Bone mineral density in patients with inherited bone marrow failure syndromes.

BackgroundPatients with inherited bone marrow failure syndromes (IBMFS) may have several risk factors for low bone mineral density (BMD). We aimed to evaluate the prevalence of low BMD in IBMFS and determine the associated risk factors.MethodsPatients with IBMFS with at least one dual-energy X-ray absorptiometry (DXA) scan were evaluated. Diagnosis of each IBMFS, Fanconi anemia (FA), dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome was confirmed by syndrome-specific tests. Data were gathered on age, height, and clinical history. DXA scans were completed at the lumbar spine, femoral neck, and forearm. BMD was adjusted for height (HAZ) in children (age ≤20 years). Low BMD was defined as a BMD Z-score and HAZ ≤-2 in adults and children, respectively, in addition to patients currently on bisphosphonate therapy.ResultsNine of thirty-five adults (26%) and eleven of forty children (27%) had low BMD. Adults with FA had significantly lower BMD Z-scores than those with other diagnoses; however, HAZ did not vary significantly in children by diagnosis. Risk factors included hypogonadism, iron overload, and glucocorticoid use.ConclusionsAdults and children with IBMFS have high prevalence of low BMD. Prompt recognition of risk factors and management are essential to optimize bone health

Orthodontic Treatment Need among Nepalese High School Students

Objective: To assess the need for orthodontic treatment among Nepalese high school students. Material and Methods: This is a quantitative, cross-sectional descriptive study. The sample comprises 938 children (537 males and 401 females) with an age group above 14 years. The subjects were selected voluntarily from seven different schools of Kathmandu valley using a multistage sampling technique. The Index of Orthodontic Treatment Need comprises two components: Dental Health Component (DHC) and Aesthetic Component (AC). Two trained and calibrated examiners performed the oral examination. Results: On analysis of the DHC component, it was found that 21% had no need, 18.1% had mild/little need, 24.3% had moderate/borderline need, 35.8% had severe need, and 0.7% had extreme treatment need. Similarly on analysis of AC component, it was found that 33% were AC-1, 30.8% were AC-2, 7.2% were AC-3, 8.2% were AC-4, 2.1% were AC-5, 3.6% were AC-6, 1.8% were AC-7, 7.4% were AC-8, 1.8% were AC-9, and 3.9% were AC-10. Conclusion: The Index of Orthodontic Treatment Need can be used as a tool for planning dental health resources and prioritizing the treatment need of different populations

Clinical profile of Neurosurgical Patients Admitted into the Intensive Care Unit of Rural Tertiary Care Center

Background:Intensive Care Unit (ICU) is a special department of a tertiary hospital for patients with the most severe and life‐threatening conditions which will often require constant and close intensive monitoring, support from specialist equipment and medications in order to maintain normal physiological functions. Teaching Hospital of Karnali Academy of Health Science (KAHS) is the largest tertiary institution in the mid-western region of Nepal providing specialist care. This study will provide information about the clinical profile  and outcome of the neurosurgical patient admitted in our ICU. Methods:This is a hospital based secondary data analysis carried out in the teaching hospital of KAHS, Jumla, Nepal. This study was conductedbetween March 2019 to June 2020. Data were retrieved from ICU record book and which had included demographic characteristics, diagnosis on admission, reason for admission, duration of admission, medical/surgical specialty requesting admission, nature of interventions, and outcome of patients admitted. Results:A total of 31 patients were admitted into the ICU, there were 74.2%(n=23) males and 25.8%(n=8) females giving a male to female ratio of 3:1.  The ages ranged from 3 month to 70 years . The age group of 15−59 years accounted for highest 51.6% (n=16) of all the ICU admissions. Among all cases, highest 64.5%(n=20) cases were presented from Juma. Out of the 31  admissions  77.4% (n=24) was due to head injury ,while other neurosurgical cases (Stroke, spinal cord injury) accounted 22.6%(n=7). Further dividing head injuries, highest 38.7% (n=12) is due to severe head injury, 22.6% (n=7) moderate head injury and 16.1% (n=5) were mild head injury.  Conclusion:Head injuries are the  highest number of neurosurgical admissions into the ICU with  relatively high mortality. Developing a viable trauma team and well equipped neurosurgical ICU with adequately trained staff will help to improve the outcome of patients.  

Effect of dietary supplementation of chromium on growth and biochemical parameters of Labeo rohita (Hamilton) fingerlings

A 60-day feeding experiment was conducted to evaluate the effect of dietary chromium on growth, feed efficiency and biochemical parameters of Labeo rohita fingerlings. Four isonitogenous (crude protein 35%) and isocaloric (415 k cal 100 g-1) experimental feeds were prepared by supplementing different levels of dietary chromium picolinate viz., control (0.0 mg kg-1), T1 (0.4 mg kg-1), T2 (0.8 mg kg-1) and T3 (1.2 mg kg-1). Weight gain WG (%), specific growth rate (SGR), feed efficiency ratio (FER) and protein efficiency ratio (PER) and apparent net protein utilisation (ANPU %) were significantly improved (p<0.05) when chromium was supplemented at 0.8 mg kg-1 feed. The protein retention (PR %) value increased with the dose of chromium, showing the highest value in T2 group. Chromium supplementation significantly increased (p<0.05) liver glycogen in T1 and T2 groups but decrease was observed at high level of chromium supplementation in T3 group. Chromium supplementation significantly reduced (p<0.05) serum cholesterol and triglycerides in all the experimental groups compared to control showing the highest reduction in T2 group. The serum high density lipoproteins-cholesterol (HDL-C) was increased (p<0.05)in all experimental groups due to chromium supplementation and the highest blood HDL-C was observed in T2 group. However, no difference (p<0.05) in the serum low density lipoproteins-cholesterol (LDL-C) and phospholipid was observed in any of the experimental groups. Similarly, highest muscle protein as well as lowest liver AST and ALT were observed in T2 group. The results of the present study indicates that growth, feed utilisation and biochemical parameters in Labeo rohita can be significantly improved by feeding the fingerlings with chromium picolinate supplemented diet (0.8 mg kg-1feed)

Genotype-phenotype and outcome associations in patients with Fanconi anemia: the National Cancer Institute cohort

Fanconi anemia (FA) is caused by pathogenic variants in the FA/BRCA DNA repair pathway genes, and is characterized by congenital abnormalities, bone marrow failure (BMF) and increased cancer risk. We conducted a genotype-phenotype and outcomes study of 203 patients with FA in our cohort. We compared across the genes, FA/BRCA DNA repair pathways (upstream, ID complex and downstream), and type of pathogenic variants (hypomorphic or null). We explored differences between the patients evaluated in our clinic (clinic cohort) and those who provided data remotely (field cohort). Patients with variants in upstream complex pathway had less severe phenotype [lacked VACTERL-H (Vertebral, Anal, Cardiac, Trachea-esophageal fistula, Esophageal/duodenal atresia, Renal, Limb, Hydrocephalus) association and/or PHENOS (Pigmentation, small-Head, small-Eyes, Neurologic, Otologic, Short stature) features]. ID complex was associated with VACTERL-H. The clinic cohort had more PHENOS features than the field cohort. PHENOS was associated with increased risk of BMF, and VACTERL-H with hypothyroidism. The cumulative incidence of severe BMF was 70%, solid tumors (ST) 20% and leukemia 6.5% as the first event. Head and neck and gynecological cancers were the most common ST, with further increased risk after hematopoietic cell transplantation. Among patients with FANCA, variants in exons 27-30 were associated with higher frequency of ST. Overall median survival was 37 years; patients with leukemia or FANCD1/BRCA2 variants had poorest survival. Patients with variants in the upstream complex had better survival than ID or downstream complex (p=0.001 and 0.016, respectively). FA is phenotypically and genotypically heterogeneous; detailed characterization provides new insights towards understanding this complex syndrome and guiding clinical management

Liver disease and transplantation in telomere biology disorders: An international multicenter cohort.

BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes. METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study. RESULTS: Group A (Advanced) included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M (Mild) included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6-13.2&nbsp;y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant. CONCLUSIONS: LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration

Genotype-phenotype association and variant characterization in Diamond-Blackfan anemia caused by pathogenic variants in <i>RPL35A</i>

Diamond Blackfan anemia (DBA) is predominantly an autosomal dominant inherited red cell aplasia primarily caused by pathogenic germline variants in ribosomal protein genes. DBA due to pathogenic RPL35A variants has been associated with large 3q29 deletions and phenotypes not common in DBA. We conducted a multi-institutional genotype-phenotype study of 45 patients with DBA associated with pathogenic RPL35A germline variants and curated the variant data on 21 additional cases from the literature. Genotype-phenotype analyses were conducted comparing patients with large deletions versus all other pathogenic variants in RPL35A. Twenty-two of the 45 cases had large deletions in RPL35A. After adjusting for multiple tests, a statistically significant association was observed between patients with a large deletion and steroid-resistant anemia, neutropenia, craniofacial abnormalities, chronic gastrointestinal problems, and intellectual disabilities (p<0.01) compared with all other pathogenic variants. Non-large deletion pathogenic variants were spread across RPL35A with no apparent hot spot and 56% of the individual family variants were observed more than once. In this, the largest known study of DBA patients with pathogenic RPL35A variants, we determined that patients with large deletions have a more severe phenotype that is clinically different from those with non-large deletion variants. Genes of interest also deleted in the 3q29 region that could be associated with some of these phenotypic features include LMLN and IQCG. Management of DBA due to large RPL35A deletions may be challenging due to complex problems and require comprehensive assessments by multiple specialists including immunologic, gastrointestinal, and developmental evaluations to provide optimal multidisciplinary care

Lung transplantation for pulmonary fibrosis in dyskeratosis congenita: Case Report and systematic literature review

<p>Abstract</p> <p>Background</p> <p>Dyskeratosis congenita (DC) is a progressive, multi-system, inherited disorder of telomere biology with high risks of morbidity and mortality from bone marrow failure, hematologic malignancy, solid tumors and pulmonary fibrosis. Hematopoietic stem cell transplantation (HSCT) can cure the bone marrow failure, but it does not eliminate the risks of other complications, for which life-long surveillance is required. Pulmonary fibrosis is a progressive and lethal complication of DC.</p> <p>Case presentation</p> <p>In this report, we describe a patient with DC who developed pulmonary fibrosis seven years after HSCT for severe aplastic anemia, and was successfully treated with bilateral lung transplantation. We also performed a systematic literature review to understand the burden of pulmonary disease in patients with DC who did or did not receive an HSCT. Including our patient, we identified 49 DC patients with pulmonary disease (12 after HSCT and 37 without HSCT), and 509 with no reported pulmonary complications.</p> <p>Conclusion</p> <p>Our current case and literature review indicate that pulmonary morbidity is one of the major contributors to poor quality of life and reduced long-term survival in DC. We suggest that lung transplantation be considered for patients with DC who develop pulmonary fibrosis with no concurrent evidence of multi-organ failure.</p

Impact of a package of diagnostic tools, clinical algorithm, and training and communication on outpatient acute fever case management in low- and middle-income countries: protocol for a randomized controlled trial.

BACKGROUND: The management of acute febrile illnesses places a heavy burden on clinical services in many low- and middle-income countries (LMICs). Bacterial and viral aetiologies of acute fevers are often clinically indistinguishable and, in the absence of diagnostic tests, the 'just-in-case' use of antibiotics by many health workers has become common practice, which has an impact on drug-resistant infections. Our study aims to answer the following question: in patients with undifferentiated febrile illness presenting to outpatient clinics/peripheral health centres in LMICs, can we demonstrate an improvement in clinical outcomes and reduce unnecessary antibiotic prescription over current practice by using a combination of simple, accurate diagnostic tests, clinical algorithms, and training and communication (intervention package)? METHODS: We designed a randomized, controlled clinical trial to evaluate the impact of our intervention package on clinical outcomes and antibiotic prescription rates in acute febrile illnesses. Available, point-of-care, pathogen-specific and non-pathogen specific (host markers), rapid diagnostic tests (RDTs) included in the intervention package were selected based on pre-defined criteria. Nine clinical study sites in six countries (Burkina Faso, Ghana, India, Myanmar, Nepal and Uganda), which represent heterogeneous outpatient care settings, were selected. We considered the expected seasonal variations in the incidence of acute febrile illnesses across all the sites by ensuring a recruitment period of 12 months. A master protocol was developed and adapted for country-specific ethical submissions. Diagnostic algorithms and choice of RDTs acknowledged current data on aetiologies of acute febrile illnesses in each country. We included a qualitative evaluation of drivers and/or deterrents of uptake of new diagnostics and antibiotic use for acute febrile illnesses. Sample size estimations were based on historical site data of antibiotic prescription practices for malarial and non-malarial acute fevers. Overall, 9 semi-independent studies will enrol a minimum of 21,876 patients and an aggregate data meta-analysis will be conducted on completion. DISCUSSION: This study is expected to generate vital evidence needed to inform policy decisions on the role of rapid diagnostic tests in the clinical management of acute febrile illnesses, with a view to controlling the rise of antimicrobial resistance in LMICs. TRIAL REGISTRATION: Clinicaltrials.gov NCT04081051 . Registered on 6 September 2019. Protocol version 1.4 dated 20 December 2019