Investigation of health inequities in maternal and neonatal outcomes of patients with placenta accreta spectrum: a multicenter study.

BACKGROUND: Placenta accreta spectrum (PAS) is associated with significant maternal and neonatal morbidity and mortality. There is limited established data on healthcare inequities in outcomes of patients with PAS. OBJECTIVE: To investigate health inequities in maternal and neonatal outcomes of pregnancies with PAS. STUDY DESIGN: This multicentered retrospective cohort study included patients with histopathological diagnosis of PAS at four regional perinatal centers between 1/1/2013 - 6/30/2022. Maternal race and/or ethnicity were categorized as either Hispanic, non-Hispanic Black, non-Hispanic White, or Asian or Pacific Islander. Primary outcome was a composite adverse maternal outcome: transfusion of 4+ units of packed red blood cells, vasopressor use, mechanical ventilation, bowel or bladder injury or mortality. Secondary outcomes were composite adverse neonatal outcome (APGAR < 7 at 1-minute, morbidity, or mortality), gestational age at PAS diagnosis, and planned delivery by a multidisciplinary team. Multivariable logistic regression was used to estimate the associations of race/ethnicity with maternal and neonatal outcomes. RESULTS: 408 pregnancies with PAS were included. In 218 patients (53%), the diagnosis of PAS was made antenatally. Patients predominantly self-identified as non-Hispanic White (31.6%) or non-Hispanic Black (24.5%). After adjusting for institution, age, BMI, income and parity, there was no difference in composite adverse maternal outcome among racial and ethnic groups. Similarly, adverse neonatal outcomes, gestational age at prenatal diagnosis, rate of planned delivery by a multidisciplinary team and cesarean hysterectomy were similar between groups. CONCLUSION: In our multicenter PAS cohort, race and/or ethnicity were not associated with inequities in composite maternal or neonatal morbidity, timing of diagnosis and planned multi-disciplinary care. We hypothesize that comparable incidence of individual risk factors for perinatal morbidity as well as geographic proximity reduce potential inequities that may exist in the larger population.

Neutrophilic panniculitis associated with myelodysplastic syndrome/myeloproliferative neoplasm: a case report and literature review.

Introduction: Neutrophilic panniculitis (NP) is a rare subtype of neutrophilic dermatosis, a group of neutrophil-rich inflammatory skin disorders that can present in association with myeloid neoplasms. NP is defined by the presence of a neutrophilic infiltrate in the fat lobules of the subcutis in the absence of either infection or vasculitis. We herein describe a 65-year-old woman with a recent diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome (MDS/MPN) who abruptly developed painful, pruritic nodules consistent with NP. Case presentation: A 65-year-old woman with MDS/MPN presented for evaluation of painful and pruritic nodules on her upper and lower extremities. A biopsy revealed a lobular neutrophilic infiltrate in the subcutis without evidence of microorganisms or vasculitis. The patient was diagnosed with NP and treated with oral prednisone. Within 1 month of treatment, she reported complete resolution of the nodules. Discussion: Similar to other neutrophilic dermatoses, NP may arise in association with hematologic malignancies of myeloid origin, such as MDS/MPN. A literature review revealed that most cases of NP associated with MDS occur after the onset of MDS and respond to systemic corticosteroids, not antibiotics. Infection should be ruled out before initiating treatment with systemic steroids. Conclusion: Although the mechanism is still unknown, it is important for clinicians to be aware that NP is associated with MDS; thus, hematological malignancies should be investigated upon diagnosis of NP. Once diagnosed, NP is easily treated and has an excellent response to systemic corticosteroids.

SARS-CoV-2 Infection in Unvaccinated High-Risk Pregnant Women in the Bronx, NY, USA Is Associated with Decreased Apgar Scores and Placental Villous Infarcts.

Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2)-infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, mostly unvaccinated, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Under IRB approval, 56 SARS-CoV-2-positive patients infected during the "first wave" of the pandemic with alpha and beta strains of the virus, 48 patients infected during the "second wave" of the pandemic with delta and omicron strains and 61 negative third-trimester high-risk patients were randomly selected from Montefiore Medical Center (MMC), Bronx, NY. In addition, two positive cases from Yale New Haven Hospital, CT were included as controls. All 104 placentas delivered by SARS-CoV-2-positive mothers were uninfected by the virus, based on immunohistochemistry, in situ hybridization, and qPCR analysis. However, placental villous infarcts were significantly increased in first-wave cases compared to second-wave cases or negative controls. Significantly lower Apgar scores at 1 min and 5 min were observed in neonates born to infected mothers with severe symptoms. These findings suggest that even without entering the placenta, SARS-CoV-2 can affect various systemic pathways, culminating in altered placental development and function, which may adversely affect the fetus, especially in a high-risk patient population such as ours. These results underline the importance of vaccination among pregnant women, particularly in low-resource areas.

A Practical Approach to the Diagnosis of Lymphedema: A Narrative Review.

INTRODUCTION: Lymphedema often presents as progressive, unremitting swelling and skin changes that are extremely distressing to patients. Hereditary lymphedema (HL) constitutes a type of primary lymphedema that is passed down through generations. OBJECTIVES: The primary aims of this narrative review are to illustrate a framework to distinguish lymphedema from other causes of swelling and to differentiate the hereditary lymphedemas from each other. RESULTS: A literature search was undertaken using relevant search terms. The articles were evaluated to generate a diagnostic algorithm to approach the swelling of an extremity using clinical and laboratory data. First, the stemmer sign should be evaluated. If it is negative, other causes should be considered. History and additional physical exam findings suggest either a primary or secondary cause of lymph-edema. CONCLUSIONS: The hereditary lymphedemas have been classified by age of onset and then stratified by clinical criteria and genetic testing.

Recalcitrant Cutaneous Mastocytosis Treated With Genetically Informed Targeted Therapy: A Case Report.

Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from cutaneous lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management. We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis. Case presentation: We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis. The analysis revealed a aspartic acid to valine substitution at codon 816 (D816V) mutation in the protein c-KIT. Based on these results, we initiated treatment with the multi-kinase/KIT inhibitor midostaurin, a treatment effective against the D816V c-KIT mutation. After 3 months of treatment, the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms. Discussion: The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic. However, there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management. In the present report describing a patient with recalcitrant cutaneous mastocytosis, we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy. Conclusion: Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.

Emergence of Malignant T-Cell Intraclonal CDR3 Variants in Mycosis Fungoides.

This case report describes 3 patients with mycosis fungoides with CDR3 variants.

Dysphagia and pill swallowing in HIV/AIDS in South Africa: Results of a scoping review.

BACKGROUND:  South Africa has the highest prevalence of human immunodeficiency virus (HIV) worldwide. Highly active antiretroviral therapy (HAART) is expected to improve the quality of life for these individuals but requires long-term medication intake. Poor pill adherence and related dysphagia are undocumented for individuals on HAART regimens living in South Africa. AIM:  To conduct a scoping review describing the presentation of pill swallowing difficulties and dysphagia experiences of individuals with HIV and acquired immunodeficiency syndrome (AIDS) in South Africa. METHOD:  This review describes the presentation of pill swallowing difficulties and dysphagia experiences of individuals with HIV and AIDS in South Africa using a modified version of the Arksey and O'Malley framework. Five search engines targeting published journal articles were reviewed. Two hundred and twenty-seven articles were retrieved; however, following the exclusion criteria based on PICO, only three articles were included. Qualitative analysis was completed. RESULTS:  The reviewed articles identified swallowing difficulties that adults with HIV and AIDS experienced and confirmed non-adherence to medical regimens. Barriers and facilitators of pill swallowing with dysphagia due to the side-effects of the pill itself were documented with physical properties of the pill not influencing adherence. CONCLUSION:  The speech-language pathologists (SLPs) role with individuals with HIV/AIDS to facilitate improved pill adherence was lacking with limited research on the management of swallowing difficulties in this population. The review identified dysphagia and pill adherence management by the SLP in South Africa as caveats for further research.Contribution: Speech-language pathologists must monitor swallowing during mealtimes as well as pill swallowing in individuals with HIV/AIDS due to the compromise of their oral health and oral structures. Speech-language pathologists therefore have to advocate for their role in the team managing this population of patients. Their involvement may reduce the risk of nutritional compromise as well as patient non-compliance with medication stemming from pain and inability to swallow solid oral dosage forms of medication.

Combination cryotherapy and intralesional corticosteroid versus steroid monotherapy in the treatment of keloids.

BACKGROUND: Keloids are common and have significant negative effects on quality of life. There is a need for more effective treatment approaches for keloids. AIMS: We investigated treatment outcomes of intralesional triamcinolone acetonide (IL TAC) compared with combination IL TAC and cryotherapy, including changes in pruritus, pain, and keloid size. PATIENTS/METHODS: We performed a prospective study of patients referred to one provider who treated patients with combination therapy and compared them to a historic control cohort treated with IL TAC alone. All patients were seen at Thomas Jefferson University between 2019 and 2021. Patient demographics, location of keloids, and inciting events were recorded. Pruritus and pain scores were self-reported by patients using a 10-point Likert scale administered as standard of care. Changes in keloid size were denoted as "No change," "up to 50% decrease," "more than 50% decrease," and "completely flattened." RESULTS: While both treatments produced a significant reduction in mean pruritus and pain scores, there was no difference between the two treatment groups (p = 0.3933 and p = 0.2123, respectively). A greater percentage of keloids in the combination therapy group had a post-treatment size difference greater than 50% compared with those in the IL TAC only treatment group (p = 0.0021). In the subgroup of pubic keloids, all lesions treated with combination IL TAC and cryotherapy responded remarkably well to treatment. CONCLUSIONS: While both IL TAC and IL TAC with cryotherapy were effective at reducing pruritus and pain, combination therapy was more effective in reducing keloid size, specifically for pubic keloids.

Keloid Disorder: Genetic Basis, Gene Expression Profiles, and Immunological Modulation of the Fibrotic Processes in the Skin.

Keloid disorder, a group of fibroproliferative skin disorders, is clinically comprised of keloids, hypertrophic scars, keloidalis nuchae, and acne keloidalis. The prototype of these disorders is keloids, which manifest as cutaneous lesions with excessive deposition of collagen following an initiating trauma of varying degrees. The principal cell type responsible for collagen accumulation is the myofibroblast, and its gene expression is modulated by a network of regulatory factors, including cytokines, growth factors, and noncoding RNA species. In addition, keloids harbor a number of inflammatory cells, including macrophages and mast cells, that interact with fibroblastic cells by direct contact or by paracrine actions. Transforming growth factor-ß1/Smad signaling regulates the expression of genes encoding extracellular matrix proteins and also controls cell proliferation and apoptosis. A key profibrotic molecule is the fibronectin splice variant cellular fibronectin extracellular domain A (cFN-EDA), which interacts with a number of cell-surface integrins and TLR4, contributing to the modulation of gene expression by lesional fibroblasts. Collectively, these complex cellular interactions result in accumulation of collagen with clinical development and growth of keloid lesions. Understanding of the precise pathomechanistic details of keloid formation will provide targets for pharmacological interference toward treatment of the keloid disorder, a group of currently difficult to treat skin diseases.

Coronavirus Disease 2019 (COVID-19) Perinatal Outcomes Across the Pandemic at an Academic Medical Center in New York City.

OBJECTIVE: To investigate perinatal complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy in the four major waves of the coronavirus disease 2019 (COVID-19) pandemic in the Bronx, New York. METHODS: This retrospective cohort study included all patients who delivered at a single academic medical center between March 1, 2020, and February 13, 2022. SARS-CoV-2 positivity was defined as a positive SARS-CoV-2 test result during pregnancy. Primary outcomes were preterm birth, low birth weight, stillbirth, cesarean delivery, and preeclampsia associated with SARS-CoV-2 infection. Secondary analyses examined outcomes by predominant variant at the time of infection. Group differences in categorical variables were tested using χ 2 tests. RESULTS: Of the 8,983 patients who delivered, 638 (7.1%) tested positive for SARS-CoV-2 infection during pregnancy. Age, race, ethnicity, and major comorbidities did not differ significantly between the SARS-CoV-2-positive and SARS-CoV-2-negative cohorts ( P >.05). Primary outcomes did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative cohorts ( P >.05). There was a marked increase in positive SARS-CoV-2 test results in individuals who gave birth during the Omicron wave (140/449, 31.2%). However, among patients who tested positive for SARS-CoV-2 infection, the preterm birth rate during the Omicron wave (9.9%) was significantly lower than during the original wave (20.3%) and the Alpha (18.4%) wave ( P <.05). Vaccination rates were low before the Omicron wave and rose to 47.2% during the Omicron wave among individuals hospitalized with SARS-CoV-2 infection. Finally, second-trimester infection was significantly associated with worse perinatal outcomes compared with third-trimester infection ( P <.05). CONCLUSION: There was a general trend toward improvement in preterm birth rates across the pandemic among pregnant patients with SARS-CoV-2 infection. The Omicron variant was more infectious, but the preterm birth rate during the Omicron wave was low compared with that during the original wave and the Alpha wave.

A phase 1/2 study of ixazomib in place of bortezomib or carfilzomib in a subsequent line of therapy for patients with multiple myeloma refractory to their last bortezomib or carfilzomib combination regimen.

Identifying effective combination regimens is a high priority in multiple myeloma (MM), as most patients eventually become refractory to their current treatments. In this study, we investigated whether the proteasome inhibitor (PI) ixazomib could delay disease progression among patients who failed regimens containing another PI, bortezomib or carfilzomib. This phase 1/2, multicenter, open-label, nonrandomized study enrolled patients who were refractory to a previous regimen containing bortezomib or carfilzomib. Patients continued the other anti-MM drugs in the regimen at the same doses and frequencies. Patients with combination regimens with unknown maximum tolerated dose (MTD) of ixazomib were enrolled in phase 1, with ixazomib starting at 3 mg and then dose escalated to 4 mg. Patients on regimens with a known ixazomib MTD were enrolled in phase 2. Primary endpoints were overall response rate (ORR), clinical benefit rate (CBR), adverse events (AEs), and determination of maximum tolerated dose (MTD). Of the 46 patients enrolled, 39 were evaluable for efficacy. ORR and CBR were 12.8% and 17.9%, respectively. Ixazomib appeared to be well tolerated as a replacement for carfilzomib and bortezomib, with 23.9% of patients experiencing at least one grade ≥3 serious adverse event (SAE) and 37.0% experiencing at least one grade ≥3 AE. The most common grade ≥3 AEs were hyponatremia (8.7%), anemia (8.7%), dyspnea (8.7%), thrombocytopenia (6.5%), dehydration (4.3%), and pneumonia (4.3%). The results indicate that ixazomib is not an effective replacement for bortezomib or carfilzomib for patients with MM who have previously relapsed on other bortezomib/carfilzomib-containing regimens.

Omaveloxolone attenuates squamous cell carcinoma growth and disease severity in an Epidermolysis Bullosa mouse model.

Patients with epidermolysis bullosa (EB) are susceptible to development of squamous cell carcinomas (SCC) at sites of chronic inflammation and fibrosis. While triterpenoids such as RTA 408 (Omaveloxolone) have been shown to reduce inflammation and inhibit tumour growth in various cancer models, the utility of this class of drugs in the treatment of SCC has not been investigated. Given the dual anti-inflammatory and anti-neoplastic properties of triterpenoids, we hypothesized RTA 408 would be an effective treatment for SCCs that arise in the chronic inflammatory setting in EB. We tested the effects of topical RTA 408 on a mouse model of non-Herlitz, junctional EB. RTA 408 significantly reduced phenotypic severity in the affected ears of Lamc2jeb mice. In cultures, RTA 408 reduced cell viability in EB-associated SCC cell lines and normal human epidermal keratinocytes. When administered in vivo, RTA 408 inhibited SCC tumour growth in mice without cutaneous or systemic toxicity. These results suggest that RTA 408 can be a promising new therapy to reduce inflammation and inhibit SCC growth in patients with EB.

Recalcitrant Subcutaneous Panniculitis-Like T-Cell Lymphoma Responsive to Histone Deacetylase Inhibitor.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous T-cell lymphoma that usually presents with tender subcutaneous nodules on the trunk and extremities. Immunosuppressive therapy is considered first-line treatment for SPTCL, while multiagent chemotherapy is used for SPTCL complicated by hemophagocytic lymphohistiocytosis (HLH). Here, we report a 42-year-old Hispanic man that presented with a 5-year history of recurrent painful subcutaneous lesions in the absence of constitutional symptoms, lymphadenopathy, and hepatosplenomegaly. A punch biopsy revealed an atypical lymphoid infiltrate in between subcutaneous adipose lobules. Lymphocytes expressed CD3, CD8, and Beta F-1 and did not express CD4 and CD56. Based on clinical and histologic findings, the patient was diagnosed with SPTCL. In addition, laboratory findings did not demonstrate any evidence of HLH. He was initially started on both prednisone and hydroxychloroquine with no improvement. A trial of cyclosporine and methotrexate yielded no clinical improvement. As the lesions failed to resolve after treatment with multiple immunosuppressive agents, romidepsin, an intravenous histone deacetylase (HDAC) inhibitor, was initiated. After two cycles of romidepsin, the patient achieved complete clinical response. He continues to be in remission 12 months later with monthly maintenance therapy. This case illustrates that romidepsin can be useful as monotherapy for refractory SPTCL without HLH.

Length of ovarian stimulation does not impact live birth rate in fresh donor oocyte cycles: a SART CORS study.

PURPOSE: To evaluate the effect of controlled ovarian hyperstimulation length and total gonadotropin (GN) dose on recipient live birth rate (LBR) in fresh donor oocyte cycles. METHODS: Data was obtained from SART CORS on all fresh donor oocyte GnRH antagonist cycles (n = 1049) between 2014 and 2015 which resulted in a single embryo transferred. Donor and recipient demographic information and cycle characteristics were extracted. Binomial regression was used to estimate LBR with respect to days of stimulation (DOS) and total GN dose. Multivariate analysis was performed to evaluate these relationships after controlling for confounders. RESULTS: Overall LBR in fresh donor oocyte cycles was 57%. Average stimulation length was 14.3 ± 4.9 days, and total GN dose was 2464 ± 1062 IU. On univariate analysis, neither days of stimulation (p = 0.5) nor total GN dose (p = 0.57) was independently correlated with LBR. However, in prolonged stimulations (> 15 days) with high total GN dose (> 3000 IU), as both the cycle length and total GN dose increased, LBR significantly decreased from 63.81 to 48.15% (p = 0.02) and from 67.61 to 48.15% (p = 0.01), respectively. Multivariate analysis showed no significant effect of either DOS or total GN dose on LBR. CONCLUSIONS: LBR is significantly decreased in fresh donor oocyte cycles when cycles are prolonged with high total GN dose. However, after controlling for confounders neither DOS nor total GN dose significantly affects LBR.