Background Atypical hemolytic uremic syndrome (aHUS) is a rare genetic life-threatening disease of chronic uncontrolled complement activation leading to thrombotic microangiopathy (TMA) and severe ...end-organ damage. Eculizumab, a terminal complement inhibitor approved for aHUS treatment, was reported to improve hematologic and renal parameters in 2 prior prospective phase 2 studies. This is the largest prospective study of eculizumab in aHUS to date, conducted in an adult population. Study Design Open-label single-arm phase 2 trial. Setting & Participants Patients 18 years or older with aHUS (platelet count <150 × 103 /μL, hemoglobin ≤ lower limit of normal, lactate dehydrogenase ≥1.5 × upper limit of normal ULN, and serum creatinine ≥ ULN) were included in this multicenter multinational study. Intervention Intravenous eculizumab (900 mg/wk for 4 weeks, 1,200 mg at week 5 and then every 2 weeks) for 26 weeks. Outcomes & Measurements Primary end point was complete TMA response within 26 weeks, defined as hematologic normalization (platelet count ≥150 × 103 /μL, LDH ≤ ULN), and preservation of kidney function (<25% serum creatinine increase from baseline), confirmed by 2 or more consecutive measurements obtained 4 or more weeks apart. Results 41 patients were treated; 38 (93%) completed 26 weeks of treatment. 30 (73%) were included during their first TMA manifestation. 30 (73%) had complete TMA response. Platelet counts and estimated glomerular filtration rates increased from baseline ( P < 0.001). All 35 patients on baseline plasma exchange/plasma infusion discontinued by week 26. Of 24 patients requiring baseline dialysis, 5 recovered kidney function before eculizumab initiation and 15 of the remaining 19 (79%) discontinued dialysis during eculizumab treatment. No patients lost existing transplants. Quality-of-life measures were significantly improved. Two patients developed meningococcal infections; both recovered, and 1 remained on eculizumab treatment. Limitations Single-arm open-label design. Conclusions Results highlight the benefits of eculizumab in adult patients with aHUS: improvement in hematologic, renal, and quality-of-life parameters; dialysis discontinuation; and transplant protection.
Background Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis with possible cutaneous-specific involvement. Objectives We sought to describe the clinical, pathological, ...and molecular features of the cutaneous manifestations of 40 patients with ECD identified from a cohort of 123 patients. Methods Confirmed cases of patients with ECD were included in a single-center retrospective observational study. Clinical and pathological cutaneous features were analyzed and BRAF V600E mutation was determined. Results The most frequent ECD cutaneous manifestations were xanthelasma-like lesions (XLL), which occurred in 31 (25%) patients. Other ECD cutaneous lesions were patches or papulonodular lesions. Mixed form of ECD and cutaneous Langerhans cell histiocytosis presented with crusty papules of the folds in some patients. Compared with classic xanthelasma palpebrarum, ECD XLL pathology more frequently involved the reticular dermis, displayed more multinucleated or Touton cells, and showed less extensive fibrosis. BRAF V600E mutation was more frequently detected in patients with cutaneous involvement than in those without (76% vs 52%; P = .005) and constantly found in 10 XLL. Limitations Some clinical data were not available because of the retrospective design of the study. Conclusions XLL are the most frequent cutaneous ECD manifestations and might be targeted both for pathology and determination of BRAF mutational status.
Background Telangiectasia macularis eruptiva perstans (TMEP) has not been fully characterized. Objective We sought to estimate the frequency and clinical characteristics of TMEP in a cohort of adult ...patients with cutaneous mastocytosis, and to assess the presence of systemic involvement. Methods We included all consecutive patients evaluated for cutaneous mastocytosis in 2 centers: the Mastocytosis Competence Center of the Midi-Pyrénées from May 2006 to December 2013, and the French Reference Center for Mastocytosis from January 2008 to September 2013. Skin phenotype, histopathology, presence of KIT mutation in the skin, and assessment of systemic involvement according to World Health Organization (WHO) criteria were prospectively investigated. Results Of 243 patients with cutaneous mastocytosis, 34 (14%) were given a diagnosis of TMEP. The diagnosis of systemic mastocytosis was established in 16 patients (47%) with TMEP. Three patients (9%) had aggressive systemic mastocytosis (C-findings according to WHO). In all, 32 patients (94%) exhibited at least 1 mast cell activation–related symptom. Limitations Patient recruitment was undertaken at 2 referral centers with expertise in the diagnosis and treatment of mastocytosis so that the clinical findings and incidence of systemic involvement may be overestimated in comparison with the overall population of patients with TMEP. Conclusion TMEP accounts for about 14% of patients with cutaneous mastocytosis. The disease manifests as mast cell activation symptoms in almost all patients and can be associated with systemic involvement in about 50% of cases.
Abstract Purpose To describe gastrointestinal emergencies in cancer patients. Methods All cancer patients admitted to the medical ICU of Saint-Louis Hospital for an acute abdominal syndrome during ...the study period (1997–2011) were included. Results A total of 164 patients were included. The most common diagnoses were: neutropenic enterocolitis (NE) ( n = 54, 33%), infectious colitis and peritonitis ( n = 51, 31%), bowel infiltration by malignancy ( n = 14, 9%), and mucosal toxicity of chemotherapy ( n = 12, 7%). Microbiologically documented infections were reported in 82 patients (50%), including 12 fungal infections. Twenty-seven patients (16%) underwent urgent surgery. The hospital mortality rate was 35%. Five factors were independently associated with hospital mortality: the Simplified Acute Physiology Score II (SAPS II) score on day 1 (OR 1.03/SAPS II point, 95% CI 1.01 to 1.05), microbiological documentation (OR 0.27, 95% CI 0.11 to 0.64), neutropenia (OR 0.42, 95% CI 0.19 to 0.95), allogenic hematopoietic stem-cell transplantation (HSCT) (OR 5.13, 95% CI 1.71 to 15.4), and mechanical ventilation (OR 3.42, 95% CI 1.37 to 8.51). Conclusions Gastrointestinal emergencies in cancer patients are associated with significant mortality. Mortality correlated both with the severity of organ failure upon ICU admission and the underlying diagnosis. Interestingly, patients admitted to the ICU with neutropenia had better survival.
Objective To describe a new entity characterized by airway-centered fibroelastosis. Methods We identified cases with prominent airway-centered elastosis in lung samples, and little or no pleural ...involvement identified through a pathologic database at a single institution over an 8-year period. Results Airway-centered fibroelastosis was characterized by (1) extensive airway-centered fibroelastosis of the upper lobes on histopathology and (2) marked bronchial abnormalities with bronchial wall thickening, bronchial wall deformation, and bronchiectasis, along with progressive parenchymal retraction and predominantly subpleural upper-lobe consolidations on high-resolution CT. Pateints were five nonsmoking women aged between 38 and 56 years old. They experienced chronic dyspnea with acute attacks of wheezing and dyspnea. Moderate to severe physiological abnormalities were observed, with an obstructive pattern in three cases and a restriction in two. Despite inhaled and oral corticosteroids, the disease was progressive in all patients and evolved to chronic respiratory failure, requiring lung transplantation in two patients. Four patients had chronic asthma. Conclusions We consider airway-centered fibroelastosis to be a unique and distinct pathological entity in women that needs to be individualized, with a specific clinical, imaging, and pathological presentation. We hypothesize that airway-centered fibroelastosis may be idiopathic or asthma-associated.
Abstract Objectives Systemic capillary leak syndrome (Clarkson′s disease) is a rare entity characterized by recurrent and unpredictable attacks of capillary leakage of plasma fluid and proteins ...throughout the endothelium. Some cases are secondary. We describe the rare association between secondary capillary leak syndrome (SCLS) and auto-immune diseases. Methods We conducted a nation-wide, retrospective, observational and collaborative study throughout the hospital units of the CRI network (Club des Rhumatismes et Inflammations) between March and August 2015. Inclusion criteria were patients with 1) capillary leakage episodes characterized by edema and elevated hematocrit, low albumin count without proteinuria or other cause of protein loss; and 2) definite auto-immune diseases according to international classification criteria. Results The clinical and biological data of five patients (3 women) were reviewed. Median age was 43.2 (17 to 55) years. Four patients had Sjögren syndrome. One of these also fulfilled the criteria for systemic sclerosis (n=1). The fifth had polymyositis. During the 37.2 months of median follow-up (5.4 to 201) we recorded a total of 24 attacks, yielding an attack incidence of 91/100 patient-years. Laboratory tests revealed that three patients had anti-SSA/Ro antibodies. Only one had a monoclonal blood component (IgGκ). Three patients needed ICU supports; one died during a flare. Conclusion We reported the first case-series of a rare association of SCLS and autoimmune diseases, supporting the idea of some immune mediation in the pathogenesis of the former disease.
This study aims to assess the feasibility and efficacy of high-dose rate (HDR) brachytherapy (BT) administered in a single insertion with 4 treatment sessions for locally advanced cervical cancer and ...to identify the prognostic factors influencing outcomes.
We retrospectively analyzed the clinical data of patients with cervical cancer with locally advanced disease (International Federation of Gynecology and Obstetrics 2018 IB-IVB) treated at our institution from January 2014 through December 2021. Each patient received definitive radiation therapy with an external irradiation dosage between 45 and 50.4 Gy along with concurrent chemotherapy. HDR-BT (24 Gy) was prescribed to a high-risk clinical target volume.
One hundred thirty-nine patients were included and the HDR-BT program could be fully performed in 136 patients (98%). Over a median follow-up duration of 40.5 months, the 2-year local control (LC), overall survival (OS), and disease-free survival rates stood at 79.4%, 77.7%, and 61.7%, respectively, with 5-year rates at 78.2%, 61.6%, and 55.7%. Multivariate analysis revealed the primary determinant of LC as the tumor's response to external beam radiation therapy as determined via magnetic resonance imaging before BT. Parametrial involvement demonstrated a significant multivariate association with disease-free survival (P = .04). Regarding OS, parametrial invasion (P = .01) and the tumor's response postchemoradiotherapy (P = .02) emerged as significant factors. Regarding chronic toxicities, 18% (25 patients) experienced grade 3 complications. An optimal D2 cc (bowel) threshold of 70 Gy (P = .001) was identified to limit chronic digestive complications of grade 3 or higher.
The implementation of single-insertion, 4-session HDR-BT could be performed in 98% of the patients. It yields favorable LC and OS rates, coupled with tolerable toxicity in patients with locally advanced cervical cancer. Response to initial chemoradiotherapy evaluated on pre-BT magnetic resonance imaging is an important prognostic factor and could help to individualize therapeutic strategies.
Background Interaction between smoking and efficacy of antimalarials, the mainstay of treatment for cutaneous lupus erythematosus (CLE), remains controversial. Objectives We systematically reviewed ...the evidence for such an interaction and performed a meta-analysis to compare the efficacy of antimalarials among smoker versus nonsmoker patients with CLE. Methods Observational studies published up to March 2014 in the MEDLINE, Embase, and Cochrane databases were selected if they reported on the efficacy of antimalarials for treatment of CLE, according to smoking status. The strength of association between smoking and cutaneous response rate was expressed using the odds ratio. Individual study odds ratios were combined in the meta-analysis using a random effects model. Results Of 240 citations retrieved, 10 studies met inclusion criteria, for a total of 1398 patients. The pooled odds ratio for the response to antimalarials in smoker patients with CLE (n = 797) was 0.53 (95% confidence interval 0.29-0.98) compared with nonsmokers (n = 601). Limitations Subgroup analyses for the response to antimalarials considering CLE subtypes, type, and dosage of antimalarials could not be performed because of the lack of available data. Conclusions Smoking is associated with a 2-fold decrease in the proportion of patients with CLE achieving cutaneous improvement with antimalarials. Smoking cessation should be considered in patients with CLE and refractory cutaneous involvement.
Background Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). Objectives We sought to evaluate the efficacy of increased daily doses of HCQ on ...cutaneous response in refractory CLE. Methods We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. Results We included 34 patients (26 women; median age 45 range 28-72 years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 range 2-30 vs 1.5 range 0-30), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 range 3.06-77.4 months) was achieved in 15 of the 26 responders. Limitations The main limitations of the study are its open-label design and the limited number of patients included. Conclusions Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE.
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