Improved survival of increased-risk myeloma patients on combined triple- alkylating-agent therapy: a study of the CALGB

Two hundred fifty-two previously untreated evaluable patients with multiple myeloma were entered into a study testing a regimen of three intravenous alkylating agents, melphalan, cyclophosphamide, and carmustine (BCNU), given in combination (BCMP) against a regimen employing oral melphalan (MP). Both regimens included a tapering course of prednisone. Objective responses based on the Myeloma Task Force criteria were significantly more frequent in the group receiving BCMP. Survival for the entire group of BCMP-treated patients was not significantly better than that for MP-treated patients (p = 0.62). However, when the survival of the poor-risk (high tumor cell load) group of patients treated with BCMP was compared with the survival of the poor-risk (high tumor cell load) group of patients treated with MP, an improvement in survival attributable to BCMP therapy was seen (p = 0.049 and 0.02, respectively). In the good-risk (low and intermediate tumor cell load) group, BCMP treatment resulted in a trend toward poorer survival, but this did not achieve statistical significance (p = 0.080 and 0.23, respectively). These results indicate that optimal therapy in myeloma may be dependent on the extent of disease at the time of first treatment. Additional studies to explore the effects of treatment intensity and duration are needed in order to design improved myeloma treatment based on the patient's extent of disease.

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Improved survival of increased-risk myeloma patients on combined triple- alkylating-agent therapy: a study of the CALGB

Blood ◽

10.1182/blood.v54.1.13.13 ◽

1979 ◽

Vol 54 (1) ◽

pp. 13-22 ◽

Cited By ~ 66

Author(s):

JB Harley ◽

TF Pajak ◽

OR McIntyre ◽

S Kochwa ◽

MR Cooper ◽

...

Keyword(s):

Tumor Cell ◽

Task Force ◽

Alkylating Agents ◽

Statistical Significance ◽

Entire Group ◽

Poor Risk ◽

The Poor ◽

Increased Risk ◽

Improvement In Survival ◽

Extent Of Disease

Abstract Two hundred fifty-two previously untreated evaluable patients with multiple myeloma were entered into a study testing a regimen of three intravenous alkylating agents, melphalan, cyclophosphamide, and carmustine (BCNU), given in combination (BCMP) against a regimen employing oral melphalan (MP). Both regimens included a tapering course of prednisone. Objective responses based on the Myeloma Task Force criteria were significantly more frequent in the group receiving BCMP. Survival for the entire group of BCMP-treated patients was not significantly better than that for MP-treated patients (p = 0.62). However, when the survival of the poor-risk (high tumor cell load) group of patients treated with BCMP was compared with the survival of the poor-risk (high tumor cell load) group of patients treated with MP, an improvement in survival attributable to BCMP therapy was seen (p = 0.049 and 0.02, respectively). In the good-risk (low and intermediate tumor cell load) group, BCMP treatment resulted in a trend toward poorer survival, but this did not achieve statistical significance (p = 0.080 and 0.23, respectively). These results indicate that optimal therapy in myeloma may be dependent on the extent of disease at the time of first treatment. Additional studies to explore the effects of treatment intensity and duration are needed in order to design improved myeloma treatment based on the patient's extent of disease.

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Bortezomib (BOR)-Thalidomide-Dexamethasone (VTD) and High-Dose Melphalan (HDM) As First Line Treatment for Multiple Myeloma (MM) Is Associated with a Lower Rate of Second Primary Malignancies (SPMs) Compared to TD Plus HDM

Blood ◽

10.1182/blood.v124.21.1182.1182 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1182-1182 ◽

Cited By ~ 2

Author(s):

Annamaria Brioli ◽

Annalisa Pezzi ◽

Daniele Derudas ◽

Maria Concetta Petti ◽

Beatrice Anna Zannetti ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Alkylating Agents ◽

Statistical Significance ◽

Phase Iii ◽

High Dose ◽

Line Treatment ◽

Increased Risk ◽

Phase Iii Study

Abstract The availability of novel drugs such as immunomodulatory drugs, IMiDs, and proteasome inhibitors, PI, for the front line treatment of Multiple Myeloma (MM) has dramatically changed patients’ outcomes, significantly prolonging progression free survival (PFS) and translating into an extended overall survival (OS). Despite these impressive results, concerns have been raised regarding the possibility that IMiDs (lenalidomide and thalidomide) might increase the risk of developing SPMs, especially when associated with alkylating agents such as melphalan (MEL). It has long been known that the use of MEL can result in an increased incidence of SPMs, and this risk seems to be increased by the association with IMiDs. By the opposite, the use of PI in newly diagnosed MM (NDMM) patients (pts) was not associated with an increased risk of SPMs in a phase III study aimed at comparing BOR, MEL and prednisone (MP) vs MP.[1] Despite these results, the full impact of an upfront treatment containing both a PI and an IMiD in association with high dose MEL still has to be investigated. To address this issue, we have evaluated the incidence of SPMs in pts enrolled in the GIMEMA 26866138-MMY-3006 multicentre phase III study aimed at comparing BOR, thalidomide and dexamethasone (VTD) versus TD as induction before, and consolidation after, a double course of high dose MEL. The trial, conducted in Italy from 2006 to 2008, enrolled 480 transplant eligible NDMM, of which 474 received assigned treatment. Data on the incidence of SPMs are available for 299 pts (63%, 148 VTD and 151 TD). With a median follow up of 73 months, 25/299 pts (8%) developed a SPM: 7 (2%) SPMs were hematologic and 18 (6%) were non hematologic. The median time from trial entry to development of the SPM was 36 months (range 8.4-69.0). The number of pts developing a SPM was lower in VTD arm (5%) compared to TD arm (11%, p=0.068). Among pts developing a SPM, the proportion of solid malignancies was similar between treatment arms (75% and 71% in VTD and TD, respectively). Similarly, the percentages of hematologic SPMs was 25% for VTD pts and 29% for TD. On the overall population, the incidence rate (IR) of developing a SPM was 1% at 1 year and 9.9% at 6 years (yrs). This incidence was significantly lower for patients randomised to VTD compared with patients receiving TD (6% vs 13% at 6 yrs, p=0.037). When looking at the IR of solid tumours we noticed that only 5% of VTD-treated patients developed a solid SPM, as compared to 9.6% in TD; similarly, less hematologic SPMs were observed in the BOR arm (1% vs 4% at 6 yrs for VTD and TD, respectively). When the analysis was performed according to SPMs type, no statistical significance could be demonstrated. Our data compare favourably with data previously reported on the incidence of developing SPMs in NDMM treated with BOR frontline in association with MEL. With a follow up of 6 years, we were able to confirm that treatment with PI is associated with a low risk of developing SPM. Interestingly our data suggest that treatment with PI might decrease the risk of developing a SPM compared to IMiDs based treatment. Randomised trials with PI and IMiDs treatment should prospectively evaluate this issue. References 1. San Miguel, J.F., et al., Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol, 2013. 31(4): p. 448-55. Disclosures Musto: Janssen: Honoraria; Celgene: Honoraria. Cavo:Onyx: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Millenium Pharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau.

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Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease – a Review

Interventional Cardiology Review ◽

10.15420/icr.2012.7.1.37 ◽

2012 ◽

Vol 7 (1) ◽

pp. 37

Author(s):

Donald E Cutlip ◽

Keyword(s):

Percutaneous Coronary Intervention ◽

Coronary Artery ◽

Statistical Significance ◽

Bare Metal Stents ◽

Coronary Intervention ◽

Metal Stents ◽

Increased Risk ◽

Percutaneous Coronary ◽

Patients With Diabetes ◽

The Impact

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.

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COVID-19 and Its Symptoms’ Panoply: A Case-Control Study of 919 Suspected Cases in Locked-Down Ovar, Portugal

Portuguese Journal of Public Health ◽

10.1159/000514925 ◽

2021 ◽

pp. 1-8

Author(s):

Regina Sá ◽

Tiago Pinho-Bandeira ◽

Guilherme Queiroz ◽

Joana Matos ◽

João Duarte Ferreira ◽

...

Keyword(s):

Large Scale ◽

Case Control Study ◽

Statistical Significance ◽

Case Control ◽

Case Definition ◽

Suspected Case ◽

Risk Characteristics ◽

Increased Risk ◽

Wide Range ◽

Control Study

Background: Ovar was the first Portuguese municipality to declare active community transmission of SARS-CoV-2, with total lockdown decreed on March 17, 2020. This context provided conditions for a large-scale testing strategy, allowing a referral system considering other symptoms besides the ones that were part of the case definition (fever, cough, and dyspnea). This study aims to identify other symptoms associated with COVID-19 since it may clarify the pre-test probability of the occurrence of the disease. Methods: This case-control study uses primary care registers between March 29 and May 10, 2020 in Ovar municipality. Pre-test clinical and exposure-risk characteristics, reported by physicians, were collected through a form, and linked with their laboratory result. Results: The study population included a total of 919 patients, of whom 226 (24.6%) were COVID-19 cases and 693 were negative for SARS-CoV-2. Only 27.1% of the patients reporting contact with a confirmed or suspected case tested positive. In the multivariate analysis, statistical significance was obtained for headaches (OR 0.558), odynophagia (OR 0.273), anosmia (OR 2.360), and other symptoms (OR 2.157). The interaction of anosmia and odynophagia appeared as possibly relevant with a borderline statistically significant OR of 3.375. Conclusion: COVID-19 has a wide range of symptoms. Of the myriad described, the present study highlights anosmia itself and calls for additional studies on the interaction between anosmia and odynophagia. Headaches and odynophagia by themselves are not associated with an increased risk for the disease. These findings may help clinicians in deciding when to test, especially when other diseases with similar symptoms are more prevalent, namely in winter.

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Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study

Archives of Dermatological Research ◽

10.1007/s00403-021-02211-4 ◽

2021 ◽

Author(s):

Khalaf Kridin ◽

Jennifer E. Hundt ◽

Ralf J. Ludwig ◽

Kyle T. Amber ◽

Dana Tzur Bitan ◽

...

Keyword(s):

Bullous Pemphigoid ◽

Statistical Significance ◽

Large Population ◽

Underlying Mechanism ◽

Population Based ◽

Control Subjects ◽

Increased Risk ◽

Bidirectional Association ◽

History Of ◽

Incident Cases

AbstractThe association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case–control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14–2.06). This risk was higher among males (OR 1.66; 95% CI 1.09–2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11–2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14–2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73–1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.

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Impact of Diagnosed and Undiagnosed Respiratory Pseudomonas on VAP and VAE During Long-Term Acute Care

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.823 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s258-s259

Author(s):

James Harrigan ◽

Ebbing Lautenbach ◽

Emily Reesey ◽

Magda Wernovsky ◽

Pam Tolomeo ◽

...

Keyword(s):

Bacterial Community ◽

Acute Care ◽

Statistical Significance ◽

Rrna Gene ◽

Care Hospital ◽

16S Sequencing ◽

Increased Risk ◽

Wide Range ◽

The Impact

Background: Clinically diagnosed ventilator-associated pneumonia (VAP) is common in the long-term acute-care hospital (LTACH) setting and may contribute to adverse ventilator-associated events (VAEs). Pseudomonas aeruginosa is a common causative organism of VAP. We evaluated the impact of respiratory P. aeruginosa colonization and bacterial community dominance, both diagnosed and undiagnosed, on subsequent P. aeruginosa VAP and VAE events during long-term acute care. Methods: We enrolled 83 patients on LTACH admission for ventilator weaning, performed longitudinal sampling of endotracheal aspirates followed by 16S rRNA gene sequencing (Illumina HiSeq), and bacterial community profiling (QIIME2). Statistical analysis was performed with R and Stan; mixed-effects models were fit to relate the abundance of respiratory Psa on admission to clinically diagnosed VAP and VAE events. Results: Of the 83 patients included, 12 were diagnosed with P. aeruginosa pneumonia during the 14 days prior to LTACH admission (known P. aeruginosa), and 22 additional patients received anti–P. aeruginosa antibiotics within 48 hours of admission (suspected P. aeruginosa); 49 patients had no known or suspected P. aeruginosa (unknown P. aeruginosa). Among the known P. aeruginosa group, all 12 patients had P. aeruginosa detectable by 16S sequencing, with elevated admission P. aeruginosa proportional abundance (median, 0.97; IQR, 0.33–1). Among the suspected P. aeruginosa group, all 22 patients had P. aeruginosa detectable by 16S sequencing, with a wide range of admission P. aeruginosa proportional abundance (median, 0.0088; IQR, 0.00012–0.31). Of the 49 patients in the unknown group, 47 also had detectable respiratory Psa, and many had high P. aeruginosa proportional abundance at admission (median, 0.014; IQR, 0.00025–0.52). Incident P. aeruginosa VAP was observed within 30 days in 4 of the known P. aeruginosa patients (33.3%), 5 of the suspected P. aeruginosa patients (22.7%), and 8 of the unknown P. aeruginosa patients (16.3%). VAE was observed within 30 days in 1 of the known P. aeruginosa patients (8.3%), 2 of the suspected P. aeruginosa patients (9.1%), and 1 of the unknown P. aeruginosa patients (2%). Admission P. aeruginosa abundance was positively associated with VAP and VAE risk in all groups, but the association only achieved statistical significance in the unknown group (type S error <0.002 for 30-day VAP and <0.011 for 30-day VAE). Conclusions: We identified a high prevalence of unrecognized respiratory P. aeruginosa colonization among patients admitted to LTACH for weaning from mechanical ventilation. The admission P. aeruginosa proportional abundance was strongly associated with increased risk of incident P. aeruginosa VAP among these patients.Funding: NoneDisclosures: None

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Is a Four-Week Ketogenic Diet an Effective Nutritional Strategy in CrossFit-Trained Female and Male Athletes?

Nutrients ◽

10.3390/nu13030864 ◽

2021 ◽

Vol 13 (3) ◽

pp. 864 ◽

Cited By ~ 1

Author(s):

Krzysztof Durkalec-Michalski ◽

Paulina M. Nowaczyk ◽

Natalia Główka ◽

Anna Ziobrowska ◽

Tomasz Podgórski

Keyword(s):

Ketogenic Diet ◽

Aerobic Capacity ◽

Alanine Aminotransferase ◽

Aerobic Performance ◽

Entire Group ◽

Acid Base Balance ◽

Acid Base ◽

Relevant Effect ◽

Increased Risk ◽

Specific Performance

This single-arm interventional study examined the effect of a 4-week ketogenic diet (KD) on aerobic capacity and discipline-specific performance in female (n = 11) and male (n = 11) CrossFit-trained athletes. The participants performed incremental cycling (ICT) and Fight Gone Bad (FGB) tests after consuming a customary diet and a KD. Pre- and post-ICT exercise blood samples were also analysed. Consuming a KD had a slight impact on aerobic capacity and no relevant effect on CrossFit-specific performance. In females, consuming a KD led to an 10.4% decrease in peak oxygen uptake during the ICT (p = 0.027) and resulted in certain alterations in haematological parameters (haemoglobin (HGB), mean corpuscular HGB, and mean corpuscular HGB concentration). Furthermore, in males, alanine aminotransferase activity increased with a simultaneous improvement in the post-ICT blood acid–base balance after consuming a KD. The pre-exercise bilirubin concentration was also elevated in the entire group after consuming a KD. In conclusion, female CrossFit-trained athletes seem to be prone to aerobic performance decrements and increased risk of developing haematological disturbances when consuming a KD. In males who consumed a KD, there was an undesirable alanine aminotransferase elevation and a small tendency towards improved acid–base status. Moreover, consuming a KD had no effect on discipline-specific performance in CrossFit-trained athletes.

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Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series

Urologia Journal ◽

10.1177/03915603211035191 ◽

2021 ◽

pp. 039156032110351

Author(s):

Alessandro Uleri ◽

Rodolfo Hurle ◽

Roberto Contieri ◽

Pietro Diana ◽

Nicolòmaria Buffi ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Advanced Disease ◽

Independent Predictor ◽

Small Sample Size ◽

Statistical Significance ◽

Locally Advanced ◽

Small Sample ◽

Locally Advanced Disease ◽

Increased Risk

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

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How Is Geriatric Assessment Used in Clinical Practice for Older Adults With Cancer? A Survey of Cancer Providers by the American Society of Clinical Oncology

JCO Oncology Practice ◽

10.1200/op.20.00442 ◽

2020 ◽

pp. OP.20.00442

Author(s):

William Dale ◽

Grant R. Williams ◽

Amy R. MacKenzie ◽

Enrique Soto-Perez-de-Celis ◽

Ronald J. Maggiore ◽

...

Keyword(s):

Older Adults ◽

Geriatric Assessment ◽

Online Survey ◽

Task Force ◽

Statistical Significance ◽

Geriatric Oncology ◽

Perceived Barriers ◽

Patients With Cancer ◽

Change Behavior ◽

American Society

PURPOSE: For patients with cancer who are older than 65 years, the 2018 ASCO Guideline recommends geriatric assessment (GA) be performed. However, there are limited data on providers’ practices using GA. Therefore, ASCO’s Geriatric Oncology Task Force conducted a survey of providers to assess practice patterns and barriers to GA. METHODS: Cancer providers treating adult patients including those ≥ 65 years completed an online survey. Questions included those asking about awareness of ASCO’s Geriatric Oncology Guideline (2018), use of validated GA tools, and perceived barriers to using GA. Descriptive statistics and statistical comparisons between those aware of the Guideline and those who were not were conducted. Statistical significance was set at P < .05. RESULTS: Participants (N = 1,277) responded between April 5 and June 5, 2019. Approximately half (53%) reported awareness of the Guideline. The most frequently used GA tools, among those aware of the Guideline and those who were not, assessed functional status (69% v 50%; P < .001) and falls (62% v 45%; P < .001). Remaining tools were used < 50% of the time, including tools assessing weight loss, comorbidities, cognition, life expectancy, chemotherapy toxicity, mood, and noncancer mortality risk. GA use was two to four times higher among those who are aware of the Guideline. The most frequent barriers for those who reported being Guideline aware were lack of resources, specifically time (81.7%) and staff (77.0%). In comparison, those who were unaware of the Guideline most often reported the following barriers: lack of knowledge or training (78.4%), lack of awareness about tools (75.2%), and uncertainty about use of tools (75.0%). CONCLUSION: Among providers caring for older adults, 52% were aware of the ASCO Guideline. Some domains were assessed frequently (eg, function, falls), whereas other domains were assessed rarely (eg, mood, cognition). Guideline awareness was associated with two to four times increased use of GA and differing perceived barriers. Interventions facilitating Guideline-consistent implementation will require various strategies to change behavior.

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