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1.
Clinical and Experimental Dermatology ; 47(5):982-983, 2022.
Article in English | EMBASE | ID: covidwho-1822048
2.
Radiology Case Reports ; 17(6):2215-2219, 2022.
Article in English | EMBASE | ID: covidwho-1821461

ABSTRACT

Posterior reversible encephalopathy syndrome is a rare underestimated condition, that generally complicates a rise in blood pressure in an acute setting. This entity has been increasingly identified in patients with systemic lupus erythematosus disease. PRES is challenging to diagnose seeing as it presents with nonspecific neurological symptoms, such as head-aches, confusion, seizures, visual changes or a coma, and can mimic neuropsychiatric lupus. Imaging plays a necessary role in confirming this diagnosis, as it is characterized by vasogenic edema of the posterior white matter, in which the distribution is bilateral and symmetrical. Although this syndrome is rare, early diagnosis allows a prompt treatment and therefore a favorable outcome. We present a case report of PRES in a 14-year-old female previously diagnosed with lupus nephropathy, who presented to the emergency department with seizures and uncontrolled hypertension, that was unfortunately not reversible is this patient.

3.
Asian Journal of Pharmaceutical and Clinical Research ; 15(4):1-3, 2022.
Article in English | EMBASE | ID: covidwho-1818972

ABSTRACT

Thrombotic thrombocytopenic purpura (TTP) is a rare but fatal thrombotic microangiopathy. Circulating AntiADAMTS13 antibodies produced in response to various triggering events, such as vaccinations, autoimmune disorders, malignancy, and administration of several drugs lead to acquired TTP (aTTP). This case concerns a 26-year-old male with aTTP after receiving the second dose of the Covishield vaccine (Oxford-AstraZeneca COVID-19 vaccine, code-named AZD1222). He presented with bruises, petechia, fatigue, dyspnea, and arthralgia post-vaccination. Laboratory reports showed thrombocytopenia, hemolytic anemia, a significant ADAMTS13 deficiency, and a high level of autoantibody titer against ADAMTS13. We treated the patient with plasma exchange therapy and prednisolone, and after the treatment, he recovered.

4.
Environmental Health and Toxicology ; 37(1), 2022.
Article in English | EMBASE | ID: covidwho-1818600

ABSTRACT

Sodium hypochlorite is widely used as the main component of cleaners and has an excellent bleaching and sterilizing effect in living and medical environments. In addition to bleaching, it is used for wastewater treatment and for sterilization in food factories, and also for disinfectants during the COVID-19 pandemic. This study analyzed reports of the health effects of sodium hypochlorite and classified them by toxicity along the exposure pathway. Most case reports described the health effects of acute high-concentration exposure, with a common case being dental exposure, mainly during treatment.

5.
BMC Rheumatology ; 5(1), 2021.
Article in English | EMBASE | ID: covidwho-1817296

ABSTRACT

Background: Adult-onset Still’s disease (AOSD) is an autoinflammatory multi-systemic syndrome. Macrophage activation syndrome (MAS) is a potentially life-threatening complication of AOSD with a mortality rate of 10–20%. Especially viral infection is thought to be a common trigger for development of MAS. On the other hand, the occurrence of MAS following vaccinations is extremely rare and has been described in a few cases after measles or influenza vaccinations and more recently after ChAdOx1 nCoV-19 (COVID-19 viral vector vaccine, Oxford-AZ). Case presentation: We report the case of a twenty-year-old female with adult-onset Still’s disease (AOSD), who developed a MAS six days after receiving her first COVID-19 vaccine dose of BNT162b2 (mRNA vaccine, BioNTech/Pfizer) with ferritin levels of 136,680 µg/l (ref.: 13–150 µg/l). Conclusions: To the best of our knowledge, this is the first case report of development of MAS in a patient with preexisting AOSD after vaccination in general, and SARS-CoV-2 vaccination in particular. The new mRNA vaccines have generally shown a reassuring safety profile, but it has been shown that nucleic acids in general, including mRNA can act as pathogen-associated molecular patterns that activate toll-like receptors with extensive production of pro-inflammatory cytokines and further activation of immune cells. Proving an interferon 1 response in our patient directly after vaccination, we think that in this particular case the vaccination might have acted as trigger for the development of MAS. Even if it remains difficult to establish causality in the case of rare adverse events, especially in patients with autoimmune or autoinflammatory conditions, these complications are important to monitor and register, but do not at all diminish the overwhelming positive benefit-risk ratio of licensed COVID-19 vaccines.

6.
Journal of Surgical Case Reports ; 2021(12), 2021.
Article in English | EMBASE | ID: covidwho-1816148

ABSTRACT

Bacillus Calmette-Guerin (BCG) immunotherapy is a mainstay of adjunctive therapy for non-muscle-invasive bladder cancer. The instillation of BCG in the upper urinary tract after complete tumour eradication has also been studied and used after kidney-sparing management. It is effective in increasing the length of remission. However, it is also associated with rare but severe local and systemic side effects which may potentially become life-threatening. We present a case report of a 37-year-old gentleman who developed BCGosis following intra-renal instillation of BCG immunotherapy. The patient presented with systemic symptoms of jaundice, fever, myalgia and arthralgia, rather than local symptoms. Mycobacterium bovis infection was confirmed on blood cultures. The patient also developed hepatosplenomegaly, dyspnoea and pancytopaenia. BCGosis following intravesical instillation has been well documented in literature;to the best of our knowledge, this is the first case report documenting BCGosis following intra-renal instillation.

7.
Allergo Journal International ; 2022.
Article in English | Scopus | ID: covidwho-1813965
8.
Environ. Sci.-Wat. Res. Technol. ; : 14, 2022.
Article in English | Web of Science | ID: covidwho-1795655

ABSTRACT

As a class of endocrine disrupting compounds (EDCs), corticosteroids (CSs) have attracted increasing attention due to their large excretion masses and toxic effects. However, compared to the very well-studied estrogens and androgens, few studies have been made dealing with the removal of CSs at environmentally relevant concentrations using advanced water and wastewater treatment processes. In this study, degradation performances of 26 natural and synthetic CSs in secondary effluent at environmentally relevant concentrations were comparatively investigated during UV/free chlorine (UV/Cl-2), UV/monochloramine (UV/NH2Cl) and UV/hydrogen peroxide (UV/H2O2) treatments. The 26 CSs could be divided into two groups: UV sensitive CSs, which have two double bonds in ring A (Delta(1,4)), and UV insensitive CSs, which have only one double bond in ring A (Delta(4)). The UV sensitive CSs could be effectively removed (removal efficiency >60%) by a UV dose of 100 mJ cm(-2) while the UV insensitive CSs could be removed (removal efficiency >40%) by a UV dose of 800 mJ cm(-2). The removal efficiencies of UV insensitive CSs increased with the increase of UV dose. Most of the CSs were poorly removed by sole Cl-2, NH2Cl, or H2O2 treatment (removal efficiency <40%). However, the addition of Cl-2, NH2Cl, and H2O2 promoted the UV degradation of CSs, especially for UV-insensitive CSs. UV photolysis would be the predominant mechanism in the UV/Cl-2, UV/NH2Cl, and UV/H2O2 processes for removing CSs in water. Besides the UV photolysis, HO radicals also functioned for CS removal. Compared with the insignificant effects of reactive chlorine species (RCS), the reactive nitrogen species (RNS) showed obvious selectivity in CS degradation. This study expanded the UV induced oxidation performances of CSs, which lays a foundation for exploring degradation mechanisms and eliminating the pollution from CSs.

9.
J Investig Med High Impact Case Rep ; 10: 23247096221090843, 2022.
Article in English | MEDLINE | ID: covidwho-1794049

ABSTRACT

Covid 19 positive patients requiring oxygen therapy to maintain saturations above 90% were given a trial of oral prednisolone between 15 and 30 mg until they were weaned to room air maintaining saturations >95%. This treatment resulted in the rapid resolution of worsening respiratory function of 4 Covid 19 positive patients within the High Dependency unit in a tertiary medical center. The cases are from the "first wave" in Trinidad, March 2020. The signs and symptoms of respiratory failure resolved after 72 hours of prednisolone treatment and none of these patients were escalated to non-invasive or invasive respiratory support. The patients were kept for a further 48 hours after the steroids were discontinued to monitor for relapse of symptoms, all patients were discharged home after quarantine. The initiation of a prednisolone steroid trial must be considered in Covid 19 positive patients needing supplementary oxygen therapy or developing worsening shortness of breath. Early Covid respiratory failure responds to a low dose for a short duration and prevents escalation to non-invasive/invasive respiratory support.

10.
Archives of Clinical Infectious Diseases ; 16(2), 2021.
Article in English | CAB Abstracts | ID: covidwho-1771665

ABSTRACT

In the pandemic era of coronavirus disease 2019 (COVID-19), vaccines have been developed and approved to control the pandemic that might reduce the COVID-19 mortality. Transplant recipients are among the high-risk groups and are more susceptible to COVID-19 infection. According to the available data about COVID-19 vaccines, some platform technologies include vector-based, inactivated, protein subunit, virus-like particles, mRNA, and DNA vaccines (1). There are several guidelines about vaccination in immunocompromised individuals for both non-live- and live vaccines. However, there are still limited evidence-based data about COVID-19 vaccines in the hematopoietic stem cell transplantation (HSCT), and establishing a proper recommendation for vaccination in these patients would be challenging (2, 3). Transplant recipients may have shown lesser responses to the vaccines compared with the general population, and it is unknown to what extent the vaccine is effective in this group of patients. Also, in many countries, the vaccination schedule is not adjustable by the patients or physicians, and selecting a particular time window for the best efficacy of immunization is impossible. In this regard, the main concern in the patients treated with immunosuppressive drugs is not worsening symptoms and disease following vaccination. The most critical issue is determining the best time for vaccination to increase its efficacy. Here are some considerations about vector-based, inactivated, and mRNA- nanoparticle vaccines, but most evidence is not based on the results of cohort or clinical trial studies. Before HSCT, patients could receive the COVID-19 vaccine if they are not already immunosuppressed. According to evidence about other inactivated vaccines, such as the influenza vaccine, the interval to start the conditioning regimen could be considered 2 - 4 weeks following the vaccination (4). In autologous HSCT patients, COVID-19 vaccination can be considered 1 - 3 months after transplantation if there has been a community outbreak. If acquiring or transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was well controlled, vaccination could be withheld after six months of transplantation. In the current pandemic, COVID-19 vaccination in allogeneic HSCT patients could be considered at least three months after transplantation. If transmission of SARS-CoV-2 was controlled, vaccination could be withheld after six months of transplantation (4-6). Vaccination of patients with chronic graft versus host disease (cGVHD) receiving less than 20 mg/day prednisolone (or equivalent) for less than 2 weeks, can be considered similar to the HSCT recipients with no GVHD (5). Vaccines in HSCT recipients with active SARS-CoV-2 infection are not effective thus, receiving the vaccine is not recommended. If an HSCT recipient has received the COVID-19 vaccine before HSCT, re-vaccination after transplantation is suggested (6). The administration of the vaccine is considered when the immune system acquired functional competence. Transplant donation should not be delayed due to the vaccination of the donor to protect the patients in case the transplant is urgent (6). It was reported that recipients who have received anti-B cell antibodies might get the vaccine at 3 - 6 months after the administration and four weeks before the next course of B cell-depleting therapy. If this time window was not possible, vaccination can be regarded under B-cell depleting therapy, considering a suboptimal response to the vaccine (7). It should be noted that the effects of rituximab may last for six months or even a year. Also, the decision to order vaccines following the use of rituximab should be based on the level of immunoglobulins and CD19. There is no strong evidence for the short duration of vaccination following the use of rituximab (such as 3 to 6 months). However, despite the low efficacy of the vaccine in such conditions, it is recommended to get the vaccine whenever available. It is reasonable that recipients who have received therapy with antithy

11.
International Journal of Pharmaceutical Sciences and Research ; 13(3):1271-1273, 2022.
Article in English | EMBASE | ID: covidwho-1761271

ABSTRACT

Bell's palsy is an idiopathic, unilateral, acute weakness of the face in a pattern consistent with peripheral facial nerve dysfunction and may be partial or complete, occurring with equal frequency on either side of the face. The incidence is about 20 in 100,000 people a year, with about 1 in 60-lifetime risks. Bell's palsy has a peak incidence between the ages of 15 and 40 years. Viral infections are commonly associated with facial nerve pathology, which leads to peripheral facial paralysis. A potential cause of peripheral facial paralysis might be COVID-19 and neurological symptoms could be the first and only manifestation of the disease. Possible mechanisms related to nerve damage in idiopathic facial nerve paralysis include ischemia of vasa nervorum and demyelination induced by an inflammatory process. Direct viral damage or an autoimmune reaction toward the nerve-producing inflammation would be alternative or contributing mechanisms to dysfunction. Acyclovir (aciclovir) is a nucleoside analogue antiviral drug active against some of the herpes virus groups of DNA viruses and RNA viruses. The mechanism of prednisolone may involve modulation of the immune response to the causative agent or direct reduction of edema around the facial nerve within the facial canal. Prednisolone and acyclovir are commonly prescribed separately and in combination, although evidence of their effectiveness is weak. We report a case diagnosed with COVID-19 after presenting with isolated peripheral facial palsy.

12.
Kidney International Reports ; 7(2):S231-S232, 2022.
Article in English | EMBASE | ID: covidwho-1748028

ABSTRACT

Introduction: Systemic lupus erythematosus (SLE) is a chronic, multifaceted autoimmune inflammatory disease with a wide range of clinical presentations resulting from its effect on multiple organ systems. We report a case of SLE associated with autoimmune pancreatitis. Methods: In this study, we present a patient diagnosed as having SLE who developed acute auto-immune pancreatitis. Results: This is a 36-year-old woman, with lupus diagnosed since 2009. Initially, the manifestations of her disease were dermatological and articular. Then appeared the renal involvement with a lupus nephropathy class IV at the renal biopsy (PBR). She was previously treated with the NIH protocol then oral prednisolone with improvement in her symptoms. She continued these medications but was lost to follow-up since 2016 and presented after 6 years with pigmented skin lesions on her upper and lower limbs, abdominal pain and distension, vomiting, and an altered general condition. In biology, the patient presented a functional acute kidney failure, an elevated amylasemia (30 times normal), an elevated lipasemia (6 times normal), a normocytic normochromic hemolytic anemia with positive direct coombs test, lymphopenia, a positive immunological assessment (AAN, anti DNA AC, anti Sm, anti SSA, anti RNP), a low C3, a low C4. The patient presented a lupus flare with a SLEDAI score of 6 points: moderate lupus activity. Ultrasound confirmed a large abundance of ascites. Ascites fluid puncture showed an exudate with hyperleukocytosis with predominantly PNN and no germ on direct examination nor on culture.The infectious origin of the pancreatitis was eliminated (CMV, tuberculosis, covid19), as well as the tumoral origin (negative tumor markers, abdominal CT scan showed a swollen pancreas in its caudal portion with loss of physiological lobulations and normal spontaneous density.Necrosis flows difficult to individualize. In addition, no deep neoplastic focus). The autoimmune origin of the pancreatitis due to its lupus attack was retained. She was put on corticosteroids (500mg intravenously for 3 days) then relayed by oral route, albumin infusion, evacuation puncture. The subsequent evolution was marked by the progressive normalization of the pancreatic balance and the slower disappearance of the ascites. Conclusions: Acute pancreatitis is an unusual manifestation of SLE and it should be suspected in any SLE patient with these similar symptoms. In many cases, this complication has been attributed to the drugs administered. In our case, a favorable course of pancreatitis with corticosteroids adds further evidence to the idea that lupus-related pancreatitis is not a side effect of corticosteroid therapy. Moreover, treatment with these medications improves the prognosis. No conflict of interest

13.
Leukemia and Lymphoma ; 62(SUPPL 1):S70-S72, 2021.
Article in English | EMBASE | ID: covidwho-1747047

ABSTRACT

The BCL2-specific inhibitor, venetoclax, has demonstrated remarkable clinical activity in the treatment of chronic lymphocytic leukemia (CLL), either alone or in combination with CD20 antibodies. Nevertheless, patients who fail to attain a complete remission relapse, and require further therapy. Data on retreatment with venetoclax at disease progression are currently limited. Here, we report patterns of clonal evolution in an R/R CLL patient that has demonstrated successful retreatment. A 57 year-old lady with chemotherapy- refractory (FCR, RCHOP, high dose methyl prednisolone) TP53 mutant CLL was treated for 21 months with single-agent venetoclax in 2014 (NCT01889186). She attained an MRD positive CR with the resolution of massive lymphadenopathy and with only low-level (0.01%) disease in the bone marrow. However, she subsequently progressed rapidly with a lymphocyte doubling time of only 4 weeks and was treated with tirabrutinib and idelalisib in combination (NCT02968563) from December 2015 for 37 months before progressing December 2019. She was retreated with venetoclax and rituximab but died of COVID-19-induced respiratory failure in March 2020. To study the clonal evolution underlying these events, in vitro drug sensitivity assays and whole exome sequencing (WES) were used to study peripheral blood mononuclear (PBMC) and bone marrow samples. WES of sample 1 showed multiple mutations in CLL driver genes: SF3B1 R625C, KMT2C R4434Q, and TP53 R110L at VAFs of 37, 17, 35%, respectively. Mutations in other genes associated with CLL included FANCA L217F (47%) and SPEN P3402S (46%). At disease progression (sample 2), following venetoclax, there was the loss of detectable (WES at 100× coverage) TP53 R110L (with loss of 17p deletion on interphase FISH and analysis of copy number) but maintenance of SF3B1 R625C (44%), KMT2C R4434Q 30%), FANCA L217F (47%), and SPEN P3402S (55%). These data, therefore, suggest the TP53 mutant subclone was largely lost during therapy. No other mutations were identified as possible resistance mediators. There were no detectable BCL2 mutations. In vitro drug sensitivity testing to venetoclax showed an EC50 of 228nM (CLL EC50 usually 3-5 nM). The patient was then treated with the BTK inhibitor tirabrutinib in combination with idelalisib, with an excellent clinical response. After 10 months (sample 3, during the lymphocytosis induced by BTKi/PI3Kdi) SF3B1, KMT2C, FANCA, and SPEN mutations were detected at VAFs of 26, 30, 54, and 56%, respectively. At this point the TP53 R110L mutation was detected again at a VAF of 4%, indicating that stopping venetoclax allowed the clone to re-emerge. At this time, there were no detectable BTK or PLCG2 mutations. The patient then responded for a further 37 months before disease progression. At progression (sample 4), SF3B1, KMT2C, FANCA, and SPEN mutations were still detected in the peripheral blood at VAFs of 43, 31, 48, and 50%, respectively. The VAF of the TP53 R110L mutation had increased to 33%. Additionally, a BTK mutation (T474I) was identified with a VAF of 16%. Identical results were obtained using a bone marrow sample. Now, however, in vitro analysis demonstrated a high degree of sensitivity to venetoclax (EC50 0.72 nM). The patient was, therefore, retreated with venetoclax and rituximab. At the point of re-treatment, VAFs were maintained, with the emergence of a new subclonal NOTCH1 G1001D mutation at a VAF of 3%. The patient, unfortunately, died 4 months after commencing therapy due to COVID-19 associated pneumonitis. A full disease reassessment was not made but the patient's blood count had normalized, with rapid clearance of CLL cells from the peripheral blood, recovery of normal hematological indices, resolution of splenomegaly, and partial resolution of lymphadenopathy on CT scan. These data, therefore, suggest that re-treatment with venetoclax in CLL can be successful. Regaining sensitivity to venetoclax may largely depend on shifting clonal dynamics. The molecular basis of venetoclax resistance in this case is currently being investigated. A so in this particular case, it appears that the TP53 mutant subclone was more sensitive to BCL2 inhibition than TP53 wild-type subclone(s), and was largely eliminated by initial venetoclax treatment, contrasting with recently published data suggesting resistance of TP53 mutant hematological malignancies to BCL2 inhibition due to increased thresholds for BAX/BAK activation (Thijssen et al., 2021).

14.
Open Forum Infectious Diseases ; 8(SUPPL 1):S244-S245, 2021.
Article in English | EMBASE | ID: covidwho-1746715

ABSTRACT

Background. Most individuals diagnosed with mild to moderate COVID-19 are no longer infectious after day 10 of symptom onset and those with severe or critical illness from COVID are typically not infection after day 20 day of symptom onset. Recovered persons can continue to test positive for SARS-CoV-2 by PCR via detection of non-viable RNA in nasopharyngeal specimens for up to three months (or longer) after illness onset. It is also know known that severely immunocompromised patients may produce replication-competent virus greater than 20 days from symptom onset and may require, per CDC recommendations, "additional testing and consultation with infectious diseases specialists and infection control experts". We aim to discuss four case studies of severely immunocompromised patients who exhibited signs of persistent COVID-19 infection of COVID and how we managed transmission-based precautions in our hospital through sequencing and evaluation of cycle thresholds (CT) values and subgenomic RNA detection. Methods. Residual nasopharyngeal (NP) samples were collected on patients exhibiting persistent COVID like symptoms. These samples underwent N gene and N gene subgenomic RNA (sgRNA) real-time reverse transcription polymerase chain reaction (rRT-PCR) testing. Results. Analysis of longitudinal SARS-CoV-2 sequence data demonstrated within-patient virus evolution, including mutations in the receptor binding domain and deletions in the N-terminal domain of the spike protein, which have been implicated in antibody escape. See Figures 1 and 2. Figure 1. Timelines of Identified Patients 1 and 2 Patient 1: 46-year-old woman with recently diagnosed stage IV diffuse large B-cell lymphoma for which she was treated with 2 cycles of R-CHOP. Patient 2: 38-year-old woman with history of myelodysplastic syndrome, peripheral blood stem cell transplant with chronic graft versus host disease of the GI tract, skin, and eyes as well as CMV enteritis, and she was maintained on rituximab, mycophenolate mofetil, prednisone, and monthly IVIG without recent changes to her immunosuppression. Figure 2. Timeline of Identified Patients 3 and 4 Patient 3: 44 year-old man with prior history of thymoma s/p thymectomy Patient 4: 46 year-old man who was initially diagnosed with marginal zone lymphoma approximately 2.5 years ago. He was initially treated with bendamustine and rituximab and achieved remission. He was then continued on maintenance rituximab without significant complications for a planned two years. Conclusion. Differentiating between prolonged viral shedding of non-infectious RNA and persistent replicating viable virus can be difficult to determine without full evaluation of a patient's clinical picture and timeline. Consultation between laboratory, infectious diseases, and infection prevention experts to provide appropriate level of guidance for precautions and treatment may be warranted. Testing by PCR and analysis of CT values may provide key findings of viral replication in immunocompromised hosts, indicating the need for evaluation of additional treatment and maintaining isolation status in healthcare settings.

15.
US Ophthalmic Review ; 15(2):50-54, 2021.
Article in English | EMBASE | ID: covidwho-1737463

ABSTRACT

Micro-pulse transscleral laser therapy (MP-TLT) is a non-invasive laser procedure for the treatment of glaucoma, and was introduced in 2015. The aim of the procedure is to achieve a reduction in intraocular pressure while minimizing collateral tissue damage. The favourable risk profile of this non-cyclodestructive procedure makes it applicable to a broad spectrum of glaucoma cases, including patients with good central vision, and does not limit its usability to late-stage refractive cases. In 2019, a revised delivery device simplified the procedure, and more recently, a ‘topical-plus’ anaesthesia protocol has been introduced. The revised delivery system and topical-plus protocol reinforce the utility of MP-TLT as a practical treatment option in an office setting or procedure room, with minimal patient discomfort during and after treatment. Additionally, with minimal follow-up requirements, MP-TLT is ideal for glaucoma management during COVID-19 social restrictions. The following article provides an overview of the use of MP-TLT under topical anaesthesia (topicalplus), the potential role of MP-TLT in the glaucoma treatment algorithm during the COVID-19 pandemic, and the advantages of the revised MicroPulse P3® probe (IRIDEX Corporation, Mountain View, CA, USA).

16.
Blood ; 138:2479, 2021.
Article in English | EMBASE | ID: covidwho-1736288

ABSTRACT

Background: Over a third of pts with 1L DLBCL do not respond to, or relapse after, rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP;[Sarkozy and Sehn. Ann Lymphoma 2019]). Despite recent advances, pts with R/R NHL have limited curative options. Glofitamab (Glofit) is a novel, T-cell-engaging bispecific antibody with a 2:1 molecular configuration that allows bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells. Unlike other CD20xCD3 bispecific antibodies, this format uniquely enables combination with anti-CD20 antibodies, including rituximab. Glofit monotherapy induces high response rates in R/R B-cell NHL (Hutchings et al. J Clin Oncol 2021). We present results of the ongoing NP40126 study (NCT03467373), designed to assess the feasibility and safety of Glofit + R-CHOP in R/R NHL (dose-escalation phase) and 1L DLBCL (safety run-in phase). Methods: R/R NHL dose-escalation: Pts (Eastern Cooperative Oncology Group performance status [ECOG PS] 0-2) received increasing Glofit doses in separate cohorts (70µg, 1800µg, 10mg and 30mg) plus standard R-CHOP for 6-8 cycles (each 21-day). To mitigate CRS risk, R- or obinutuzumab (G)-CHOP was given in Cycle (C)1, with the aim of tumor debulking. Glofit was given from C2 onwards. For 70µg and 1800µg cohorts, fixed-dose Glofit was given on C2 Day (D)8 and onwards. For 10mg and 30mg cohorts, step-up dosing was used to further mitigate CRS risk (2.5mg C2D8, 10mg C2D15, target dose C3D8 and onwards). Optional Glofit maintenance was permitted (every 2 months for <2 years;dose-escalation phase only). 1L DLBCL safety run-in: Pts (ECOG PS 0-3) received Glofit 30mg plus standard R-CHOP for 6-8 cycles (each 21-day). Pts received R-CHOP in C1;Glofit step-up dosing began in C2 (2.5mg C2D8, 10mg C2D15, 30mg C3D8 and onwards). Response rates were assessed by PET-CT (Lugano criteria;[Cheson et al. J Clin Oncol 2014]). CRS events were graded by ASTCT criteria [Lee et al. Biol Blood Marrow Transplant 2019]. Results: R/R NHL dose-escalation: At data cut-off (June 10, 2021), 31 pts (23 follicular lymphoma [FL];6 transformed FL;1 marginal-zone lymphoma;1 mantle-cell lymphoma) had received Glofit with R/G-CHOP. Median age was 62 years, median prior lines of therapy was 2 (range: 1-5). In efficacy-evaluable pts (n=31), after a median 9.0 months' (range: 0-29) follow-up, the overall response rate (ORR) was 90% (n=28) and complete response rate (CRR) was 77% (n=24). Median duration of response was not reached. The Figure shows change in tumor size. Grade (Gr) ≥3 adverse events (AEs) occurred in 28 (90%) pts, serious AEs in 21 (68%) pts and CRS in 17 (55%) pts (mostly low grade;majority after the first 2.5mg Glofit dose;Table). One (3%) pt had a Gr 5 AE (COVID-19 pneumonia not related to study treatment). AEs led to Glofit dose modification/interruption in 2 (6%) pts and Glofit withdrawal in 1 (3%) pt. Neurologic AEs (NAEs) occurred in 20 (65%) pts: Gr 1-2 (16 pts, 52%);Gr 3 (4 pts, 13%). Immune effector cell-associated neurotoxicity syndrome (ICANS)-like AEs were uncommon;a serious AE was reported in 1 pt only (Gr 3 epilepsy during the maintenance phase;resolved in 3 days). Neutropenia occurred in 24 (77%) pts. Median dose intensity was 100% for all R-CHOP components. 1L DLBCL safety run-in: At data cut-off, 13 pts were enrolled (safety population);of these, 4 pts received Glofit 30mg with R-CHOP and were efficacy-evaluable. Median age was 68 years, all pts had Ann Arbor Stage 3/4 disease. At interim assessment (C3), CRR was 100% (4/4). Of 13 pts, 1 (8%) had a CRS event (Gr 1 with fever only) after the first 2.5mg Glofit dose;no other CRS events observed. Gr ≥3 AEs occurred in 8 (62%) pts and Gr ≥3 AEs related to Glofit in 1 (8%) pt only. One (8%) pt had a serious AE and 1 (8%) pt had a Gr 5 AE (infusion-related reaction related to rituximab on C1D1). No AEs led to Glofit or R-CHOP dose interruptions. NAEs occurred in 3 (23%) pts (all Gr 1-2;none were ICANS-like). Neutropenia occurred in 6 (46%) pts. Median dose intensity was 10 % for all R-CHOP components. Conclusions: Initial data show that Glofit + R-CHOP has tolerable safety in R/R NHL and 1L DLBCL. R-CHOP dose intensity was maintained in all pts. The very low CRS rate and no neurotoxicity in 1L DLBCL may render Glofit particularly suitable for the outpatient setting without the need for hospitalization. Updated data, including end-of-treatment responses from the 1L DLBCL safety run-in phase, will be presented. [Formula presented] Disclosures: Ghosh: Seattle Genetics: Consultancy, Honoraria, Speakers Bureau;Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau;Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau;AbbVie: Honoraria, Speakers Bureau;Karyopharma: Consultancy, Honoraria;AstraZeneca: Consultancy, Honoraria, Speakers Bureau;ADC Therapeutics: Consultancy, Honoraria;Adaptive Biotech: Consultancy, Honoraria;TG Therapeutics: Consultancy, Honoraria, Research Funding;Genmab: Consultancy, Honoraria;Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau;Epizyme: Honoraria, Speakers Bureau;Incyte: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Speakers Bureau;Genentech: Research Funding. Townsend: Celgene (Bristol-Myers Squibb): Consultancy, Honoraria;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria. Dickinson: Amgen: Honoraria;Celgene: Research Funding;Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau;Takeda: Research Funding;Gilead Sciences: Consultancy, Honoraria, Speakers Bureau;MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau;Janssen: Consultancy, Honoraria;Bristol-Myers Squibb: Consultancy, Honoraria;Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau. Topp: Celgene: Consultancy, Research Funding;Janssen: Consultancy;Universitatklinikum Wurzburg: Current Employment;Kite, a Gilead Company: Consultancy, Research Funding;Novartis: Consultancy;Roche: Consultancy, Research Funding;Gilead: Research Funding;Regeneron: Consultancy, Research Funding;Macrogeniecs: Research Funding;Amgen: Consultancy, Research Funding. Santoro: Sandoz: Speakers Bureau;Eli-Lilly: Speakers Bureau;Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AstraZeneca: Speakers Bureau;Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene: Speakers Bureau;Amgen: Speakers Bureau;AbbVie: Speakers Bureau;Roche: Speakers Bureau;BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Eisai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Takeda: Speakers Bureau;Sanofi: Consultancy;Arqule: Consultancy, Speakers Bureau;Novartis: Speakers Bureau;Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Crump: Novartis: Membership on an entity's Board of Directors or advisory committees;Kyte/Gilead: Membership on an entity's Board of Directors or advisory committees;Epizyme: Research Funding;Roche: Research Funding. Morschhauser: Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech, Inc.: Consultancy;Genmab: Membership on an entity's Board of Directors or advisory committees;Roche: Consultancy, Speakers Bureau;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees;Chugai: Honoraria;Incyte: Membership on an entity's Board of Directors or advisory committees;Servier: Consultancy;AstraZenenca: Membership on an entity's Board of Directors or advisory committees;Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees;F. Hoffmann-La Roch Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria. Mehta: Kite/Gilead;Roche-Genetech;Celgene/BMS;Oncotartis;Innate Pharmaceuticals;Seattle Genetics;Incyte;Takeda;Fortyseven Inc/Gilead;TG Therapeutics;Merck;Juno Pharmaceuticals/BMS: Research Funding;Seattle Genetics;Incyte;TG Therapeutics: Consultancy;Seattle Genetics;Incyte;TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Panchal: F. Hoffmann-La Roche Ltd: Current Employment. Wu: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Barrett: Roche Products Ltd: Current Employment;F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Humphrey: Roche: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Qayum: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Hutchings: Novartis: Research Funding;Janssen: Honoraria, Research Funding;Incyte: Research Funding;Genentech: Honoraria, Research Funding;Celgene: Research Funding;Takeda: Consultancy, Honoraria, Research Funding;Roche: Consultancy, Honoraria, Research Funding;Genmab: Consultancy, Honoraria, Research Funding. OffLabel Disclosure: Glofitamab is a full-length, humanized immunoglobulin G1 bispecific antibody with a 2:1 molecular format that facilitates bivalent binding to CD20 on B-cells, and monovalent binding to CD3 on T-cells. Glofitamab redirects T cells to engage and eliminate malignant B cells. Glofitamab is an investigational agent. Rituximab (Rituxan) is aCD20-directed cytolytic antibody indicated for the treatment of adult pts with: relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL as a single agent;previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy (chemo) and, in pts achieving a CR or PR to a rituximab product in combination with chemo, as single-agent maintenance therapy;non-progressing (including stable disease), low-grade, CD20 positive, B-cell NHL as a single agent after first-line CVP chemo;previously untreated diffuse large B-cell, CD20-positive, NHL in combination with CHOP or other anthracycline-based chemo regimens;previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide.

17.
Allergo J Int ; : 1-2, 2022 Mar 07.
Article in English | MEDLINE | ID: covidwho-1734095
18.
Open Access Macedonian Journal of Medical Sciences ; 10(B):180-191, 2022.
Article in English | EMBASE | ID: covidwho-1726121

ABSTRACT

BACKGROUND: New-onset diabetes after kidney transplant (NODAT) is a severe metabolic complication that frequently occurs in recipients following transplantation. AIM: The study aims to verify NODAT, compare cases and non-cases of this entity, and explore potential predictors in recipients within 1 year following kidney transplantation. METHODS: The research is a retrospective study of 90 renal transplant recipients (n = 90). Demographic factors and clinical aspects were analyzed using non-Bayesian statistics and machine learning (ML). The clinical aspects included the glycated hemoglobin (HbA1c) level, associated viral infections (hepatitis B virus [HBV], hepatitis C virus [HCV], and cytomegalovirus [CMV]), prior kidney transplant, hemodialysis status, body mass index (BMI) at transplant time, and 3 months later, primary causes of renal failure, and post-transplant therapeutics. All individuals were on cyclosporine and prednisolone treatment. RESULTS: The mean age was 39 (±1.5) years;recipients included 27 females (30%) and 63 males (70%). Donor type was live related (16, 17.8%) or live unrelated (74, 82.2%);27 recipients (30%) had O+ blood group, while 70% belonged to other groups. Thirteen recipients (14.4%) were not on dialysis. Only 32 individuals (35.6%) developed NODAT. Concerning virology, confirmed by real-time polymerase chain reaction before transplantation, 19 recipients (21.1%) were CMV positive, 9 (10%) were HCV positive, and 2 (2.2%) had HBV. CONCLUSIONS: In reconciliation with frequentist statistics, the dual ML model validated several predictors that either negatively (protective) or positively (harmful) influenced HbA1c level, the majority of which were significant at 95% confidence interval. Individuals who are HCV and CMV positive are predicted to develop NODAT. Further, older individuals, with blood group O+ve, prior history of hemodialysis, a relatively high BMI before the transplant, and receiving higher doses of prednisolone following the transplant are more likely to develop NODAT. The current study represents the first research from Iraq to explore NODAT predictors among kidney transplant recipients using frequentist statistics and artificial intelligence models.

19.
Haemophilia ; 28(SUPPL 1):105, 2022.
Article in English | EMBASE | ID: covidwho-1723173

ABSTRACT

Introduction: Delivery in type 3 VWD with alloantibodies, a rare clinical entity with few treatment options, is a very high-risk situation. Methods: Case report Results: A 28 yo patient with type 3 VWD and alloantibodies to VWF and FVIII became pregnant after extensive preconceptional counselling. Previous ITI was unsuccessful and complicated by anaphylaxis. The pregnancy was complicated by a mild COVID-19 infection in the 2nd trimester, but otherwise uncomplicated. Delivery was induced at 38 4/7 weeks with prostaglandin and rFVIIa (NovoSeven®) started when in active labor. After a rapid vaginal delivery and afterbirth, manual placental removal was performed and a Bakri balloon inserted for ongoing bleeding despite rFVIIa 90μg/kg every 2h. As bleeding still continued, plasma-derived VWF was infused with initial excellent recovery and successful embolization of the aa uterinae was performed. Another infusion of VWF to prevent rebleeding resulted in minimal recovery and an allergic reaction despite prednisolone and clemastine. Rebleeding did not occur and patient was discharged at day 8. At day 12 she was readmitted because of endometritis followed by vaginal bleeding unresponsive to rFVIIa. Re-embolization was performed and off label emicizumab started to prevent rebleeding. A loading dose of 6mg/kg on day 1 and 3mg/kg on day 2 was given, followed by 3mg/kg EOW from the 2nd week onwards. As the infection was uncontrolled by broadspectrum antibiotics, hysterectomy was performed at dag 29, again complicated by diffuse bleeding requiring direct intra-abdominal packing and rFVIIa 90μg/kg every 2 hours in addition to emicizumab. A week after unpacking, asymptomatic pulmonary embolisms and thrombosis of the left v iliaca were discovered on CT. rFVIIa was stopped, prophylactic LMWH started and a third embolization performed when bleeding reoccurred. Two months after delivery she was discharged with low dose LMWH, emicizumab and antibiotics because of an intra-abdominal abcess. Discussion/Conclusion: Delivery in patients with severe bleeding disorders in the presence of alloantibodies is a high-risk situation. Emicizumab was partially helpful in maintaining hemostatic control. Besides bleeding, postpartum patients receiving intensive correction of coagulation and especially with additional risk factors like surgery and infection, are also at risk for thrombotic events.

20.
Developmental Medicine and Child Neurology ; 64(SUPPL 1):22, 2022.
Article in English | EMBASE | ID: covidwho-1723132

ABSTRACT

Objective: Paediatric neurologists are concerned about the risk of COVID-19 in children with demyelinating disorders receiving immunomodulatory treatment. To investigate this, we collected data via the UK Childhood Neuro-Inflammatory Disorders (UK-CNID) network of the British Paediatric Neurology Association (BPNA). Methods: Survey of paediatric neurologists managing unvaccinated UK children (<18 years) with a demyelinating disorder (multiple sclerosis [MS];neuromyelitis optica spectrum disorder [NMOSD] and myelin oligodendrocyte glycoprotein antibody disease [MOGAD]) on immunomodulatory therapy with SARS-CoV-2 infection confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs between March and December 2020. Results: Of 151 UK children (MS 98, MOGAD 37, NMOSD 16) with a median age of 9 years (range 6-18y), with a demyelinating disorder, nine (6.0%) had a positive PCR for SARS-CoV-2. Five had MS and four MOGAD. Four were from south Asian or south-east Asian, four were White and one was mixed White and south Asian. Seven children had COVID-19 symptoms;two were asymptomatic. Two required a brief hospital admission for typical COVID-19 respiratory symptoms and the remaining five had mild symptoms including fever, rash, cough and headache. One with MOGAD, treated with azathioprine, developed transverse myelitis 12 days after COVID-19 onset. She recovered fully with a course of corticosteroids. MS patients were on following disease modifying therapies;dimethylfumarate (n=2), fingolimod (n=1);natalizumab (n=1) and ocrelizumab (n=1). MOGAD cases were on the following immune therapy: combination of oral prednisolone and intravenous immunoglobulin (n=2), prednisolone steroids (n=1) and azathioprine (n=1). Conclusions: In contrast to adult patients, who often have underlying co-morbidities and advanced neurological disabilities, we have identified that children treated for demyelinating disorders appear to have a milder COVID-19 course. Whilst the number of children treated for demyelinating disorders that developed COVID-19 is low, the overall mild course described may provide reassurance to neurologists, patients and family members.

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