Extended Interval Dosing of Ocrelizumab Reduces Risk of Developing Hypogammaglobulinaemia

Introduction Disruption to clinical services, triggered by the COVID-19 pandemic, led to extended intervals between ocrelizumab treatments for some patients. Objectives To assess the rates of developing low immunoglobulin levels and timing of CD19+ B-cell count repopulation in a real-world clinical population. To assess for evidence of clinical or radiological MS disease activity with extended interval dosing of ocrelizumab. Methods We audited 712 patients given ocrelizumab by our seven clinical services. All monitoring of immunoglobulin levels and CD19+ cell counts were recorded. Disease activity was defined as on treatment clinical relapse, radiological activity, and EDSS progression. Results Low immunoglobulin levels developed in 102 patients, the odds ratio for developing hypogam- maglobulinaemia comparing extended to standard interval dosing was 0.42 (CI 0.22-0.81). Disease activity included 20 participants with clinical relapses and 72 with new MRI lesions. There was no evidence of excess clinical or radiological disease activity on switching to extended interval dosing. 38 had EDSS progression, giving an odds ratio comparing extended to standard interval dosing of 0.77 (CI 0.38-1.56). Conclusions This real-world data of extended interval dosing of ocrelizumab indicates lower rates of hypogammaglobulinaemia and no detrimental effect on short-term treatment efficacy.

Organ preservation and total neoadjuvant therapy for rectal cancer: Investigating longcourse chemoradiation versus short-course radiation therapy

Background: Interest in organ preservation (OP) strategies for rectal cancer (RC) patients persists. The efficacy of long course chemoradiation (LCRT) vs. short course radiation therapy (SCRT) relative to OP is unknown. We compared OP rates between SCRT and LCRT total neoadjuvant therapy (TNT) strategies. Method(s): During the COVID-19 pandemic we established an institutional SCRT mandate with no exceptions. For comparison, we identified RC patients treated with LCRT immediately before and after the mandate period. After completion of TNT, patients were restaged by clinical exam, endoscopy, and MRI. A watch and wait (WW) approach was recommended for patients with a clinical complete response (cCR), defined by the MSK regression schema. Total mesorectal excision (TME) was recommended for non-cCR patients. OP was defined as alive, TME-free, and with no evidence of disease in the pelvis. We performed survival analysis for: local regrowth rate, OP, disease-free survival (DFS), and overall survival (OS). Result(s): We identified 563 consecutive patients with RC treated with TNT, of whom 231 were excluded due to either metastatic disease, synchronous/metachronous malignancies, or non-adenocarcinoma histology (Jan. 2018-Jan. 2021). Patient and tumor characteristics were similar in the LCRT (n = 256) and SCRT (n = 76) cohorts. No significant differences in high-risk features were noted. Most patients had clinical stage III disease (82% in LCRT vs. 83% in SCRT). Induction chemotherapy followed by consolidative radiation was the most common treatment order (78% (LCRT) vs. 70% (SCRT)). The median interval from end of TNT to clinical restaging was 8 weeks (LCRT) and 9 weeks (SCRT). The cCR rate was 46% in both cohorts. The cCR rate was numerically higher in patients treated with radiation first, as compared to chemotherapy first (53% vs. 44% (LCRT) and 52% vs. 43% (SCRT)). Among patients with a cCR, the likelihood of WW management was similar (98% (LCRT) vs. 94% (SCRT)). From start of TNT, the median follow-up was 32 and 28 months respectively for LCRT and SCRT. The 2-year OS (95% vs. 92%), DFS (78% vs 70%), and distant recurrence (20% vs. 21%) rates were similar. Among all patients, the 2-year OP rate was 40% (95% CI 35-47%) for LCRT and 29% (95% CI 20-42%) with SCRT. In those patients managed by WW, the 2-year local regrowth rate was 20% (95% CI 12-27%) with LCRT vs. 36% (95% CI 16-52%) with SCRT. Conclusion(s): In this nonrandomized comparison, while cCR rates were similar, we observed a numerically higher OP rate with LCRT-TNT than with SCRT-TNT. The ongoing ACO/ARO/AIO-18.1 trial, hypothesizing that LCRT-TNT will increase OP rates relative to SCRT-TNT, should definitively answer this question.

Short-course remdesivir for healthcare-associated COVID-19: Case series from a non-acute care hospital

Healthcare-associated COVID-19 among vulnerable patients leads to disproportionate morbidity and mortality. Early pharmacologic intervention may reduce negative sequelae and improve survival in such settings. This study aimed to describe outcome of patients with healthcare-associated COVID-19 who received early short-course remdesivir therapy. We reviewed the characteristics and outcome of hospitalized patients who developed COVID-19 during an outbreak that involved two wards at a non-acute care hospital in Japan and received short-course remdesivir. Forty-nine patients were diagnosed with COVID-19, 34 on a comprehensive inpatient rehabilitation ward and 15 on a combined palliative care and internal medicine ward. Forty-seven were symptomatic and 46 of them received remdesivir. The median age was 75, and the median Charlson comorbidity index was 6 among those who received it. Forty-one patients had received one or two doses of mRNA vaccines, while none had received a third dose. Most patients received 3 days of remdesivir. Of the patients followed up to 14 and 28 days from onset, 41/44 (95.3%) and 35/41(85.4%) were alive, respectively. Six deaths occurred by 28 days in the palliative care/internal medicine ward and two of them were possibly related to COVID-19. Among those who survived, the performance status was unchanged between the time of onset and at 28 days. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

Early Short-Term Use of Different Doses of Corticosteroid in Hospitalized Pediatric Patients with Coronavirus Disease 2019 Pneumonia

Objective Encouraged by reports of favorable outcomes following the use of corticosteroids in patients with moderate-to-severe coronavirus 2019 (COVID-19) pneumonia, we aimed to present our experience with early short-term corticosteroid use at our center in pediatric patients with COVID-19 pneumonia. Methods One hundred and twenty-nine pediatric patients were included in the study. Patients were divided into four groups according to the type and dose of corticosteroids given: Group 1 (those receiving dexamethasone 0.15 mg/kg/d);Group 2 (those receiving methylprednisolone 1 mg/kg/d);Group 3 (those receiving methylprednisolone 2 mg/kg/d);and Group 4 (those receiving pulse methylprednisolone 10-30 mg/kg/d). Results Of 129 patients, 19 (14.7%) patients were assigned to Group 1, 30 (23.3%) patients to Group 2, 30 (23.3%) patients to Group 3, and 50 (38.8%) patients to Group 4. Thirty-two (24.8%) patients were followed in the pediatric intensive care unit (PICU), of whom 13 (10%) required mechanical ventilation, and 7 (%5.4) died. In Group 4, the hospitalization length was significantly longer than in other groups (p < 0.001, p < 0.001). No significant difference was found among the groups in terms of mortality (p = 0.15). The most common comorbidity was obesity (33%). A significant association was found between the presence of comorbidity and mortality (p < 0.001). All patients who died had an underlying disease. Cerebral palsy was the most common underlying disease among the patients who died. Worsening of lymphopenia was significant in patients with severe COVID-19 pneumonia at the time of transfer to the PICU (p = 0.011). Conclusion Although children usually have a milder course of COVID-19 than adults, underlying diseases and obesity increase the severity of disease manifestations also in children. Further studies are needed to define the exact role of corticosteroids in COVID-19 patients. © 2022. Thieme. All rights reserved.

REGRESSIVE BONE MINERAL DENSITY TRENDS SEEN with DELAY in FOLLOW UP of DENOSUMAB TREATMENT DUE to the PANDEMIC INDUCED LOCKDOWN-A SINGLE CENTRE INDIAN EXPERIENCE

Background: Denosumab (Dmab), a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-β ligand (RANKL), which selectively inhibits osteoclastogenesis can be used for a long period unlike the relatively short period with Teriparatide.1-2 However the effects of Dmab can quickly regress if the treatment is delayed.3 Objectives: The pandemic led to multiple prolonged lockdowns since March 2020 to Jan 2022 in India. This resulted in follow up Dmab treatment delays. The retrospective study was aimed to look for the effect of the delays. Methods: The bone mineral density (BMD) trends from the central dual-energy X-ray absorptiometry (DXA) at our centre were studied. The trends of patients under Dmab for one year and delay in follow up for 10-12 months for the forth dose were evaluated. 21 postmenopausal women who had been under treatment with Dmab 60 mg subcutaneous injection at 6 monthly interval for one year followed up with such delays. 6 were excluded because of history of sars-cov-2 infection and glucocorticoid use. In the study group of 15 (n=15), the mean BMD at L2, L3 & L4 (sp BMD) and Right and Left Hip (hip BMD) were studied from before treatment (a BMD), 6 months after 1st and at the time of 2nd injection (b BMD), 6 months of the 2nd and at the time of 3 rd injection of Dmab (c BMD), and that due to delay in follow up of 10-12 months (d BMD). The mean percentage trend change between a-b, b-c, and c-d BMDs was evaluated. The least signifcant change (LSC) 4 from a single centre DXA was used to validate the fndings. Results: The mean percentage change after the treatment for the 1st 6 months of Dmab (a-b BMD) was 4.08% and 3.60% and the second injection resulted in a further change (b-c BMD) of 5.98% and 4.52% in the sp BMD & hip BMD respectively. The delay in follow up of 10-12 months resulted in a change (c-d BMD) of-7.81% in the sp BMD and-2.96% in the hip BMD. The LSC from a single centre DXA is 2.6% and 3.6% for sp BMD and hip BMD respectively. A p>0.05 was considered statistically signifcant. Table 1 shows the BMD changes. Conclusion: These fndings suggest that regressive trend in BMD are seen when the treatment with Dmab is delayed even as early as 10 to 12 months. It was seen much faster in the spine compared to the hip. It is therefore advised that short term treatment with Dmab without follow up could lead to loss of all gains and may also worsen the osteoporosis.

BEHAVIORAL SELF-CONTROL TRAINING VERSUS MOTIVATIONAL ENHANCEMENT THERAPY FOR INDIVIDUALS WITH ALCOHOL USE DISORDER WHO AIM FOR CONTROLLED DRINKING: A RANDOMIZED CONTROL

Background: Controlled drinking is an attractive treatment goal among a large proportion of individuals with alcohol use disorder (AUD), with Behavioral Self-control Training (BSCT) as the most established treatment intervention, for this purpose. Yet, few controlled trials have aimed at investigating the efficacy of interventions with controlled drinking as treatment goal, and the implementation of these treatments in addiction care is scarce. Methods: A multi-site randomized controlled parallel superiority trial compared the efficacy of BSCT (5 sessions) to the active comparator Motivational Enhancement Therapy (MET) (4 sessions). A sample of 250 patients fulfilling criteria for AUD (DSM 5) with a goal of controlled drinking were included. As a result of the covid pandemic, a total of 76 participants received treatment via video meeting instead of face-to-face. Follow-ups were conducted at 12- and 26 weeks after inclusion. Primary outcome measure was mean weekly alcohol consumption. Treatment effects were analyzed by linear mixed-models. Results: Both treatment arms showed significant treatment effects for the primary outcome as well as binge drinking days (BDD) and measures of alcohol-related harm at 26 weeks after inclusion. There were no significant differences between treatment groups for the primary outcome. A total of 41,6 % of the patients obtained a level of low-risk drinking at the 26-week follow-up (9/14 standard drinks of 12 g of alcohol for women/men). No significant differences based on how the treatment was delivered i.e., between the face-to-face or video based intervention were detected. A subgroup of individuals (n = 25) with 75% or more of BDD before inclusion, reduced their drinking to 29% BDD at the 26-week follow-up. Conclusions: These results suggest that BSCT and MET designed as short-term treatments, are efficacious for a wide range of patients with AUD. This is evident in that a substantial proportion of patients obtained low-risk drinking levels, and individuals with more heavy consumption patterns, also significantly reduced their consumption. These results highlight a need for a more diverse approach within health care services to recovery from AUD with possibility of offering psychological treatments with controlled drinking as a treatment goal.

Re-analyzing randomized trials with incorporation of COVID-19 risk associated with cancer therapy

Background: Cancer therapy may put patients at risk of mortality from COVID-19. The impact of abbreviated treatment courses on outcomes in the setting of COVID-19 is unknown. We incorporated COVID-19-associated risks in re-analysis of practice-defining randomized trials in oncology that compared different radiation therapy (RT) regimens. Methods: We extracted individual patient level data (IPLD) from published survival curves from randomized trials in rectal cancer (Dutch TME, TROG 01.04), early stage breast cancer (CALGB 9343, OCOG hypofractionation trial, FAST-Forward, NSABP B-39), and localized prostate cancer (CHHiP, HYPO-RT-PC). Trials were simulated with incorporation of varying risk of SARS-CoV-2 infection and mortality associated with receipt of therapy. Results: IPLD from 14,170 patients were re-analyzed. In scenarios with low COVID-19-associated risks (0.5% infection risk per fraction [IRF], 5% case fatality rate [CFR]), fractionation did not significantly affect outcomes. In locally advanced rectal cancer, short-course RT appeared preferable to long-course chemoradiation (TROG 01.04) or RT omission (Dutch TME) in most settings. While moderate hypofractionation in early stage breast cancer (OCOG hypofractionation trial) and prostate cancer (CHHiP) was not associated with survival benefits in the setting of COVID-19, more aggressive hypofractionation (FAST-Forward, HYPO-RT-PC) and accelerated partial breast irradiation (NSABP B-39) were associated with improved survival in higher risk scenarios (≥5% IRF;≥ 20% CFR). In settings where RT can be omitted, such as favorable early stage breast cancer in the elderly (CALGB 9343), RT was associated with worse survival in higher risk pandemic scenarios (≥5% IRF, ≥ 20% CFR). Conclusions: Our framework, which can be adapted to dynamic changes in COVID-19 risk, provides a flexible, quantitative approach to assess the impact of treatment recommendations across oncology. The magnitude of potential benefit from abbreviated RT courses depends on the degree of hypofractionation and local COVID-19-associated risk. Abbreviated RT courses should be prioritized when possible and are increasingly beneficial in higher risk pandemic settings. With increased understanding and precautions against COVID-19 that can minimize risks for patients, our results support the continued use of evidence-based treatments for cancer patients in the COVID-19 era.

IMPACT-ReCaP: Rectal cancer management during the COVID-19 pandemic

Purpose/Background: With enhanced strain on healthcare systems and avoidance of routine surgery and systemic therapy during the COVID-19 period due to increased morbidity and mortality alternative oncological approaches have been employed. We aimed to determine the variation in strategies adopted nationally across the United Kingdom (UK) and long-term associated outcomes. Methods/Interventions: A UK multi-centre prospective observational study was performed from the date of National Governmental lockdown (23/3/20) until the lifting of restrictions (17/5/21). Patients with a new diagnosis of rectal cancer or those rediscussed at MDT on an existing treatment pathway were eligible for inclusion. Results/Outcomes: The first 900 patients were reported from 70 registered sites;65.4% male, 73.6% >60 years old. 62.4% of patients were diagnosed following lockdown. 65.8% of MDTs had a partial or entirely virtual format. 22.8% of tumours were T4, with 4.3% local recurrence. Following lockdown there was a significant increase in the use of SCRT + delay from 10.0% to 18.7% (p < 0.0005), with a rate of 26.7% during the first wave. Comparably the rate of LCRT fell 53.3% to 18.0% (p < 0.0001). 86.2% of those undergoing surgery during the first wave had stoma formation, 26.0% of which due to COVID-19 concerns alone. 18.6% of patients were deemed to have received different management plans due to COVID-19. Conclusion/Discussion: The COVID-19 pandemic has led to variation in oncological treatment strategies for rectal cancer, most notably an increase in the use of SCRT radiotherapy, deferral of surgery and stoma formation. Whilst short-term data appears to suggest equivalence in outcomes compared to LCRT, caution needs to be shown whilst awaiting longer-term outcomes and ensuring robust follow up and safety netting to avoid long term harm.

I9MASKS: FROM A MULTIDISCIPLINARY SUMMER PROJECT TO A NON-ACCREDITED SHORT COURSE

This study presents a research experience with engineering students at undergraduate and graduate levels, during the summer of 2020 at the School of Engineering, University of Minho, Portugal. Following the first pandemic event in Portugal, from March to May 2020, the Foundation for promoting Science and Technology (FCT) has opened a call for research projects among students and researchers at different Universities. The main aim of these projects was to motivate students to return physically to the campus during a summer course, and to promote a research environment among them. i9Masks was one of the projects approved by the University of Minho and its main objective was the development of innovative masks in a silicone elastomer for the protection of COVID-19 with the use of state-of-the-art technologies. The development of masks was at the time a very hot topic as well as a fashionable subject for research. Considering the results obtained, from the final works presented by students, a very positive balance of the experience was achieved. The i9Masks project was a useful learning experience for engineering education, particularly in Portugal, where the opportunity to participate in this type of "learning by doing" experience is very small. Copyright © 2021 by ASME

COVID-19 and pulmonary tuberculosis - A diagnostic dilemma.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Meanwhile, pulmonary tuberculosis(TB) is one of the most common infective lung diseases in developing nations. The concurrence of pulmonary TB and COVID-19 can lead to poor prognosis, owing to the pre-existing lung damage caused by TB. Case presentation: We describe the imaging findings in 3 cases of COVID-19 pneumonia with co-existing pulmonary TB on HRCT thorax. The concurrence of COVID-19 and pulmonary TB can be a diagnostic dilemma. Correct diagnosis and prompt management is imperative to reduce mortality and morbidity. Hence it is pertinent for imaging departments to identify and report these distinct entities when presenting in conjunction.

Clinical Use of Short-Course and Low-Dose Corticosteroids in Patients With Non-severe COVID-19 During Pneumonia Progression.

Background: The emerging coronavirus disease 2019 (COVID-19) has become a serious public health concern with a high number of fatalities. It is unclear whether corticosteroids could be a candidate for an early intervention strategy for patients with COVID-19. Methods: In this retrospective cohort study, we analyzed data from 28 corticosteroid-treated patients with non-severe but advanced COVID-19, in which short-course and low-dose corticosteroids were administered because of unremitting or worsening clinical conditions during hospitalization. To compare the effect of corticosteroids on viral clearance, 44 corticosteroid-untreated patients were included as controls. Results: At the time of admission, corticosteroid-treated patients (n = 28) had a more advanced baseline illness compared with corticosteroid-untreated patients (n = 44), as reflected by poorer blood laboratory parameters (lymphocytes, C-reactive protein, and lactate dehydrogenase) and more extensive chest computed tomography (CT) abnormalities. Corticosteroids were given because of radiological evidence of pneumonia progression (26/28) and/or unremitting fever (22/28) after admission. The median time from illness onset to corticosteroid treatment was 9 days (IQR, 7-10). The median duration and accumulated dose of corticosteroid treatment were 4.5 days [interquartile range (IQR), 3-5] and 140 mg of methylprednisolone (IQR, 120-200). Intravenous immunoglobulin (20 g per day for 3-5 days) was co-administered with corticosteroids. With the corticosteroid treatment, all patients achieved an abatement of fever within 1 day, and 78.6% (22/28) of the patients achieved radiological remission when evaluated about 3 days later. Only one (3.6%) patient progressed to severe COVID-19, and all patients recovered and were discharged without any sequela. The median time from illness onset to viral clearance was similar, as compared with 44 corticosteroid-untreated patients with relatively milder disease [18 (IQR 14.3-23.5) days vs. 17 (IQR, 12-20) days, p = 0.252]. When adjusted for age, sex, underlying comorbidities, baseline blood laboratory parameters, viral load, and chest radiological findings, the causal hazard ratio of corticosteroid treatment for the viral clearance was 0.79 (95%CI, 0.48-1.30, p = 0.34). Conclusion: Short-course and low-dose applications of corticosteroids, when co-administered with intravenous immunoglobulin, in non-severe COVID-19 patients during the stage of clinical deterioration may possibly prevent disease progression, while having a negligible impact on the viral clearance.