Bone marrow transplant: A two-decade single centre hematology experience.

Background: Bone Marrow Transplant (BMT) is a curative form of therapy for many hematological disorders in both the adult and pediatric patients. The availability of BMT in the AFMS at AHRR for the last 02 decades has been a game changer for the patients. Methods: We reviewed our BMT data since the inception of the program till Feb 2023. Results: Over 700 patients with more than 23 different types of hematological disorders have undergone this procedure 58%% patients underwent an Autologous BMT and 42% an allogenic BMT. Autologous BMT for Multiple Myeloma and Allogenic BMT for Aplastic Anemia and Acute Leukemias have been the most common indications. 73% patients were adults, and 27% patients were of the pediatric age group. The male: female ratio was 2:1. The spectrum of allogenic Hematopoietic Stem Cell Transplant (HSCT) has expanded from Matched Sibling Donor (MSD) transplants to Matched Unrelated Donor (MUD) Transplants and Haploidentical Donor Transplants. 93% of our Allogenic BMT patients underwent a MSD BMT, 1% MUD BMT and 06% Haploidentical BMT. Today no patient with a malignant hematological disorder requiring a BMT is denied the procedure due to the lack of an HLA donor due to the availability of haploidentical BMT. Conclusion: The evolution of a BMT program has a long learning curve and the expanded pool of eligible donors has led to a situation of "transplant for all". Haploidentical HSCT for nonmalignant hematological disorders is an unmet need. CART cell therapy and Cellular therapies need to be prioritized for future inclusion.

Use of COVID-19 Convalescent Plasma for Treatment of Symptomatic SARS-CoV-2 Infection at a Children's Hospital: A Contribution to a Still Inadequate Body of Evidence.

Data on COVID-19 convalescent plasma (CCP) safety and efficacy in children and young adults are limited. This single-center prospective, open-label trial evaluates CCP safety, neutralizing antibody kinetics, and outcomes in children and young adults with moderate/severe COVID-19 (April 2020-March 2021). A total of 46 subjects received CCP; 43 were included in the safety analysis (SAS); 7.0% < 2 years old, 2.3% 2-<6, 27.9% 6-<12, 39.5% 12-<19, and 23.3% > 19 years old; 28 were included in the antibody kinetic analysis (AbKS); 10.7% < 2 years old, 10.7% 6-<12, 53.8% 12-<19, and 25.0% > 19 years old. No adverse events occurred. The median COVID-19 severity score improved (5.0 pre-CCP to 1.0 by day 7; p < 0.001). A rapid increase in the median percentage of inhibition was observed in AbKS (22.5% (13.0%, 41.5%) pre-infusion to 52% (23.7%, 72%) 24 h post-infusion); a similar increase was observed in nine immune-competent subjects (28% (23%, 35%) to 63% (53%, 72%)). The inhibition percentage increased until day 7 and persisted at 21 and 90 days. CCP is well tolerated in children and young adults, providing rapid and robust increased antibodies. CCP should remain a therapeutic option for this population for whom vaccines are not fully available and given that the safety and efficacy of existing monoclonal antibodies and antiviral agents have not been established.

Healthcare-associated viral respiratory infections in paediatric intensive care unit settings: More than just a sneeze.

Healthcare-associated infections (HAIs) affect patient health. Patients with Paediatric Intensive Care Unit (PICU) acquired viral respiratory infections had longer use of respiratory support. We found it's uncommon in ICUs to have high risk HAIs. RSV, parainfluenza, and hMPV are the most common, and 1/3 of patients required escalation in respiratory support and/or escalation in antibiotics. All patients had underlying comorbidities. In our series there were two deaths within 2 weeks of infection.

Real-world experience of anti-D immunoglobulin in immune thrombocytopenia.

In developing countries, anti-D has been used in immune thrombocytopenia (ITP) as a cheaper alternative to human immunoglobulin. We aim to analyze the response and safety profile of anti-D in patients with severe ITP. A retrospective study was conducted at a tertiary care hospital in Northern India. Patients received a single intravenous infusion of 75 µg/kg anti-D. In total, 36 patients (20 females) were included in this study. The median duration from ITP diagnosis to anti-D therapy was 235 days (range 1-1613 days). Four (11.1%) patients received anti-D as an upfront treatment. The patients' platelet counts rose significantly by the end of day three and continued to be significantly high until day 30 of receiving anti-D (p ≤ 0.001). The overall response rate (ORR) by day seven was 88.89%. There was no effect of age, sex, duration of disease, prior therapy, and platelet count on the ORR. Patients were followed up for a median duration of 52 days (longest follow-up: 3080 days). Six (6/36, 16.67%) patients continued to be in remission till the last follow-up. The hemoglobin fall was statistically significant on day three and day seven (p < 0.001 and p = 0.001) and got normalized by day 30. We observed equally good ORR in mixed populations and different phases of ITP along with long-term sustained response. The study demonstrates a quick and high response rate along with good safety profile to anti-D in all forms of ITP.

Human Metapneumovirus Infection in a Children's Hospital - It Should Get More Attention.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza infections are a major cause of hospitalization and intensive care unit (ICU) admission to children's hospitals and are closely tracked. We compared data over 6 seasons of human metapneumovirus (hMPV), RSV and influenza infections. METHODS: During the 2014-2019 winter viral seasons, hMPV, RSV and influenza infections were tracked. For hMPV admissions, rates of hospitalizations, ICU admissions, hospital-acquired infections (HAIs) and mortalities were assessed and compared with RSV and influenza admissions. Retrospective data was used to study patients infected with hMPV. RESULTS: During the winter seasons of 2014-2019, the rates of hospitalization due to hMPV were significantly higher than both RSV and influenza. ICU admissions, deaths and HAIs for hMPV were similar to RSV and influenza.Of the 471 total cases with hMPV, 58 (12.3%) had chronic lung disease (CLD) and 23 (4.9%) were tracheostomy dependent. Among 104 hMPV ICU admissions from 2013 to 2019, 86 (82%) had an underlying medical diagnosis, 30 (29%) had CLD, 21 (20%) had tracheostomies and 33 (32%) required mechanical ventilation. The average age of hMPV infected children in our ICU is 3 years and 10 months. CONCLUSIONS: Our large descriptive study of hMPV infected children over 6 seasons showed higher rates of hospitalization compared with RSV and influenza, similar ICU and HAI rates, and deaths. ICU admitted children often had associated co-morbidities, including CLD. Further studies for focused disease surveillance and potential vaccine development for high-risk children are needed.

How do patient-provider relationship continuity, gender, and language affect pediatric HPV vaccine acceptance?

Increasing human papillomavirus (HPV) vaccine uptake remains a challenge. We compared reasons for HPV vaccine acceptance between two Southern California pediatric clinics serving diverse populations: an academically affiliated resident clinic that offered little continuity of care (n = 53) and a private-practice clinic with well-established physician-patient relationships (n = 200). We found strong doctor recommendation and information dissemination about the importance of HPV vaccination were the most important drivers of acceptance across these distinct settings. The top-cited reasons for vaccine acceptance also varied by gender, language (English vs. Spanish), and clinic type. Findings point to the need for (1) robust provider education on vaccines, vaccine-preventable diseases, and vaccine hesitancy and (2) increased efforts to raise public awareness of the importance of HPV vaccination.

Case Report: Pseudomonas can take a toll on a patient.

Pseudomonas aeruginosa ( P. aeruginosa) is an aerobic Gram-negative bacterium that is implicated in the development of severe systemic infections among pediatric patients.  It is identified in hospitalized chronically ill pediatric patients in association with genitourinary, respiratory tract, and skin or soft tissue infections as well as severe and life-threating infection including sepsis.  A variety of immunologic mechanisms play a vital role in the host defense mechanisms against invasive infections with P. aeruginosa. Rarely, specific inborn errors of immune function are implicated in deficiencies that predispose to invasive infections with P. aeruginosa.  Innate immune function including germ-line encoded pattern recognition receptors such as toll-like receptors (TLRs) and their downstream signaling is vital in the host defense against P. aeruginosa through the generation of antimicrobial peptides, cytokines/chemokines, and shaping of adaptive immune responses. Herein, we describe a previously healthy two-year-old female with an invasive skin, soft tissue, and central nervous system infection secondary to P. aeruginosa.  The invasive nature of this infection prompted a careful evaluation for an inborn error of immunity. Decreased cytokine response to agonists of TLRs was documented. Targeted sequencing of interleukin-1 receptor-associated kinase (IRAK)-4 documented a homozygous deletion of exons 8-13 consistent with IRAK-4 deficiency.  This report provides a vital educative message in the existing scientific literature by underscoring the importance of considering inborn errors of immunity in all patients with severe P. aeruginosa infections.  Functional assessments of immune function often in combination with sequencing can accurately assign a diagnosis in a timely fashion allowing for definitive treatment and the use of necessary supportive care.

Safety and efficacy of splenectomy in immune thrombocytopenia.

BACKGROUND: Immune Thrombocytopenia (ITP) is characterized by low platelet counts. Splenectomy has been in practice for the treatment of ITP since the early 20th century. We aimed to analyze the data of ITP patients from our hospital who underwent splenectomy and further present the long-term outcome and safety profile in these patients. METHOD: This study was a single-center, registry based study conducted at a tertiary care hospital in Northern India. Patients aged 18 years or more, who underwent splenectomy after at least one line of therapy, were included in the study. The primary outcome was the overall response rate (ORR) at one month after splenectomy. Secondary outcomes were sustained response, relapse-free survival, factors affecting the ORR, and adverse events after splenectomy. RESULTS: Forty-five patients of ITP were included in the study. Thirty-six patients underwent splenectomy in the first half (2001-2010), of the study period. The median age of the patients was 38 (19-56) years. The median duration from diagnosis to splenectomy was 1.76 (0.47-2.58) years. The median number of therapy received before splenectomy was 3 (1-6). The overall response rate (ORR) post-splenectomy at day 30 was 89.2% with 61.8% complete response (CR). The ORR was 88.5% at 1-year, with 48.8% CR. The relapse-free survival (RFS) at 5-years was 57.38% (95% Confidence Interval 40.59-71.02%), There was no effect of duration of disease, age, gender, and prior therapy received, on the ORR at one-month. At one year, the platelet response was significantly better in patients who had a CR at one-month than patients who had a partial response at one month. The relapse-free survival was better in patients who achieved CR after 1-month of splenectomy. During the median follow-up of 5.02 (1 month-20 years) years, there were five cases of overwhelming post-splenectomy infection (OPSI). There was no recorded incidence of perioperative mortality, deep vein thrombosis, or mesenteric thrombosis. DISCUSSION: Despite the variation in outcome from different studies, splenectomy gives the best possible long-term treatment-free remission amongst all the available second-line agents. It is also, one of the most financially affordable therapies. Despite advantages, the number of ITP patients undergoing splenectomy has been on the decline and largely attributable to the newer and more effective second-line therapies. There is no pre-surgery variable predicting the ORR after splenectomy. CONCLUSION: Splenectomy in ITP offers a long-term sustained response at an economical cost.

The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings.

INTRODUCTION: Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30-66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML. METHOD: This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included. RESULT: A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12-71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days (p = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 (p = 0.063). Thirteen patients (23.63%) died during the study period. DISCUSSION: Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections. CONCLUSION: Infections continues to be a major cause of morbidity and mortality among AML patients.

Safety and efficacy of azathioprine in immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is a benign hematological disorder characterized by low platelet counts in peripheral blood and spectrum of various bleeding manifestations. Azathioprine is one of the effective, readily available, and affordable immunosupressants available for ITP management in developing countries. We aimed to study the efficacy and long-term safety profile of our patients with ITP who were treated with azathioprine. METHOD: This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India. The patients who had received at least one line of therapy before receiving azathioprine were included in this study. All patients received oral azathioprine at a dose of 1 mg/kg/day (50 mg or 100 mg tablet formulations were used), which was increased up to 2 mg/kg/day depending upon the response and adverse effects. RESULT: Sixty-three patients were analyzed. Their median age was 28 years (range 15-68); 29/63 patients (46.03%) were females. The median duration from diagnosis to azathioprine initiation was 539 days (323 days-980.5 days). The patients included in the study had received a median of 3 (range 1-6) prior lines of therapies; 38/63 patients (60.32%) had received ≥3 prior therapies. Six patients (9.5%) had relapsed after splenectomy, and 16 patients (25.4%) had relapsed after receiving rituximab. The mean baseline platelet count was 10000/µL. The median time to response was 95 days (90 days-not reached) and the cumulative overall response rate (complete and partial response) at day 90 was 38.1%. Only one patient achieved complete response with azathioprine in our study. The cumulative rate of relapse at five years was 21.2%. Twenty-six patients stopped azathioprine after achieving some response (CR/PR) with Azathioprine for a median duration of 1067.5 days (range: 236 days-2465 days). They were followed up for a median of 870 days (range: 392 days-1928 days), and twelve of them relapsed. Twenty-six patients (26/63, 41.27%) reported one or more adverse events while on azathioprine. Leucopenia was the most frequent adverse event, followed by anemia and hepatobiliary laboratory abnormalities. Serious adverse events (grade ≥3 CTCAEv4) were noted in three patients (4.7%). One patient succumbed to severe sepsis multiorgan dysfunction while being on treatment. CONCLUSION: We conclude that azathioprine has a good response rate in chronic ITP patients. It is well-tolerated with minimal and manageable side effects.

Real-world Experience of Rituximab in Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is a relapsing-remitting disease often requiring more than one line of therapy. Rituximab is a recommended second-line therapy, but the real-world data on its efficacy and safety from resource constraint settings is limited. We aimed to analyze the safety and efficacy of rituximab in ITP. This is a single-center, retrospective study. This study was conducted at a tertiary care hospital in Northern India from 2005 to 2019. On audit of medical records, all patients of ITP (n-513) who had received rituximab (n-81) were screened for inclusion. Patients whose response assessment was not possible were excluded. Finally, 66 patients were analyzed using statistical packages of Python v3.7. The cumulative incidence of overall response on day 20 was 30.61%, and day 30 was 51.72%. The median time to response was 28 day (range 21-51 day). Cumulative incidence of complete response was 16.67%, and partial response 37.88%. After a median follow-up of 789 day (range 181-5260 day), the cumulative incidence of relapse was 30.32%, 36.12%, and 56.57% at 1, 2, and 5 years respectively. There was no effect of age, sex, duration of disease, lines of therapy received, and platelet count on either cumulative incidence of overall response or relapse. ANA positivity was significantly related to the better cumulative incidence of overall response (p = 0.012), but not with relapse. Infusion-related reactions were the commonest adverse event noted (n-4, grade ≥ 3 CTCAEv4). Rituximab and its generic version are safe and effective second line agent in ITP with a good overall response and sustained response.

Invasive Mycobacterium abscessus Outbreak at a Pediatric Dental Clinic.

BACKGROUND: Mycobacterium species, specifically M. abscessus and M. chelonae (MABs), are known to contaminate water systems and are uncommon causes of health care-associated infection, but morbidity can be significant and treatment complex. METHODS: Odontogenic MAB infections occurred in patients following pulpotomy procedures at dental clinic A from 1 January to 6 September 2016. We identified confirmed and probable cases using culture data, imaging, pathology results, and surgical findings. Epidemiologic and clinical data including demographics, symptoms, laboratory findings, treatment regimens, and outcomes were extracted. RESULTS: Of 1082 at-risk patients, 71 case patients (22 confirmed; 49 probable) were identified. Median age was 6 years. Median symptom onset was 85 days postpulpotomy. Pain and/or swelling on admission occurred in 79%. On imaging, 49 of 70 had abnormalities of the mandible or maxilla, 13 of 70 had lymphadenopathy, and 19 of 68 had pulmonary nodules. Seventy were hospitalized (average of 8.5 days). Intravenous antibiotics were administered to 32 cases for a median length of 137 days. Clofazimine was administered to 29 patients as part of their multidrug regimen. Antibiotic treatment was associated with many adverse effects. Treated children showed evidence of jaw healing with resolved/improving pulmonary nodules at 1-year follow-up. CONCLUSIONS: This is the largest outbreak of invasive MAB infections associated with a pediatric dental practice. While infections were indolent, patients suffered medical and surgical consequences of treatment, including permanent tooth loss. Identification of this outbreak led to a change in water standards for pediatric dental procedures in California. Enhanced national dental water quality standards are needed to prevent future outbreaks.

Safety and Antibody Kinetics of COVID-19 Convalescent Plasma for the Treatment of Moderate to Severe Cases of SARS-CoV-2 Infection in Pediatric Patients.

BACKGROUND: Therapies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its life-threatening respiratory infection coronavirus disease 2019 (COVID-19) have been evaluated, including COVID-19 convalescent plasma (CCP). Multiple large reports of CCP treatment in adults exist. Pediatric data on CCP safety and efficacy are limited. METHODS: Single-center prospective, open-label trial looking at safety, antibody kinetics and outcomes of CCP (10 mL/kg, max 1 unit) treatment for COVID-19 in hospitalized pediatric patients with moderate to severe disease or at high-risk for serious illness. RESULTS: Thirteen patients were enrolled. No infusion-related adverse events occurred. No hematologic or metabolic adverse events were noted during hospitalization or at 3-weeks. Ten patients had clinical improvement by day 7 (WHO eight-category ordinal severity scale for COVID-19). Following CCP, anti-SARS-CoV-2 anti-nucleocapsid IgG increased significantly at 24 hours and high levels were sustained at 7- and 21-days. Transient IgM response was noted. Twelve patients (92.3%) were discharged home, 9 (75%) by day 7 post-CCP. One remained on invasive ventilatory support 42 days after CCP and was eventually discharged to an intermediate care facility. The single patient death was retrospectively confirmed to have had brain death before CCP. CONCLUSION: CCP was well tolerated in pediatric patients, resulted in rapid antibody increase, and did not appear to interfere with immune responses measured at 21 days. More pediatric data are necessary to establish the efficacy of CCP, but our data suggest benefit in moderate to severe COVID-19 when used early. Other immunologic or antiviral interventions may be added as supported by emerging data.

Survival Outcomes of Newly Diagnosed Multiple Myeloma at a Tertiary Care Center in North India (IMAGe: 001A Study).

PURPOSE: The outcomes of patients with myeloma from developing countries are often lacking because of poor record maintenance. Publications from such settings are also limited because of the retrospective nature of the data collection. Information technology can bridge these gaps in developing countries with real-time data maintenance. We present the real-time survival data of the patients with myeloma from a tertiary care center in North India using one such indigenously built software. PATIENTS AND METHODS: These are real-time data of all patients with myeloma presenting to a tertiary care center from North India. The patient characteristics (demographics, baseline disease characteristics, risk stratification, and outcomes) were recorded contemporaneously. The survival of the study population was analyzed and grouped based on various disease characteristics at diagnosis. RESULTS: The median age of the study population (N = 696) was 65.9 (34.9-94.9) years with male predominance (65%). The median follow-up was 3.7 years (0-18.6 years) with the median overall survival (OS) not achieved. The OS of the study population at 1, 3, and 5 years was 94% (n = 558), 87.5% (n = 394), and 83.1% (n = 267), respectively. Most of the patients presented in advanced stages based on International Staging System (III:70%). On Kaplan-Meier analysis, the presence of weight loss (P = .01), renal dysfunction (P = .047), and anemia at diagnosis (P = .004) had a significant impact on survival. On Cox proportional model univariate analysis, the presence of renal dysfunction, anemia, and weight loss had the significant hazard ratio of 1.68 (1-2.82, P = .049), 3.18 (1.39-7.29, P = .0063), and 2.81 (1.22-6.42, P = .014), respectively, whereas on multivariate analysis of hypercalcemia, renal disease, anemia, and bone disease (CRAB) features, only anemia was found to have a significant hazard ratio of 2.56 (1.01-6.47, P = .046). CONCLUSION: The real-world data show OS comparable with the published western literature. Only anemia was found to have significant impact on survival. The use of such software can aid in better data-keeping in resource-constrained settings.

SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges.

As the nation implements SARS-CoV-2 vaccination in adults at an unprecedented scale, it is now essential to focus on the prospect of SARS-CoV-2 vaccinations in pediatric populations. To date, no children younger than 12 years have been enrolled in clinical trials. Key challenges and knowledge gaps that must be addressed include (1) rationale for vaccines in children, (2) possible effects of immune maturation during childhood, (3) ethical concerns, (4) unique needs of children with developmental disorders and chronic conditions, (5) health inequities, and (6) vaccine hesitancy. Because COVID-19 is minimally symptomatic in the vast majority of children, a higher acceptable risk threshold is required when evaluating pediatric clinical trials. Profound differences in innate and adaptive immunity during childhood and adolescence are known to affect vaccine responsiveness for a variety of childhood diseases. COVID-19 and the accompanying social disruption, such as the school shutdowns, has been disproportionately damaging to minority and low-income children. In this commentary, we briefly address each of these key issues, specify research gaps, and suggest a broader learning health system approach to accelerate testing and clinical trial development for an ethical and effective strategy to implement a pediatric SARS-CoV-2 vaccine as rapidly and safely as possible. IMPACT: As the US begins an unprecedented implementation of SARS-CoV-2 vaccination, substantial knowledge gaps have yet to be addressed regarding vaccinations in the pediatric population. Maturational changes in the immune system during childhood have influenced the effectiveness of pediatric vaccines for other diseases and conditions, and could affect SARS-CoV-2 vaccine responsiveness in children. Given that COVID-19 disease is far milder in the majority of children than in adults, the risk-benefit of a pediatric SARS-CoV-2 vaccine must be carefully weighed. The needs of children with developmental disabilities and with chronic disease must be addressed. Minority and low-income children have been disproportionately adversely affected by the COVID-19 pandemic; care must be taken to address issues of health equity regarding pediatric SARS-CoV-2 vaccine trials and allocation. Research and strategies to address general vaccine hesitancy in communities must be addressed in the context of pediatric SARS-CoV-2 vaccines.

When Screening for Severe Combined Immunodeficiency (SCID) with T Cell Receptor Excision Circles Is Not SCID: a Case-Based Review.

Newborn screening efforts focusing on the quantification of T cell receptor excision circles (TRECs), as a biomarker for abnormal thymic production of T cells, have allowed for the identification and definitive treatment of severe combined immunodeficiency (SCID) in asymptomatic neonates. With the adoption of TREC quantification in Guthrie cards across the USA and abroad, typical, and atypical SCID constitutes only ~ 10% of cases identified with abnormal TRECs associated with T cell lymphopenia. Several other non-SCID-related conditions may be identified by newborn screening in a term infant. Thus, it is important for physicians to recognize that other factors, such as prematurity, are often associated with low TRECs initially, but often improve with age. This paper focuses on a challenge that immunologists face: the diagnostic evaluation and management of cases in which abnormal TRECs are associated with variants of T cell lymphopenia in the absence of a genetically defined form of typical or atypical SCID. Various syndromes associated with T cell impairment, secondary forms of T cell lymphopenia, and idiopathic T cell lymphopenia are identified using this screening approach. Yet there is no consensus or guidelines to assist in the evaluation and management of these newborns, despite representing 90% of the patients identified, resulting in significant work for the clinical teams until a diagnosis is made. Using a case-based approach, we review pearls relevant to the evaluation of these newborns, as well as the management dilemmas for the families and team related to the resolution of genetic ambiguities.

Real-world experience of eltrombopag in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is characterized by decreased platelet count in the peripheral circulation. The first-line therapy is corticosteroids with 53-80% overall response rate. Eltrombopag has been used as second-line therapy in ITP for over a decade now. The long-term efficacy and safety profile have been widely reported in the western world. However, the data from the resource-constraint settings of the developing world is scarce. We aim to present the real-life experience of efficacy and safety of eltrombopag from the resource-constraint settings. This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India from 2012-2019. On audit of medical records, patients of ITP receiving eltrombopag were screened for inclusion. Patients whose treatment outcomes were not available were excluded. Finally, 53 patients were analyzed using statistical packages of Python v3.7. The patients' median age was 35 years (range 17-78), with 23 (43.4%) being female. The median time to response was 35 days (range 28-50 days) and the cumulative overall response rates (ORR) at day 30, day 60 and day 90 were 41.5%, 69.8%, and 81.1% respectively. A total of 10 patients on eltrombopag relapsed during follow up. The cumulative rate of relapse at one year, three years, and five years were 6.6%, 25.3%, and 47.7%, respectively. There was no significant difference in outcome (response rate or relapse) in any subgroups depending on age, sex, duration of disease, number of prior lines of treatment, splenectomy, or baseline platelet count. Six patients stopped eltrombopag after having a median sustained response for 796 days (range 658-1185), and after a median follow up of 624 days (range 92-1339), they continued to be in remission. Seventeen patients (17/53, 32%) reported one or more adverse events while on eltrombopag therapy. A total of 49 adverse events (n=4, grade ≥3 CTCAEv4) were noted. Anemia was the most frequent adverse event followed by hepatobiliary dysfunction as reflected by deranged AST/ALT or raised bilirubin. The use of eltrombopag among adult ITP patients in resource-constraint settings was well-tolerated and yielded excellent overall response. The benefit was found to be sustained on long-term follow up. However, events like anemia, hepatobiliary, and thrombotic complications merit closer follow up.

Targeted gene expression study using TaqMan low density array to gain insights into venous thrombo-embolism (VTE) pathogenesis at high altitude.

Venous thrombo-embolism (VTE) is multi-factorial disease involving several genetic and acquired risk factors responsible for its onset. It may occur spontaneously upon climbing at High Altitude (HA). Several studies demonstrated that hypoxic conditions prevailing at HA pose an independent risk factor for VTE; however, molecular mechanism remains unknown. Present study aims to identify genes associated with HA-induced VTE pathophysiology using real time TaqMan Low-Density Array (TLDA) of known candidate genes. Gene expression of total 93 genes were studied and analyzed in patients of VTE from HA (HA-VTE) and from sea level (SL-VTE) in comparison to respective controls. Both HA-VTE and SL-VTE patients showed up-regulation of 37 genes involved in blood coagulation cascade, clot formation, platelet formation, endothelial response, angiogenesis, cell adhesion and calcium channel activity. Seven genes including ACE, EREG, C8A, DLG2, USF1, F2 and PCDHA7 were up-regulated in both HA-controls and VTE patients (both HA-VTE and SL-VTE) indicating their role during VTE event and also upon HA exposure. Ten genes; CDH18, FGA, EDNBR, GATA2, MAPK9, BCAR1, FRK, F11, PCDHA1 and ST8SIA4 were uniquely up-regulated in HA-VTE. The differentially expressed genes from the present study could be determining factors for HA-VTE susceptibility and provide insights into VTE occurrence at HA.

Safety and Tolerability of Clofazimine in a Cohort of Children With Odontogenic Mycobacterium abscessus Infection.

Mycobacterium abscessus infections can be challenging to treat. Clofazimine has excellent in vitro activity against M abscessus, but reports of its use, particularly in children, have been limited. In this study, clofazimine was given to 27 children during an outbreak of odontogenic mycobacterial infections and seemed to be well tolerated as part of a multidrug regimen.

Pediatric Mandible Reconstruction for Osteomyelitis During Largest Reported Mycobacterium Abscessus Outbreak.

In 2016, water lines at a children's dental clinic in Orange County, California were contaminated with Mycobacterium abscessus (MA), a non-tuberculosis rapidly-growing mycobacterium, leading to the largest MA outbreak ever reported. Mandatory reporting and active case finding directed by the Public Health Department was conducted in collaboration with community Pediatric Infectious Disease physicians for patients who underwent dental pulpotomies at the contaminated Dental Clinic from January 1 to September 6, 2016. Seventy-one cases (22 confirmed and 49 probable) were identified. One case that required extensive debridement and reconstruction of the mandible is presented in detail. CT maxillofacial demonstrated osteomyelitis extending from the right mandibular angle to the left ramus with multifocal periapical lucencies. CT chest and neck revealed numerous pulmonary nodules and bilateral cervical lymphadenopathy. Extraction of several involved teeth, bilateral selective neck dissection, and extensive mandibular debridement was performed, followed by mandibular stabilization with a custom pre-bent 2.0-mm locking plate. CT images 1-year post-operative showed clearance of infection and sufficient bony stability. Subsequent removal of hardware and bone grafting was performed and the patient is doing well. In the event of a future odontogenic mycobacterium outbreak, the experience at our institution can inform multidisciplinary treatment approaches. Prophylactic extraction of primary teeth that received pulpotomies with contaminated water should be performed. Early and thorough debridement of affected bone, including enucleation of secondary teeth, should be performed if necessary for early source control.