Esophageal Mucosal Calcinosis: A Rare Site of Calcium Deposition in End-Stage Renal Disease

Introduction: Calciphylaxis, otherwise known as calcium uremic arteriolopathy, is defined as calcium deposition around blood vessels in skin and fat tissue which occurs in 1-4% of patients with end-stage renal disease (ESRD). Calcium deposition in the esophagus is extremely rare;to date, there have been only 4 cases reported worldwide. We report the fifth case of esophageal mucosal calcinosis occurring in a young male with ESRD. Case Description/Methods: A 37-year-old Thai man with ESRD on peritoneal dialysis since 2005 presented with generalized weakness and odynophagia due to oral ulcers, resulting in poor PO intake. He denied drinking alcohol, illicit drug use, or smoking. On exam his abdomen was soft, non-distended, non-tender, without any guarding. Past medical history included hypertension and COVID-19 in January 2022. Laboratory tests revealed neutropenia and pancytopenia, hyperphosphatemia, and hypocalcemia. EGD revealed distal esophageal esophagitis and hemorrhagic erosive gastropathy. Biopsy showed ulcerative esophagitis with dystrophic calcification, consistent with esophageal mucosal calcinosis .No intestinal metaplasia was noted. Immunohistochemistry was negative for CMV, HSV1, and HSV2. The patient was treated with pantoprazole 40mg IV every 12 hours, Magic Mouthwash 5ml qid, and Carafate 10mg qid. He was transferred to a cancer center where he had a bone marrow biopsy formed which was negative. His symptoms resolved and the patient was discharged to home (Figure). Discussion(s): Esophageal mucosal calcinosis is extremely rare. It is due to a combination of factors involving acidosis and the phenotypic differentiation (and apoptosis) of vascular smooth muscle cells (VSMC) into chondrocytes or osteoblast-like cells. These changes, along with the passive accumulation of calcium and phosphate, induce calcification. Acidosis is well-known to promote inflammation of the arterial walls, releasing cytokines that induce vascular calcification. The benefits of treatment with sodium thiosulfate remain unclear. An ample collection of cases should help devise standardized treatment options and establish management guidelines for this condition.

Long-Term Efficacy and Safety of Upadacitinib in Patients with Psoriatic Arthritis Refractory to Biologic Therapies: 2-Year Results from the Phase 3 Select-Psa 2 Study

Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to >=1 biologic disease modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECTPsA 2. Methods Pts were randomized to UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatmentemergent adverse events (TEAEs) were summarized for pts who received >=1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received >=1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to>=1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension.

The Effects of GCSF Primary Prophylaxis on Survival Outcomes and Toxicity in Patients with Advanced Non-Small Cell Lung Cancer on First-Line Chemoimmunotherapy: A Sub-Analysis of the Spinnaker Study.

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10−20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1−2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1−2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1−2 adverse effects and Grade 1−2 immunotherapy-related adverse effects.

Efficacy of plasmapheresis in neutropenic patients suffering from cytokine storm because of severe COVID-19 infection.

Background: With the emergence of the coronavirus disease 2019 (COVID-19) and inability of healthcare systems to control the disease, various therapeutic theories with controversial responses have been proposed. Plasmapheresis was administered as a medication. However, the knowledge of its efficacy and indications is inadequate. This study evaluated the use of plasmapheresis in critically ill patients with cancer. Methods: This randomized clinical trial was conducted on 86 patients with malignancies, including a control group (N=41) and an intervention group (N=45) with severe COVID-19 during 2020-21. Both groups were treated with routine medications for COVID-19 management according to national guidelines, and plasmapheresis was applied to the intervention group. C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, hemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. Other variables included neutrophil recovery, intensive care unit admission, intubation requirements, length of hospital stay, and hospitalization outcomes. Results: CRP (p<0.001), D-dimer (p<0.001), ferritin (p=0.039), and hemoglobin (p=0.006) levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the case than in the control group (p<0.001). However, plasmapheresis did not affect the length of hospital stay (p=0.076), which could have significantly increased survival rates (p<0.001). Conclusion: Based on the study findings, plasmapheresis led to a significant improvement in laboratory markers and survival rate in patients with severe COVID-19. These findings reinforce the value of plasmapheresis in cancer patients as a critical population suffering from neutropenia and insufficient immune responses.

Infectious complications of chimeric antigen receptor (CAR) T-cell therapies.

CAR T-cells have revolutionized the treatment of many hematological malignancies. Thousands of patients with lymphoma, acute lymphoblastic leukemia, and multiple myeloma have received this "living medicine" and achieved durable remissions. Their place in therapy continues to evolve, and there is ongoing development of new generation CAR constructs, CAR T-cells against solid tumors and CAR T-cells against chronic infections like human immunodeficiency virus and hepatitis B. A significant fraction of CAR T-cell recipients, unfortunately, develop infections. This is in part due to factors intrinsic to the patient, but also to the treatment, which requires lymphodepletion (LD), causes neutropenia and hypogammaglobulinemia and necessarily increases the state of immunosuppression of the patient. The goal of this review is to present the infectious complications of CAR T-cell therapy, explain their temporal course and risk factors, and provide recommendations for their prevention, diagnosis, and management.

Impact of socio-behavioral measures implemented during the SARS-CoV-2 pandemic on the outcomes of febrile neutropenia episodes in pediatric cancer patients: a single center quasi-experimental pre-post study.

During COVID-19, public health measures including masks and social distancing decreased viral upper respiratory infections (URI). Upper respiratory infections are the most common infectious etiology for low-risk pediatric febrile neutropenia (FN). This single-center, quasi-experimental, pre-post study was designed to understand the impact of public health measures on FN admissions and outcomes in the general pediatric oncology population during the COVID (March 2020-February 2021) vs. pre-COVID era (January 2018-February 2020) and their respective respiratory seasons (November-February). Episodes were risk-stratified using a tool recommended by the Children's Oncology Group. Descriptive and bivariate statistics were used to compare admission characteristics and outcomes. Comparing respiratory seasons, the Covid-era season had 60% fewer URI diagnoses (5/12), while high-risk episodes (63.6% [28/44] vs. 44.2% [23/52]) and intensive care admissions (18.2% [8/44] vs. 3.8% [2/52]) increased. Between eras, URIs were lower in the COVID-era (10.8% [16/148] vs. 19.9% [67/336]; p = 0.01), but admission characteristics and severe outcomes were not different. The impact of public health measures was most prominent during the respiratory season. Despite decreased incidence of URIs, the overall admission characteristics and severe outcomes were minimally impacted due to the brevity of respiratory seasons, but larger studies are warranted.

Clinical impact of reducing the frequency of clozapine monitoring: controlled mirror-image cohort study.

BACKGROUND: To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust. AIMS: To investigate the impact of this temporary policy change on clinical and safety outcomes. METHOD: All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined. RESULTS: Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02-28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection. CONCLUSIONS: There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.

COVID-19 in a Patient with Accidental Drug-Induced Neutropenia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) presents with a wide range of illness severity, from asymptomatic disease to severe acute respiratory distress syndrome (ARDS). Immunosuppression is considered a risk factor for severe COVID-19, but there are only few reports on disease progression in immunocompromised patients. CASE SUMMARY: We report the case of a 50-year-old patient with acute COVID-19 pneumonia, who had iatrogenic, clinically relevant bone marrow suppression due to accidental overdose with hydroxyurea, and decreased lung capacity due to a left-sided pneumonectomy 6 months earlier. Symptomatic treatment with oxygen supplementation and pulmonary physical therapy was initiated, and hydroxyurea was discontinued. Over 14 days, the patient's blood counts slowly recovered, and his clinical condition gradually improved, such that supplemental oxygen was no longer necessary and he could be discharged. DISCUSSION: A gradual increase in neutrophil and lymphocyte counts may be preferable to dampen a potentially detrimental immunological response triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether patients with severe COVID-19 benefit from immunosuppressive therapy should be further evaluated. LEARNING POINTS: Acute respiratory distress syndrome is a serious complication in COVID-19 and appears to be triggered by a proinflammatory cytokine storm.Immunosuppression may avoid an immune hyper-response triggered by SARS-CoV-2.