Nivolumab-Induced Pericardial Tamponade: A Case Report and Discussion.

Nivolumab, a programmed death 1 (PD1) inhibitor, belongs to a family of drugs known as immune checkpoint inhibitors that share a similar toxicity profile, which includes rash, pruritus, colitis, hepatitis, pneumonitis and thyroid dysfunction. Nivolumab has a proven efficacy in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. We present the case of a 67-year-old male patient with metastatic squamous cell carcinoma of the lung who suffered from a massive pericardial effusion secondary to treatment with nivolumab, which he began in June 2015. After five cycles the patient was hospitalized due to acute respiratory failure requiring mechanical ventilation. An echocardiogram revealed a massive pericardial effusion with tamponade. After pericardiocentesis and corticosteroid treatment, the patient's condition improved rapidly. A CT scan revealed a response of the tumor. Although anti-PD1 treatment is usually regarded as less toxic than chemotherapy, a wide spectrum of life-threatening immune-related side effects may still occur and clinical vigilance is required.

Perceptions and attitudes of medical oncologists regarding fertility preservation and pregnancy in high-risk cancer patients: A survey among Canadian medical oncologists.

PURPOSE: Infertility is a critical late toxicity that impacts adolescent and young adult (AYA, ages 15-39 years) cancer survivors. International oncology societies recommend discussing fertility preservation (FP) for all AYA patients, regardless of stage or prognosis. We aim to understand Canadian medical oncologists' perceptions, attitudes, and knowledge toward FP and pregnancy in patients with cancer, including advanced stages and high risk for recurrence. METHODS: An anonymous electronic survey utilizing hypothetical scenarios was sent to medical oncologists in the province of Ontario, Canada. Descriptive statistics were used to summarize all data. Logistic regression models were constructed to identify factors that predicted FP discussions and referrals. RESULTS: The survey was received by 91 medical oncologists, and the response rate was 44%. Fifty-eight percent of respondents offer FP for all patients. Physicians are more likely to refer patients for FP before curative intent therapy than before palliative chemotherapy (95% vs. 39.5%, p < 0.001). Most respondents (86%) are comfortable discussing FP; however, only 31% self-reported feeling up-to-date on knowledge of current FP methods. Female physicians were more likely to report up-to-date knowledge and confidence discussing FP with patients. Forty percent of respondents identified that concerns about the welfare of the resulting offspring should not be a cause for denying patients assistance in reproduction. CONCLUSION: There is a significant difference in physician attitude toward offering FP based on the cancer stage. Increased awareness of standard of care guidelines and resources for difficult situations may improve the frequency of discussions about FP in motivated cancer patients.

A population-based study of factors associated with systemic treatment in advanced prostate cancer decedents.

INTRODUCTION: Life-prolonging therapies (LPTs) are rapidly evolving for the treatment of advanced prostate cancer, although factors associated with real-world uptake are not well characterized. METHODS: In this cohort of prostate-cancer decedents, we analyzed factors associated with LPT access. Population-level databases from Ontario, Canada identified patients 65 years or older with prostate cancer receiving androgen deprivation therapy and who died of prostate cancer between 2013 and 2017. Univariate and multivariable analyses assessed the association between baseline characteristics and receipt of LPT in the 2 years prior to death. RESULTS: Of 3575 patients who died of prostate cancer, 40.4% (n = 1443) received LPT, which comprised abiraterone (66.3%), docetaxel (50.3%), enzalutamide (17.2%), radium-223 (10.0%), and/or cabazitaxel (3.5%). Use of LPT increased by year of death (2013: 22.7%, 2014: 31.8%, 2015: 41.8%, 2016: 49.1%, and 2017: 57.9%, p < 0.0001), driven by uptake of all agents except docetaxel. Adjusted odds of use were higher for patients seen at Regional Cancer Centers (OR: 1.8, 95% CI: 1.5-2.1) and who received prior prostate-directed therapy (OR: 1.3, 95% CI: 1.0-1.5), but lower with advanced age (≥85: OR: 0.54, 95% CI:0.39-0.75), increased chronic conditions (≥6: OR: 0.62, 95% CI: 0.43-0.92), and long-term care residency (OR: 0.38, 95% CI: 0.17-0.89). Income, stage at presentation, and distance to the cancer center were not associated with LPT uptake. CONCLUSION: In this cohort of prostate cancer-decedents, real-world uptake of novel prostate cancer therapies occurred at substantially higher rates for patients receiving care at Regional Cancer Centers, reinforcing the potential benefits for treatment access for patients referred to specialist centers.

Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Long-Term Results of a Prospective Phase II Study.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol®-Modified citrus pectin (P-MCP) is a food supplement categorized as GRAS (Generally Recognized As Safe) by the FDA. It is a competitive inhibitor of the galectin-3 protein, which is involved in cancer pathogenesis. In an early report of the present phase 2 study, P-MCP treatment for 6 months led to prostate-specific antigen doubling time (PSADT) improvement in 75% of patients with BRPC-M0. Herein, we report the second long-term treatment phase of an additional 12 months of P-MCP therapy (4.8 g × 3/day orally) in patients without disease progression after the initial 6 months of therapy. Of the 46 patients that entered the second treatment phase, 7 patients withdrew consent and decided to continue therapy out of pocket, and 39 initiated the second treatment phase. After a total of 18 months of P-MCP treatment, 85% (n = 33) had a durable long-term response, with 62% (n = 24) showing decreased/stable PSA, 90% (n = 35) PSADT improvement, and all with negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long-term durable efficacy and is safe in BRPC-M0.

Erdafitinib treatment in metastatic urothelial carcinoma: a real-world analysis.

Background: Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor is a standard post chemotherapy advanced treatment line for metastatic urothelial carcinoma harboring FGFR2/3 genomic alterations. It was approved based on a phase 2 clinical trial, revealing a 40% response rate, and 13.8 months overall survival. These FGFR genomic alterations are uncommon. Thus, real-world data on erdafitinb use is scant. We herein describe erdafitinib treatment outcome in a real world patient cohort. Methods: We retrospectively reviewed the data of patients treated with erdafitinib from 9 Israeli medical centers. Results: Twenty-five patients with metastatic urothelial carcinoma (median age 73, 64% male, 80% with visceral metastases) were treated with erdafitinib between January 2020 to October 2022. A clinical benefit (complete response 12%, partial response 32%, stable disease 12%) was seen in 56%. Median progression-free survival was 2.7 months, and median overall survival 6.73 months. Treatment related toxicity ≥ grade 3 occurred in 52%, and 32% discontinued therapy due to adverse events. Conclusions: Erdafitinib therapy is associated with a clinical benefit in the real world setting, and associated with similar toxicity as reported in prospective clinical trials.

Estimation of left ventricular function using a novel acoustic-based device.

BACKGROUND: We examined the feasibility of estimating left ventricular ejection fraction (LVEF) by a novel acoustic-based device [vibration response imaging (VRI); Deep Breeze]. METHODS: One hundred and forty-one subjects (117 patients and 24 healthy volunteers; age 55 ± 15 years, 82% men) were examined by both VRI and echocardiography. LVEF was determined by echocardiography (echo-LVEF) using the biplane Simpson's method. Low-frequency acoustic signals (10-70 Hz) were recorded by VRI from the left posterior thorax by a matrix of 36 microphones during 8 s of breath holding, and an electrocardiogram was recorded simultaneously. The acoustic signals were processed digitally, and an algorithm designed to estimate LVEF was developed (VRI-LVEF), based on a combination of multiple acoustic (systolic and diastolic acoustic signals, beat-to-beat variability of acoustic signals and propagation of acoustic signals throughout the matrix), electrocardiographic and clinical parameters. RESULTS: Mean echo-LVEF was 51 ± 15% (range, 11-76%). Echo-LVEF was reduced (< 50%) in 55 subjects (39%) and severely reduced (< 35%) in 28 subjects (20%). VRI-LVEF calculated by a multivariate algorithm correlated significantly with echo-LVEF (R(2) = 0·59; P < 0·001). VRI-LVEF accurately predicted the presence of reduced (< 50%) or severely reduced (< 35%) echo-LVEF, with sensitivities of 84% and 82%, specificities of 86% and 91%, positive predictive values of 79% and 70% and negative predictive values of 89% and 95%, respectively. CONCLUSIONS: LVEF can be estimated using a novel acoustic-based device. This device may assist in triage of patients according to LVEF prior to definitive assessment of LVEF by echocardiography.

Attitudes towards open-label versus placebo-control designs in oncology randomized trials: A survey of medical oncologists.

RATIONALE, AIMS AND OBJECTIVES: Randomized trials are considered the gold standard when assessing the efficacy of new therapeutic agents. In clinical situations where no standard of care therapy is approved, randomized trials usually compare experimental agents to either a placebo or an open-label nonintervention arm (i.e., best supportive care). We surveyed Canadian medical oncologists to understand their attitudes towards each design. METHODS: Members of the Canadian Association of Medical Oncologists were invited to participate in an anonymous online survey. Standardized case scenarios were used to determine participants' attitudes regarding the role of open-label versus placebo-controlled trials. RESULTS: A total of 322 medical oncologists and trainees were invited to participate and 86 responded (response rate 27%). Fifty-one (59%) believed that open-label trials are an acceptable alternative to placebo-controlled design when investigating a therapeutic agent in the adjuvant setting. Thirty-eight (49%) deemed it acceptable to compare the investigational agent to an open-label arm instead of a placebo to assess progression-free survival in the metastatic setting. Twenty-eight (38%) of respondents felt that open-label design was acceptable when assessing the quality of life endpoint. Most physicians were unsure whether the US Food and Drug Administration require a placebo-controlled arm in oncology trials. CONCLUSION: Canadian medical oncologists participating in this survey are divided in their opinions regarding the acceptability of an open-label design in randomized-controlled trials, where no standard therapy is approved. Clearer guidance from regulatory bodies on the adequacy of different trial designs is needed.

Efficacy of treatment for glioblastoma multiforme in elderly patients (65+): a retrospective analysis.

BACKGROUND: Glioblastoma multiforme (GBM) is an ultimately fatal disease that affects patients of all ages. Elderly patients (65 years and older) constitute a special subgroup of patients characterized by a worse prognosis and frequent comorbidities. OBJECTIVES: To assess the efficacy of different treatment modalities in terms of survival in elderly patients with GBM. METHODS: Using retrospective analysis, we extracted, anonymized and analyzed the files of 74 deceased patients (aged 65 or older) treated for GBM in a single institution. RESULTS: Mean survival time was 8.97 months and median survival time 7.68 months. Patients who underwent tumor resection had a mean survival of 11.83 months, as compared to patients who underwent no surgical intervention or only biopsy and had a mean survival of 5.22 months (P < 0.0001). Patients who underwent full radiation treatment had amean survival of 11.31 months, compared to patients who received only partial radiotherapy or none at all and had a mean survival of 4.09 months (P < 0.0001). Patients who underwent chemotherapy had a mean survival of 12.4 months, compared to patients who did not receive any chemotherapy andhad a mean survival of 5.89 months (P < 0.001). CONCLUSIONS: Age alone should not be a factor in the decision on which treatment should be given. Treatment should be individualized to match the patient's overall condition and his or her wishes, while taking into consideration the better overall prognosis expected with aggressive treatment.

Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Results of a Prospective Phase II Study.

Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis. Based on PSA dynamics, we report on the safety and the primary outcome analysis of a prospective phase II study of P-MCP in non-metastatic BRPC based. Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months. The primary endpoint was the rate without PSA progression and improved PSA doubling time (PSADT). Secondary endpoints were the rate without radiologic progression and toxicity. Patients that did not progress by PSA and radiologically at six months continued for an additional twelve months. After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.

Active Surveillance in Metastatic Renal Cell Carcinoma: Results From the Canadian Kidney Cancer Information System.

BACKGROUND: Active surveillance (AS) is a commonly used strategy in patients with slow-growing disease. We aimed to assess the outcomes and safety of AS in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: We used the Canadian Kidney Cancer information system (CKCis) to identify patients with mRCC diagnosed between January 1, 2011, and December 31, 2016. The AS strategy was defined as (1) the start of systemic therapy ≥ 6 months after diagnosis of mRCC, or (2) never receiving systemic therapy for mRCC with an overall survival (OS) of ≥1 year. Patients starting systemic treatment <6 months after diagnosis of mRCC were defined as receiving immediate systemic treatment. OS and time until first-line treatment failure (TTF) were compared between the two cohorts. RESULTS: A total of 853 patients met the criteria for AS (cohort A). Of these, 364 started treatment >6 months after their initial diagnosis (cohort A1) and 489 never started systemic therapy (cohort A2); 827 patients received immediate systemic treatment (cohort B). The 5-year OS probability was significantly greater for cohort A than for cohort B (70% vs. 33.6%; P < .0001). After adjusting for International Metastatic RCC Database Consortium risk criteria and age, both OS (hazard ratio [HR] = 0.58; 95% confidence interval [CI], 0.47-0.70; P < .0001) and TTF (HR = 0.72; 95% CI, 0.60-0.85; P = .0002) were greater in cohort A1 compared with B. For cohort A1, the median time on AS was 14.2 months (range, 6-71). CONCLUSIONS: Based on the largest analysis of AS in mRCC to date, our data suggest that a subset of patients may be safely observed without immediate initiation of systemic therapy.

A randomised trial of 4- versus 12-weekly administration of bone-targeted agents in patients with bone metastases from breast or castration-resistant prostate cancer.

BACKGROUND: Optimal dosing of bone-targeted agents (BTAs), in patients with bone metastases remains an important clinical question. This trial compared 4-weekly versus 12-weekly therapy. PATIENTS AND METHODS: Patients with bone metastases from breast or castration-resistant prostate cancer (CRPC), who were going to start or already on BTAs, were randomised 1:1 to 4-weekly or 12-weekly BTA treatment for one year. Primary end point was change in health-related quality of life (HRQoL)-physical function European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30). Secondary end points included pain (EORTC-QLQ-BM22), global health status (EORTC-QLQ-C30), symptomatic skeletal events (SSEs) rates and time to SSEs. Primary analysis was per protocol and a non-inferiority margin of 5 points was used. RESULTS: Of 263 patients (160 breast cancer, 103 CRPC), 133 (50.6%) and 130 (49.4%) were randomised to the 4- and 12-weekly groups, respectively. BTAs included denosumab (56.3%), zoledronate (24.0%) and pamidronate (19.8%). Using repeated-measures analysis, across all time points, patients in the 4-weekly arm had a mean HRQL-physical subdomain score which was 1.2 (95% confidence interval: -1.6 to 4.0) higher than the 12-weekly arm. The study met the definition of non-inferiority for our primary outcome. Secondary outcomes showed no significant difference in scores for pain, global health status, SSE rates and SSE-free survival between arms. Subgroup analyses for cancer type, prior BTA use or BTA type showed no significant difference between arms. CONCLUSION: These results in addition to those previously reported for de-escalating zoledronate and systematic reviews in both breast and prostate cancers, would support that de-escalation of commonly used BTAs is a reasonable treatment option.

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer.

BACKGROUND: Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis, we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS). METHODS: All patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 and September 2017 were identified. The association between relative dose intensity (RDI) and OS was assessed using univariate and multivariable Cox model adjusting for age, Gleason score, burden of disease, visceral involvement, de novo metastases and baseline prostate-specific antigen (PSA). RESULTS: Eighty-one patients were included in the analysis. Only 35 patients (43%) were able to complete the planned treatment with a RDI of at least 90%. On a univariate analysis, higher RDI and number of cycles of docetaxel received were associated with longer OS. For every 10% decrease in RDI, the risk of death increased by 23% (HR 1.23, 95% CI 1.09-1.4, P = 0.001). For every increment of one cycle (and up to six), the risk of death decreased by 27% (HR 0.73, 95% CI 0.61-0.88, P = 0.001). On multivariate analysis, reduced RDI was the only predictor significantly associated with OS (HR 1.18, 95% CI 1.02-1.36, P = 0.026). CONCLUSIONS: Our study suggests that in mCSPC, reduced docetaxel RDI is associated with shorter survival. Unnecessary dose reductions, treatment delays and early discontinuation should be avoided. Granulocyte colony-stimulating factor may be considered to maintain standard DI.

Identification of Hypermutation and Defective Mismatch Repair in ctDNA from Metastatic Prostate Cancer.

PURPOSE: DNA mismatch repair defects (MMRd) and tumor hypermutation are rare and under-characterized in metastatic prostate cancer (mPC). Furthermore, because hypermutated MMRd prostate cancers can respond to immune checkpoint inhibitors, there is an urgent need for practical detection tools. EXPERIMENTAL DESIGN: We analyzed plasma cell-free DNA-targeted sequencing data from 433 patients with mPC with circulating tumor DNA (ctDNA) purity ≥2%. Samples with somatic hypermutation were subjected to 185 × whole-exome sequencing and capture of mismatch repair gene introns. Archival tissue was analyzed with targeted sequencing and IHC. RESULTS: Sixteen patients (3.7%) had somatic hypermutation with MMRd etiology, evidenced by deleterious alterations in MSH2, MSH6, or MLH1, microsatellite instability, and characteristic trinucleotide signatures. ctDNA was concordant with mismatch repair protein IHC and DNA sequencing of tumor tissue. Tumor suppressors such as PTEN, RB1, and TP53 were inactivated by mutation rather than copy-number loss. Hotspot mutations in oncogenes such as AKT1, PIK3CA, and CTNNB1 were common, and the androgen receptor (AR)-ligand binding domain was mutated in 9 of 16 patients. We observed high intrapatient clonal diversity, evidenced by subclonal driver mutations and shifts in mutation allele frequency over time. Patients with hypermutation and MMRd etiology in ctDNA had a poor response to AR inhibition and inferior survival compared with a control cohort. CONCLUSIONS: Hypermutated MMRd mPC is associated with oncogene activation and subclonal diversity, which may contribute to a clinically aggressive disposition in selected patients. In patients with detectable ctDNA, cell-free DNA sequencing is a practical tool to prioritize this subtype for immunotherapy.See related commentary by Schweizer and Yu, p. 981.

The timing of docetaxel initiation in metastatic castrate-sensitive prostate cancer and the rate of chemotherapy-induced toxicity.

Docetaxel pharmacokinetics are affected by androgen deprivation therapy (ADT), which is attributed to changes in liver metabolism induced by castration. In this retrospective analysis, we assessed whether initiating docetaxel treatment in close proximity to the start of ADT therapy for metastatic castrate-sensitive prostate cancer (mCSPC) is associated with more treatment-related toxicity. We identified all patients with mCSPC treated at The Ottawa Hospital that received docetaxel chemotherapy between June 2014 and September 2017. For each patient, we calculated the time to chemotherapy (TTC) interval between the start of ADT and the first cycle of docetaxel. We checked for an association between TTC and febrile neutropenia (FN), toxicity-induced dose reduction, toxicity-induced treatment delay, and toxicity-induced treatment discontinuation. Eighty-three patients were identified. The median TTC was 67 days (range 3-189). Twenty-three patients (27.7%) experienced FN. Docetaxel toxicity resulted in 8 patients (9.6%) having their treatment delayed, 30 patients (36.1%) having their dose reduced and 18 (21.6%) having their treatment discontinued before completing the scheduled 6 cycles. No correlation was found between the TTC and FN (P = 0.99), docetaxel dose reduction (P = 0.95), treatment delay (P = 0.06), and treatment discontinuation (P = 0.88). The timing of docetaxel treatment initiation in relation to ADT initiation in patients with mCSPC did not affect the rate of treatment-related toxicity. Therefore, there is no indication for upfront chemotherapy delay from start of ADT unless clinical factors warrant a delay in starting chemotherapy. A higher than expected FN rate was identified, and primary prophylaxis should be considered.

Validation of automatic wheeze detection in patients with obstructed airways and in healthy subjects.

Computerized lung-sound analysis is a sensitive and quantitative method to identify wheezing by its typical pattern on spectral analysis. We evaluated the accuracy of the VRI, a multi-sensor, computer-based device with an automated technique of wheeze detection. The method was validated in 100 sound files from seven subjects with asthma or chronic obstructive pulmonary disease and seven healthy subjects by comparison of auscultation findings, examination of audio files, and computer detection of wheezes. Three blinded physicians identified 40 sound files with wheezes and 60 sound files without wheezes. Sensitivity and specificity were 83% and 85%, respectively. Negative predictive value and positive predictive value were 89% and 79%, respectively. Overall inter-rater agreement was 84%. False positive cases were found to contain sounds that simulate wheezes, such as background noises with high frequencies or strong noises from the throat that could be heard and identified without a stethoscope. The present findings demonstrate that the wheeze detection algorithm has good accuracy, sensitivity, specificity, negative predictive value and positive predictive value for wheeze detection in regional analyses with a single sensor and multiple sensors. Results are similar to those reported in the literature. The device is user-friendly, requires minimal patient effort, and, distinct from other devices, it provides a dynamic image of breath sound distribution with wheeze detection output in less than 1 minute.

Dynamic visualization of lung sounds with a vibration response device: a case series.

BACKGROUND: The field of computer-assisted mapping of lung sounds is constantly evolving and several devices have been developed in this field. OBJECTIVES: Our objective was to evaluate a new computer-assisted lung sound imaging system, 'vibration response imaging' (VRI), that records and creates a dynamic image of breath sounds. We postulated that the VRI display format would qualitatively and quantitatively reveal breath sound distribution throughout the breathing cycle. METHODS: Lung sounds were recorded from 5 healthy adults and 14 patients with various respiratory illnesses using VRI. The lung sounds were processed by the VRI software, which incorporates an algorithm to convert breath sounds in the frequency range of 150-250 Hz to a dynamic image and quantitative assessment of breath sound distribution. RESULTS: Images and quantifications from recordings of the healthy adults showed distinct patterns for inspiration and expiration. Images and quantifications from the subjects with respiratory illness differed substantially from the images of the healthy subjects. Both healthy and pathological subjects presented some expected characteristics of breath sound distribution. CONCLUSIONS: The VRI device may provide a new perspective in acoustic imaging and quantification of breath sounds by adding aspects of time analysis and quantification of distribution to existing methods. Further studies will be required in order to establish reliability of repeated recordings and to validate the sensitivity of the system in detecting various lung pathologies.

Safety and Efficacy of an Autologous Blood Clot Product in the Management of Texas 1A or 2A Neuropathic Diabetic Foot Ulcers: A Prospective, Multicenter, Open Label Pilot Study.

OBJECTIVE: This pilot study evaluates safety in terms of the occurrence of adverse events (AEs) as well as the efficacy in terms of complete wound healing rates of a blood clot product when applied to chronic neuropathic diabetic foot ulcers (DFUs). MATERIALS AND METHODS: Participants were chosen from patients with DFUs visiting the wound care clinic. Up to 10 mL of blood drawn from each participant was injected into the product's clotting tray. Within 12 minutes, the blood clot product was formed, applied to the single DFU of each participant, and covered with primary and secondary dressings. Patients received up to 12 blood clot product applications every 5 to 9 days for up to 12 weeks. RESULTS: Twenty patients were enrolled; 20 were analyzed in the intent-to-treat (ITT) population and 18 were in the per-protocol (PP) population. Thirty-two AEs occurred (only 2 were possibly device related). The mean AE rate for both the ITT and PP populations was 1.6. The proportion of wounds healed in the ITT and PP populations was 13 out of 20 (65%) and 13 out of 18 (72.2%), respectively. Percentage area reduction (PAR) for the ITT population at 4 and 12 weeks was 61.6% and 67.1%, respectively; the PARs for the PP population were 60.3% and 76.2% at 4 and 12 weeks, respectively. Mean times to wound healing were 59 days and 56 days in the ITT and PP populations, respectively. CONCLUSIONS: This study demonstrates that the blood clot product is safe and efficacious for treating DFUs.

Breath sound distribution images of patients with pneumonia and pleural effusion.

OBJECTIVE: To determine whether breath sound distribution maps can differentiate between patients with pneumonia or pleural effusion versus healthy controls. METHODS: We recorded breath sounds from 20 patients conventionally diagnosed as having pleural effusion, 20 patients conventionally diagnosed as having pneumonia, and 60 healthy controls, of whom 20 served as a learning sample. All subjects were examined with a computer-based multi-sensor breath sound mapping device that records, analyzes, and displays a dynamic map of breath sound distribution. The physicians who interpreted the breath sound images were first trained in identifying common characteristics of the images from the learning sample of normals. Then the images from the 40 patients and the 40 controls were interpreted as either normal or abnormal. RESULTS: In the normal images, the left and right lung images developed synchronously and had similar size, shape, and intensity. The sensitivity and specificity of blinded differentiation between normal and abnormal images when the physician interpreter did not know the patient's workup were 82.5% and 80%, respectively. The sensitivity and specificity of blinded detection of normal and abnormal images when the interpreter did know the patient' workup were 90% and 88%, respectively. CONCLUSIONS: Computerized dynamic imaging of breath sounds is a sensitive and specific tool for distinguishing pneumonia or pleural effusion from normal lungs. The role of computerized breath sound analysis for diagnosis and monitoring of lung diseases needs further evaluation.

Efficacy and Safety of a Novel Autologous Wound Matrix in the Management of Complicated, Chronic Wounds: A Pilot Study.

INTRODUCTION: The objective of this pilot study was to evaluate the efficacy and safety of a novel method using an autologous whole blood clot formed with the RedDress Wound Care System (RD1, RedDress Ltd, Israel), a provisional whole blood clot matrix used in the treatment of chronic wounds of various etiologies. METHODS AND MATERIALS: Patients were treated at the bedside with the whole blood clot matrix. Blood was withdrawn from each patient using citrate, mixed with a calcium gluconate/kaolin suspension, and injected into an RD1 clotting tray. Within 10 minutes, a clot was formed, placed upon the wound, and fixed with primary and secondary dressings. Wounds were redressed weekly with a whole blood clot matrix. Treatment was terminated when complete healing was achieved, or when the clinician determined that the wound could not further improve without additional invasive procedures. RESULTS: Seven patients with multiple and serious comorbidities and 9 chronic wounds were treated with 35 clot matrices. Complete healing was achieved in 7 of 9 wounds (78%). In 1 venous ulcer with a nonhealing fistula, 77% healing was achieved. Treatment was terminated in 1 pressure ulcer at 82% closure, because an unexpected mechanical trauma resulted in deterioration; this was the only adverse event reported, unrelated to the product. No systemic adverse events occurred. CONCLUSIONS: This pilot study demonstrates the in vitro autologous whole blood clot matrix is effective and safe for treating patients with chronic wounds of different etiologies. A larger clinical trial is needed to assess the relative success rate of the matrix in different types of wounds in a diverse population with comorbidities.