Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.     

Aspiration cytology diagnosis of a primary amyloid tumor of thoracic vertebra: a case report

Isolated primary amyloid tumor of bone is rare; however, preoperative diagnosis can be rewarding because the prognosis is excellent. There are no clinical or roentgenographic criteria that can establish this diagnosis. There are few previous reports of fine-needle aspiration (FNA) where diagnosis of amyloidoma was made retrospectively. They describe the presence of extracellular hyaline material along with plasma cells and lymphocytes. A 35-year-old female was referred to the FNA clinic with swelling in the right upper chest wall. Radiologic findings revealed a destructive lytic lesion involving the bodies of D1 and D2 vertebrae with extension into surrounding soft tissue. Repeated FNA smears were hypocellular but had abundant homogeneous flocculent material, which stained positive with Congo red. A few plasma cells and foreign-body giant cells were also seen. We conclude that preoperative FNA cytology diagnosis of amyloid tumor is possible. Hypocellular smears with flocculent material, plasma cells, and foreign-body giant cells in absence of granulation tissue should suggest the diagnosis.     

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.     

Restarting LDLT During COVID-19: Early Results After Restructuring

IntroductionLiving-donor liver transplantation (LDLT) has been mostly suspended and deceased-donor living transplantation activity has been considerably reduced because of coronavirus disease 2019 (COVID-19). We modified our protocols and procedures in line with COVID-19 guidelines. Since the restructuring, we have performed 20 LDLTs. Our study reports the outcomes of these cases and demonstrates the feasibility of LDLT during this pandemic.Materials and MethodsThe changes were influenced by experiences and communications from across the globe. A month-long self-imposed moratorium was spent in restructuring the program and implementing new protocols. Twenty LDLTs were performed between April 18 and September 15 using the new protocols. Our experience includes 2 simultaneous liver-kidney transplants, 1 ABO-incompatible LDLT, and 1 pediatric case (age 11 months).ResultsNineteen patients recovered and 1 patient died. We maintained our postoperative immunosuppression protocol without many changes. Major complications were observed in 30% of recipients but none of the donors. One recipient was infected with COVID-19 during the postoperative period. A donor-recipient couple contracted COVID-19 after discharge from the hospital. All patients recovered from COVID-19 and liver enzymes were unaffected.ConclusionThis study represents a microcosm of experience in LDLT during the COVID-19 era. Outcomes of LDLT are not affected by COVID-19 per se, provided that we make necessary changes.     

When should pediatrician reach the delivery room?

Indian Journal of Pediatrics -     

Under fives mortality in the urban slums of Lucknow

The main objective of this study was to elicit proportional cause specific mortality in the underfives in the urban slums of Lucknow in North India. The families with under five mortality in the 28 randomly selected slums in 1993 were located from the records of the slum health workers and verbal autopsy was conducted to assign a cause of death. There were 71 deaths among 2796 children. The annual under five mortality was 25.4 and the under five mortality rate was 126.7. After the neonatal period, “high fever” that could not be classified into any other disease incorporated in the verbal autopsy instrument, was the most common symptom associated with death, seen in 21.1% cases (95% C.I.: 15.5–34.4%) followed by these diseases: pheumonia in 19.7%, diarrhea in 18.3% and measles in 11.4%. “High fever” as the leading symptom associated with death is being reported for the first time from the urban slums of India. There is an urgent need to identify the underlying etiologies of death due to “high fever” and the policy implications are that children with fever must receive immediate and continued medical attention till the symptom persists.     

The cost of coverage: rural health insurance in China

China has undergone great economic and social change since 1978 with far reaching implications for the health care system and ultimately for the health status of the population. The Chinese Medical Reform of the 1980s made cost recovery a primary objective. The urban population is mostly protected by generous government health insurance. A high share government budget is allocated to urban health care. Rural cooperative health insurance reached a peak in the mid-1970s when 90% of the rural population were covered. In the 1980s rural cooperative health insurance collapsed and present coverage is less than 8%. The decline has been accompanied by reports of growing equity problems in the financing of and access to health care. This article is the first in a four-year study of the impact on equity of the changes in Chinese health care financing. The article examines the relationship between rural cooperative health insurance as the explanatory variable and health care expenditure, curative vs. preventive expenditure and tertiary curative care expenditure as dependent variables using a natural experimental design with a 'twin' county as a control. The findings support the hypothesis that cooperative health insurance will induce higher growth of health care expenditure. The findings also support the hypothesis that cooperative health insurance will lead to a shift from preventive medicine to curative medicine and to a higher level of tertiary curative care expenditure. The empirical evidence from the Chinese counties is contradicting World Bank health financing policies.     

Poloxamer gel as vehicle for transdermal iontophoretic delivery of arginine vasopressin: evaluation of in vivo performance in rats

The present study describes the formulation and evaluation for pharmacokinetic and pharmacodynamic activity of arginine vasopressin (AVP), a nanopeptide with antidiuretic activity on being delivered by transdermal iontophoresis. Poloxamer 407 was used to form stable gels that did not reduce the release of AVP. The release rate from the gel followed Higuchi kinetics indicating that the dominant mechanism of release is diffusion. Iontophoresis alone and in combination with chemical enhancers was used to augment the transdermal permeation of AVP. The results of both pharmacokinetic and pharmacodynamic studies emphasize the dimension of 'rapid onset' achieved by iontophoresis. The correlation between pharmacokinetic data and pharmacodynamic activity was only qualitative. Histopathological studies revealed that skin toxicity caused by either iontophoresis or chemical enhancers when used alone could be reduced by using a combination of both the techniques in tandem.     

Effect of iontophoresis and fatty acids on permeation of Arginine Vasopressin through rat skin

The aim of this study was to assess the effects of fatty acids and iontophoretic mode of penetration enhancement on transdermal delivery of Arginine Vasopressin (AVP). Sprague-Dawley (SD) rat skin was pretreated with fatty acids (e.g. 5% w/v, lauric acid, oleic acid, and linoleic acid in ethanol:water (EtOH:W, 2:1 system) for 2h and iontophoresis in vitro, separately or together. The results indicate that all fatty acids studied increased (P<0.05) the flux of AVP in comparison to control (not pretreated with enhancer) and their effectiveness in flux enhancement was comparable. Further, oleic acid in combination with iontophoresis significantly increased the permeation of AVP both in comparison to pretreatment with fatty acids and iontophoresis alone. However, iontophoresis did not further increase the permeation of AVP through linoleic acid pretreated skin. Fourier transform infrared (FT-IR) spectroscopic studies revealed that EtOH:W (2:1) system is not effective in lipid extraction. The shift to higher wavenumbers of the symmetric and asymmetric stretching peaks at 2850 and 2920cm(-1) revealed that at the concentration used, oleic acid and linoleic acid caused fluidization of stratum corneum (SC) lipids. This study provides direct evidence that oleic acid in EtOH:W (2:1) system causes disruption of the SC lipid lamellae and that a combination of oleic acid with iontophoresis further enhances the effects of oleic acid in a synergistic manner.