Renal Biopsy in Systemic Infections: Expect the Unexpected

Introduction: Infection-related glomerulonephritis is well recognized and often included in the differential diagnosis in patients with ongoing infections. It can be missed, however, if the infection is unusual or undetected. We present three cases where the renal biopsy findings prompted the identification or treatment of systemic infections. Case Description: Case 1: A 84-year-old male presented with acute kidney injury (AKI) and a new purpuric rash. Clinically, IgA nephropathy was suspected. A renal biopsy showed active glomerulonephritis with abundant neutrophils, focal segmental tuft necrosis, and one cellular crescent. Predominantly mesangial immune complex deposits containing IgA and IgG were seen. The findings suggested IgA-rich infection-associated glomerulonephritis. Infectious workup was positive for COVID-19, suggesting exacerbation of IgA nephropathy by recent COVID-19 infection. Case 2: A 31-year-old female status post kidney transplant for granulomatosis with polyangiitis (GPA) had recent pregnancy with preterm delivery, disseminated herpes simplex virus (HSV) infection with HSV hepatitis, and AKI. Urine culture was positive for E. coli. The differential diagnosis included HSV nephritis, drug reaction, rejection, recurrent GPA, thrombotic microangiopathy (TMA), and pyelonephritis. A renal biopsy showed proliferative glomerulonephritis with subendothelial and mesangial immune complex deposits containing IgG and C3. The findings were most consistent with infection-related immune complex glomerulonephritis, most likely related to the HSV infection. Case 3: A 78-year-old female presented with AKI, proteinuria, hematuria, and positive p-ANCA. Clinically, ANCA vasculitis was suspected, and the renal biopsy did show focal, segmental, necrotizing glomerulonephritis. However, immunofluorescence and electron microscopy showed IgM-rich immune complex deposits in the mesangium. The unusual presentation of ANCA glomerulonephritis was suggestive of an underlying infection. Bartonella antibody panel showed very high titers;the patient was treated with antibiotics for Bartonella endocarditis. Discussion(s): Infection-related glomerulonephritis has a wide variety of presentations histologically and clinically. The three cases we present here emphasize the importance of recognizing these entities to help guide treatment and improve patient care.

Randomized controlled trial (RCT) of symptom screening with targeted early palliative care (STEP) versus usual care in patients with advanced cancer

Background: To direct limited specialized palliative care resources to patients in greatest need, we developed STEP (Symptom screening with Targeted Early Palliative care). STEP entails symptom screening (ESAS-r) at each oncology clinic visit and triggered alerts (for moderate-high physical and psychological symptoms) to a nurse who calls the patient to offer a palliative care clinic (PCC) visit. We conducted a phase III RCT to assess the impact of STEP versus usual care on quality of life and other patient-reported outcomes (PROs). Methods: Adults with advanced cancer were recruited from medical oncology clinics at the Princess Margaret Cancer Centre, Toronto, Canada. Consenting patients with oncologist-assessed ECOG 0-2 and estimated survival of 6-36 months were enrolled and block randomized (stratified by tumour site and symptom severity) to STEP or usual care. Participants completed measures of quality of life (FACT-G7), depression (PHQ-9), symptom control (ESASr-CS), and satisfaction with care (FAMCARE-P16) at baseline, 2, 4 and 6 months. The primary outcome was FACT-G7 at 6 months, with a planned sample size of 261/arm. Results: From 8/2019 to 3/2020, 69 patients were enrolled: 33 randomized to STEP and 36 to usual care. The trial was then halted permanently due to the COVID-19 pandemic, owing to substantial changes to elements of STEP (shift to virtual symptom screening and palliative care) and usual care (shift to virtual oncology care). Median age was 64 years (range 25-87) and 62% (43/69) were women;study arms were balanced at baseline except gender, with more women randomized to STEP. Within the STEP arm, 20 (61%) participants triggered a nurse's call to offer a PCC visit, of whom 13 attended the clinic at least once. All outcomes tended to be better in the STEP arm compared to usual care, particularly depression and satisfaction with care at 6 months;however, results were not statistically significant (Table). Conclusions: STEP holds promise for improving quality of life and other PROs in patients with advanced cancer and effectively directing early palliative care towards those who need it most. In response to the pandemic, an online version of STEP has been developed and a further trial is in progress.

SYMPTOM SCREENING WITH TARGETED EARLY PALLIATIVE CARE (STEP) VERSUS USUAL CARE FOR PATIENTS WITH ADVANCED CANCER: A RANDOMIZED CONTROLLED TRIAL

Introduction To direct scant specialized palliative care (PC) resources to patients in greatest need, we developed the STEP intervention (Symptom screening with Targeted Early Palliative care). STEP entails symptom screening with ESAS-r at each oncology visit and triggered alerts (for moderatehigh symptoms) to a nurse who calls the patient to offer a PC clinic visit. Methods Consenting adults with advanced cancer, ECOG 0-2, attending medical oncology clinics at the Princess Margaret Cancer Centre, were randomized to STEP or usual care. Participants completed quality of life (FACTG7), depression (PHQ-9), symptom control (ESASr-CS), and satisfaction with care (FAMCARE-P16) measures at baseline, 2, 4, and 6 months. The primary outcome was FACT-G7 at 6 months. Results From August 2019 to March 2020, 33 patients were randomized to STEP and 36 to usual care. The trial was subsequently permanently halted due to the COVID-19 pandemic. Groups were balanced at baseline except gender, with more females in the STEP arm (Table 1). In the STEP arm, 20 participants triggered a nurse 's call, of whom 13 had ≥1 PC clinic visit. At 6 months, all outcomes tended to be better in the STEP arm compared to usual care, particularly depression and satisfaction with care;however, results were not statistically significant (Table 2, Figure 1). Conclusions STEP holds promise for improving outcomes in patients with advanced cancer. An online version (eSTEP) is being developed in response to the COVID-19 pandemic.

COMPARING ACADEMIC CHALLENGES AND QUALITY OF LIFE IN CONCUSSED ADOLESCENTS PRIOR TO AND DURING THE COVID-19 PANDEMIC

Background: Post-concussion sequelae in adolescents include physical, cognitive, and psychosocial effects that may result in reduced quality of life (QOL) and academic challenges when returning to school. The COVID-19 pandemic resulted in altered teaching and learning models outside the traditional in-person classroom, and elevated psychosocial stress and isolation among adolescents. It is unknown whether these changes affected QOL or academic challenges postconcussion. Hypothesis/Purpose: To compare self-reported QOL and academic challenges among concussed adolescents prior to and during the COVID-19 pandemic. Methods: Concussed adolescents were enrolled from secondary schools and children's medical centers across seven sites into the Sport Concussion Outcomes in Pediatrics (SCOPE) study (PRiSM Concussion RIG). Participants completed demographics, medical history, symptom report, the Concussion Learning Assessment and School Survey (CLASS) and QOL via PROMIS Pediatric Global 25 during their first evaluation visit. Participants were grouped by date ranges: September 2018-January 2020 (Pre-COVID-19) and September 2020-May 2021 (COVID-19). No participants were enrolled between February-August 2020 (cessation of clinical research activities during this time.) Results: A total of 141 patients were enrolled. Mean age=14.9±2.4 years, 61% self-reported as male, 82% white and 85% not Hispanic or Latino, 5.2+3.1 days post-injury (range=1-14 days). Seventy-four patients were enrolled prior to COVID, and 67 were enrolled during COVID (Table 1). No significant differences were found between the 'Pre-COVID-19' group versus 'During COVID-19' group in symptom resolution, symptom severity score, QOL, or academic concerns (Table 2). The only difference was the 'person at school who is best to coordinate support.' A significantly lower proportion of participants who sustained their concussion during COVID-19 reported their principal/assistant principal would be the best person to coordinate support compared to those who sustained their concussion before the COVID-19 pandemic. In contrast, a significantly higher proportion of those who sustained their concussion during the COVID-19 pandemic reported their coach would be the best person to coordinate support. Conclusion: In this convenience yet nationally representative sample, students who sustained a concussion during the pandemic did not report increased academic concerns or reduced QOL compared to those whose injury was prior to the pandemic. Median symptom severity was lower during the pandemic, though not statistically significant. These findings could represent shifted priorities of the principal/assistant principal but still adequate support from medical and schoolbased staff;less academic stress and greater flexibility during the COVID-19 pandemic;or may represent limitations in the CLASS instrument to detect differences that occurred during the pandemic.

SPORTS AND PHYSICAL ACTIVITY ATTENUATE THE EMOTIONAL TOLL OF THE COVID-19 PANDEMIC

Background: The COVID-19 pandemic resulted in the alterations or restrictions of youth sports and physical activity. These changes may have had negative ramifications on anxiety and both physical and psychological readiness to return to sport in youth athletes. Hypothesis/Purpose: Our purpose was to investigate the relationships between the physical and mental health ramifications on youth athletes during restricted sport activities that resulted from COVID-19 stay-at-home orders. Our hypothesis was that youth athletes who participated in a similar or greater volume of organized sports would have less anxiety during the COVID-19 stay-at-home orders compared with those who reported a decrease in organized sport volume. Methods: Our cross-sectional study evaluated male and female athletes who competed in club sports (e.g., non-school sponsored) at the time of questionnaire completion. All participants completed an online questionnaire between July 15, 2020 and August 10, 2020. We asked participants to report the average hours/week they spent in organized sports or physical activity unrelated to their sport prior to COVID-19 and currently. We grouped participants on whether they had a decrease or increase/no change in their reported activity level. Participants also completed the Generalized Anxiety Disorder-7 questionnaire. Results: A total of 192 participants (13.0±2.2 years of age;range= 6-18 years, 56% female) completed the study. On average, participants reported 2.3 (SD+5.2) fewer hours of sport training per week during the COVID-19 stay-at-home orders compared to prior. Over half (56%) of participants reported a decreased training volume during stay-at-home orders, and 44% reported a similar or increased training volume (Table 1). The respondents reporting decreased training volumes had significantly greater anxiety scores than those who reported similar training volumes (Figure 1). After adjusting for the potential confounders of age, sex, and body size, decreased training volumes during stay-at-home orders were significantly associated with higher anxiety levels (β coefficient = 2.02;95% confidence interval = 0.64, 3.41;p = 0.005). Those with decreased training volumes were more likely to report feeling undertrained (72% vs 30%, p<0.001) and less physically ready to return to sport (56% vs 88%, p<0.001) compared to those with similar/increased training volumes (Table 1). Conclusion: The COVID-19 pandemic resulted in decreased training volumes and higher anxiety scores (mean difference= 1.9 GAD-7 points, 95% confidence interval= 0.6, 3.2) compared with athletes who reported similar/increased training volumes. Lastly, those in the decreased training cohort felt both under-trained and less physically ready to return to sports.

Improved models of care for cancer survivors

The number of survivors of cancer is increasing substantially. Current models of care are unsustainable and fail to address the many unmet needs of survivors of cancer. Numerous trials have investigated alternate models of care, including models led by primary-care providers, care shared between oncology specialists and primary-care providers, and care led by oncology nurses. These alternate models appear to be at least as effective as specialist-led care and are applicable to many survivors of cancer. Choosing the most appropriate care model for each patient depends on patient-level factors (such as risk of longer-term effects, late effects, individual desire, and capacity to self-manage), local services, and health-care policy. Wider implementation of alternative models requires appropriate support for non-oncologist care providers and endorsement of these models by cancer teams with their patients. The COVID-19 pandemic has driven some changes in practice that are more patient-centred and should continue. Improved models should shift from a predominant focus on detection of cancer recurrence and seek to improve the quality of life, functional outcomes, experience, and survival of survivors of cancer, reduce the risk of recurrence and new cancers, improve the management of comorbidities, and reduce costs to patients and payers. This Series paper focuses primarily on high-income countries, where most data have been derived. However, future research should consider the applicability of these models in a wider range of health-care settings and for a wider range of cancers.

Cardiovascular disease and severe hypoxemia are associated with higher rates of non-invasive respiratory support failure in COVID-19 pneumonia

RATIONALE Acute hypoxemic respiratory failure (AHRF) is the major complication of coronavirus disease 2019 (COVID-19), yet optimal respiratory support strategies are uncertain. We aimed to describe outcomes with highflow oxygen delivered through nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) in COVID-19 AHRF and identify individual factors associated with non-invasive respiratory support failure. METHODS We conducted a retrospective cohort study of hospitalized adults with COVID-19 within a large academic health system in New York City early in the pandemic to describe outcomes with HFNC and NIPPV. Patients were categorized into the HFNC cohort if they received HFNC but not NIPPV, whereas the NIPPV cohort included patients who received NIPPV with or without HFNC. We described rates of HFNC and NIPPV success, defined as live discharge without endotracheal intubation (ETI). Further, using Fine-Gray sub-distribution hazard models, we identified demographic and patient characteristics associated with HFNC and NIPPV failure, defined as the need for ETI and/or in-hospital mortality. RESULTS Of the 331 patients in the HFNC cohort, 154 (46.5%) patients were successfully discharged without requiring ETI. Of the 177 (53.5%) who experienced HFNC failure, 100 (56.5%) required ETI and 135 (76.3%) patients ultimately died. Among the 747 patients in the NIPPV cohort, 167 (22.4%) patients were successfully discharged without requiring ETI, and 8 (1.1%) were censored. Of the 572 (76.6%) patients who failed NIPPV, 338 (59.1%) required ETI and 497 (86.9%) ultimately died. In adjusted models, significantly increased risk of HFNC and NIPPV failure was observed among patients with co-morbid cardiovascular disease (sub-distribution hazard ratio (sHR) 1.82;95% confidence interval (CI), 1.17-2.83 and sHR 1.40;95% CI 1.06-1.84, respectively). Conversely, a higher oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) at HFNC and NIPPV initiation was associated with reduced risk of failure (sHR, 0.32;95% CI 0.19-0.54, and sHR 0.34;95% CI 0.21-0.55, respectively). CONCLUSIONS A subset of patients with COVID-19 AHRF was effectively managed with non-invasive respiratory modalities and achieved successful hospital discharge without requiring ETI. Notably, patients with co-morbid cardiovascular disease and more severe hypoxemia experienced lower success rates with both HFNC and NIPPV. Identification of specific patient factors may help inform more selective use of non-invasive respiratory strategies, and allow for a more personalized approach to the management of COVID-19 AHRF in pandemic settings.