Blood-conserving and therapeutic efficacy of intravenous tranexamic acid at different time points after primary total knee arthroplasty with tourniquet application: a randomised controlled trial.

BACKGROUND: The use of a tourniquet in combination with tranexamic acid (TXA) not only ensures clear vision, reduces intraoperative blood loss and shortens operative time but also improves cement-bone inter-digitation in total knee arthroplasty (TKA). However, there is no proof whether the blood flow blocking effect of tourniquet affects the antifibrinolytic effect of TXA, and the optimal timing of TXA administration is still unclear. Therefore, this study aims to investigate the effect of the first dose of TXA administered intravenously before tourniquet compression and release in TKA on perioperative blood loss and therapeutic efficacy in patients. METHODS: In this double-blind trial, 90 patients undergoing primary TKA were randomised into 2 groups: Group A, patients received intravenous TXA 10 min before tourniquet compression (20 mg/kg) and 3, 6 and 24 h later (10 mg/kg), and Group B, patients were treated the same as those in Group A but received intravenous TXA before tourniquet release. The primary outcomes were changes in blood loss, haemoglobin and haematocrit. Secondary outcomes included operation and tourniquet times, blood transfusion rate, subcutaneous petechiae and circumferential changes in the operated limb, visual analogue scale (VAS) score, hospital for special surgery (HSS) score, length of stay (LOS) postoperatively, complications and patient satisfaction. RESULTS: No statistically significant difference was found between the 2 groups with regard to age, sex, weight, body mass index (BMI), Kellgren-Lawrence class, preoperative blood volume, preoperative laboratory values, operation and tourniquet times, transfusion rate, knee circumference, preoperative HSS, or VAS score (P:n.s.). There was no significant difference in intraoperative blood loss (IBL) (52.7 ml vs. 63.4 ml, P = 0.07), hidden blood loss (HBL) (91.4 ml vs. 119.9, P = 0.4) or total blood loss (TBL) (144.1 ml vs. 183.3 ml, P = 0.72) between Groups A and B. Haemoglobin, haematocrit and red blood cell count (RBC) dropped to a low point on postoperative day 3 and then rebounded, returning to normal levels on day 21, and the trend of change between the 2 groups was not statistically significant (P:n.s.). There was no significant difference in subcutaneous ecchymosis incidence, knee swelling rate, HSS score, VAS score, LOS postoperatively, complication rate or patient satisfaction (P:n.s.). CONCLUSION: TXA was administered intravenously prior to tourniquet compression could effectively reduce blood loss in patients who had undergone total knee arthroplasty. However, there was no significant difference in knee swelling rate, subcutaneous bruising and petechiae incidence, knee function, complication rate or satisfaction between patients who TXA was given intravenously before tourniquet compression and release in primary TKA.

Uso de hidroxiapatita de cálcio no tratamento da dermatoporose / Use of calcium hydroxyapatite in the treatment of dermatoporosis

A dermatoporose é a síndrome de fragilidade cutânea. Acomete principalmente indivíduos acima de 60 anos, com maior prevalência no sexo feminino. Os principais fatores de risco são: envelhecimento, exposição solar intensa e uso de corticoterapia tópica e sistêmica. Se manifesta clinicamente por atrofia cutânea, púrpuras senis, pseudo cicatrizes estrelares e lacerações, podendo evoluir com hematomas dissecantes e infecções graves. Trata-se de uma doença com grande impacto na qualidade de vida dos pacientes e, até o presente momento, não há terapias com resultados satisfatórios. Hidratação, vitamina C tópica e oral, luz intensa pulsada foram algumas das terapêuticas estudadas. A hidroxiapatita de cálcio é um bioestimulador de colágeno composto por microesferas em um veículo de carboximetilcelulose (Radiesse®). Tem sido usada para estimular a produção endógena de colágeno e consequentemente melhorar a qualidade e espessura da pele. Este efeito do produto poderia melhorar o quadro clínico da dermatoporose. O estudo teve como objetivo avaliar a melhora das lesões purpúricas e da atrofia da pele após aplicação de Radiesse® no antebraço de 5 pacientes portadores de dermatoporose no setor de Dermatologia do Hospital do Servidor Público Municipal de São Paulo. Os 5 pacientes foram submetidos a aplicação de Radiesse® nos antebraços e foram avaliadas 45 e 90 dias após o procedimento, o número de lesões purpúricas, grau de atrofia da pele através do teste de pinçamento e realizado comparação fotográfica. Após o tratamento, observou-se melhora do número das lesões purpúricas, melhora da atrofia da pele e melhora da qualidade de pele quando comparada fotograficamente. Dessa forma, o tratamento com Radiesse® mostrou-se promissor, com resultados satisfatórios e com um bom perfil de segurança. Palavras-chave: Dermatoporose. Púrpura senil. Radiesse. Bioestimulador. Tratamento.

Chronic venous disease, platelet and haemostatic abnormalities contribute to the pathogenesis of pigmented purpuric dermatoses.

BACKGROUND: To investigate the aetiology of pigmented purpuric dermatoses (PPD). METHODS: 63 patients with a provisional diagnosis of PPD were assessed. Skin biopsies were performed to confirm the clinical diagnosis. Haemostasis was assessed using platelet function analyser-100 (PFA-100), light transmission aggregometry (LTA), impedance aggregometry (Multiplate) and measurement of clotting times and clotting factors. Chronic venous disease (CVD) was assessed by duplex ultrasound. When not contraindicated, patients were advised to discontinue haemostatic-modifying drugs or supplements for 4 weeks after which the laboratory measurements were repeated and the clinical resolution of PPD was assessed. Subsequently, a cohort of patients identified with CVD underwent endovenous interventions and further resolution of PPD was assessed. RESULTS: CVD was found in 48 patients (76.2%) while haemostatic abnormalities were found in 36 (57.1%). 30 patients (47.6%) had concurrent CVD and haemostatic abnormalities. Modifiable risk factors such as the intake of platelet inhibitors or other drugs and supplements such as fish oil were identified in 53 patients (84.1%). These could be ceased in 35 patients of whom 28 (80.0%) achieved either complete or partial resolution of PPD. Treatment of the underlying CVD was performed in 18 patients resulting in complete or partial resolution in 17 (94.4%). In seven patients (11.1%), no CVD or haemostatic abnormalities were identified, and the risk factors included dietary factors such as excessive caffeine or soft drink consumption. CONCLUSION: Haemostatic abnormalities and CVD contribute to the pathogenesis of PPD. Resolution of PPD in the vast majority of patients may be achieved by cessation of modifiable risk factors and in particular platelet-modifying drugs or supplements and treatment of the underlying venous disease.

Complete Remission of Refractory Immunothrombocytopenic Purpura After Tacrolimus Replacement With Cyclosporine in a Case of Living Related Liver Transplant.

Immunothrombocytopenic purpura is a possible complication after liver transplant. The therapy for immunothrombocytopenic purpura after liver transplant is similar to that of primary immunothrombocytopenic purpura. This therapy consists of corticosteroids, intravenous immunoglobulin, and immunosuppressive agents such as cyclosporine and rituximab. There are a few cases of immunothrombocytopenic purpura in patients who recovered after cessation of tacrolimus administration. Here, we show an intractable case of immunothrombocytopenic purpura in a living related liver transplant recipient treated with some of these. We observed complete remission after switch ofthe immunosuppressive agent from tacrolimus to cyclosporine. The patient was an infant girl aged 18 months who underwent livingr elated liver transplant for biliary atresia when she was 6 months old. Liver graft was a left lateral segment from her father. Purpura and severe thrombocytopenia developed after 11 months.There was no effect of the first-line therapies, as described in the Japan guidelines for immunothrombocytopenic purpura.Thrombocytopenia was extreme, as shown by a blood count of 0 platelets/µL. Administration of rituximab was started. However, her platelet count had not increased 8 weeks after rituximab initiation. As a trial therapy, we switched tacrolimus to cyclosporine. She showed complete remission 1 month after this drug conversion. Thus, a switch from tacrolimus to other immunosuppressive agents as a therapy for immunothrombocytopenic purpura after living related liver transplant should be considered.

Young child with painful edema and purpura: a case report.

BACKGROUND: We reported the case of a two-old-year boy with a painful acute hemorrhagic edema. This is a self-limited benign condition: usually, affected children are well appearing and this strongly support the diagnosis. In the opposite, in our case, we observed a painful presentation of the edema. Therefore, we demonstrated that rarely, this condition could have also a painful presentation. CONCLUSIONS: This case report helps clinician to know that also acute hemorrhagic edema could have a painful presentation, so we must considered it in the differential diagnosis with sepsis, sickle cell crisis and child abuse. We believe that these findings will be of interest to pediatricians.

Skin manifestations of COVID-19 in children: Part 3.

The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions, and in Part 2 we expanded to other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In this part of the review, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.

Cryoglobulinemic glomerulonephritis: clinical presentation and histological features, diagnostic pitfalls and controversies in the management. State of the art and the experience on a large monocentric cohort treated with B cell depletion therapy.

Cryoglobulinemia is defined by the presence of immunoglobulins having the following characteristics: forming a gel when temperature is <37 °C, precipitate in a reversible manner in the serum, and redissolve after rewarming. The presence of both polyclonal IgG and monoclonal IgM (type II), or of polyclonal IgG and polyclonal IgM (type III) identifies the mixed cryoglobulinemia (MC). The identification of the Hepatitis C virus (HCV) infection in most of the cases previously defined as "essential" represented a cornerstone in the understanding the pathogenesis of this condition. The picture of MC comprehends heterogeneous clinical presentations: from arthralgias, mild palpable purpura, fatigue to severe vasculitis features with skin necrotic pattern, peripheral neuropathy and, less commonly, lungs, central nervous system, gastrointestinal tract, and heart involvement. The kidney represents the most common organ presentation, and the presence of glomerulonephritis is a key element when considering prognosis. We discuss the clinical presentation and histological features, diagnostic pitfalls, and controversies in the management of patients with cryoglobulinemic glomerulonephritis, with a special focus on reporting our experience in treating patients with B cell depletion therapy.

Acne fulminans concomitant with vasculitis-like symptoms mimicking Henoch-Schoenlein purpura.

Acne fulminans is a severe form of acne vulgaris accompanied by systemic symptoms. A 17-year-old Chinese boy presented with an outbreak of necrotic lesions on his face eight days after the onset of palpable purpura, arthralgia, fever, abdominal pain, and proteinuria. He was successfully treated with oral prednisolone and isotretinoin. Vasculitis-like symptoms are rarely reported in acne fulminans; therefore, the physician needs to maintain awareness of this uncommon presentation.

Retiform Purpura as a Sign of Necrotizing Cellulitis in an Immunocompetent Boy.

Severe group A streptococcus (GAS) infections, particularly necrotizing soft tissue infections (NSTIs), have been associated with the development of streptococcal toxic-shock syndrome (STSS), a systemic illness caused by GAS-derived toxins. Traditional physical examination findings in NSTIs include skin necrosis, crepitus, and hemorrhagic bullae. However, these findings are limited in sensitivity and additional clinical markers may aid in making an early diagnosis of NSTI. We present a case of a superficial infection, specifically GAS necrotizing cellulitis, complicated by STSS in a healthy boy with an associated skin finding of retiform purpura that aided in early diagnosis of a NSTI.

Pigmented purpuric dermatosis in children: a retrospective cohort with emphasis on treatment and outcomes.

BACKGROUND: Data regarding the course and treatment of pigmented purpuric dermatoses (PPD) in the paediatric population are limited. Although treatments for pigmented purpura are not well established, vitamin C and rutoside have been reported to be an effective treatment option and are widely utilized. OBJECTIVE: To assess the clinical course and utility of vitamin C and rutoside in paediatric patients with PPD treated at Ann & Robert H. Lurie Children's Hospital of Chicago between 2008 and 2018. METHODS: A retrospective review of all children with PPD managed at our hospital between 2008 and 2018 was performed. Additional follow-up was obtained via telephone interviews. RESULTS: A total of 101 patients met inclusion criteria. The female: male ratio was 1.3 : 1, and the median age at diagnosis was 8.8 years (IQR, 5.7-12.9). Median follow-up was 7.13 months (IQR, 3-17.4). The most common PPD subtypes were lichen aureus (43%) and Schamberg (34%). Fifty-three (52%) patients had evaluable follow-up documentation via their medical record or phone questionnaire. Twenty-eight patients were treated with vitamin C or rutoside or combination therapy. Twenty-five patients received no treatment. Clearance of the rash was noted in 24 (45.3%) patients overall, including 10 (42%) patients in the treated group and 14 (58%) patients in the untreated group. Recurrence was noted in seven (13.2%) patients. Treatment with vitamin C and/or rutoside was well tolerated without side effects. None of the patients were subsequently diagnosed with vasculitis, coagulopathy or cutaneous T-cell lymphoma. CONCLUSION: Pigmented purpuric dermatosis in children is a benign disorder with high rates of complete resolution. Treatment with vitamin C and rutoside is well tolerated, but in this cohort, there did not appear to be an advantage over watchful waiting without therapy.

Experimental design in formulation optimization of vitamin K1 oxide-loaded nanoliposomes for skin delivery.

Due to the vitamin K1 sensitizing potential, the oxidized-isoform of vitamin K1 (vitamin K1 oxide, VKO), has been recently used for treating laser-induced purpura and hyperpigmentation in cosmetics. The objective of this study was to formulate VKO in nanoliposomes by using Box-Behnken experimental design to obtain an optimized formula with higher efficiency. The ratio of phospholipid to cholesterol (PC/CHO ratio), VKO concentration and sonication time in low, medium, and high levels were independent variables, while the percent of VKO entrapment efficiency (EE%) and vesicle size were selected as dependent variables. Optimum desirability was identified and an optimized formulation was prepared, characterized, and selected for in vitro VKO release and ex vivo skin permeation. The PC/CHO ratio showed the greatest effect on both responses (P < 0.0001). This effect was positive on EE%, while a negative effect was shown on vesicle size. The optimized formulation showed controlled drug release of 79.2% through a silicon membrane, and achieved flux of 327.36 ± 22.1 µg/cm2 through human skin after 24 h. So, nanoliposomes were proven as a suitable drug delivery system for topical delivery of VKO.

Purpuric rash and fever among hospitalized children aged 0-18 years: Comparison between clinical, laboratory, therapeutic and outcome features of patients with bacterial versus viral etiology.

BACKGROUND: The evaluation of children with purpuric rash and fever (PRF) is controversial. Although many of them have viral infections, on occasion such patients may be infected with Neisseria meningitidis. We described all children aged 0-18 years with PRF in southern Israel during the period 2005 ̶ 2016 and compared their microbiologic, laboratory, clinical and outcome characteristics in relation to various etiologies of this syndrome. METHODS: Data were summarized from electronic patient and microbiology files. Viral diagnoses were made by serology and/or PCR. RESULTS: Sixty-nine children with PRF were admitted; 30 (43.48%), 9 (13.04%) and 30 (43.48%) had a syndrome of bacterial, viral or non-established etiology, respectively. N. meningitidis infection was diagnosed in 16/69 (23.19%) patients and in 16/30 (53.33%) patients with bacterial etiology; 14/30 (46.67%) patients suffered from a non-invasive bacterial disease (9 with Rickettsial disease). Adenovirus and Influenza B (3 and 2 cases, respectively) represented the most frequent etiologic agents among patients with viral etiology. More patients with PRF of bacterial etiology were older, of Bedouin ethnicity, looked ill on admission, had higher rates of meningitis and were treated more frequently with antibiotics compared with patients with non-bacterial PRF. Fatality rates among patients with bacterial, viral and non-established etiology were 5/30 (16.7%), 0% and 2/39 (5.1%). CONCLUSIONS: Although PFR was uncommon, high rates of meningococcal infections were recorded in children with PRF, which was associated with high fatality rates. Rickettsial infections were frequent, emphasizing the need for a high index of suspicion for this disease in endemic geographic areas.