Somatic mosaicism in B cells of a patient with autosomal dominant hyper IgE syndrome

Hyper IgE syndrome (HIES) is characterized by recurrent skin abscesses, eczema, pneumonia, and high levels of serum IgE. Nonimmunologic manifestations of HIES include a characteristic face, pathologic dentition, scoliosis, bone alterations, hyperextensible joints, and vascular abnormalities. Somatic mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. In this report, we describe one patient with classical HIES and another patient with a mild phenotype, both harboring the same genetic mutation. The patient with a mild phenotype did not present the characteristic face, had normal production of IL‐17A by T CD4⁺ cells, but had low phosphorylation of STAT‐3 in B cells. Interestingly, the mutation found in B cells was absent in other cell types analyzed, in agreement with the presence of a somatic mosaic genotype. The clinical and functional differences observed between these patients justify the use of complementary tools for a better definition of the cases. These approaches allow for a better understanding of complex phenotypes associated with somatic mosaicisms, and present the possibility to analyze the role of B lymphocytes in the pathophysiology of this disease. This knowledge has an impact on not only the treatment but also the provision of appropriate genetic counseling.     

Congenital melanocytic nevi: treatment modalities and management options

Congenital melanocytic nevi can be cosmetically disfiguring, give rise to melanoma, and suggest the presence of neurocutaneous melanocytosis. Management decisions must be tailored for each patient and each nevus, taking into consideration the risk for developing malignancy, risk for developing symptomatic neurocutaneous melanocytosis, cosmetic implications of having the nevus, cosmetic implications of any resultant surgical scars from their removal, adverse effects that the nevus may have on psycho-social development, and the adverse effects and long-term sequelae of any surgical intervention. The advantages and disadvantages of different modalities used in the treatment of congenital melanocytic nevi are discussed. Organizational flow diagrams are presented to help clinicians in managing patients with different sized congenital melanocytic nevi.     

Mutations in the DNA mismatch repair gene MLH1 associated with early-onset colon cancer

Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominant disorder characterized by the predisposition to develop a number of cancers, especially colorectal cancer (CRC). We present a HNPCC family with CRC at age 12 years. Our observations suggest that the germline mutation of the both copies of the MLH1 gene may play a role in the early onset of CRC.     

Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06)

Background

Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients.

Methods

This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel.

Results

173 and 172 were tested at all three timepoints for NT-proBNP and TnT, respectively. The incidence of biomarker elevation was overall low at all timepoints for all the three treatment arms. A total of 13 CEs in 11 patients occurred. Biomarker elevations in patients with CEs were very rare; only one patient with subsequent CE had a NT-proBNP elevation at baseline and at week 2.

Conclusion

These results suggest that TnT and proBNP may not be useful as early predictors of cardiac toxicity in anthracycline-naïve patients receiving trastuzumab and/or lapatinib.

     

Coverage of supraumbilical abdominal wall defects: The tunnelled‐pedicled ALT technique

Abdominal wall defects are a challenge for reconstructive surgeons. Although the utility of anterolateral thigh perforator (ALT) flap has been well established for lower abdominal wall reconstruction, pedicled ALT flap is usually not considered for supraumbilical defects in the most recent algorithms. The purpose of this paper is to report the results of a tunneled pedicled ALT flap for reconstruction of supraumbilical defect from a series of patients. From July 2009 to September2014, six patients underwent delayed abdominal wall coverage using pedicled ALT flaps and reinforcement with polypropylene meshes. Defects occurred after surgical complications and abdominal trauma. Flaps were tunneled beneath the rectus femoris and sartorius muscles to increase the pedicle length. The size of the skin islands ranged from 22–29 × 10–14 cm. All flaps survived and the healing of the wounds was successful. Partial dehiscence of donor site occurred in one patient, and small wound dehiscence due to minimal distal necrosis was observed in another patient. No functional problems were reported in donor site, and no complications occurred in 6–68 months of follow‐up. The tunneled pedicled ALT flap may provide a reliable alternative method for abdominal wall reconstruction, including supraumbilical defects. © 2015 Wiley Periodicals, Inc. Microsurgery 37:119–127, 2017.     

Total Knee Arthroplasty After Failed Unicompartmental Knee Arthroplasty. Clinical Results,Radiologic Findings,and Technical Tips

Background

The loss of anatomic references and bone stock turns unicompartmental knee arthroplasty (UKA) revision surgery difficult, and according to some authors, it is technically as challenging as a total knee arthroplasty (TKA) revision surgery.

Regulatory T cells and IL-17A levels in noninfectious uveitis

Graefe's Archive for Clinical and Experimental Ophthalmology - Regulatory T cells (Tregs) have been intensively studied in a myriad of autoimmune diseases. As for noninfectious uveitis (NIU),...