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1.
Rassegna di Patologia dell'Apparato Respiratorio ; 37(1):S46-S49, 2022.
Article in Italian | EMBASE | ID: covidwho-1822772

ABSTRACT

Patients affected by COVID-19 can benefit from rehabilitation intervention that must be cali-brated according to the severity of the disease: it can therefore vary from pronation and early mobilization maneuvers for patients admitted to intensive care, to re-training programs and exercise after remission;in case of difficulty in managing secretions, rehabilitation intervention can be combined with bronchial clearance interventions.

2.
Frontiers in Psychiatry ; 13, 2022.
Article in English | EMBASE | ID: covidwho-1822404

ABSTRACT

Introduction: The study aimed to explore the psychometric properties of the Stress and Anxiety to Viral Epidemics-6 (SAVE-6) scale among patients with cancer who are in serious situations in the current COVID-19 pandemic. Methods: The survey included questions on the participants' demographic information, clinical history of cancer (including cancer type, stage, current treatment or diagnosis of complete remission), and scores on rating scales, including the SAVE-6 scale, Coronavirus Anxiety Scale (CAS), and the Patient Health Questionnaire-9 (PHQ-9). Results: The confirmatory factor analysis (CFA) results determined that the model fits the single factor structure of the SAVE-6 scale among patients with cancer. The multi-group CFA showed that SAVE-6 can measure the anxiety response in a similar way across multiple variables, such as sex, presence of clinical depression, being in a state of complete remission, or currently undergoing cancer treatment. The SAVE-6 scale showed good reliability (Cronbach's alpha = 0.819) and convergent validity with the rating scales, such as CAS [r = 0.348 (95% CI, 0.273–0.419), p < 0.001] and PHQ-9 items score [r = 0.251 (95% CI, 0.172–0.328), p < 0.001]. Conclusions: This study confirms SAVE-6 as a reliable and valid rating scale for measuring the anxiety response of patients with cancer during the current COVID-19 pandemic.

3.
Clinical Rheumatology ; 2022.
Article in English | EMBASE | ID: covidwho-1820937

ABSTRACT

SARS-CoV-2 infections in children are frequently asymptomatic or mild and can go unnoticed. This study aimed to describe the seroprevalence and clinical course of SARS-CoV-2 in a cohort of children with rheumatic diseases in a real-life setting and assess possible risk factors. A cross-sectional study was performed in a paediatric rheumatology unit (September 2020 to February 2021). At inclusion, a specific questionnaire was completed and SARS-CoV-2 serology was performed. Demographics, treatment and disease activity of patients with and without laboratory-confirmed SARS-CoV-2 infection were compared. A total of 105 children were included. SARS-CoV-2 infection was demonstrated in 27 patients (25.7%). The mean age was 11.8 years, and most patients were females (72.4%). The most frequent underlying condition was juvenile idiopathic arthritis (70.3%;19/27). Patients received immunosuppressive treatment in 78% of cases (21/27). Overall, 44.4% (12/27) of infected patients were asymptomatic. A total of 66.7% (18/27) of patients did not require medical assistance. Three patients required hospital admission because of COVID-19. Children with confirmed SARS-CoV-2 infection were less frequently in remission (52% vs 72%;p 0.014). Moderate disease activity and treatment with oral corticosteroids were associated with higher risk for SARS-CoV-2 (OR 5.05;CI 95%: 1.56–16.3 and OR 4.2;CI 95%: 1.26–13.9, respectively). In a cohort of Spanish paediatric patients with rheumatic diseases, clinical course of COVID-19 was mild, with more than one third of asymptomatic cases. Higher disease activity and oral corticosteroids appear to be risk factors for SARS-CoV-2 infection.Key Points• We aimed to investigate the seroprevalence of SARS-CoV-2 infection in a cohort of Spanish paediatric patients with RD, testing both symptomatic and asymptomatic patients. We also compared treatment and disease activity of patients with and without laboratory-confirmed SARS-CoV-2 infection.• In our cohort of 105 paediatric patients with rheumatic diseases, the clinical course of COVID-19 was mild and 44% of cases were asymptomatic. Three cases required hospital admission with no complications. Seroprevalence was 20%.• No association was found between disease activity or treatment with corticosteroids and symptomatic or asymptomatic infection. Higher disease activity and treatment with oral corticosteroids appeared to be risk factors for laboratory-confirmed SARS-CoV-2 infection.

4.
Our Dermatology Online / Nasza Dermatologia Online ; 13(2):148-151, 2022.
Article in English | Academic Search Complete | ID: covidwho-1811205

ABSTRACT

Background: Patients with pemphigus receiving immunosuppressive therapy are considered at risk of developing severe forms of COVID-19. We aimed to analyze the clinical and evolutionary characteristics of COVID-19 infection in patients with pemphigus receiving general corticosteroid therapy by a retrospective descriptive study of twelve cases. Patients and Methods:We identified pemphigus cases that developed a COVID-19 infection. The data collected included the characteristics and treatment of pemphigus and the features and course of COVID-19 infection.Results: Twelve patients were followed at our department for pemphigus and a developed COVID-19 infection. Nine patients had a severe form of pemphigus, and three were in clinical remission. The infection was severe in three patients. The evolution was good in all patients. Discussion: Our study suggests that systemic corticosteroid therapy in patients with severe forms of pemphigus may be a protective factor against severe forms of SARS-CoV-2 infection. This theory should be evaluated by a larger study. [ FROM AUTHOR] Copyright of Our Dermatology Online / Nasza Dermatologia Online is the property of Our Dermatology Online and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

5.
Medicina ; 58(4):511, 2022.
Article in English | ProQuest Central | ID: covidwho-1810018

ABSTRACT

Dabrafenib and trametinib are two available molecules that have been approved for the treatment of metastatic melanoma with BRAF-V600E or V600K mutations. Their combined therapy has led to long-lasting survival benefits and substantially improved outcomes. Until now, only a few cases of severe hypersensitivity reactions to dabrafenib and vemurafenib have been reported, and even fewer desensitization protocols to these molecules have been documented. We report the case of a 71-year-old female patient with metastatic melanoma harboring a BRAF-V600E mutation undergoing targeted therapy with dabrafenib and trametinib. Two weeks after the initiation of the combined treatment, she developed a hypersensitivity reaction. The cause–effect relationship between dabrafenib and the hypersensitivity reaction was demonstrated twice, when symptoms recurred upon dabrafenib reintroduction. We started a rapid 3-day dabrafenib desensitization protocol, which was well tolerated. When the patient discontinued the drug administration, we decided on a longer protocol that included more steps and more days in order to prevent the occurrence of other hypersensitivity reactions. Our patient tolerated both rapid and slow-going schedules, the first one reaching the final dose within 3 days and the second one reaching the total daily dose within 14 days. Depending on the patient’s needs, the severity of the hypersensitivity reaction and the hospital’s availability, the doctor may choose either the rapid or slow-going desensitization protocol.

6.
Deutsche Medizinische Wochenschrift ; 147(08):470-480, 2022.
Article in German | Web of Science | ID: covidwho-1805699

ABSTRACT

Autoimmune hepatitis is a rare but chronic autoimmune-mediated liver disease. Key features are elevated transaminases, hypergammaglobulinemia, presence of specific autoantibodies and typical histological features. Diagnostic scores are helpful in establishing the diagnosis. Immunosuppressive therapy should be initiated in every patient with inflammatory activity. First-line therapy includes steroids and azathioprine and results in biochemical and histological remission in the majority of patients. In most cases, lifelong therapy is required. Every patient should receive regular follow-up surveillance including biochemical parameters as well as sonography and elastography.

7.
Journal of IMAB - Annual Proceeding (Scientific Papers) ; 28(1):4289-4291, 2022.
Article in English | EMBASE | ID: covidwho-1798799

ABSTRACT

Currently in Bulgaria the two messenger RNA vaccines used to vaccinate the population against COVID-19 are Pfizer-BioNTech COVID-19 Vaccine (COMIRNATY) and Moderna COVID-19 Vaccine. We present a case of a patient with palmoplantar form of psoriasis (in remission in the last 2 years), who has an attack of psoriasis of the nails, which began two weeks after the second dose of Pfizer-BioNTech COVID-19 Vaccine. Within the next two months, onychopathy of the nails of the ten fingers developed with the manifestation of almost all known psoriatic changes in the nail bed and nail matrix. The toenails are not affected. Topical therapy with calcipotriol/betamethasone ointment under occlusive dressings was prescribed for two months. The monitoring continues.

8.
American Family Physician ; 105(4):406-411, 2022.
Article in English | ProQuest Central | ID: covidwho-1790714

ABSTRACT

This rapid evidence review summarizes risk factors, symptoms, and testing for ulcerative colitis. Treatment depends on severity and can include pharmacologic, surgical, complementary, and behavioral interventions. Preventive care considerations and recommendations for patients with ulcerative colitis and SARS-CoV-2 exposure are also reviewed.

9.
Trials ; 23(1): 263, 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1779666

ABSTRACT

BACKGROUND: Antiretroviral therapy (ART) has led to dramatic improvements in survival for people living with HIV, but is unable to cure infection, or induce viral control off therapy. Designing intervention trials with novel agents with the potential to confer a period of HIV remission without ART remains a key scientific and community goal. We detail the rationale, design, and outcomes of a randomised, placebo-controlled trial of two HIV-specific long-acting broadly neutralising antibodies (bNAbs): 3BNC117-LS and 10-1074-LS, which target CD4 binding site and V3 loop respectively, on post-treatment viral control. METHODS: RIO is a randomised, placebo-controlled, double-blinded prospective phase II study. Eligible individuals will have started ART within 3 months of primary HIV infection and have viral sequences that appear to be sensitive to both bNAbs. It will randomise 72 eligible participants 1:1 to the following arms via a two-stage design. In Stage 1, arm A participants are given dual long-acting (LS-variants) bNAbs infusions, followed by intensively monitored Analytical Treatment Interruption (ATI) (n = 36); in arm B, participants receive placebo infusions followed by ATI. The primary endpoint will be time to viral rebound within 36 weeks after ATI. Upon viral rebound, the participant and researcher are unblinded. Participants in arm A recommence ART and complete the study. Participants in arm B are invited to restart ART and enroll into Stage 2 where they will receive open-label LS bNAbs, followed by a second ATI 24 weeks after. Secondary and exploratory endpoints include adverse events, time to undetectable viraemia after restarting ART, immunological markers, HIV proviral DNA, serum bNAb concentrations in blood, bNAb resistance at viral rebound, and quality of life measures. DISCUSSION: The two-stage design was determined in collaboration with community involvement. This design allows all participants the option to receive bNAbs. It also tests the hypothesis that bNAbs may drive sustained HIV control beyond the duration of detectable bNAb concentrations. Community representatives were involved at all stages. This included the two-stage design, discussion on the criteria to restart ART, frequency of monitoring visits off ART, and reducing the risk of onward transmission to HIV-negative partners. It also included responding to the challenges of COVID-19. TRIAL REGISTRATION: The protocol is registered on Clinical. TRIALS: gov and EudraCT and has approval from UK Ethics and MHRA.


Subject(s)
COVID-19 , HIV Infections , HIV-1 , Broadly Neutralizing Antibodies , Clinical Trials, Phase II as Topic , Community Participation , HIV Antibodies , HIV Infections/diagnosis , HIV Infections/drug therapy , Humans , Prospective Studies , Quality of Life , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
10.
Klinicheskaya Dermatologiya i Venerologiya ; 21(1):59-67, 2022.
Article in Russian | EMBASE | ID: covidwho-1780348

ABSTRACT

Background. Patients with hand eczema account for 30–40% of dermatological patients. With the pandemic of new coronavirus infection COVID-19 and the need for frequent antiseptics use, there has been a steady increase in hand eczema incidence. The dominant symptoms in exacerbating eczema are skin inflammation and itching, which requires effective and safe skincare that is effective and safe. Objective. To evaluate the efficacy of the therapy with synthetic tannin and polidocanol-based agents and modern emollients, the time of resolution and degree of severity of clinical symptoms of eczema in patients, as well as the time and duration of remission, safety and compliance with sodium hypochlorite hand antiseptic spray. Materials and methods. Thirty-four patients with exacerbation of hand eczema were examined. The study was conducted in two stages. At the stage 1, before the remission, the patients received synthetic tannin and polidocanol-based agents and modern emollients;at the stage 2, monotherapy with modern emollients was used. Patients used sodium hypochlorite spray as a hand sanitizer throughout the study period. Results. The NESCI score became zero in 33 (96%) patients after the complex treatment of hand eczema. The Dermatology Life Quality Index by the end of stage 2 decreased 6-fold compared to the beginning of the study. No exacerbation of the dermatosis was observed in any of the patients included in the study during the use of sodium hypochlorite hand spray. Conclusion. The complex therapy with synthetic tannin, polidocanol-based agents, and modern emollients in hand eczema helps to achieve stable medical remission, decreases the itching intensity, and improves the patients’ quality of life. The use of new hand sanitizers during the pandemic in patients with hand eczema did not result in dermatosis exacerbations.

11.
Journal of Clinical Oncology ; 40(6 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779699

ABSTRACT

Background: The immuno-oncology (IO) therapy combination nivolumab + ipilimumab, and the IO-tyrosine kinase inhibitor (TKI) combination pembrolizumab + axitinib, received US FDA approvals in 2018 and 2019, respectively, as first-line (1L) therapy for advanced renal cell carcinoma (aRCC). We examined physician perceptions of concerns about and barriers to 1L treatment by class of regimen (IO-IO, IO-TKI, and single-agent TKI [SA-TKI]) in the United States. Methods: US-based oncologists treating ≥ 5 aRCC patients in the prior 12 months were identified from the Cardinal Health network, a community of > 800 oncologists. Physicians were surveyed about concerns in prescribing and barriers to treating by class (scale of 1-5;1 = no concern/not a barrier, 5 = most concerning/major barrier);mean scores are reported. Adverse events (AEs) of concern were selected from a prespecified list and respondents rank-ordered from most to least concerning by class. Physicians were also asked to gauge affordability and to rank-order 13 characteristics to identify key factors in prescribing preference. The impact of COVID-19 on aRCC care in practice was also assessed. Results: A total of 49 providers (84% community, 16% academic) treating a median of 20 (IQR 14-30) aRCC patients from across the United States participated. For IO-IO, the top 3 concerns in prescribing were AEs (4.3), patient out-of-pocket costs (OOP;3.7), and unexpected late AEs (3.6), whereas patient OOP (4.3), AEs (4.1), and patient adherence (3.9) were of most concern for IO-TKI. For SA-TKIs, the top 3 concerns were patient adherence (3.9), patient OOP (3.9), and AEs (3.6). High patient OOP and impact on quality of life were the top 2 barriers in using IO-TKI therapy. The most concerning AEs were colitis, pneumonitis, and hypertension for IO-IO or IO-TKI, and diarrhea, fatigue, hand-foot syndrome, and hypertension for SA-TKI. Overall survival (OS), progression-free survival (PFS), and complete response (CR) were ranked 1st, 2nd, and 3rd factors in prescribing preferences while patient compliance, patient preference, and practice reimbursement ranked 11th, 12th, and 13th. Patient OOP and drug acquisition costs (DAC) were the most important factors when considering the affordability of treatment, with the perception that IO-IO was the most expensive among the classes of therapy. The overall impact of COVID-19 on caring for aRCC patients was very limited, with a moderate increased use of telemedicine and a slight impact on the timing and number of routine care visits. Conclusions: OS, PFS, and CR ranked highest among the most important factors influencing selection of 1L treatment for aRCC. Factors of concern and barriers varied by class of treatment, with patient adherence and OOP affecting use of TKI or IO-TKI therapies, and AEs affecting the use of IO-based therapy. This study revealed perceptions of high patient OOP and DAC of IO-IO therapy, in contrast to our expectations.

12.
Journal of Clinical Oncology ; 40(6 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779698

ABSTRACT

Background: The KEYNOTE 426 trial demonstrated pem 200mg plus axi twice daily (bd) is effective in aRCC. Pharmacokinetic modelling of pem 400 mg every six weeks demonstrated similar observed exposures to pem 200 mg every three weeks. In NHS Scotland, pem6w + axi was used during the COVID-19 pandemic to reduce hospital visits and for pts' convenience. Here, we evaluate the RWE of pem6w + axi in aRCC. Methods: Electronic medical records of pts on pem6w + axi between 1 May 2020 & 1 Jun 2021 in two large cancer centers in Scotland were analyzed retrospectively for pts' characteristics, treatment related adverse events (TRAE) and efficacy. Results: Total of 93 pts were identified (Table). At data cut off of 8 Sep 2021, with a median follow-up of 7 months (mo) (interquartile range (IQR) 5 mo;range 0-15 mo), 73 pts (78%) were alive. Clinician assessed radiological response was evaluable in 87 pts. Overall response rate (ORR) including partial response + complete response was noted in 49 pts (56%) with median time to response of 80 days (d). Clinical benefit rate including pts with ORR and stable disease was seen in 72 pts (83%). At data cut off, 24 pts (26%) had progressed with a median time to progression of 117 d (IQR: 85d). Median overall and progression free survival were not reached and follow-up continues. 81 pts (87%) had any grade and 28 pts (30%) had grade 3/4 TRAE. Immune related AE (irAE) of any grade occurred in 60 pts (65%) and grade 3/4 in 19 pts (20%). Common grade 3/4 irAE were transaminitis (10%), colitis (8%), nephritis (2%) and skin (2%). 28 (30%) and 14 pts (15%) respectively required steroids and hospitalisation for irAE with median hospital stay 6 d (range: 2-43 d). 10 pts suffered a second irAE requiring steroids and 5 pts had a second hospital stay with median hospital stay of 6 d. Any grade AE and grade 3/4 AE related to axi occurred in 67 (72%) and 14 pts (15%) respectively. Axi dose was escalated from 5mg to 7mg bd in 12 pts (13%), reduced to 3mg bd in 35 pts (38%) and 2mg bd in 10 pts (11%). 21pts (23%) on Pem and 15pts (16%) on axi discontinued treatment due to TRAE. Conclusions: Our RWE demonstrates that pem6w + axi appears to have comparable safety profile to pem 200mg + axi reported in Keynote 426 study, with the added benefits of less frequent hospital visits. Further follow up continues for efficacy in this heterogeneous pts population. Pt characteristics, total=93 (%).

13.
Cancer Research ; 82(4 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779477

ABSTRACT

Background: Social isolation is associated with increased risk and mortality from many diseases, such as breast cancer. Socially isolated breast cancer survivors have a 43% higher risk of recurrence and a 64% higher risk of breast cancer-specific mortality than socially integrated survivors. Since Covid-19 has dramatically increased the incidence of social isolation, it is important to determine if social isolation affects the response to endocrine therapy and/or recurrence after the therapy is completed. Further, since previous studies indicate that social isolation increases circulating inflammatory cytokines, we investigated if an anti-inflammatory herbal mixture Jaeumkanghwa-tang (JEKHT) prevents the adverse effects of social isolation on breast cancer mortality. METHODS: Estrogen receptor positive mammary tumors were initiated with 7, 12-dimethylbenz[a]anthracene. When a rat developed a palpable mammary tumor, it was either socially isolated (SI) by housing it singly or a rat was allowed to remain group-housed (GH). Tamoxifen (340ppm via diet) or tamoxifen + JEKHT (500ppm via drinking water) started when the first mammary tumor was detected. Tamoxifen administration ended when a complete response to this therapy had lasted for 9 weeks (corresponds to 5 years in women). Rats which received JEKHT during tamoxifen therapy continued to take it also after tamoxifen therapy ended. RESULTS: During tamoxifen therapy, social isolation non-significantly reduced the rate of complete responses to 21%, from 31% in GH group (p>0.05). After the therapy was completed, SI significantly increased local mammary tumor recurrence (p<0.001;45% GH vs 75% SI). RNAseq analysis was performed in the mammary glands, since only tamoxifen resistant or recurring mammary tumors were available for analysis. Gene set enrichment analysis (GSEA) of transcriptome showed that the increased recurrence risk in socially isolated rats was associated with an enrichment of IL6/JAK/STAT3 signaling: this result was confirmed in the tumors. In addition, oxidative phosphorylation (OXPHOS) pathway was suppressed: the suppressed genes included those involved in mitochondrial pyruvate transport and conversion of pyruvate to acetyl CoA as well as genes in the TCA cycle and mediating electron transport in mitochondrial complexes I-IV. Despite the reduction in pyruvate transporting and converting genes, lactate levels or lactate dehydrogenase activity were not increased in socially isolated rats, indicating no changes in Warburg effect. Social isolation also increased the expression of inflammatory receptor for advanced glycation end-products (RAGE) (p≤0.05). Consumption of an anti-inflammatory JEKHT inhibited IL6/JAK/STAT3 signaling, upregulated OXPHOS signaling and prevented the increased risk of mammary cancer recurrence in socially isolated animals. The percentage of recurrences in the SI rats dropped from 75% without JEKHT to 22% with JEKHT (p<0.001). CONCLUSION: Breast cancer mortality among socially isolated survivors may be most effectively prevented by focusing on the period following endocrine therapy using tools that inhibit IL6/JAK/STAT3 inflammatory cytokine signaling and correct disrupted OXPHOS and mitochondrial dysfunction.

14.
Cancer Research ; 82(4 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779466

ABSTRACT

Introduction: The COVID-19 pandemic has caused an extraordinary challenge for global health. New guidelines were implemented, including postponing non-essential surgical procedures to conserve resources. In response, the COVID19 Pandemic Breast Cancer Consortium expert opinion suggested the use of core biopsies for genomic testing to help triage patients for surgical vs. systemic treatment. To better understand how expedited genomic results could impact peri-operative care, we performed a pre-operative quality project to assess testing Mammaprint (MP), a 70-gene risk of recurrence assay, and Blueprint (BP), an 80-gene molecular subtyping assay, on core biopsies. Here we report our experience with MP and BP testing on core biopsies, and the correlation between test results and response to neoadjuvant therapy.Design: From April to December 2020, all core biopsies with a breast carcinoma diagnosis from our clinic (300 patients) were routinely sent for MP and BP testing as part of a rapid result program that was initiated to see whether test results could be obtained in time and whether they would lead to more informed pre-operative treatment decisions. Unstained slides were sent for genomic and receptor testing concurrently. When genomic results differed from IHC/FISH results or suggested a different S treatment plan vs. clinical factors alone, we referred to this as "reclassification." For those patients who completed their neoadjuvant chemotherapy, we grouped them by their genomic results and by their conventional IHC/FISH/Clinical classification, and compared the outcome. Results: MP and BP results from core biopsy were available for 96.6% of patients (n=290/300). The average time from biopsy to test results was 10 days, and the average lab turnaround time was 5 days. Results were available for tumor conference discussions 100% of the time. MP and BP re-classified 84 of 300 patients (28%) from conventional IHC/FISH subtyping, and reclassified 42 of 195 patients (22%) of patients from their risk category based on traditional clinical factors (Table-1). Of the 38 patients with available post-neoadjuvant therapy outcome, 13 patients (34%) achieved pathologic complete response (pCR). 16 patients were classified as Her-2 enriched by IHC/FISH of which 9 (56%) achieved pCR. MP/BP aligned with the IHC/FISH Her-2 enriched classification in 11/16 patients, while 5 patients were reclassified to Luminal B by MP/BP. Of the 11 patients with concordant IHC/FISH and MP/BP results, 8 achieved pCR (73%), while one of the 5 cases reclassified to Luminal B achieved pCR (20%). Of the patients who were classified Luminal by IHC (9 patients), one patient achieved pCR (11%), and of the patients classified luminal (A or B) by MP/BP (12 patients) two achieved pCR (16%). Of the IHC-triple negative patients and genomic basal patients, three patients achieved pCR in each group (23% and 20%, respectively). Conclusion: Performing MP/BP tests on core needle biopsies hold a high success rate. Incorporating test results into peri-operative discussions may result in better-informed decisions about treatment planning and timing of surgery versus systemic therapy. A higher rate of pCR was seen in the MP/BP Her-2 enriched group compared to the IHC/FISH Her-2 enriched group. Although this workflow was designed to triage patients during the COVID pandemic, this approach has great potential beyond the pandemic.

15.
Cancer Research ; 82(4 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779458

ABSTRACT

Background: Adjuvant endocrine therapy remains the standard of care for patients (pts) with early stage, HR+ BC who can safely omit chemotherapy based on RS results;however, the role of NET remains unclear. There are limited data regarding the optimal duration of treatment with NET and the ideal patient (pt) population for NET in terms of age and RS result. This question rose to critical importance amidst the COVID-19 pandemic, during which NET was utilized more broadly in attempts to delay surgery or chemotherapy while preserving optimal pt outcomes. This study re-examines the use of NET among a cohort of pts with HR+ BC randomized to NET or neoadjuvant chemotherapy (NCT) based on RS (performed on initial core biopsy specimens). Methods:Data were pooled from two independent studies performed at Emory's Winship Cancer Institute and Massey Cancer Center at Virginia Commonwealth University (VCU) from 2010-2012. These studies evaluated rates of clinical and pathologic complete response (pCR) among pts with early stage, HR+ BC assigned to treatment groups based on RS results. Pts with RS 0-10 received NET (Group (Grp) A), RS 11-24/25 (Emory 11-24 vs VCU 11-25) were randomized to NET (Grp B) or NCT (Grp SC), and those with RS 25/26-100 received NCT (Grp D). Associations between RS result, neoadjuvant therapy and pCR in the breast, lymph nodes (LN) and breast plus LN were evaluated using Fisher's exact test. Results:109 pts were included in this analysis. The Emory cohort was younger (median age 56 years (yrs) vs 63 yrs in VCU cohort) and more diverse (37.5% African American (AA) vs 18.6% AA in VCU cohort). The pts were predominantly post-menopausal (69.6% Emory vs 83.1% VCU). Nodal status among the Emory cohort was evenly divided with 50% N0 and 50% N+, while the majority of VCU pts were N0 (76.3% N0 vs 22.0% N+). Pts were grouped based on RS result: RS <11 (18% Emory vs 20.3% VCU), RS 11-24/25 (36% Emory vs 55.9% VCU) and RS 24/25 or higher (46% Emory vs 23.7% VCU). Pts with low RS result were older (median 64 yrs vs 59 yrs among RS > 24/25) with higher percentage of low-grade tumors (47.6% grade 1 vs 5.4% grade 1 among RS >24/25). With regard to pCR, there were no significant differences among pts with low or intermediate RS results, as no pts in these groups achieved pCR in the breast or breast + LN (Table). Pts with RS result 25/26-100 (Grp D) were the only pts shown to achieve pCR in breast + LN (18.9%, p= 0.0043 across groups). Notably, while pts on the Emory study received longer courses of NET (median 10 months vs 5.5 months), there were no significant differences in pCR across RS result subgroups noted between the two institutions. Conclusion:Our results demonstrate that the use of Oncotype DX Breast Recurrence Score® or other genomic assays in the neoadjuvant setting may help guide treatment decisions when considering the use of NET versus NCT. Pt age and length of endocrine therapy as well as pt preferences should be considered when determining neoadjuvant treatment plans. There are currently ongoing studies evaluating the use of NET with CDK4/6 inhibitors that will offer further insight into optimal neoadjuvant treatment strategies in HR+ BC. Subsequent phase III evaluation of the role of genomic assays in the neoadjuvant setting is feasible and may help determine whether NET + CDK 4/6 inhibitors could replace NCT for pts with higher RS values.

16.
Cancer Research ; 82(4 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779448

ABSTRACT

Background: The impact of some medical decisions hurriedly taken during the COVID-19 first wave remains unknown. We tried to assess the consequences of one of these precautionary measures, namely the interruption of a 4/6 cyclin D-dependent kinase inhibitor (CDK4/6i) in metastatic patients with clinical benefit (complete response/partial response and patients with stable disease for at least 6 months) on endocrine treatment (ET). The main reason for this interruption was to limit the risk of myelosuppression (assumed as a serious risk factor for COVID-19) and other adverse effects that could overlap with symptoms and clinical signs described in the SARS-CoV-2 infection. Methods: We included 60 patients (median age: 64 years old) in whom the CDK4/6i was stopped during the first COVID-19 outbreak. It was a non-interventional, retrospective, multicentric study. A univariate analysis was performed to assess risk factors associated with disease progression: odds ratios (OR) were estimated along with their confidence intervals (CI). Key patient characteristics, all included in the statistical model, are presented in Table 1. Results: The average duration of a CDK4/6i interruption was 8 weeks. During this therapeutic break, 22 (37 %) patients Shad a radiological and/or clinical progression of the disease. Among them, CDK4/6i were taken back for the majority of patients (n=16/22;73 %) when the sanitary situation improved.For four patients (n=4/22;18 %), a new specific treatment (chemotherapy or targeted therapy) was initiated for rapid or symptomatic tumor progression. Two patients died while CDK4/6i was withdrawn. All the results of the univariate analysis are summarized in Table 2. During the CDK4/6i discontinuation, the risk of disease progression was significantly increased in the presence of liver metastases. This was the only variable with a significant effect in univariate analysis. Although not statistically significant, the risk of disease progression was higher when CDK4/6i withdrawal was longer, when patients had a more aggressive breast cancer (Luminal B) and when the tumor was considered as resistant to ET. Conclusions: The importance of maintaining the cell cycle inhibitor in addition to ET does not seem to be debatable as 36 % of patients progressed during CDK4/6i withdrawal. This is important in clinical practice when the question of CDK4/6i discontinuation arises for other reasons (analgesic radiotherapy or programmed surgery for example). Special attention should be paid to patients with liver metastases for whom stopping such a treatment seems to accelerate the natural course of the disease.

17.
Journal of Integrative Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1778329

ABSTRACT

Theoretically, a new diagnosis of type 2 diabetes mellitus (T2DM) requires a dramatic change in an individual’s way of life. Weight loss and physical activity can lead to remission of diabetes, which has been associated with a lower risk of developing complications. Today, the importance of a healthy lifestyle is further highlighted by data showing that obesity and diabetes increase the risk of severe complications from coronavirus disease 2019. However, remission rarely occurs in reality, probably due to the inability of people with T2DM to adhere to the intensive lifestyle interventions that are necessary. The complexity of contributing factors may explain why making these changes is so challenging and underscore the fact that there is no magical solution for T2DM. Instead, hard work from both patients and health care providers is needed for the conversion to be achieved. This article calls for more research on the underlying reasons why adhering to a healthy way of life is so difficult for people with diabetes and obesity. Clearly defining these barriers would facilitate the planning of effective policies to promote the adoption of appropriate lifestyle changes early in the course of the disease.

18.
Pediatr Diabetes ; 2022 Apr 02.
Article in English | MEDLINE | ID: covidwho-1774892

ABSTRACT

BACKGROUND: This study investigated the diagnostic delay and the subsequent quality of care during the Covid-19 pandemic among children with new-onset type 1 diabetes. METHODS: We compared the HbA1c levels of 3111 children at diagnosis of type 1 diabetes and of 2825 children at a median follow-up of 4.7 months (interquartile range, 4.1-5.4) together with their daily insulin requirement during the Covid-19 pandemic with the two previous years via multivariable linear regression, using data from the German Diabetes Registry DPV. RESULTS: During the Covid-19 pandemic, HbA1c levels were higher at diagnosis of type 1 diabetes (mean estimated difference, 0.33% [95% confidence interval, 0.23-0.43], p < 0.001), but not at follow-up (mean estimated difference, 0.02% [-0.02-0.07]). Children with diabetes onset during the Covid-19 pandemic had a significantly higher daily insulin requirement after initiation of therapy (mean estimated difference, 0.08 U/kg [0.06-0.10], p < 0.001). Both the increase in HbA1c and daily insulin requirement were evident only after the first wave of the pandemic. CONCLUSIONS: This increase in HbA1c at diagnosis of type 1 diabetes during the Covid-19 pandemic may indicate a delay in seeking medical care due to the pandemic. However, this did not affect short-term glycemic control. The increased insulin requirement at follow-up could suggest a more rapid autoimmune progression during the pandemic.

19.
Breast ; 56:S12-S13, 2021.
Article in English | EMBASE | ID: covidwho-1768660

ABSTRACT

Neoadjuvant treatment (NAT) has become a standard treatment in locally advanced breast cancer and an option in early stage (stage I–II) breast cancer (EBC). It is known that patients who achieve a pathologic complete response (pCR) have better long-term out comes, especially Her2 positive and triple negative (TN) breast cancer. Selection of patients for NAT in early stage breast cancer rely in several factors, as patient characteristics (i.e., age and comorbid ities), tumor histology, stage at diagnosis and the potential changes in surgical or adjuvant treatments when NAT is administered. Early stage breast cancer patients that are not candidates for breast conservative surgery (BCS) at front, may benefit from NAT to reduce tumor size and facilitate surgery. In other cases, as young patients with TN tumors between 1–2 cm may benefit from NAT, even if BCS can be performed up front, as chemotherapy will be given anyway along the treatment and there is a high likelihood of pCR. Patients with a positive axilla at diagnosis, regardless of tumor size, may also benefit from less axillary surgery if axillary pCR is achieved. Rates of axillary pCR are especially high in TN and Her2 positive tumors. A distinct approach is suggested in luminal tumors subtypes. In these patients, besides the factors already mentioned, intensity of hormone receptor expression would help to decide on neoadjuvant hormone or chemotherapy treatment. Immunohistochemistry differentiation between luminal A and B by Ki67 assessment and in some cases, the use of genomic platforms may help defining type of NAT. Assessing breast cancer patients for NAT include incorporating all factors into the decision making process. In the COVID era, we have witnessed the use of NAT in patients who may be directed to surgery, unable to have it performed, as surgery has been reserved for emergency cases only. In this situation, it has been a great challenge managing breast cancer patients and tailoring individualized treatment decisions. Besides physical examination, breast imaging is performed to assess extent of disease and to determine BCS eligibility before NAT. Breast imaging should include mammogram with tomosynthesis, breast and axillary US and in most of cases MRI. MRI may be omitted in S12 Speakers’ s / The Breast 56S1 (2021) S1–S16 selected cases (i.e. fatty breasts, neoadjuvant hormone therapy). Contrast enhanced mammogram is an emerging technique, whether it will add accuracy to the MRI findings or replace it in selected cases is still to be defined. Shear wave elastography is under investigation for assessment of response to neoadjuvant therapy as well as for predicting response. Generally, in EBC no further body imaging (CT or bone scan) is needed unless metastatic disease is suspected. PET scan is reserved for patients with inconclusive metastatic dissemination or with more advanced disease. Pathology confirmation by core biopsy and evaluation of estrogen and progesterone receptor, Her2, and Ki67 must be obtained before treatment. Axillary US will characterize axillary lymph nodes and will guide biopsy of axillary nodes. If planning NAT, markers need to be placed in breast tumor/s and in biopsy proven positive axillary node. Same breast imaging should be repeated after NAT to assess response and to determine type of breast and axillary surgery. Sentinel lymph node biopsy after NAT is the preferred method. After NAT, surgical plan is delineated taking into account baseline characteristics, tumor response and patient desire. Conflict of Interest: Honoraria: Agendia. Advisory Board: Sirius medical.

20.
Blood ; 138(SUPPL 1):3801, 2021.
Article in English | EMBASE | ID: covidwho-1770457

ABSTRACT

BACKGROUND: Multiple myeloma (MM) and Waldenström macroglobulinemia (WM) are associated with significant immunoparesis. Based on the ongoing COVID-19 pandemic, there is an urgent need to understand whether patients are able to mount a sufficient response to COVID-19 vaccines. METHODS: MM and WM patients are vaccinated with mRNA-1273 (Moderna), BNT162b2 mRNA (Pfizer/BioNTech), or JNJ-78436735 (Johnson & Johnson) in a prospective clinical trial. Primary endpoint is SARS-CoV-2 spike protein (S) antibody (Ab) detection 28 days after final vaccination. Secondary endpoints include functional serologic assessments and T-cell responses at 28 days, 6 months, 9 months, and 12 months following vaccination. S Abs were detected by Elecsys assay (Roche Diagnostics), with 3 0.80 U/mL defined as positive and titers > 250 U/mL considered stronger correlates of neutralization. SARS-CoV-2 wildtype and variant S-specific Ab isotypes and FcγR binding profiles were quantified by custom Luminex assay. Antibody-dependent neutrophil and cellular phagocytosis (ADNP and ADCP) were assessed using flow cytometry. RESULTS: To date 141 patients have been enrolled, 137 (91 MM and 46 WM) of whom had an S Ab assessment. Median Ab titer was 178.0 (IQR, 16.10-1166.0) for MM and 3.92 (IQR, 0-278.9) for WM. S Ab response rate was 91% (83/91) in MM and 56% (27/46) in WM. However, responses achieving S Ab >250 U/mL were 47.3% (43/91) in MM and 26.1% (12/46) in WM. In patients 375 years, responses >250 u/mL were 13.3% (2/15;p<0.05). Vaccine-specific S Ab responses >250 u/mL following mRNA-1273, BNT162b2, and JNJ-78436735 were 67.6% (23/34;p<0.05), 38.3% (18/47;p=NS), and 20% (2/10;p=NS) in MM and 50.0% (8/16;p<0.05), 14.8% (4/27;p<0.05), and 0% (0/3;p=NS) in WM. Among MM patients with progressive disease, S Ab response >250 u/mL occurred in 30% (6/20) as opposed to 55.6% (30/54) for VGPR+ (p<0.05). MM patients having autologous stem cell transplant within 12 months demonstrated 100% (5/5;p<0.05) S Ab responses. For MM patients actively receiving an anti-CD38 monoclonal Ab or an immunomodulatory drug, S Ab response occurred in 38.9% (14/36;p=NS) and 50.9% (28/55;p<0.05). Among WM patients, S Ab responses >250 U/mL occurred in 63.6% (7/11;p<0.05) previously untreated;0% (0/9;p<0.05) who received rituximab within 12 months;10% (2/20);p<0.05) on an active Bruton Tyrosine Kinase (BTK) inhibitor;and 20% (3/15;p=NS) who received other therapies. Functional Ab studies were performed on 14 MM patients, 14 WM, patients, and 14 healthy donors (HD) (Figure 1). All patients were assessed 28 days following their final vaccination and myeloma patients had an additional assessment 28 days following initial vaccination. MM and WM patients demonstrated less IGG1 and IGG3 S Ab production than HD. MM patients showed increased IgA and IgM S Ab production as well as increased FcgR2A binding following a second vaccine in contrast to HD. Both ADNP and ADCP were reduced in MM and WM patients. MM patients demonstrated improved ADCP in SARS-CoV-2 variants B.1.351, B.1.117, and P.1 versus wildtype (p<0.05). CONCLUSIONS: We report the first known evidence of impaired functional humoral responses following COVID-19 vaccines in patients with MM and WM. Overall, WM patients showed more severe impairment of COVID-19 S Ab responses. Most previously untreated WM patients achieved S Ab responses, however the most significant reduction in S Ab responses were seen in WM patients who received rituximab within 12 months or active BTK inhibitors. For MM patients, being in disease remission associated with improved S Ab response. Among MM and WM patients, age 375 years associated with significantly lower rates and vaccination with MRNA-1273 (Moderna) elicited significantly higher S Ab response rates than other vaccines. A defect in ADNP and more profound defect in ADCP suggests overall compromised opsinophagocytic activity among MM and WM patients. Data comparing first and second vaccine responses in MM patients, suggest less efficient class switching to IGG as well as incomple e maturation of their FcgR2A binding profiles but normal maturation of FcgR3A. Interestingly, ADCP was improved in several emerging SARS-CoV-2 variants. T-cell studies are pending and will be updated. Further understanding of the immunological response to COVID19 vaccination is needed to clarify patients risks, and necessity for booster or alternative protective measures against COVID-19. (Figure Presented).

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