Assessment of renal outcome following therapy in monoclonal immunoglobulin deposition disease: Emphasizing the need for a consensus approach.

Monoclonal immunoglobulin deposition disease (MIDD), often associated with plasma cell dyscrasias, predominantly affects the kidneys. In this disease, hematologic response (HR) to treatment can be reliably assessed by International Myeloma Working Group (IMWG) consensus criteria, while uniform criteria for assessing renal response are lacking. We report a retrospective analysis of renal outcomes among 34 patients with MIDD. With most patients treated with bortezomib and autologous stem cell transplantation, 26 of 28 (94%) achieved very good partial HR or better. We demonstrate that both IMWG (based on estimated glomerular filtration rate, eGFR) and amyloid (based on proteinuria) criteria are needed to capture renal response: among 28 evaluable patients, 6 (21%) had isolated proteinuria, while 13 (46%) had isolated decreased eGFR. Using both criteria, which were concordant in patients with both decreased eGFR and proteinuria, 22 of 28 patients (79%) achieved a renal response, including 2 of 7 discontinuing dialyses. All 6 patients (100%) with isolated proteinuria and 7 of 13 (54%) with isolated decreased eGFR achieved renal response, suggesting that isolated proteinuria is an early manifestation of MIDD associated with reversible renal damage. Baseline eGFR predicted renal response (p = .02 by quartile) and survival (p = .02), while HR (CR vs. non-CR) did not, probably because of high HR rate. With a median follow-up of 110 months, the median overall survival was 136 months (95% CI: 79-NR) and median renal survival had not been reached. Prospective studies using uniform renal response criteria are needed to optimize the management of MIDD.

Prognostic value of procalcitonin in cancer patients with coronavirus disease 2019.

OBJECTIVES: Many biomarkers have been studied to assist in the risk stratification and prognostication of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Procalcitonin (PCT), a circulating precursor of the hormone calcitonin, has been studied with mixed results as a predictor of severe coronavirus disease 2019 (COVID-19) in the general population; however, to date, no studies have focused on the utility of PCT in predicting disease severity and death from COVID-19 in the cancer population. METHODS: We conducted a retrospective study of cancer patients hospitalized with COVID-19 at a comprehensive cancer center over a 10-month period who had PCT recorded on admission. We assessed associations between variables of clinical interest and the primary outcomes of progression of COVID-19 and death during or within 30 days of hospitalization using univariable and multivariable logistic regression. RESULTS: The study included 209 unique patients. In the univariate analysis, elevated PCT on admission was associated with higher odds of progression of COVID-19 or death (Odds ratio [OR] 1.40, 95% CI 1.08-1.93) and mortality alone (OR 1.53, 95% CI 1.17-2.11). In multivariate regression, PCT remained significantly associated with progression or death after holding chronic kidney disease (CKD) status constant (OR 1.40, 95% CI: 1.08, 1.93, p=0.003). Similarly, the association of PCT and death remained significant after adjusting for age (OR 1.54, 95% CI: 1.17-2.15). CONCLUSIONS: In hospitalized COVID-19 patients with underlying cancer, initial PCT levels on admission may be associated with prognosis, involving higher odds of progression of COVID-19 and/or mortality.

Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma.

Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.

Mediation of Movement-Induced Breakthrough Cancer Pain by IB4-Binding Nociceptors in Rats.

Cancer-induced bone pain is characterized by moderate to severe ongoing pain that commonly requires the use of opiates. Even when ongoing pain is well controlled, patients can suffer breakthrough pain (BTP), episodic severe pain that "breaks through" the medication. We developed a novel model of cancer-induced BTP using female rats with mammary adenocarcinoma cells sealed within the tibia. We demonstrated previously that rats with bone cancer learn to prefer a context paired with saphenous nerve block to elicit pain relief (i.e., conditioned place preference, CPP), revealing the presence of ongoing pain. Treatment with systemic morphine abolished CPP to saphenous nerve block, demonstrating control of ongoing pain. Here, we show that pairing BTP induced by experimenter-induced movement of the tumor-bearing hindlimb with a context produces conditioned place avoidance (CPA) in rats treated with morphine to control ongoing pain, consistent with clinical observation of BTP. Preventing movement-induced afferent input by saphenous nerve block before, but not after, hindlimb movement blocked movement-induced BTP. Ablation of isolectin B4 (IB4)-binding, but not TRPV1+, sensory afferents eliminated movement-induced BTP, suggesting that input from IB4-binding fibers mediates BTP. Identification of potential molecular targets specific to this population of fibers may allow for the development of peripherally restricted analgesics that control BTP and improve quality of life in patients with skeletal metastases.SIGNIFICANCE STATEMENT We present a novel preclinical measure of movement-induced breakthrough pain (BTP) that is observed in the presence of morphine controlling ongoing pain. Blockade of sensory input before movement prevented BTP, whereas nerve block after movement failed to reverse BTP. These observations indicate that blocking peripheral sensory input may prevent BTP and targeting central sites may be required for pain relief once BTP has been initiated. Preventing sensory input from TRPV1-expressing fibers failed to alter movement-induced BTP. In contrast, preventing sensory input from isolectin B4 (IB4)-binding fibers blocked movement-induced BTP. Therefore, examining molecular targets on this population of nociceptive fibers may prove useful for developing an improved strategy for preventing BTP in cancer patients with skeletal metastases.

Short-term mortality of adult inpatients with community-acquired pneumonia: external validation of a modified CURB-65 score.

OBJECTIVE: The management of community-acquired pneumonia (CAP) continues to be a challenge, especially in older people. To enable better risk stratification, a variation of the severity scores CRB-65 and CURB-65, called CURB-age, has been suggested. We compared the association between risk groups as defined by the scores and 30-day mortality for a cohort of mainly older inpatients with CAP. METHODS: We retrospectively analysed data from the CAP database from the years 2005 to 2009 of a single centre in Herne, Germany. Patient characteristics, criteria values within the severity scores CURB-65, CRB-65 and CURB-age, and 30-day mortality were assessed. We compared the association between score points and score-defined risk groups and mortality. Sensitivity and specificity with corresponding 95% CIs were calculated, and receiver operating characteristic (ROC) curve analysis was performed. RESULTS: Data from 559 patients were analysed (mean age 74.1 years, 55.3% male). Mortality at day 30 was 10.9%. CURB-age included more patients in the low-risk category than CRB-65 (195 vs 89), and the patient group had a lower mortality (2.6% vs 3.4%). When compared with CURB-65, CURB-age included slightly fewer patients (195 vs 214) with lower mortality (2.6% vs 4.2%). CURB-age sorted the most patients who died within 30 days into the high-risk CAP group (CURB-age, 32; CURB-65, 28; CRB-65, 9), which had the highest mortality (CURB-age, 26.4%; CURB-65, 19.4%; CRB-65, 21.4%). Advantages of CURB-age categories were depicted through ROC curve analysis (area under the curve 0.73 (95% CI 0.67 to 0.79) for CURB-age categories, 0.67 (95% CI 0.60 to 0.74) for CURB-65 categories, and 0.59 (95% CI 0.52 to 0.66) for CRB-65 categories). CONCLUSIONS: In comparison with CRB-65 and CURB-65, risk stratification as defined by CURB-age showed the closest association with 30-day mortality in our sample. Further prospective studies are needed to assess the potential of CURB-age for better risk prediction, especially in older patients with CAP.

Viewing an ultra-brief chest compression only video improves some measures of bystander CPR performance and responsiveness at a mass gathering event.

BACKGROUND: CPR training at mass gathering events is an important part of health initiatives to improve cardiac arrest survival. However, it is unclear whether training lay bystanders using an ultra-brief video at a mass gathering event improves CPR quality and responsiveness. OBJECTIVE: To determine if showing a chest-compression only (CCO) Ultra-Brief Video (UBV) at a mass gathering event is effective in teaching lay bystanders CCO-CPR. METHODS: Prospective control trial in adults (age >18) who attended either a women's University of Arizona or a men's Phoenix Suns basketball game. Participants were evaluated using a standardized cardiac arrest scenario with Laerdal Skillreporter™ mannequins. CPR responsiveness (calling 911, time to calling 911, starting compressions within two minutes) and quality (compression rate, depth, hands-off time) were assessed for participants and data collected at Baseline and Post-intervention. Different participants were tested before and after the exposure of the UBV. Data were analyzed via the intention to treat principle using logistic regression for binary outcomes and median regression for continuous outcomes, controlling for clustering by venue. RESULTS: A total of 96 people were consented (Baseline=45; Post intervention=51). CPR responsiveness post intervention improved with faster time to calling 911 (s) and time to starting compressions (sec). Likewise, CPR quality improved with deeper compressions and improved hands-off time. CONCLUSIONS: Showing a UBV at a mass gathering sporting event is associated with improved CPR responsiveness and performance for lay bystanders. This data provides further support for the use of mass media interventions.

Viewing a brief chest-compression-only CPR video improves bystander CPR performance and responsiveness in high school students: A cluster randomized trial.

BACKGROUND: CPR training in schools is a public health initiative to improve out of hospital cardiac arrest (OHCA) survival. It is unclear whether brief video training in students improves CPR quality and responsiveness and skills retention. OBJECTIVES: Determine if a brief video is as effective as classroom instruction for chest compression-only (CCO) CPR training in high school students. METHODS: This was a prospective cluster-randomized controlled trial with three study arms: control (sham video), brief video (BV), and CCO-CPR class. Students were randomized and clustered based on their classrooms and evaluated using a standardized OHCA scenario measuring CPR quality (compression rate, depth, hands-off time) and responsiveness (calling 911, time to calling 911, starting compressions within 2min). Data was collected at baseline, post-intervention and 2 months. Generalized linear mixed models were used to analyze outcome data, accounting for repeated measures for each individual and clustering by class. RESULTS: 179 students (14-18 years) were consented in 7 classrooms (clusters). At post-intervention and 2 months, BV and CCO class students called 911 more frequently and sooner, started chest compressions earlier, and had improved chest compression rates and hands-off time compared to baseline. Chest compression depth improved significantly from baseline in the CCO class, but not in the BV group post-intervention and at 2 months. CONCLUSIONS: Brief CPR video training resulted in improved CPR quality and responsiveness in high school students. Compression depth only improved with traditional class training. This suggests brief educational interventions are beneficial to improve CPR responsiveness but psychomotor training is important for CPR quality.