Summary Calcineurin inhibitors (cyclosporine and tacrolimus; CNIs) continue to be used as constituents of post‐transplant immunosuppression in most centers. However, renal toxicity associated with the use of these drugs remains a problem adversely affecting the long‐term graft survival. Fifteen adequate protocol renal allograft biopsies, with histological features of CNI toxicity among 140 protocol biopsies performed at 1‐, 6‐, and 12‐month post‐transplant, were included. Mitochondrial alterations in the tubular epithelial cells and endothelia of glomerular, peritubular capillaries and arterioles were graded semiquantitatively and further ultrastructural morphometric evaluation of numerical density and area of the mitochondria was performed. Immunohistochemical staining for nitrotyrosine (marker of peroxynitrite formation) and vascular endothelial growth factor (VEGF) was performed and expression graded semiquantitatively. Higher grades of alterations were seen in endothelial mitochondria as compared with tubular mitochondria in biopsies with calcineurin inhibitor toxicity (CNIT). Endothelial mitochondrial numerical density showed progressive decline over 1‐, 6‐ and 12‐month biopsies while area showed progressive increase in biopsies with CNIT as compared with controls. Upregulation of nitrotyrosine was seen even at 1‐month post‐transplant, persisted at 6 and 12 months, and was significantly greater than that in control biopsies. Intense VEGF expression was noted in early CNIT while progressive reduction was seen in  6‐ and 12‐month protocol biopsies. This study shows a relatively high incidence of CNIT in protocol renal allograft biopsies, indicating that this might be an important mechanism of background damage to the allograft. Structural alterations in endothelial mitochondria are consistent findings in protocol biopsies with CNIT and this relatively specific mitochondrial damage may stem from the peroxynitrite‐mediated damage associated with progressive loss of protective function of VEGF.

Thalassemia is a heterogeneous group of genetic disorder with the defective synthesis of one or more globin chains. β-thalassemia is a global disease with high prevalence in Africa, Southeast Asia and Mediterranean countries. In Malaysia, the α and β-thalassemia are the commonest. In the articles that we reviewed, transfusion-dependent β-thalassemia is highly associated with complications related to thalassemia such as cardiovascular disease, endocrine disorders, skeletal deformities and others. Following advancements in β-thalassemia major treatment, cardiovascular disease remains the leading cause of mortality in β-thalassemia major patients. Thalassemia-associated cardiac pathology includes several conditions, such as myocardial dysfunction, arrhythmias and atrial fibrillation. Endocrine disorders, caused by iron deposition in the gland, resulting in impaired endocrine function. The commonest presentation is short stature followed by impaired puberty, abnormal thyroid function and diabetes mellitus. Moreover, skeletal complications remain a challenge. The most prevalent complications are malocclusion of the teeth, frontal bossing and chipmunk facies whilst osteoporosis, osteopenia and fracture are seen in a minority of the patient. Although comprehensive care has resulted in long-term survival and good quality of life, poor management will lead to complications that increase the treatment cost. However, genetic study (DNA analysis) examines the deletions and mutations in the α and β-globin-producing genes that help to correct diagnosis and improve management in thalassemia patients.

Hemophilia A is an X-linked recessive disorder which is due to factor VIII deficiency. It is a life-threatening coagulation disorder leading to complications including hemophilic-arthropathy, development of inhibitors, transfusion-related infections and profound psychosocial impact on the life of the patients. The aim of this study is to analyze the challenges in complications and the latest advancements in managing those complications. A thorough and systemic literature review was done to fulfill the objective of this study. The emergence of hemophilic arthropathy due to repeated symptoms of hemarthrosis is the most frequent complication found in haemophiliacs. Another critical complication, mainly seen in resource-poor settings is the development of lethal and severe bleeding episodes including episodes of intracranial hemorrhage. The development of inhibitors is another major challenge which often adds profoundly to the financial burden faced by hemophilia patients. Another major challenge is acquiring various transfusion-transmitted infections which was particularly more common few decades back. Studies also have revealed that there are myriads of significant psychosocial effects affecting the quality of life of hemophiliacs. Emerging treatments such as gene therapy, non-clotting factor concentrate products and extended half-life therapy can usher a new era in the management and the quality of life in hemophilia patients.

Testicular neoplasm is the most common solid tumor in male. The recent advancement in the medical field has made it possible to become one of the most highly treatable neoplasms. Testicular neoplasm is mainly classified into two main groups: non-seminomatous germ cell tumor and seminomatous germ cell tumor. In this review article, we analyzed the current role of serum biomarkers in diagnosis, prognosis, staging, measurement of response to therapy and early detection of relapse of testicular neoplasm. The commonly used tumor markers are alpha-fetoprotein (AFP), beta-human chorionic gonadotrophins and lactate dehydrogenase. Apart from them, a new set of tumor biomarkers like placental­like alkaline phosphatase, gamma­glutamyltranspeptidase, miRNA, mitochondrial DNA and serum trace elements are also proven to be potentially helpful in the management of testicular neoplasm. Progressive elevation of serum tumor markers often indicates the presence of testicular cancer and aids in histological classifications. According to an additional category, the rate of elevation of respective biomarkers is advantageous to appropriately stage testicular neoplasm (S) in the tumor nodes metastases (TNM) staging classification. Besides, it is found that higher elevation of serum tumor markers is associated with a poorer prognosis. Post-treatment assessment where there is a rate of reduction of serum tumour biomarkers suggests the effectiveness of initial management of testicular neoplasm.