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Severe congenital protein C deficiency (SCPCD) is a rare disorder associated with life-threatening purpura fulminans and disseminated intravascular coagulation that typically present within hours after birth. Treatment options for patients with SCPCD include replacement therapy with a plasma-derived protein C concentrate. In this targeted literature review, we summarize information on the use of protein C concentrate as long-term prophylaxis (>1 week of treatment) for patients with SCPCD. In total, 18 publications were included in the review, of which 15 were case studies. Treatment with protein C concentrate (Ceprotin; Baxalta US Inc, a Takeda company; Takeda Manufacturing Austria AG) was reported in 11 publications, and treatment with protein C concentrate (Protexel; LFB Biomedicaments) was reported in 2 publications. One publication reported on both Ceprotin and Protexel. Details of protein C concentrate treatment regimens, including the dose, administration frequency, and route of administration, were reported in 11 publications. Dosing regimens varied across all 11 publications, possibly due to different protein C trough levels among patients or the administration of concomitant medications. Seven of the 11 publications reported on patients who initially received intravenous protein C concentrate and subsequently switched to subcutaneous administration. Treatment outcomes with protein C concentrate were generally favorable, including the prevention of coagulopathy and thrombosis and the healing of cutaneous lesions. Three adverse events in 1 publication were identified as being possibly related to Ceprotin administration. Although published data are limited, this review provides valuable insights into the treatment of patients with SCPCD in clinical practice, including protein C concentrate dosing regimens, administration routes, and associated clinical outcomes., (© 2024 The Authors.)

Background: This retrospective cohort study compared patient characteristics and burden of infection in patients with mature B cell malignancies with and without secondary immunodeficiency disease (SID)., Patients and Methods: Data were extracted from the Humedica database (H-DB) and Guardian Research Network (GRN) database from October 1, 2015 to March 10, 2020, including a 6-month pre-index period (PIP) and 12-month follow-up. Patients aged ≥18 years diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma, or non-Hodgkin's lymphoma in the PIP were stratified into 2 cohorts: SID (hypogammaglobulinemia [using ICD-10-CM codes] or serum IgG levels <5.0 g/L, both with signs and symptoms of SID or at least 1 infection) and no-SID. Patients with SID or primary immunodeficiency diseases in the PIP were excluded., Results: Overall, 2221 patients with SID (H-DB/GRN: n = 1959/262), and 19,141 patients without SID (n = 17,598/1543) were included. Baseline characteristics were similar across cohorts. At 12-month follow-up, significantly more patients with SID had experienced ≥1 infection and ≥1 severe bacterial infection than those without SID (both P < .001). H-DB/GRN mean (standard deviation) number of severe bacterial infections was 7.6 (9.9)/2.9 (2.7) for the SID cohort versus 5.2 (6.8)/2.4 (2.2) for the no-SID cohort., Conclusion: This study confirms that patients with mature B cell malignancies and SID face a significantly higher burden of infections than those without SID., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Infants born extremely premature (EP) (<28 weeks gestational age) are at high risk of complications, particularly bronchopulmonary dysplasia (BPD), which can develop into chronic lung disease (CLD)., Methods: The burden of respiratory complications in EP infants up to 2 years corrected age (CA) was evaluated using real-world data from the US Medicaid program. Data recorded between 1997 and 2018 on EP infants without major congenital malformations were collected from Medicaid records of six states. EP infants were divided into three cohorts: BPD, CLD, and without BPD or CLD. The incidence of respiratory conditions, respiratory medication use, and healthcare resource utilization were compared between the BPD cohort and CLD cohort versus the cohort without BPD or CLD, using unadjusted and adjusted generalized linear models., Results: A total of 4462 EP infants were identified (17.4% of all premature infants in the database). Of these, BPD and CLD were diagnosed in 61.9% and 72.1%, respectively, and 14.5% were diagnosed with neither BPD nor CLD. Compared with infants without BPD or CLD, infants with BPD or CLD had more complications and a longer length of birth hospitalization stay. Respiratory distress syndrome was the most frequently reported complication (94.6%, 92.5%, and 82.3% of EP infants in the BPD, CLD, and without BPD or CLD cohorts, respectively). After the birth hospitalization, respiratory conditions, respiratory medication use, and incidence rates of rehospitalizations, emergency room visits, and outpatient visits were higher for infants with BPD or CLD. Rehospitalization occurred in 50.5%, 51.6%, and 27.3% of EP infants with BPD, CLD, or without BPD or CLD, respectively; most hospitalizations occurred for respiratory-related reasons., Conclusion: In this analysis of a large population of EP infants up to 2 years CA, respiratory conditions were prevalent after the birth hospitalization and were associated with high rates of medication and healthcare resource utilization., Competing Interests: Declaration of competing interest MEM has no conflict of interest to declare. WG, HS, and RA are employees of Analysis Group, which was contracted through Shire, a Takeda company, to perform this study. PZ and HW were employees of Analysis Group at the time of the study. SS was an employee of Takeda at the time of the study. CS is a full-time employee of and holds stock/stock options in Takeda., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Preterm birth is a leading cause of infant mortality, particularly for those born extremely prematurely (EP; <28 weeks' gestational age [GA]). Survivors are predisposed to complications such as bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP)., Aims: To examine the epidemiology, complications, and mortality/survival among EP infants., Study Design: Retrospective analysis of electronic medical records from the Kaiser Permanente Northern California database., Subjects: EP infants live-born between 22 and <28 weeks' GA from 1997 to 2016., Outcome Measures: Cumulative all-cause mortality/survival were analyzed and stratified by GA (22 to <24, 24 to <26, 26 to <28 weeks), complications (BPD/CLD, IVH, ROP), and birth period (1997 to 2003, 2004 to 2009, 2010 to 2016). Cox proportional hazard models were constructed to assess the mortality risk associated with BPD/CLD or IVH., Results: 2154 EP infants were identified; of these, 916 deaths were recorded. Mortality was highest during the first 3 months (41.7 % cumulative mortality), and few were reported after 2 years (42.5 % cumulative mortality). Mortality decreased with higher GA and over more recent birth periods. BPD/CLD and IVH grade 3/4 were associated with increased mortality risk versus no complications (adjusted hazard ratios 1.41 and 1.78, respectively)., Conclusions: The risk of mortality is high during the first few months of life for EP infants, and is even higher for those with BPD and IVH. Despite an overall trend toward increased survival for EP infants, strategies targeting survival of EP infants with these complications are needed., (Copyright © 2022 Takeda Pharmaceuticals Americas Inc. Published by Elsevier B.V. All rights reserved.)

Experimental studies indicated that the mouse zygote is susceptible to experimental induction of developmental anomalies including defects (mainly hydrops), growth retardation and mid- and late-gestational death with certain mutagenic agents. The material of the Hungarian Optimal Family Planning Program is appropriate to check this finding in a human material because participants were asked to visit the coworkers of the Program immediately after the first missed menstrual period and data concerning potentially hazardous environmental factors were obtained. At that time participants were immediately after the pre- and implantation period and they had no knowledge about their pregnancy outcomes. In 1994 the data of their pregnancy outcomes are available. Of 5453 evaluated pregnancies, 1167 were selected for this study because they visited the coworkers of the Program within 28 days post conception. Of 1167 pregnancies, 316 (27%) were exposed to some environmental factors, mainly drugs. A mild intrauterine growth retardation was found in the exposed group. The rate of congenital abnormalities and infant death did not differ between the exposed and unexposed groups. The detailed analysis of different congenital abnormality groups also did not show any significant difference between the exposed and unexposed groups. These negative results are explained by the fact that the observed environmental factors are not mutagenic, at least not in the dosage which was used, or the human zygote is not sensitive to mutagenic agents in the post-conceptional days.