Whole genome SNP genotyping in a family segregating developmental dysplasia of the hip detected runs of homozygosity on chromosomes 15q13.3 and 19p13.2

Developmental dysplasia of the hip (DDH) is one of the most prevalent developmental orthopedic diseases worldwide. DDH is a spectrum of anatomical abnormalities of the hip joint and is characterized by premature arthritis in later life. Sporadic cases have been reported more frequently; however, some studies have reported families segregating DDH. Studies have suggested that the genetic factors play a significant role in the development of DDH. In order to detect genetic defect underlying DDH, we performed Sanger sequencing of all DDH associated genes, whole genome SNP genotyping and exome sequencing in a Saudi family with four individuals having DDH. Sanger sequencing of all known genes did not identify any pathogenic variant. Genotype data analysis using HomozygosityMapper identified shared homozygous regions on chromosome 15q13.3 and chromosome 19p13.2 flanked by rs17228178‐rs1534200 and rs466123‐rs2112461, respectively. These data were also analyzed by cnvpartition software for identification of DDH associated copy number variations (CNV). A shared copy number gain of approximately 15 kb on chr6p21.32 (chr6:33 053 906–33 069 893) was discovered in all affected individuals. Partial gain of this region has also been found in unaffected sibling of this family. Exome data did not reveal any candidate sequence variant. Whole genome sequencing is required to identify deep intronic variants in the shared homozygous regions. Identification of genetic variants involved in pathogenesis of DDH may open up interesting perspectives into the function of the gene(s) in hip joint development.     

Accuracy of shade matching performed by colour blind and normal dental students using 3D Master and Vita Lumin shade guides

The purpose of this study was to investigate whether 3D Master or VitaLumin shade guides could improve colour selection in individuals with normal and defective colour vision. First, colour perception of 260 dental students was evaluated. Afterwards, 9 colour blind and 9 matched normal subjects tried to detect colours of 10 randomly selected tabs from each kit and the correct/false answers were counted. Of the colour-defective subjects, 47.8% and 33.3% correctly detected the shade using 3D Master and VitaLumin, respectively. These statistics were 62.2% and 42.2% in normal subjects. In normal participants, but not in colour blind ones, 3D Master significantly improved shade matching accuracy compared to VitaLumin.     

Effectiveness of stenting and subsequent re-implantation of disconnected pulmonary artery to restore the pulmonary hemodynamics

Introduction::Early intervention in patients with congenitally disconnected pulmonary artery improves long-term outcome.Case presentation::We present 3 cases of...     

Orthopaedic manifestations of campomelic dysplasia

Campomelic dysplasia is a rare form of congenital dwarfism associated with potentially fatal respiratory insufficiency. There are several types of campomelic dysplasia; however, it is characterized by the presence of anteriorly bowed tibias with cutaneous dimpling, anterolaterally bowed femurs, thoracic kyphoscoliosis, hypoplastic scapulas, and absence or delayed ossification of thoracic pedicles. With improving treatment of respiratory insufficiency, the survival rate of affected infants has increased, thereby necessitating treatment of the musculoskeletal malformations to prevent additional morbidity. In an attempt to increase awareness of the presentation of infants with campomelic dysplasia and to emphasize the difficulties of treating associated developmental dislocation of the hip early, the current authors report the case of a 2-year-old girl with campomelic dysplasia who was treated for dislocation of the right hip. The postoperative course of this child was complicated seriously by several apneic episodes secondary to tracheobronchial malacia for which she required admission to the pediatric intensive care unit.     

Displaced fracture of the distal radius in children: factors responsible for redisplacement after closed reduction

We retrospectively reviewed 183 children with a simple fracture of the distal radius, with or without fracture of the ulna, treated by closed reduction and cast immobilisation. The fracture redisplaced after an initial, acceptable closed reduction in 46 (25%). Complete initial displacement was identified as the most important factor leading to redisplacement. Other contributing factors were the presence of an ipsilateral distal ulnar fracture, and the reduction of completely displaced fractures under deep sedation or local haematoma block. We recommend that completely displaced fractures of the distal radius in children should be reduced under general anaesthesia, and fixed by primary percutaneous Kirschner wires even when a satisfactory closed reduction has been achieved.     

The role of arthrography-guided closed reduction in minimizing the incidence of avascular necrosis in developmental dysplasia of the hip

Avascular necrosis of the femoral head is the most serious complication after closed reduction in developmental dysplasia of the hip. Although arthrography has a well-established role in the treatment of developmental dysplasia of the hip, its use is not universal. A prospective study was conducted to compare the incidence of avascular necrosis after closed reduction in developmental dysplasia of the hip performed with and without arthrography in 85 patients, with a minimum of 5 years follow up. Arthrographic criteria were evaluated including lateralization of the femoral head and the type of limbus encountered. Hips treated by closed reduction based on arthrographic evaluation had significantly less incidence of avascular necrosis when compared with those treated by closed reduction without arthrographic guidance. Closed reduction with lateralization of more than 4 mm, and those hips with an inverted limbus were associated with an increased risk of avascular necrosis.     

Pulmonary atresia with intact ventricular septum and antenatal left ventricular failure

Pulmonary atresia with intact ventricular septum has been described extensively, and it is recognized that associated abnormalities of the coronary arteries may cause ischemia. We describe a fetus, diagnosed antenatally as having pulmonary atresia with intact ventricular septum and severe hypoplasia of the right ventricle, who developed severe left ventricular dysfunction. We hypothesize that this is due to reduced coronary blood flow because of falling right ventricular volume in the presence of complete right ventricular coronary arterial dependence.     

Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy

Breast cancer is the most prevalent type of cancer among women. Several types of drugs, targeting the specific proteins expressed on the breast cancer cell surface (such as receptor tyrosine kinases and immune checkpoint regulators) and proteins involved in cell cycle and motility (including cyclin-dependent kinases, DNA stabilisers, and cytoskeleton modulators) are approved for different subtypes of breast cancer. However, breast cancer also has a poor response to conventional chemotherapy due to intrinsic and acquired resistance, and an Akt fingerprint is detectable in most drug-resistant cases. Overactivation of Akt and its upstream and downstream regulators in resistant breast cancer cells is considered a major potential target for novel anti-cancer therapies, suggesting that Akt signalling acts as a cellular mechanism against chemotherapy. The present review has shown that sustained activation of Akt results in resistance to different types of chemotherapy. Akt signalling plays a cellular defence role against chemotherapy and (1) enhances multi-drug resistance, (2) increases reactive oxygen species at breast tumor microenvironment, (3) enhances anaerobic metabolism, (4) inhibits the tricarboxylic cycle, (5) promotes PD-L1 upregulation, (6) inhibits apoptosis, (7) increases glucose uptake, and more importantly (8) recruits and interconnects the plasma membrane, nucleus, endoplasmic reticulum, and mitochondria to hijack breast cancer cells and rescue these cells from chemotherapy. Therefore, Akt signalling is considered a cellular defence mechanism employed against chemotherapeutic effects. In addition, interfering roles of PI3K/Akt signalling on the current cytotoxic and molecularly targeted therapy as well as immunotherapy of breast cancer are discussed with a clinical approach. Although, alpelisib, a PIK3CA inhibitor, is the only PI3K/Akt pathway inhibitor approved for breast cancer, we also highlight well-evaluated inhibitors of PI3K/Akt signalling based on different subtypes of breast cancer, which are under clinical trials whether as monotherapy or in combination with other types of chemotherapy.