence, risk factors and outcome of MR-AB infections in a burn unit (BU).
A prospective study was conducted from April to November, 2014 during an outbreak in a BU in Paris. Weekly surveillance cultures were performed to determine MR-AB colonization. MR-AB nosocomial infections, discharge or death without MR-AB infection were considered as competing events. To identify risk factors for MR-AB infection, baseline characteristics and time-dependent variables were investigated in univariate analyses using Cox models.
Eighty-six patients admissions were analyzed during the study period. Among them, 15 (17%) acquired MR-AB nosocomial infection. Median time to infection was 22days (interquartile range: 10–26 days). Cumulative incidence of MR-AB infections was 15% at 28days (95% CI=8–24). Risk factors for MR-AB infection in univariate analysis were SAPS II (Hazard Ratio (HR):1.08; 95% CI:1.05–1.12; P<0.0001) and ABSI (Abbreviated Burn Severity Index) scores (HR:1.32; 95% CI:1.12–1.56; P=0.001), MR-AB colonization (HR:10.2; 95%CI:2.05–50.3; P=0.004), invasive procedures (ventilation, arterial and/or venous catheter) (P=0.0001) and ≥2 skin grafts (HR:10.2; 95% CI:1.76–59.6; P=0.010). MR-AB infection was associated with an increased risk of death (HR: 7.11; 95%CI: 1.52–33.2; P=0.013) and longer hospital stay with a median estimated increase of 10days (IQR: 6; 14).
Incidence of MR-AB nosocomial infection was high during this outbreak, and was associated with prolonged hospitalization and increased risk of death. High patient severity scores, prior MR-AB colonization, invasive procedures and repeated skin grafts were associated with an increased risk of nosocomial infection.
Mucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have ...already been reported in burn units without extensive microbiological investigations. We faced an outbreak of IWM in our center and investigated the clinical isolates with whole-genome sequencing (WGS) analysis. We analyzed
isolates from patients in our burn unit (BU1, Hôpital Saint-Louis, Paris, France) together with nonoutbreak isolates from Burn Unit 2 (BU2, Paris area) and from France over a 2-year period (2013 to 2015). A total of 21 isolates, including 14 isolates from six BU1 patients, were analyzed by whole-genome sequencing (WGS). Phylogenetic classification based on
assembly and assembly free approaches showed that the clinical isolates clustered in four highly divergent clades. Clade 1 contained at least one of the strains from the six epidemiologically linked BU1 patients. The clinical isolates were specific to each patient. Two patients were infected with more than two strains from different clades, suggesting that an environmental reservoir of clonally unrelated isolates was the source of contamination. Only two patients from BU1 shared one strain, which could correspond to direct transmission or contamination with the same environmental source. In conclusion, WGS of several isolates per patients coupled with precise epidemiological data revealed a complex situation combining potential cross-transmission between patients and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.
Invasive wound mucormycosis (IWM) is a severe infection due to environmental molds belonging to the order Mucorales. Severely burned patients are particularly at risk for IWM. Here, we used whole-genome sequencing (WGS) analysis to resolve an outbreak of IWM due to
that occurred in our hospital (BU1). We sequenced 21 clinical isolates, including 14 from BU1 and 7 unrelated isolates, and compared them to the reference genome (1006PhL). This analysis revealed that the outbreak was mainly due to multiple strains that seemed patient specific, suggesting that the patients were more likely infected from a pool of diverse strains from the environment rather than from direct transmission among them. This study revealed the complexity of a Mucorales outbreak in the settings of IWM in burn patients, which has been highlighted based on WGS combined with careful sampling.
Natural Killer (NK) cells participate in the defense against infection by killing pathogens and infected cells and secreting immuno-modulatory cytokines. Defects in NK cell activity have been ...reported in obese, diabetic, and elderly patients that are at high risk of developing infected chronic wounds. Calcium alginate dressings are indicated for the debridement during the inflammatory phase of healing. Since calcium ions are major activators of NK cells, we hypothesized that these dressings could enhance NK functions, as investigated
herein. Primary human blood NK cells were freshly-isolated from healthy volunteers and exposed to conditioned media (CM) from two alginate dressings, Algosteril
(ALG, pure Ca
alginate) and Biatain
Alginate (BIA, Ca
alginate with CMC), in comparison with an exogenous 3mM calcium solution. Our results demonstrated that exogenous calcium and ALG-CM, but not BIA-CM, induced NK cell activation and enhanced their capacity to kill their targets as a result of increased degranulation. NK cell stimulation by ALG depended on the influx of extracellular Ca
the SOCE Ca
permeable plasma membrane channels. ALG-CM also activated NK cell cytokine production of IFN-γ and TNF-α through a partly Ca
-independent mechanism. This work highlights the non-equivalence between alginate dressings for NK cell stimulation and shows that the pure calcium alginate dressing Algosteril
enhances NK cell cytotoxic and immuno-modulatory activities. Altogether, these results underline a specific property of this medical device in innate defense that is key for the cutaneous wound healing process.
Introduction
In light of the concerns regarding the occurrence of anaplastic large-cell lymphoma, seromas, and scar capsules, there appears to be merit in analysis and presentation of the results of ...our series of inflatable smooth implants filled with saline solution, for which the follow-up was more than 10 years.
Patients and Method
We carried out a retrospective study, including all of the patients who underwent a first breast implant for cosmetic reasons, between 2003 and 2006.
Results
A total of 383 patients with 766 smooth implants filled with saline solution were included in our study. No cases of lymphoma and seroma were diagnosed. Eleven patients exhibited a postoperative hematoma, and four went on to develop a capsule. Twenty-two patients (5.7%) developed a Baker Grade III or IV capsule that required revision surgery. Two patients (0.5%) opted for a bilateral prosthesis replacement due to visual rippling. In total, there were 26 (3.4%) early deflations of prostheses.
Discussion
There is not a statistically significant correlation between the occurrence of hematomas and the formation of a capsule. We found a lower shell rate with smooth-walled versus textured implants. The fact of having a decline of 10 years allows to be exhaustive. As for wrinkling and ripples, their occurrence has not been increased by the use of inflatable retropectoral implants.
Conclusion
Smooth inflatable implants filled with saline solution have numerous advantages such as the possibility of a very small approach route and perioperative adaptability of the volume. In light of the lack of indication of anaplastic large-cell lymphoma with smooth implants, they are clearly an attractive alternative to textured implants filled with silicone gel.
Level of Evidence IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors
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.
Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and ...burning sensation, leading to poor patient adherence. To overcome these downsides, pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A– or tacrolimus-loaded poly(lactic-co-glycolic) acid nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induced psoriasis-like mouse model. Results showed that both emulsions significantly inhibited nuclear factor of activated T cell translocation in T lymphocytes as well as their IL-2 production, cell activation, and proliferation. In keratinocytes, inhibition of nuclear factor of activated T cell translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivo showed accumulation of rhodamin B–coupled poly(lactic-co-glycolic) acid nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation to a reduced expression of activation markers CD40, CD86, and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T-cell markers, proinflammatory cytokines, chemokines, and specific epidermal cell genes. Altogether, pickering emulsion might be a very efficient formulation for treating inflammatory dermatoses.
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In well-selected cases, flaps can play a pivotal role in optimizing outcomes in the acute phase of burns. A previous redundant flap could be reused or recycled as a donor site from which a new flap ...could be raised.
We report the case of a patient with full thickness burns on both legs, leading to the exposure of joints of the right ankle and the right foot and left patellar tendon. The right lower extremity was covered with a free musculo-cutaneous latissimus dorsi flap. Then, a musculo-cutaneous cross-leg flap pedicled on the anterior branch and centered on a perforator was harvested from the previous redundant flap to cover the controlateral knee.
Sequential flap coverage can be considered in cases of extensive soft tissue defects and particularly in burns. This case illustrates that re-using a redundant part of a previous flap to cover another defect is a safe and interesting alternative in the event of a lack of donor sites or to save donor sites for later reconstruction of contracted burn scars.
Thin-skin grafts taken from the thigh or buttock take a long time to heal and leave permanent scars.
The authors conducted a retrospective study based on their experience with 945 thin-skin grafts ...(0.2 mm) taken from the scalps of 757 adult patients between January of 1999 and December of 2003.
Of the 757 patients, 89 had grafts taken repeatedly from the scalp. The mean healing time was 6.2 days for a single harvest and 10.2 days for repeated (same hospitalization) harvests. During follow-up, eight patients had microalopecia and three developed "concrete scalp deformity." Of these 11 patients, eight had undergone repeated harvests. None of the other patients had any scarring; they were completely healed by day 15.
The results of this study confirm the rapidity of scalp healing compared with other donor sites. Providing patients with clear, detailed explanations helps minimize the psychological impact of having their heads shaved, and a rigorous technique can contain the two major potential risks: hemorrhage and alopecia. The adult scalp seems to be a donor site to be exploited whenever possible.
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