Targeted therapies in interstitial lung disease secondary to systemic autoimmune rheumatic disease. Current status and future development

Autoimmune rheumatic diseases (ARD) are characterized by systemic manifestations and multiple organ involvement, including the lung. Interstitial Lung Disease (ILD) is a cardinal manifestation of lung involvement in patients with ARD and is associated with significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are used as first –line treatment. Targeted therapies, such as biological disease modifying antirheumatic drugs (DMARDS) and anti- fibrotic agents are new treatment options. In this review we discuss the role of targeted therapies in patients with ILD secondary to ARD.     

DNA methylation biomarkers as diagnostic and prognostic tools in colorectal cancer

Colorectal cancer (CRC) is the third most common type of cancer and is responsible for 9 % of cancer deaths in both men and women in the USA for 2013. It is a heterogenous disease, and its three classification types are microsatellite instability, chromosomal instability, and CpG island methylator phenotype. Biomarkers are molecules, which can be used as indicators of cancer. They have the potential to achieve great sensitivities and specificities in diagnosis and prognosis of CRC. DNA methylation biomarkers are epigenetic markers, more specifically genes that become silenced after aberrant methylation of their promoter in CRC. Some methylation biomarkers like SEPT9 (ColoVantage®) and vimentin (ColoSure^TM) are already commercially available. Other blood and fecal-based biomarkers are currently under investigation and clinical studies so that they can be used in the near future. Biomarker panels are also currently being studied since they show great potential in diagnosis as they can combine robust biomarkers to achieve even greater sensitivities than single markers. Finally, methylation-sensitive microRNAs (miRNAs) are very promising markers, and their investigation as biomarkers, is only at primitive stage.     

Ogilvie's syndrome following posterior spinal arthrodesis for scoliosis

We report Ogilvie''s syndrome following posterior spinal arthrodesis on a patient with thoracic and lumbar scoliosis associated with intraspinal anomalies. Postoperative paralytic ileus can commonly complicate scoliosis surgery. Ogilvie''s syndrome as a cause of abdominal distension and pain has not been reported following spinal deformity correction and can mimic post-surgical ileus. 12 year old female patient with double thoracic and lumbar scoliosis associated with Arnold-Chiari 1 malformation and syringomyelia. The patient underwent posterior spinal fusion from T₄ to L₃ with segmental pedicle screw instrumentation and autogenous iliac crest grafting. She developed abdominal distension and pain postoperatively and this deteriorated despite conservative management. Repeat ultrasounds and abdominal computer tomography scans ruled out mechanical obstruction. The clinical presentation and blood parameters excluded toxic megacolon and cecal volvulus. As the symptoms persisted, a laparotomy was performed on postoperative day 16, which demonstrated ragged tears of the colon and cecum. A right hemi-colectomy followed by ileocecal anastomosis was required. The pathological examination of surgical specimens excluded inflammatory bowel disease and vascular abnormalities. The patient made a good recovery following bowel surgery and at latest followup 3.2 years later she had no abdominal complaints and an excellent scoliosis correction. Ogilvie''s syndrome should be included in the differential diagnosis of postoperative ileus in patients developing prolonged unexplained abdominal distension and pain after scoliosis correction. Early diagnosis and instigation of conservative management can prevent major morbidity and mortality due to bowel ischemia and perforation.     

Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies

Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency as well as the identification of "CLL-biased" features in BCR Ig stereotypes. To this end, we examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times the size of the largest published series, with an updated version of our purpose-built clustering algorithm. We document that CLL may be subdivided into 2 distinct categories: one with stereotyped and the other with nonstereotyped BCRs, at an approximate ratio of 1:2, and provide evidence suggesting a different ontogeny for these 2 categories. We also show that subset-defining sequence patterns in CLL differ from those underlying BCR stereotypy in other B-cell malignancies. Notably, 19 major subsets contained from 20 to 213 sequences each, collectively accounting for 943 sequences or one-eighth of the cohort. Hence, this compartmentalized examination of VH sequences may pave the way toward a molecular classification of CLL with implications for targeted therapeutic interventions, applicable to a significant number of patients assigned to the same subset.     

Tear of Retinal Pigment Epithelium following YAG Laser Posterior Capsulotomy in a Patient on Anti-VEGF Treatment for AMD: Six Months’ Follow-Up

Purpose

To present a rare case of retinal pigment epithelium (RPE) rupture following YAG laser posterior capsulotomy (YAG PC) in a patient with exudative age-related macular degeneration (AMD).

Materials and Methods

An 85-year-old pseudophakic male patient on ranibizumab 0.5 mg/0.05 ml treatment due to exudative AMD received YAG PC for dense posterior capsule opacification (PCO) in his right eye. The patient had received his last intravitreal ranibizumab injection 3 months before YAG PC; his macula appeared stable on fundoscopy and optical coherence tomography scans at repeated visits, but his vision deteriorated to counting fingers due to PCO.

Results

Following left eye posterior YAG PC, his best-corrected visual acuity (BCVA) improved to 6/12 (Snellen chart). Despite satisfactory visual results, the patient developed a parafoveal inferotemporal RPE rupture. A decision for further treatment with ranibizumab (0.5 mg/0.05 ml) intravitreal injections was made. After a total of 7 injections, the patient was clinically stable and his BCVA was 6/18 (Snellen chart).

Conclusions

RPE rupture is a well-known, serious complication in patients with exudative AMD, which often has devastating results on patients’ vision. Offering YAG PC to those patients could lead to a rupture of the RPE even in cases which appear to be stable and well controlled. Clinicians should be aware of this complication and inform the patients accordingly.Key Words: Retinal pigment epithelium tear, YAG Laser, Age-related macular degeneration, Pigment epithelial detachment rupture, Ranibizumab