Activin A: a marker of mineral bone disorder in children with chronic kidney disease?

BACKGROUND: Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease (CKD-MBD) and its relationship with other markers has not been studied in children with CKD. METHODS: A cross sectional study was conducted among 40 children aged 2 to 18 years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant. RESULTS: The mean age of children with CKD was 9.30 ± 3.64 years. Mean levels of activin A in cases were 485.55 pg/ml compared to 76.19 pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18 pg/ml while in controls it was 6.93 pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001). CONCLUSIONS: Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children.

Coagulation Profile and its Correlation with Severity of Liver Dysfunction and Gastrointestinal Bleed in Alcoholic Liver Disease Patients.

INTRODUCTION: The study aimed to determine coagulation factor abnormalities in alcoholic liver disease (ALD) and correlate these with severity of liver dysfunction (Child's class) and gastrointestinal (GI) bleeding. METHODS: 60 patients of ALD (alcohol intake >10years and clinical, biochemical or radiological evidence of chronic liver disease) were included. Patients with Hepatitis B, Hepatitis C, HIV infection, DIC, low platelet count due to other causes, or on drugs which affect coagulation profile were excluded. OBSERVATIONS: Age was 44.42 ± 10.26 years (100% males), 53% in Childs class C. Severity of liver dysfunction showed a significant association (p<0.05) with prolongation of prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), increasing factor VIII and D-Dimer level, low platelet counts, low protein S and factor VII activity; as well as decreasing fibrinogen levels, protein C and antithrombin (AT) III. GI bleed is associated significantly (p<0.05) with PT >20 sec and decreased plasma fibrinogen levels, while normal protein C, normal AT III, normal factor VII, normal factor VIII, normal TT, increased plasma fibrinogen levels, normal PT and normal platelet count appeared to be protective. CONCLUSIONS: Several coagulation parameters are altered in ALD variably. Alterations in PT, aPTT, TT, factor VIII, D-Dimer, fibrinogen, protein C and AT III levels can be used for grading severity of liver disease. Decreased fibrinogen, protein C activity, AT III activity, factor VII activity, and increased factor VIII activity, are associated with GI bleed.

Bioavailable Vitamin D Levels in Children With First Episode Nephrotic Syndrome: A Longitudinal Study.

OBJECTIVE: To estimate the levels of serum bioavailable vitamin D in children presenting with first episode nephrotic syndrome (FENS) at diagnosis and after 4 weeks of standard steroid therapy while the child is in remission, and compare the same with age-sex matched healthy controls. METHODS: We included children aged 1 month to 12 years presenting as FENS and estimated the serum calcium, phosphorus, alkaline phosphatase, 25-hydroxy vitamin D [25(OH)D], parathormone, serum and urine vitamin D binding protein (VDBP) at diagnosis and after 4 weeks of standard steroid therapy while the child is in remission. We also included age-sex matched healthy controls for comparison. Bioavailable and free 25(OH)D were estimated at enrolment and at 4 weeks of therapy. RESULTS: The mean (SD) 25(OH)D level (ng/mL) in children with FENS was 11.3 (6.1) at diagnosis and 13.6 (6.2) at 4 weeks follow-up, while the observed value in healthy controls was 16 (7) ng/mL. The median (IQR) serum VDBP level in FENS at enrolment was 223.0 (144, 305.5) µg/mL. There was significant correlation between serum VDBP and serum albumin levels (P = 0.04). At 4 weeks (remission), the median (IQR) VDBP levels increased to 554.5 (383, 644.75) µg/mL (P < 0.001). The median (IQR) free 25(OH)D levels (pg/mL) in children with FENS was 1.07 (0.8, 1.6) at enrolment and 0.53 (0.37, 0.86) at 4 weeks follow-up. The median (IQR) bioavailable vitamin D in FENS during proteinuria was 0.58 (0.4, 0.83) ng/ml, much lower as compared to controls 0.97 (0.85, 1.08) ng/mL (P < 0.001). On follow-up at 4 weeks of remission the median (IQR) bioavailable vitamin D levels increased to 0.87 (0.59, 1.42) ng/mL (P = 0.015). There was a very strong positive correlation between free vitamin D and bioavailable vitamin D (r = 0.9, P < 0.001); a strong negative correlation between serum VDBP and bioavailable vitamin D (r = - 0.69, P < 0.001). There was a positive correlation between 25 (OH)D and bioavailable vitamin D (r = 0.63, P < 0.001). Serum VDBP and serum albumin showed statistically significant positive correlation (r = 0.37, P < 0.05). CONCLUSION: Children with FENS are deficient in vitamin D. The free and bioavailable vitamin D levels are reduced in children with FENS during the proteinuric phase. Further studies to assess the association between bioavailable vitamin D and 25(OH)D with bone mineral density are needed in children with nephrotic syndrome to validate the utility of bioavailable vitamin D in clinical practice.

Correlation Between Morphological Patterns and Multidetector Computed Tomography (MDCT) Enhancement Patterns in Gallbladder Carcinoma With Locoregional Infiltration.

OBJECTIVE: This study aimed to explore the correlation between morphological patterns and multidetector computed tomography (MDCT) enhancement patterns in gallbladder cancer with locoregional infiltration among the Indian population. METHODOLOGY: This cross-sectional study was conducted across the pathology, surgery, and radiodiagnosis departments at Lady Hardinge Medical College, New Delhi. It focused on patients diagnosed with gallbladder disorders during the study period, identified through clinical examination or MDCT. Each patient underwent a fasting computed tomography (CT) scan using a Philips Brilliance 40-slice MDCT scanner. A neutral oral contrast, consisting of 1200 ml of water and 300 ml of 20% w/v mannitol, was administered. Additionally, for two patients suspected of gallbladder perforation extending to the pyloric duodenal area, a 2% non-ionic water-soluble contrast agent was used. RESULTS: The study found no statistically significant association between intraluminal polypoidal growth and other infiltration sites. However, wall thickening was significantly associated with various infiltration sites, including the liver, colon, bile ducts, and vascular structures. A strong positive correlation was observed between portovenous hyperenhancement and all examined morphological patterns, with the most notable correlations found with non-contrast CT (NCCT) hypo-isoenhancement. Conversely, arterial hyperenhancement showed an inverse relationship with some morphological patterns, with correlation coefficients of -0.60 for intraluminal polypoidal growth versus gallbladder wall thickening and mass replacement of the gallbladder versus intraluminal polypoidal growth. CONCLUSION: Gallbladder cancer frequently leads to the replacement or damage of the gallbladder, with both focal and diffuse wall thickening being common findings. Hypo-isoenhancement was the most prevalent imaging pattern, while hyperenhancement was less common. Although intraluminal polypoidal growth did not significantly correlate with metastasis, wall thickening was significantly associated. These results emphasize the importance of specific imaging patterns in assessing the severity of gallbladder cancer and informing treatment strategies.

Unusual association of Wilms' tumor with cystic diseases of kidney: A pathologic surprise.

Wilms' tumor (or nephroblastoma) is the most common renal malignancy in the pediatric population which consists of blastemal, epithelial, and stromal elements in variable proportions. The occurrence of renal cysts in children and infants is a rare phenomenon and is possibly an outcome of developmental aberrations in mesonephric blastema. The coincidental association of nephroblastoma with renal cysts is a very rare finding. Here, we describe two cases of Wilms' tumor with an unusual association between glomerulocystic kidney disease and multicystic dysplastic kidney.

Myelofibrosis: a cause of increased transfusion requirement in a child with ß-thalassemia intermedia.

A 10-year-old girl presented with gradually increasing pallor and abdominal distension for 1 year and fever for 6 months. She required 3 packed cell transfusions during this interval. Investigations done revealed that the child had thalassemia intermedia and parents were carrier of ß-thalassemia gene. The increased transfusion requirement in this case prompted further investigations, which revealed the presence of myelofibrosis. Case reports of myelofibrosis and myelodysplastic syndromes with acquired hemoglobin disorders exist in literature, especially α-thalassemia. To the best of our knowledge, this is the first reported case of ß-thalassemia intermedia in association with myelofibrosis.

Neutral lipid storage disease with unusual presentation: report of three cases.

Neutral lipid storage disease is a nonlysosomal multisystemic triglyceride storage disease. It is characterized by leukocyte vacuolization (Jordans' anomaly), variable systemic involvement, and ichthyosis. Two of our patients presented with congenital ichthyosis. Lipid vacuoles were demonstrated in granulocytes and monocytes and in basal keratinocytes on skin biopsy. They were diagnosed as Chanarin Dorfman syndrome. In contrast to these cases, the third case presented with progressive symmetric erythrokeratoderma without ichthyosis. Lipid vacuoles were demonstrated in blood cells on peripheral smear and in basal keratinocytes. Only screening of peripheral smear led to the correct diagnosis.

Morvan's syndrome: An unusual presentation of a solid pseudopapillary pancreatic tumor.

Morvan's syndrome is a rare anti-contactin-associated protein-like 2 (CASPR2) antibody-mediated autoimmune disorder. The clinical features of this syndrome include muscular twitching, insomnia, dysautonomia, peripheral nerve hyperexcitability, and fluctuating delirium. An underlying tumor is commonly found among Morvan's syndrome cases, with thymoma being the most frequent association. We describe an unusual case of a 39-year-old female with excruciating bilateral leg pain, insomnia, hyperhidrosis, peripheral nerve hyperexcitability, serum anti-CASPR2 antibody positivity, and a solid pseudopapillary tumor of the pancreas on histopathology. Furthermore, the patient's symptoms improved after receiving intravenous immunoglobulin (0.4 g/kg per day for 5 days). To the best of our knowledge, this is the first case of Morvan syndrome associated with a solid pseudopapillary pancreatic tumor to be reported in the literature to date. Our case adds to the spectrum of malignancies that are associated with Morvan's syndrome. The recognition of this rare syndrome and its various associations are important for the neurologist, as it is a potentially treatable condition.

Resection of a large Solid Pseudopapillary Neoplasm of the Pancreas: A multidisciplinary feat and review of literature.

Solid pseudopapillary neoplasm (SPN) is an extremely rare tumor with low malignant potential which is generally located in the tail of the pancreas. The prevalence of SPN has increased with the recent advancement in radiological imaging. CECT abdomen and Endoscopic ultrasound-FNA are excellent modalities in preoperative diagnosis. Surgery is the main treatment modality of choice and a successful R0 resection is curative. We present a case of solid pseudopapillary neoplasm and included a summary of the current literature to provide a reference for the management of this rare clinical entity.

Analysis of the Coagulation Profile in Children with HIV Infection-Effect of Disease and Anti Retroviral Therapy.

The pathogenesis of hypercoagulability in HIV infection is multifactorial and usually more than one factor is responsible for a thromboembolic episode. The present study was conducted to evaluate the effect of HIV infection and antiretroviral therapy on various coagulation parameters in paediatric patients. Forty two newly diagnosed paediatric patients with HIV infection who were enrolled at the Anti-Retro viral Therapy (ART) centre of Kalawati Saran Children's Hospital were included in the study. The patients were grouped into 4 clinical stages according to the WHO clinical staging of HIV disease. Coagulation tests [PT, aPTT, fibrinogen, D-Dimer and coagulation inhibitors i.e. Protein C (PC), Protein S (PS) and antithrombin III (AT III), Lupus anticoagulant (LA) and Anti phospholipid antibody (APLA)] were performed in all the patients at the time of diagnosis and repeated after 6 months. All the patients were started on antiretroviral therapy within 2 months of their diagnosis. At the time of diagnosis, prolonged PT and aPTT were observed in 30.9% and 23% of the cases respectively. Hyperfibinogenemia was seen in 11.9% of patients. D-Dimer was raised in 83.3% of patients. PS, PC & AT activities were reduced in 90.4%, 42.8% & 11.9% of cases respectively. A reduction in the PC and AT activity was seen from clinical stage 1 to 4, but the change was not statistically significant. On follow up after 6 months, a statistically significant reduction in the level of fibrinogen and D-Dimer was seen. Even though there was improvement in the activity of all the coagulation inhibitor after 6 months, statistically significant improvement was seen only for PS. The current study shows that HIV produces a hypercoagulable state in children. Raised d-dimer level and deficiency of natural anticoagulants contribute to the thrombophilic state.

Endothelial Activation Markers in Polytransfused Children with Beta Thalassemia: Study from a Tertiary Care Centre in India.

Beta thalassemia major is associated with a subclinical hypercoagulable state. Endothelial activation markers like soluble Intercellular adhesion molecule (sICAM-1) and E-selectin have been implicated in the pathogenesis of endothelial dysfunction and hemostatic alterations. In this study we aimed to study serum levels of sICAM-1 and E-selectin in polytransfused children with ß thalassemia major and their association with serum ferritin and D-dimer levels. Sixty-two polytransfused ß-thalassemia major children aged between 5 and 17 years and 26 age and gender matched healthy controls were enrolled in the study. Complete blood count with peripheral smear, liver function tests, serum ferritin, coagulation tests [PT, APTT, D-dimer] and endothelial activation marker tests [ICAM-1 and E-selectin] were performed. PT, APTT and D-dimer levels were significantly higher in beta-thalassemia major patients than in control group (p = 0.003, p < 0.001, p < 0.001 respectively). Mean ICAM-1 and E-selectin levels were 731.34 ± 343.97 ng/ml and 111.75 ± 40.13 ng/ml respectively which were significantly higher than control group (p < 0.001, p < 0.001 respectively). No significant correlation of ICAM-1 and E-selectin was observed with serum ferritin, PT, APTT and D-dimer levels. The findings of the present study suggest that there is ongoing subclinical activation of coagulation cascade and fibrinolytic system in these patients. Endothelial activation markers may be used as early indicators of endothelial dysfunction to assess the thrombotic complications in beta thalassemia.

Generalized linear porokeratosis: a rare entity with excellent response to acitretin.

Linear porokeratosis is a rare disorder of keratinization that usually presents at birth. We report a 17-year-old male with generalized linear porokeratosis, a very rare variant of porokeratosis, with extensive involvement of the trunk and extremities along with nail and genital involvement. The patient was treated with oral acitretin with excellent clinical response.

Becker's Nevus Coexisting with Morphea: A Rare Case Report.

Becker's nevus (BN) is an acquired unilateral hyperpigmented hairy macule, whereas morphea is a chronic connective tissue disease of unknown etiology, characterized by skin thickening with increased quantities of collagen in the indurated lesion, usually involving the upper trunk and proximal extremity. The occurrence of both disease in the same anatomical site and individual was not reported previously. We report this rare case in a 17-year-old, Indian girl and was diagnosed after clinical histopathology and dermoscopic correlation. Morphea can be an interesting incidental occurrence within a large plaque of BN.

Serum Levels of Vascular Endothelial Growth Factor and Its Receptor in Newly Diagnosed Paediatric Acute Lymphoblastic Leukemia.

Autocrine and paracrine loop involving vascular endothelial growth factor (VEGF) and its receptor have been described in haematological malignancies. However, scarce literature is present on angiogenesis in paediatric acute lymphoblastic leukemia (ALL) with studies showing controversial results. The aim was to study serum levels of VEGF and its receptors in paediatric ALL at the time of diagnosis and at the end of induction phase and to compare these levels with clinico-haematological parameters in these patients. Serum VEGF, VEGFR-1 and VEGFR-2 levels were measured by enzyme-linked immunoabsorbant assay at diagnosis (day 0) and at the end of induction phase (day 35) in 30 newly diagnosed paediatric ALL patients and in 10 healthy controls. Median s-VEGF was significantly lower at day 0 as compared to day 35 (196.15 vs. 606.75 pg/ml: p < 0.001). s-VEGFR-1 levels were detectable only in 7 patients at day 0 and were below detection level at day 35 in all patients. Median s-VEGFR-2 at day 0 was significantly lower as compared to day 35 (17,577.5 vs. 20,507.5 pg/ml; p = 0.005). Median VEGF-R1 showed an inverse relationship with VEGF-R2 but was statistically insignificant. All patients were in remission at the end of induction. Thus, leukemic infiltration of bone marrow affects angiogenesis and reduces pro-angiogenic markers VEGF and VEGFR-2 in serum possibly due to increased local consumption by blasts. A successful induction leads to clearing of blasts causing restoration of normal hematopoiesis with normalization of VEGF and VEGFR-2 levels.

Aggressive oral granular cell tumor with periorbital involvement: An unusual case.

Granular cell tumor (GCT) of the oral cavity is rare and so is the involvement of the eye, orbit, and ocular adnexa. A 65-year-old male developed a posttraumatic ulceroproliferative mass over his left cheek for the past 1 year. The mass involved the periorbital region with accompanying blood-stained purulent discharge from multiple sinus tracts over this lesion for the past 6 months. Radiographs of the orbit suggested chronic osteomyelitis. The lesion was not responsive to treatment with antibiotics. Enlarged submandibular lymph node demonstrated reactive lymphadenitis on cytological examination. However, computed tomography scan of the paranasal sinus (PNS) revealed possibly a malignant mass extending into the maxillary sinus and left extraconal space. Surprisingly, histopathological examination and immunohistochemistry from a growth involving the left upper retromolar region that extended up to the midline and periorbital region suggested a diagnosis of GCT. This unusual and new presentation of GCT is not well known to the dentists and also to the ophthalmologists. It is imperative to examine anatomically neighboring structures, especially the eye, nasal cavity, PNSs, and oval cavity among other structures in an underlying pathology in either of these sites.

Giant Ovarian Serous Cystadenoma in an Infant: Report of a Rare Case.

The incidence of abdominal cysts in infants is 1 in 500 to 1 in 1,000 live births. Among the ovarian cysts in infants, serous cystadenoma is extremely rare with only few reported cases in the literature. Here, we report a case of a giant neonatal ovarian serous cystadenoma treated with laparoscopic cystectomy and confirmed by histopathological examination. A 27-year-old delivered a female baby with uneventful caesarean section at full term. The antenatal ultrasonography (USG) in third trimester had showed an abdominal cyst in the left side of the abdomen. Postnatal USG was suggestive of omental cyst. A contrast-enhanced computed tomography scan of the neonate showed a large cyst occupying the entire abdomen. On laparoscopic evaluation, a cystic mass filled with 500 mL of clear yellow fluid was seen in the left pelvic fossa. Left ovary could not be visualized separately. The right ovary, fallopian tubes, and uterus were normal. The entire cyst was removed and sent for histopathological examination. On gross examination, a unilocular cyst measuring 10×8×6.5 cm with a wall thickness of 0.2 cm was noted. On microscopic examination, the histomorphological features were consistent with serous cystadenoma of the ovary. There is a paucity of literature regarding pathological diagnosis of such cases and hence we report one such case.

Chronic idiopathic myelofibrosis with myeloid metaplasia presenting as refractory ascites.

Chronic idiopathic myelofibrosis (CIM) with myeloid metaplasia is a myeloproliferative disorder characterized by leukoerythroblastosis, tear drop erythrocytes, extra-medullary hematopoesis (EMH), and varying degree of myelofibrosis. CIM, presenting as refractory ascites secondary to peritoneal hematopoesis, is extremely rare with only six adult cases reported in literature. This is a report of a child with CIM presenting as refractory ascites as a consequence of EMH in the peritoneum. The patient was treated with intermittent hydroxyurea with favorable response over 3 weeks. The patient was thereafter lost to follow up.

Cytohistomorphologic features of malignant fibrous histiocytoma of the breast: a case report.

BACKGROUND: Malignant mesenchymal tumors constitute < 1% of all malignant neoplasms of the breast. These include pure primary sarcoma of the breast, metastatic sarcoma and sarcomatous patterns in metaplastic carcinomas. On fine needle aspiration cytology (FNAC), the cellular features can suggest the diagnosis of sarcoma of the breast, although the potential exists for confusion with very poorly differentiated carcinoma. CASE: A case of recurrent primary malignant fibrous histiocytoma (MFH) occurred in the breast in a 32-year-old woman. The patient presented with a fungating mass in the right breast. FNAC was suggestive of malignant mesenchymal tumor, most probably MFH. The diagnosis was confirmed on biopsy. CONCLUSION: Malignant fibrous histiocytoma of the breast is a rare entity, and a complete clinicopathologic correlation with immunohistochemical profile is essential to arrive at a correct diagnosis and guide appropriate management of the patient.

Can RBC Indices be Used as Screening Test for Beta-Thalassemia in Indian Antenatal Women?

OBJECTIVE: To determine the appropriateness of using MCV/MCH as screening test for beta-thalassemia trait in the present population and also to find the most appropriate cutoff for optimum sensitivity of these indices. METHODS: It was an analytical, observational and cross-sectional study. Complete blood count followed by high-performance liquid chromatography (HPLC) was performed. The MCV and MCH levels were noted in cases and controls. RESULTS: Thalassemia trait was found in 66 out of 1300 antenatal women with anemia. The MCV and MCH were significantly low in cases (p = 0.0001). MCV had a better AUC (0.650) than MCH (0.635). The most suitable cutoff value of MCV was calculated as 72 fl (sensitivity-63.7%, specificity-68.3%, PPV-9.7%, LR-2.0) and that for MCH was 24 pg (sensitivity-63.6%, specificity-59.4%, PPV-7.7%, LR-1.5) using Youden's index. When MCH (cutoff of 28 pg) and MCV were combined (cutoff of 74 fl), the sensitivity and specificity were 95% and 16%, respectively. CONCLUSION: The sensitivity and specificity of MCV and MCH alone had low detection rate when used in combination had high sensitivity but the specificity was low; therefore, HPLC should be the preferred screening test for beta-thalassemia in Indian women.