To date, there are only a few case reports of cyclophosphamide (Cy)-induced hemorrhagic cystitis (HC) in adult or pediatric allogeneic stem cell transplant (SCT) patients treated successfully with ...hyperbaric oxygen (HBO). In all the reported cases, Cy was used as a part of the conditioning regimen, rather than post-transplant for graft-versus-host-disease (GVHD) prophylaxis. More recently, the risk of HC in allogeneic SCT is further increased by the widespread use of post-transplantation cyclophosphamide (PTCy) as a highly effective strategy for GVHD prophylaxis. This is the first case reported of PTCy-induced HC successfully treated with HBO to the best of our knowledge.
In this article, we present a 58-year-old Caucasian male case of allogeneic SCT complicated by severe HC following PTCy, which was successfully treated with HBO, eliminating the need for cystectomy.
HBO can be a safe, noninvasive, alternative treatment modality for PTCy-induced HC developing in allogeneic SCT patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A 70-year-old, immunocompromised patient presented to the emergency room (ER) five weeks after she was started on clopidogrel. She complained of skin eruption, mouth ulcers, fatigue, and myalgia over ...the past two weeks. Labs showed severe hyponatremia, acute kidney injury, rhabdomyolysis, hyperkalemia, and elevated liver enzymes. She was treated with steroids and discharged after her condition improved. However, a month later, she returned to the ER, complaining of nausea, vomiting, diarrhea, dizziness, chills, and shortness of breath over the past two days. She was lethargic and had orthostatic hypotension. She deteriorated clinically within a few days, with worsening lethargy and the development of respiratory distress along with profound hypotension. She needed mechanical ventilation and vasopressors. In addition, she had melena, severe thrombocytopenia, and hemolytic anemia. With supportive care, she improved and was discharged after a long stay in the intensive care unit. Retrospectively, the first hospitalization was believed to be caused by drug reaction with eosinophilia and systemic symptoms (DRESS). Treating that with steroids compromised her immune system beyond her pre-existing primary immunodeficiency status. At the time of her second hospitalization, she met the Centers for Disease Control and Prevention (CDC) criteria for a toxic shock syndrome (TSS) diagnosis. Her TSS started four days after a skin biopsy, which was done as part of her skin rash workup. It was thought that the source of the exotoxin that mediated her TSS was her skin, given the temporal relationship of the skin biopsy to her TSS. Another potential source of the exotoxin was the gastrointestinal tract, given the predominant gastrointestinal symptoms she had at the time of her second admission.
•High CD4 count does not necessarily protect against aggressive AIDS-defining diseases, particularly, HIV-associated Kaposi sarcoma.•Extremely elevated HHV-8, HIV, and EBV viral loads could predict ...aggressive HIV-associated KS disease course.•Anemia and thrombocytopenia in HIV/AIDS could be autoimmune like ITP and AIHA or bone marrow infiltration-related, by Kaposi sarcoma, for instance, or both.
Bone marrow infiltration by Kaposi sarcoma (KS) in human immunodeficiency virus (HIV) patients is rare, with only a few cases reported in patients with a CD4 count greater than 200 cells/ml. To the best of our knowledge, this is the first reported case of bone marrow involvement in HIV-associated KS in which the CD4 count is greater than 400 cells/ml. In this article, we present a patient with HIV-associated KS with skin, lymph node, bone, pulmonary, gastrointestinal, and bone marrow involvement despite a high CD4 count. This is the highest CD4 count associated with bone marrow invasion in the medical literature. A high CD4 count does not protect untreated HIV patients against aggressive, diffuse KS-related lesions, including bone marrow infiltration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
Patients with hematological malignancies (HM) are uniquely immunocompromised and considered at high risk for COVID-19. However, data regarding the diagnosis, clinical course, treatment, ...and outcomes of these patients is sparse. In particular, the ability to successfully detect SARS-CoV-2 in patients with HM remains unknown. We have previously reported 2 cases of allogeneic stem cell transplant (SCT) diagnosed with COVID-19 using clustered regularly interspaced short palindromic repeats (CRISPR) technique, following multiple negative nasopharyngeal RT-PCR testing (Niu et al. Bone Marrow Transplantation - Nature). Here we examine 29 patients with a variety of HM with high suspicion for COVID-19 based on clinical presentation, lab results, and imaging, whom were tested with CRISPR and/or RT-PCR based techniques. From 3/31/20 to 7/17/20, 29 patients (age 24 to 82) with a variety of HM (20 lymphoid, 9 myeloid; Table 1), 24 of which presented with an undiagnosed respiratory illness and 5 presented while asymptomatic for testing prior to chemotherapy, were evaluated for COVID-19. While 16 patients tested positive for COVID-19 with guideline-directed nasopharyngeal RT-PCR testing (including the 5 asymptomatic patients), 13 patients tested negative with the same technique. However, based on their clinical history, imaging, and disease course, concern for COVID-19 infection remained in these 13 patients. We then used CRISPR technology available at our institution (Huang et al. Biosensors and Bioelectronics) to test 8 patients who initially tested negative by RT-PCR. Surprisingly, 7 of the 8 patients tested positive for COVID-19 with either a blood sample and/or nasal swab for the SARS-CoV-2 specific N gene and ORF1ab gene. Excluding the patients who were negative by RT-PCR and not tested by CRISPR, the rate of false negativity with RT-PCR testing is significantly elevated at 29% (7/24) in our cohort of HM, which compares unfavorably with the expected false negative rates of RT-PCR techniques.
A very high fatality rate was observed with 9 out of the 29 patients (31%) ultimately dying. Fifteen patients were undergoing active chemotherapy, 4 had received an autologous SCT, 6 had received an allogeneic SCT, and 4 were on surveillance. Of the 23 COVID-19 positive patients (by RT-PCR or CRISPR), 8 patients received COVID-19-directed therapy with either hydroxychloroquine/azithromycin, remdesivir, and/or Covid-19 convalescent plasma (CCP) depending on their clinical status, and 4 patients expired. Of the 8 treated patients, 7 improved while 1 patient expired. For the 5 patients who were negative for RT-PCR with no CRISPR completed, 1 patient received hydroxychloroquine/azithromycin proactively due to symptoms and imaging and recovered, while 3 patients expired at outside facilities due to unknown causes. Breakdown of testing and treatment is shown in Fig. 1.
The majority of our patients had undergone SCT or were actively on chemotherapy, notably lymphodepleting chemotherapy. Associated with the fact that COVID-19 is known to worsen lymphopenia, our patient's symptoms and immune response to COVID-19 is likely to differ from immunocompetent hosts. This translated into an overall worse outcome as seen by the high mortality with our patients. In our limited dataset, patients presented with a variety of symptoms ranging from asymptomatic to acute respiratory failure. Intriguingly, the 5 asymptomatic patients had lymphoid malignancies and were on chemotherapy.
It is thus imperative to establish the diagnosis of COVID-19 quickly, as faster initiation of treatment has been associated with better outcomes. The 8 patients who were diagnosed and treated improved substantially. However, as seen by our dataset, a strikingly high false negative rate was observed. Thus, a high clinical suspicion must guide further workup and therapy in patients with HM who present with an undiagnosed respiratory illness consistent with COVID-19. Patients with HM can have a wide variety of presentations when infected with COVID-19. For this select patient population we must establish an algorithm to diagnose COVID-19 efficiently as we reported a high number of initial false negative COVID-19 tests before the more sensitive CRISPR revealed a positive test. In addition, treatment pathways need to be instituted to not only treat COVID-19 infection, but also provide the best treatment for these patient's underlying HM.
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Safah:Amgen: Honoraria; Verastem: Honoraria; Janssen: Speakers Bureau; Astellas: Speakers Bureau. Saba:Kite: Other: Advisory Board; Pharmacyclics: Other: Advisory Board, Speakers Bureau; AbbVie: Consultancy, Other: Advisory Board, Speakers Bureau; Janssen: Other: Advisory Board, Speakers Bureau; Kyowa Kirin: Other: Advisory Board.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
: This study aimed to assess patients' satisfaction with the dental care provided by undergraduate students, identify factors affecting satisfaction with the treatment, and gather recommendations for ...improving dental services.
An observational study was conducted at the University of Basrah College of Dentistry between the first of July 2022 and the first of April 2023. The study involved patients who consented to participate and provided written informed consent. Ethical clearance was granted by the institution's Ethics Committee, and 348 participants were randomly selected from dental clinics to respond to the questionnaire.
Forty per cent of the study participants were aged between 20-29, with 146 (41.9%) being male and 202 (58.1%) being female. One hundred and sixty-six (33.3%) of the patients were housewives, 324 (92%) were low to moderate-income earners, and 199 (57%) lived in the city center, while 149 (42.8%) lived in district and subdistrict areas. Two hundred and forty (68.9%) of patients felt that the treatment was either cheap or too cheap. Regarding the waiting room, patients were generally satisfied with all aspects except for the waiting time, with 290 (83.3%) finding it too long. An average of 88.3% of patients were satisfied with the treatment provided by the students, but only 64.4% were satisfied with the length of the treatment period. Only 28 (8%) of patients experienced postoperative complications, with 13 related to dental treatment and 12 expected. Additionally, 24 patients reported their complications to the students, while 12 patients experienced unexpected complications. Finally, 45.4% of patients returned to the college for further treatments.
: While the patient expressed dissatisfaction with the long waiting and treatment times, most respondents expressed satisfaction with the treatment received, but improvements are necessary in certain areas.
•Blood cancers are associated with high rates of SARS-CoV-2 RT-PCR false negativity.•False negative RT-PCR COVID-19 results can be detected by CRISPR-based assays.•COVID-19 in patients with ...hematologic malignancies confers worse survival.•Lympho-depleting chemotherapy may result in higher COVID-19 mortality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Introduction
In the absence of effective and readily available therapy for COVID-19, immediate interventions to improve its mortality are a public health emergency. COVID-19 convalescent plasma ...(CCP) carries antibodies against SARS-CoV-2 and represents a promising approach. Studies regarding the clinical use of CCP have been inconsistent, and the optimal timing and frequency of CCP infusion remain largely unknown. Similarly, the role of CCP in cancer patients, particularly those with hematological malignancies (HM), remains unknown. Herein we describe the outcomes of 16 critically ill patients with COVID-19, including HM, who were treated with CCP with marked clinical improvement.
Methods
CCP donors donated 2-4 units each (200 ml per unit), 18 to 56 days following full recovery from COVID-19. 16 patients received CCP following informed consent. 5 patients were treated after obtaining individual emergency Investigational New Drug (eIND) from the FDA, while the remaining 11 patients were enrolled in our investigator-initiated clinical trial, Expanded Access to Convalescent Plasma to Treat and Prevent Pulmonary Complications Associated With COVID-19 (clinicaltrials.gov Identifier: NCT04358211). We used ELISA to determine the Spike protein IgG titers on most CCP units. Treatment was with a single unit of 200ml of CCP given over 1h, with the exception of patients 4 and 9 who received two units eight days apart.
Results
10 males and 6 females between the ages of 24-81 were treated, 6 of which with HM. 12 patients were diagnosed by an RT-PCR-based technique while 4 were diagnosed by the highly sensitive clustered regularly interspaced short palindromic repeats (CRISPR)-based qualitative COVID-19 assay. Interestingly, these 4 patients have HM and had multiple false negative RT-PCR results prior to the CRISPR diagnosis. The Spike protein IgG titers on CCP units used to treat patient-5, patient-6, patient-8, patient-9, patient-11, patient-13, patient-14, patient-15, and patient-16 were 1:1600, 1:3200, 1:3200, 1:800, 1:400, 1:1600, 1:3200, 1:6400, and 1:3200, respectively. At the time of CCP infusion, patients were either mechanically ventilated (5), on noninvasive support with high flow nasal cannula (4), bilevel ventilation (1), or nasal cannula (5). Only 1 patient was on room air at the time of CCP infusion. No adverse events were reported in all patients with the exception of a fever during CCP transfusion in patient-10 resulting in infusion of only 100 ml. Steady improvement in oxygenation levels was observed following each CCP infusion. All of the 5 intubated patients were extubated between 1- and 19-days post CCP infusion. The remaining 11 showed a dramatic decline in oxygen needs and did not require ventilatory support. Of the 16 patients included here, only 1 patient expired following extubation secondary to progression of medical co-morbidities and the family's decision to transition to comfort care. Among the 15 patients surviving, patient-12 remains inpatient for respiratory failure following extubation to tracheostomy, while the rest were successfully discharged including the 6 patients with HM (Figure 1). Although all of our patients showed improvement following CCP, we noted a strong correlation between early CCP infusion and clinical improvement (r=0.6, p=0.02, for correlation between time from disease onset to CCP, and time from CCP to oxygen independence or discharge).
Interpretation of the data could potentially be affected by the concomitant clinical trial enrollment of some patients. Patients 14, and 15 were enrolled in ACTT-1, a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of remdesivir in hospitalized adults diagnosed with COVID-19 (ClinicalTrials.gov Identifier: NCT04280705); patients 3, 15, and 16, were enrolled in REGN88, a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of sarilumab in hospitalized adults diagnosed with COVID-19 (ClinicalTrials.gov Identifier: NCT04327388), while patients 1, 2, 5 and 6 received remdesivir outside of a clinical trial context, and patients 5, 6, 7, 8 ,12, and 15 received dexamethasone.
Conclusion
While a randomized controlled clinical trial remains the gold standard, our limited data represent a signal that CCP is safe and efficacious in COVID-19 and underscores a potential role for passive immunity in this disease.
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Safah:Astellas: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Honoraria; Verastem: Honoraria. Saba:Kyowa Kirin: Other: Advisory Board; Janssen: Other: Advisory Board, Speakers Bureau; AbbVie: Consultancy, Other: Advisory Board, Speakers Bureau; Pharmacyclics: Other: Advisory Board, Speakers Bureau; Kite: Other: Advisory Board.
COVID-19 convalescent plasma is under investigation as a source of passive immunity to patients with severe COVID-19 pulmonary disease. This report highlights some of the promising results so far, especially in patients with hematological malignancies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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