Cross-sectional characteristics of pediatric-onset discoid lupus erythematosus: Results of a multicenter, retrospective cohort study.

BACKGROUND: The incidence of systemic lupus in children with discoid lupus is unknown. OBJECTIVE: This study assessed the baseline characteristics of patients with pediatric discoid lupus erythematosus (pDLE). METHODS: Medical records at 17 sites were reviewed for pediatric dermatology and rheumatology patients with discoid lupus erythematosus. The inclusion criteria were clinical and/or histopathologic diagnosis of discoid lupus erythematosus with an age at onset of <18 years. Baseline data were collected at the first documented visit. Outcomes included diagnosis of systemic lupus erythematosus (SLE) at the baseline visit using the 1997 American College of Rheumatology (primary) and the 2012 Systemic Lupus International Collaborating Clinics (secondary) criteria. RESULTS: Of the >1500 charts reviewed, 438 patients met the inclusion criteria. The cohort was predominantly female (72%) and racially/ethnically diverse. A diagnosis of SLE at the baseline visit (pDLE + SLE) was rendered in 162 (37%) patients using the American College of Rheumatology and in 181 (41%) patients using the Systemic Lupus International Collaborating Clinics criteria. Patients with pDLE + SLE were older at the time of rash onset (median, 12.9 vs 8.9 years; P < .001), with shorter time from discoid lupus erythematosus onset to diagnosis, compared with patients with pDLE-only (median, 2 vs 7 months; P < .001). Patients with pDLE + SLE were more likely to be female (P = .004), with generalized discoid lupus erythematosus and clinically aggressive disease, including end-organ involvement, positive serologies, and higher- titer levels of antinuclear antibodies (P < .001). LIMITATIONS: Retrospective study. CONCLUSION: A diagnosis of discoid lupus erythematosus in adolescence should prompt thorough screening for SLE.

A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

PHACES association: a neuroradiologic review of 17 patients.

BACKGROUND AND PURPOSE: We present neuroradiologic findings in 17 patients with posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, and sternal or ventral defects (PHACES) association and identify those at highest risk of central nervous system (CNS) structural, cerebrovascular, and neurodevelopmental abnormalities. MATERIALS AND METHODS: Patients with PHACES association were identified in the Vascular Anomalies Program at New York University Medical Center from 1998 to 2007. Many patients were followed in conjunction with other specialists at the Birthmark Institute at Roosevelt Hospital. Clinical records and imaging studies were reviewed retrospectively. Criteria for diagnosis of PHACES were based on previously published indicators. Imaging studies were independently re-reviewed by a neuroradiologist. Segmental mapping of cutaneous hemangioma distribution by photograph review and presence or absence of other PHACES-associated findings were correlated with radiologic findings. RESULTS: Patients with large facial cutaneous (S1-S4) hemangiomas were especially at risk of CNS structural and cerebrovascular anomalies; S1 with ocular anomalies; and S3 with airway, ventral, and cardiac anomalies. All patients with CNS structural malformations had a cerebrovascular abnormality, and this cohort was at risk for developmental and/or other neurologic sequelae. Four patients had supratentorial CNS anomalies, including cortical dysgenesis and migration abnormalities. Some patients with CNS arteriopathy progressed to aneurysms. CONCLUSION: Our data support and expand the work of others, identifying risk factors for segmental hemangiomas. In addition to posterior fossa CNS anomalies, supratentorial anomalies may be present in patients with PHACES, and this may correlate with significant clinical sequelae. The long-term prognosis of these patients remains unknown.

Transfusion-transmitted virus is not present in factor IX concentrates commonly used to treat haemophilia B.

Transfusion-transmitted virus (TTV) is a potential cause of post-transfusion hepatitis in patients with haemophilia. Plasma-derived clotting factor concentrates currently undergo processes that are effective in removal and inactivation of viruses such as HIV, hepatitis B and C; however, their effectiveness with respect to TTV is unknown. To determine if TTV DNA is present in plasma-derived concentrates of factor IX, we tested 14 lots of Mononine and compared the results with BeneFix. Nucleic acid isolation, followed by a two-round polymerase chain reaction (PCR) and agarose gel analysis indicated that all 17 lots were negative for TTV. Although TTV may be considered an emerging pathogen, no evidence of the virus was detected in the commercially available plasma-derived concentrate of FIX most commonly used to treat haemophilia B.

Rational design of potent human transthyretin amyloid disease inhibitors.

The human amyloid disorders, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and senile systemic amyloidosis, are caused by insoluble transthyretin (TTR) fibrils, which deposit in the peripheral nerves and heart tissue. Several nonsteroidal anti-inflammatory drugs and structurally similar compounds have been found to strongly inhibit the formation of TTR amyloid fibrils in vitro. These include flufenamic acid, diclofenac, flurbiprofen, and resveratrol. Crystal structures of the protein-drug complexes have been determined to allow detailed analyses of the protein-drug interactions that stabilize the native tetrameric conformation of TTR and inhibit the formation of amyloidogenic TTR. Using a structure-based drug design approach ortho-trifluormethylphenyl anthranilic acid and N-(meta-trifluoromethylphenyl) phenoxazine 4, 6-dicarboxylic acid have been discovered to be very potent and specific TTR fibril formation inhibitors. This research provides a rationale for a chemotherapeutic approach for the treatment of TTR-associated amyloid diseases.

Synthesis and evaluation of inhibitors of transthyretin amyloid formation based on the non-steroidal anti-inflammatory drug, flufenamic acid.

A light scattering-based amyloid fibril formation assay was employed to evaluate potential inhibitors of transthyretin (TTR) amyloid fibril formation in vitro. Twenty nine aromatic small molecules, some with homology to flufenamic acid (a known non-steroidal anti-inflammatory drug) were tested to identify important structural features for inhibitor efficacy. The results of these experiments and earlier data suggest that likely inhibitors will have aromatic-based structures with at least two aromatic rings. The ring or fused ring system occupying the outermost TTR binding pocket needs to be substituted with an acidic functional group (e.g. a carboxylic acid) to interact with complimentary charges in the TTR binding site. The promising TTR amyloid fibril inhibitors ranked in order of efficacy are: 2 > 4 approximately 7 > 3 > 9 > 6 > 21.

Synthesis and evaluation of anthranilic acid-based transthyretin amyloid fibril inhibitors.

Eight small molecules were synthesized to evaluate the structure activity relationships (SAR) of N-substituted anthranilic acids. The molecules were synthesized by benzylation or arylation of methyl anthranilate. A light scattering-based amyloid fibril formation assay was used to evaluate potential inhibitors of transthyretin (TTR) amyloid fibril formation in vitro. The m-carboxyphenylated and o-trifluoromethylphenylated anthranilic acids are potent inhibitors that will be subjected to further SAR and structural analysis.

Outbreak of viral hepatitis B in a rural community in India linked to inadequately sterilized needles and syringes.

In India, virtually all outbreaks of viral hepatitis are considered to be due to faeco-orally transmitted hepatitis E virus. Recently, a cluster of 15 cases of viral hepatitis B was found in three villages in Gujarat State. The cases were epidemiologically linked to the use of inadequately sterilized needles and syringes by a local unqualified medical practitioner. The outbreak evolved slowly over a period of 3 months and was marked by a high case fatality rate (46.7%), probably because of concurrent infection with hepatitis D virus (HDV) or sexually transmitted infections. But for the many fatalities within 2-3 weeks of the onset of illness, the outbreak would have gone unnoticed. The findings emphasize the importance of inadequately sterilized needles and syringes in the transmission of viral hepatitis B in India, the need to strengthen the routine surveillance system, and to organize an education campaign targeting all health care workers including private practitioners, especially those working in rural areas, as well as the public at large, to take all possible measures to prevent this often fatal infection.

PIP: Viral hepatitis outbreaks in India are generally due to feco-orally transmitted hepatitis E virus. Described in this paper is a cluster of 15 cases of viral hepatitis B found in three villages in Gujarat State's Mehasana District linked to the use of inadequately sterilized needles and syringes by an unqualified medical practitioner. Patients were identified by house-to-house surveys and blood tests. The outbreak, which evolved slowly over a 3-month period, had a 46.7% case fatality rate because of concurrent infection with hepatitis D infection and sexually transmitted diseases. Without fatalities, this outbreak would not have been noticed. This event indicates a need to strengthen the routine hepatitis B surveillance system in India as well as to target health care workers in rural areas for an educational campaign about the importance of sterile equipment.