Search

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from the antigen-presenting cells of the immune system. It usually involves the lymph nodes, and extranodal sites are rarely affected. Here, we report a first known case of spontaneous hemoperitoneum caused by the rupture of IDCS of the small bowel. A 61-year-old male presented with complaints of abdominal pain and fever for 3 days and breathlessness for 1 day. Ultrasound abdomen revealed a 15 cm × 7 cm heterogeneous collection with thick septations in the periumbilical region. Diagnostic peritoneal lavage revealed hemoperitoneum and gangrenous bowel. Emergency laprotomy was done and it revealed a friable mass arising from the ileum. Resection of 2 ft of the ileum and double-barrel ileostomy was done. Immunohistochemical analysis revealed a positivity of S100 and leukocyte common antigen). A diagnosis of IDCS was made. The patient had an uneventful postoperative recovery and planned for postoperative chemotherapy. [ABSTRACT FROM AUTHOR]

Bezoars are usually defined as collections of nondigestible matter that most commonly accumulates in the stomach and can sometimes extend to the small bowel. Trichobezoars are a rare entity which is most commonly observed in young psychiatric females with trichotillomania and trichophagia. Here, we report a case of giant gastric trichobezoar and a novel technique of laparoscopic removal in a 16 year old female with trichophagia. The giant gastric trichobezoar weighing about half a kilogram was removed en masse laparoscopically by a novel technique. She had an uneventful postoperative recovery and was discharged after psychiatric counseling.

Choledochal cysts are rare congenital anomalies of the biliary tract. There are 5 subtypes of choledochal cyst and in adults type 4 is the most common. Choledochal cyst rarely exceeds the size of 6cm in the reported literature. Only a handful of cases of giant choledochal cysts are reported in the literature. Here we report a case of a 33-year-old lady who presented with a huge abdominal mass and on evaluation was found to have a giant choledochal cyst type 4A. The patient underwent excision of the extrahepatic hugely dilated choledochal cyst with cholecystectomy and reconstruction was done by Roux-en-Y hepaticojejunostomy to the confluence of the right and left hepatic duct at the hilum.

Spontaneous esophageal perforation is rare and is associated with high morbidity and mortality. A spectrum of various surgical modalities ranging from primary surgical repair to esophagectomy is available for its management. The optimal management of patients presenting late in a hemodynamically stable condition is not clearly defined in the literature. A retrospective review of all patients with Boerhaave syndrome managed by a single surgical team in a tertiary care center between 2008 and 2019 was performed (n = 16). Eleven patients were initially managed in the medical intensive care unit (MICU) as non-esophageal cause and 5 patients were referred after failed management (conservative/endoscopic). Demographics, clinical presentation, characteristics of perforation, initial diagnosis, and treatment were analyzed. All patients were males with a mean age of 42.2 years. A history of ethanol use was present in 6 patients. The median delay in diagnosis and referral was 16 days (range: 11-40 days). The common presenting symptoms were chest pain (n=11), dyspnoea (n=10), vomiting (n=4) and cough (n=2). The perforation was into right, left, and bilateral pleural cavities in 6, 8, and 2 patients respectively. The location of perforation was distal esophagus except for one patient. One patient was successfully treated with conservative management. The remaining patients underwent esophagectomy as a definitive surgical procedure. There was no significant postoperative morbidity and mortality. Esophagectomy can be done as a one-stage definitive procedure for patients with Boerhaave syndrome who present late in a hemodynamically stable condition with acceptable morbidity and good long term outcome.

Immune dysregulation in autoimmune diseases (ADs) is a risk factor for the development of Non-Hodgkin's lymphoma (NHL). However, the underlying mechanisms are not well understood. Hence, this retrospective study aims to describe the clinical and demographic factors that increase the risk of NHL development in patients with ADs. Our study utilised data from National Inpatient Sample (NIS) for the duration of 2016-2020 on all adult patients aged > 18 years who had NHL. We divided them into two cohorts: one with underlying ADs and one without underlying ADs. We then compared the adjusted odds ratios (aOR) of various risk factors. It was found that 0.9% of autoimmune cases had NHL, while 0.7% of non-autoimmune cases had NHL. Among those with autoimmune conditions, various factors influenced the presence of lymphoma, such as personal history of chemotherapy or radiation, family history of lymphoid malignancy, HIV infection, advanced age of 60-69 years, Asian and Pacific Islander ethnicity and viral hepatitis. The increased risk of NHL with autoimmune conditions is well established. Studies have also shown that these patients can overall have a poor prognosis from their NHL when compared to patients without autoimmune diseases. However, there is limited literature regarding the interplay of traditional NHL risk factors with underlying autoimmunity. Hence, our study sheds light on the lesser studied risk factors, such as patient characteristics and comorbidities., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: While the exact pathogenesis of peripartum cardiomyopathy, a potentially life-threatening condition, is still unknown, its incidence is rising globally. We sought to understand the differences in outcomes and complications based on age., Methods: Records from the 2016-2020 National Inpatient Sample were used for our study. The sample consisted of females diagnosed with peripartum cardiomyopathy that required hospitalization care. They were divided into two age-based cohorts: 15-29 years and 30-40 years. We evaluated differences in in-hospital complications between the two groups using multivariable regression., Results: The analysis consisted of 20520 females diagnosed with peripartum cardiomyopathy, of whom 57.3 % were in the 30-40 years cohort and 42.7 % in the 15-29 years group. The prevalence of cardiovascular risk factors such as smoking, obesity, hypertension, diabetes and lipid disorder was higher among women aged 30-40 years (p < 0.01). These patients also demonstrated higher odds of reporting acute ischemic stroke (aOR 1.354, 95 % CI 1.038-1.767, p = 0.026) while having a reduced risk of cardiogenic shock (aOR 0.787, 95 % CI 0.688-0.901, p < 0.01) as compared to those aged 15-29 years during their hospitalisation with PPCM. No statistically significant differences were noted for events of acute kidney injury (aOR 1.074, 95 % CI 0.976-1.182, p = 0.143), acute pulmonary oedema (aOR 1.147, 95 % CI 0.988-1.332, p = 0.071) or in-hospital mortality (aOR 0.978, 95 % CI 0.742-1.290, p = 0.877)., Conclusion: Peripartum cardiomyopathy is a serious condition that requires appropriate care and management. Our study linked cases of ages 30-40 years with increased odds of acute ischemic stroke but lower odds of cardiogenic shock., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: In patients with cardiac sarcoidosis (CS), implantable cardioverter-defibrillators (ICDs) are important for preventing sudden cardiac death. This study aimed to investigate sex disparities in CS patients undergoing ICD implantation., Methods: The 2016-2020 National Inpatient Sample (NIS) database compared the characteristics and outcomes of males and females with CS receiving ICDs., Results: Among 760 CS patients who underwent inpatient ICD implantation, 66.4% were male. Males were younger (55.0 vs. 56.9 years, p < .01), had higher rates of diabetes (31.7% vs. 21.6%, p < .01) and chronic kidney disease (CKD) (16.8% vs. 7.8%, p < .01) but lower prevalence of atrial fibrillation (AF) (11.9% vs. 23.5%, p < .01), sick sinus syndrome (4.0% vs. 7.8%, p = .024), ventricular fibrillation (VF) (9.9% vs. 15.7%, p = .02), and black ancestry (31.9% vs. 58.0%, p < .01). Unadjusted major adverse cardiovascular events (MACE), defined as a composite of in-hospital death, myocardial infarction (MI), and ischemic stroke, was higher in females (11.8% vs. 6.9%, p = .024), but when adjusted for age and tCharlson Comorbidity Index (CCI), females demonstrated significantly lower odds of experiencing MACE (aOR: 0.048, 95% CI: 0.006-0.395, p = .005). Incidence of acute kidney injury (AKI) post-ICD was significantly lower in females (15.7% vs. 23.8%, p = .01) as was the adjusted odds (aOR: 0.282, 95% CI: 0.146-0.546, p < .01). There was comparable mean length of stay and hospital charges., Conclusion: ICD utilization in CS patients is more common among males, who have a higher prevalence of diabetes and CKD but a lower prevalence of AF, sick sinus syndrome, and VF. Adjusted MACE and AKI were significantly lower in females., (© 2024 The Author(s). Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Background: Racial disparities in cardiovascular conditions are well documented. Whether similar race-based discrepancies in health outcomes also exist among elderly patients undergoing surgical aortic valve replacement (SAVR) for aortic stenosis remains understudied., Methods: We abstracted data from the National (Nationwide) Inpatient Sample over a 20-year period from 2001 to 2020 using specific ICD-9 and ICD-10 codes. We included patients aged ≥ 60 and ≤ 80 years with races recorded as White, African American, or Hispanic at the time of their hospitalization for surgery. We analyzed and reported the baseline characteristics, risk-adjusted in-hospital mortality, and complications stratified by race., Results: Of 420,181 patients studied, 90.0% identified as White, 4.0% as African American and 6.0% as Hispanic. Despite a decrease in overall in-hospital mortality rates from 3.8% between 2001-2005 to 1.8% between 2016-2020, African Americans had higher odds of all-cause in-hospital deaths compared to Whites (aOR = 1.390, P < 0.001). Additionally, they were more likely to experience cardiogenic shock (aOR = 1.241, P < 0.001) and acute kidney injury (aOR = 1.314, P < 0.001) as well as more likely to require organ support such as IABP use (aOR = 1.336, P < 0.001) or invasive mechanical ventilation (aOR = 1.342, P < 0.001). Interestingly, African Americans were less likely to report events of acute ischemic stroke compared to Whites (aOR = 0.852, P < 0.001)., Conclusions: Despite a reassuring reduction in overall in-hospital mortality rates of geriatric patients undergoing SAVR for aortic stenosis, racial disparities in health outcomes remain pervasive with minorities more likely to report higher in-hospital morbidity and mortality., (© 2024 JGC All rights reserved; www.jgc301.com.)

Objectives: Endocardial fibroelastosis (EFE) is a rare form of restrictive cardiomyopathy associated with high morbidity and mortality. The literature is sparse on information pertaining to risk stratification. Thus, we sought to highlight the risk factors of acute ischemic stroke (AIS) and mortality in adults with EFE., Methods: The National Inpatient Sample (NIS) database was queried from 2001 to 2020 using the International Classification of Diseases 9th Revision (ICD-9) and 10th Revision (ICD-10) codes for adult patients with EFE. Factors associated with AIS and mortality were identified., Results: In all, 18495 cases of EFE fit the inclusion criteria, of which 2370 (12.82%) had AIS. The mean ages for patients with and without AIS were 62.37 and 54.24, respectively. Multivariate regression suggested greater odds of AIS in patients with hypertension (aOR 2.329, P<0.01), dyslipidemia (aOR: 1.566, P<0.01), peripheral vascular disease (PVD) (aOR: 1.736, P<0.01), alcohol abuse (aOR: 1.817, P<0.01), age >60 y (aOR: 1.646, P<0.01), females (vs. males, aOR: 1.238, P<0.01), and smokers (aOR: 1.697, P<0.01). Patients with cirrhosis (aOR: 0.174, P<0.01), CKD (aOR: 0.369, P<0.01), COPD (aOR: 0.402, P<0.01), atrial fibrillation (aOR: 0.542, P<0.01) had lower odds of AIS. 3.1% of EFE patients with AIS died. Diabetes (aOR: 11.665, P<0.01) and COPD (aOR: 3.201, P=0.017) were associated with the greatest odds of all-cause mortality. Dyslipidemia (aOR: 0.387, P=0.010) and females (vs. males, aOR: 0.432, P=0.012) had reduced odds of all-cause mortality., Conclusion: Several risk factors are associated with AIS in EFE, while diabetes, COPD, and being male are associated with mortality in EFE., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Cannabis is increasingly becoming a socially acceptable substance, with multiple countries having legalised its consumption. Epidemiological studies have demonstrated an association between cannabis use and an increased risk of developing coronary artery disease. However, there is a lack of studies about the influence of cannabis consumption on the outcomes following acute myocardial infarction (AMI)., Material and Methods: We retrospectively analysed hospitalised patients with a primary diagnosis of AMI from the 2001 to 2020 National Inpatient Sample (NIS). Pearson's χ 2 tests were applied to categorical variables, and t -tests for continuous variables. We conducted a 1:1 propensity score matching (PSM). Multivariate regression models were deployed on the PSM sample to estimate the differences in several events and all-cause mortality., Results: A total of 9,930,007 AMI patients were studied, of whom 117,641 (1.2%) reported cannabis use. Cannabis users had lower odds of atrial fibrillation (aOR = 0.902, p < 0.01), ventricular fibrillation (aOR = 0.919, p < 0.01), cardiogenic shock (aOR = 0.730, p < 0.01), acute ischaemic stroke (aOR = 0.825, p < 0.01), cardiac arrest (aOR = 0.936, p = 0.010), undergoing PCI (aOR = 0.826, p < 0.01), using IABP (aOR = 0.835, p < 0.01), and all-cause mortality (aOR = 0.640, p < 0.01), but with higher odds of supraventricular tachycardia (aOR = 1.104, p < 0.01), ventricular tachycardia (aOR = 1.054, p < 0.01), CABG use (aOR = 1.040, p = 0.010), and acute kidney injury (aOR = 1.103, p < 0.01)., Conclusions: Among patients aged 18-80 years admitted to hospital with AMI between 2001 and 2020 in the United States, cannabis use was associated with lower risks of cardiogenic shock, acute ischaemic stroke, cardiac arrest, PCI use, and in-hospital mortality., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia & Banach.)

Competing Interests: The authors declare no conflict of interest.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background and Objectives : Coronavirus disease 2019 (COVID-19) caused several cardiovascular complications, including acute myocardial infarction (AMI), in infected patients. This study aims to understand the overall trends of AMI among COVID-19 patients during the first two years of the pandemic and the disparities and outcomes between the first and second years. Materials and Methods : The retrospective analysis was conducted via the 2020 and 2021 National Inpatient Sample (NIS) database for hospitalizations between April 2020 and December 2021 being analyzed for adults with a primary diagnosis of COVID-19 who experienced events of AMI. A comparison of month-to-month events of AMI and mortality of AMI patients with concomitant COVID-19 was made alongside their respective patient characteristics. Results : Out of 2,541,992 COVID-19 hospitalized patients, 3.55% experienced AMI. The highest rate of AMI was in December 2021 (4.35%). No statistical differences in trends of AMI mortality were noted over the 21 months. AMI cases in 2021 had higher odds of undergoing PCI (aOR 1.627, p < 0.01). They experienced higher risks of acute kidney injury (aOR 1.078, p < 0.01), acute ischemic stroke (aOR 1.215, p < 0.01), cardiac arrest (aOR 1.106, p < 0.01), need for mechanical ventilation (aOR 1.133, p < 0.01), and all-cause mortality (aOR 1.032, 95% CI 1.001-1.064, p = 0.043). Conclusions : The incidence of AMI among COVID-19 patients fluctuated over the 21 months of this study, with a peak in December 2021. COVID-19 patients reporting AMI in 2021 experienced higher overall odds of multiple complications, which could relate to the exhaustive burden of the pandemic in 2021 on healthcare, the changing impact of the virus variants, and the hesitancy of infected patients to seek care.

Introduction: Coronavirus disease 2019 (COVID-19) can lead to cardiovascular complications. We aimed to understand the trends in admission for COVID-19 and the incidence of various cardiovascular events., Material and Methods: The 2020 and 2021 National Inpatient Sample (NIS) was studied for cases of COVID-19 between April 2020 and December 2021 in the United States. Linear-by-linear association helped us understand the trends of various events., Results: The number of cases of COVID-19 was highest in January 2021 (261,469 patients). The incidence of acute pulmonary embolism rose from 2.08% in April 2020 to 4.82% in November 2021, while deep vein thrombosis cases rose from 1.74% in April 2020 to 2.63% in December 2021. The incidence of cardiac arrest varied, with a maximum of 3.00% in August 2021. Similarly, acute ischemic stroke cases experienced their highest incidence in January 2021 (0.91%). The incidence of myocarditis was highest in April and May 2020 (0.42% each). Peak takotsubo cases were seen between October and December 2021. The highest overall all-cause mortality among COVID-19 cases was seen in April 2020 (16.74%)., Conclusions: Throughout the 21 months of our analysis, various trends in COVID-19 cases and incidence of cardiac events were noticed. This could relate to the different variants of COVID-19, their direct and indirect impact on coagulation pathways and the myocardial tissues, and the protective roles of the vaccines., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia & Banach.)

Competing Interests: The authors declare no conflict of interest.

Introduction: Sarcoidosis is a systemic inflammatory disorder characterised by non-caseating granulomas. Cardiac sarcoidosis (CS) normally causes conduction abnormalities, ventricular arrhythmias, and heart failure. Little is known about the characteristics and impact of sarcoidosis in patients admitted with ST-elevation myocardial infarction (STEMI). This study aims to fill this void., Material and Methods: Utilising the National Inpatient Sample (NIS) database (2016-2020), individuals with STEMI were identified and categorised based on sarcoidosis presence whilst adjusting for confounders via logistic regression models., Results: Among 851,290 STEMI patients, 1215 had sarcoidosis. Before propensity matching, sarcoidosis patients were notably different in demographics and comorbidities compared to non-sarcoidosis patients. After propensity score matching (PSM), sarcoidosis patients were found to have a higher incidence of supraventricular tachycardia (SVT) (2.5% vs. 1.3%, p = 0.024) and acute kidney injury (AKI) (23.3% vs. 20.8%, aOR = 1.269, 95% CI: 1.02-1.58, p = 0.033) but a lower incidence of undergoing coronary artery bypass graft (CABG) (5.5% vs. 8.5%, aOR = 0.663; 95% CI: 0.472-0.931, p = 0.018), while no significant disparities were noted in PCI, cardiogenic shock, mortality, or mean length of stay (LOS)., Conclusions: Using propensity-matched large real-world data of STEMI patients, sarcoidosis was associated with fewer cases of CABG and a greater incidence of AKI and SVT compared to non-sarcoidosis patients., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia & Banach.)

Pulmonary macrophage transplantation (PMT) is a gene and cell transplantation approach in development as therapy for hereditary pulmonary alveolar proteinosis (hPAP), a surfactant accumulation disorder caused by mutations in CSF2RA/B (and murine homologs). We conducted a toxicology study of PMT of Csf2ra gene-corrected macrophages (mGM-Rα + Mϕs) or saline-control intervention in Csf2ra KO or wild-type (WT) mice including single ascending dose and repeat ascending dose studies evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics. Lentiviral-mediated Csf2ra cDNA transfer restored GM-CSF signaling in mGM-Rα + Mϕs. Following PMT, mGM-Rα + Mϕs engrafted, remained within the lungs, and did not undergo uncontrolled proliferation or result in bronchospasm, pulmonary function abnormalities, pulmonary or systemic inflammation, anti-transgene product antibodies, or pulmonary fibrosis. Aggressive male fighting caused a similarly low rate of serious adverse events in saline- and PMT-treated mice. Transient, minor pulmonary neutrophilia and exacerbation of pre-existing hPAP-related lymphocytosis were observed 14 days after PMT of the safety margin dose but not the target dose (5,000,000 or 500,000 mGM-Rα + Mϕs, respectively) and only in Csf2ra KO mice but not in WT mice. PMT reduced lung disease severity in Csf2ra KO mice. Results indicate PMT of mGM-Rα + Mϕs was safe, well tolerated, and therapeutically efficacious in Csf2ra KO mice, and established a no adverse effect level and 10-fold safety margin., Competing Interests: B.C.T. has equity in Altius Therapeutics, a biopharmaceutical company with a license from Cincinnati Children’s Hospital Medical Center to develop PMT as a therapeutic platform beyond the planned clinical use as therapy of hPAP., (© 2024 The Authors.)

During the pandemic of COVID-19, a novel atypical set of clinical findings was seen among several children with recent or current exposure to the virus. It was termed the "multisystem inflammatory syndrome in children" (MIS-C). Our study used the 2021 National Inpatient Sample to study the associations of sex, race, and age with the incidence of MIS-C among COVID-19-positive children. Out of 69,440 COVID-19-positive children, 2,790 (4.0%) reported MIS-C. The incidence of MIS-C was highest among those aged 8 years old (17,130 MIS-C cases per 100,000 COVID-19 patients), Asian or Pacific Islanders (API) (5,346 MIS-C per 100,000 COVID-19 cases), and males (4,734 cases per 100,000 COVID-19 cases). Furthermore, 7.9% of MIS-C cases met the classification of Kawasaki disease., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Prph2 is a photoreceptor-specific tetraspanin with an essential role in the structure and function of photoreceptor outer segments. PRPH2 mutations cause a multitude of retinal diseases characterized by the degeneration of photoreceptors as well as defects in neighboring tissues such as the RPE. While extensive research has analyzed photoreceptors, less attention has been paid to these secondary defects. Here, we use different Prph2 disease models to evaluate the damage of the RPE arising from photoreceptor defects. In Prph2 disease models, the RPE exhibits structural abnormalities and cell loss. Furthermore, RPE functional defects are observed, including impaired clearance of phagocytosed outer segment material and increased microglia activation. The severity of RPE damage is different between models, suggesting that the different abnormal outer segment structures caused by Prph2 disease mutations lead to varying degrees of RPE stress and thus influence the clinical phenotype observed in patients., (© 2022 Federation of American Societies for Experimental Biology.)

The Congenital Dyserythropoietic Anemia (CDA) Registry was established with the goal to facilitate investigations of natural history, biology, and molecular pathogenetic mechanisms of CDA. Three unrelated individuals enrolled in the registry had a syndrome characterized by CDA and severe neurodevelopmental delay. They were found to have missense mutations in VPS4A, a gene coding for an ATPase that regulates the ESCRT-III machinery in a variety of cellular processes including cell division, endosomal vesicle trafficking, and viral budding. Bone marrow studies showed binucleated erythroblasts and erythroblasts with cytoplasmic bridges indicating abnormal cytokinesis and abscission. Circulating red blood cells were found to retain transferrin receptor (CD71) in their membrane, demonstrating that VPS4A is critical for normal reticulocyte maturation. Using proband-derived induced pluripotent stem cells (iPSCs), we have successfully modeled the hematologic aspects of this syndrome in vitro, recapitulating their dyserythropoietic phenotype. Our findings demonstrate that VPS4A mutations cause cytokinesis and trafficking defects leading to a human disease with detrimental effects to erythropoiesis and neurodevelopment., (Copyright © 2020. Published by Elsevier Inc.)

Peripherin 2 (PRPH2) is a retina-specific tetraspanin protein essential for the formation of rod and cone photoreceptor outer segments (OS). Patients with mutations in PRPH2 exhibit severe retinal degeneration characterized by vast inter- and intra-familial phenotypic heterogeneity. To help understand contributors to this within-mutation disease variability, we asked whether the PRPH2 binding partner rod OS membrane protein 1 (ROM1) could serve as a phenotypic modifier. We utilized knockin and transgenic mouse models to evaluate the structural, functional and biochemical effects of eliminating one allele of Rom1 (Rom1+/-) in three different Prph2 models which mimic human disease: C213Y Prph2 (Prph2C/+), K153Del Prph2 (Prph2K/+) and R172W (Prph2R172W). Reducing Rom1 in the absence of Prph2 mutations (Rom1+/-) had no effect on retinal structure or function. However, the effects of reducing Rom1 in the presence of Prph2 mutations were highly variable. Prph2K/+/Rom1+/- mice had improved rod and cone function compared with Prph2K/+ as well as amelioration of K153Del-associated defects in PRPH2/ROM1 oligomerization. In contrast, Prph2R172W/Rom1+/- animals had worsened rod and cone function and exacerbated retinal degeneration compared with Prph2R172W animals. Removing one allele of Rom1 had no effect in Prph2C/+. Combined, our findings support a role for non-pathogenic ROM1 null variants in contributing to phenotypic variability in mutant PRPH2-associated retinal degeneration. Since the effects of Rom1 reduction are variable, our data suggest that this contribution is specific to the type of Prph2 mutation., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Hereditary spherocytosis (HS) is the most common red blood cell (RBC) membrane disorder causing hereditary hemolytic anemia. Patients with HS have defects in the genes coding for ankyrin ( ANK1 ), band 3 ( SLC4A1 ), protein 4.2 ( EPB42 ), and α ( SPTA1 ) or β-spectrin ( SPTB ). Severe recessive HS is most commonly due to biallelic SPTA1 mutations. α-spectrin is produced in excess in normal erythroid cells, therefore SPTA1 -associated HS ensues with mutations causing significant decrease of normal protein expression from both alleles. In this study, we systematically compared genetic, rheological, and protein expression data to the varying clinical presentation in eleven patients with SPTA1 -associated HS. The phenotype of HS in this group of patients ranged from moderately severe to severe transfusion-dependent anemia and up to hydrops fetalis which is typically fatal if transfusions are not initiated before term delivery. The pathogenicity of the mutations could be corroborated by reduced SPTA1 mRNA expression in the patients' reticulocytes. The disease severity correlated to the level of α-spectrin protein in their RBC cytoskeleton but was also affected by other factors. Patients carrying the low expression α LEPRA allele in trans to a null SPTA1 mutation were not all transfusion dependent and their anemia improved or resolved with partial or total splenectomy, respectively. In contrast, patients with near-complete or complete α-spectrin deficiency have a history of having been salvaged from fatal hydrops fetalis , either because they were born prematurely and started transfusions early or because they had intrauterine transfusions. They have suboptimal reticulocytosis or reticulocytopenia and remain transfusion dependent even after splenectomy; these patients require either lifetime transfusions and iron chelation or stem cell transplant. Comprehensive genetic and phenotypic evaluation is critical to provide accurate diagnosis in patients with SPTA1 -associated HS and guide toward appropriate management.

Disclosures: No relevant conflicts of interest to declare., (© 2017 by The American Society of Hematology.)