Objective The anatomic and physiologic constraints for pediatric cavopulmonary assist differ markedly from adult Fontan circulations owing to smaller vessel sizes and risk of elevated pulmonary ...resistance. In this study, hemodynamic and hemolysis performance of a catheter-based viscous impeller pump (VIP) to power the Fontan circulation is assessed at a pediatric scale (∼15 kg) and performance range (0-30 mm Hg). Methods Computer simulation and mock circulation studies were conducted to assess the hydraulic performance, acute hemodynamic response to different levels VIP support, and the potential for vena caval collapse. Computational fluid dynamics simulations were used to estimate VIP hydraulic performance, shear rates, and potential for hemolysis. Hemolysis was quantified in a mock loop with fresh bovine blood. Results A VIP augmented 4-way total cavopulmonary connection flow at pediatric scales and restored systemic pressures and flows to biventricular values, without causing flow obstruction or suction. VIP generated flows up to 4.1 L/min and pressure heads of up to 38 mm Hg at 11,000 rpm. Maximal shear rate was 160 Pa, predicting low hemolysis risk. Observed hemolysis was low with plasma free hemoglobin of 11.4 mg · dL−1 · h−1. Conclusions A VIP will augment Fontan cavopulmonary flow in the proper pressure and flow ranges, with low hemolysis risk under more stringent pediatric scale and physiology compared with adult scale. This technology may be developed to simultaneously reduce systemic venous pressure and improve cardiac output after stage 2 or 3 Fontan repair. It may serve to compress surgical staging, lessening the pathophysiologic burden of repair.
Single agent PD-1 inhibitors have yielded durable responses in a minority of gastroesophageal cancers. Radiation therapy has been recognized to promote antitumor immune responses and may synergize ...with anti-PD-1 agents. We sought to evaluate if combining palliative radiation therapy with pembrolizumab can augment antitumor immune responses in gastroesophageal cancer.
Patients had metastatic gastroesophageal cancer with indication for palliative radiation therapy with ≥2 disease sites outside of the radiation field assessable for abscopal response and biopsies for laboratory correlative analyses. Palliative radiation was delivered to a dose of 30 Gy over 10 fractions. Pembrolizumab, 200 mg, was administered concurrently intravenously every 3 weeks until disease progression, unacceptable toxicity, or study withdrawal, for up to 2 years. Endpoints included PD-L1 expression in pre- and posttreatment biopsies and abscopal objective response rate per Response Evaluation Criteria in Solid Tumors.
Of 14 enrolled patients, the objective response rate was 28.6% (95% confidence interval, 8.4%-58.1%), and the median duration of response was not reached (95% confidence interval, 6.9-NR months). Overall, 2 patients had treatment-related grade 3 to 4 adverse events with no grade 5 events. One patient discontinued therapy due to grade 4 colitis. We did not observe an association between radiation and abscopal changes in PD-L1 expression via assessment of an analogous PD-L1 Combined Positive Score, Tumor Proportion Score, Mononuclear Immune Cell Density Score, or proportion of PD-L1-expressing immune cells between pre- and posttreatment tumor biopsies.
Combining palliative radiation therapy and pembrolizumab provided promising durable responses in this patient population but we were unable to definitively distinguish abscopal biologic changes. Biomarker analyses beyond PD-L1 expression are needed to better understand putative mechanisms and identify patients who will benefit from this approach.
The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up ...(primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.
To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening.
This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021.
Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation).
The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.
Of 415 357 eligible men (mean SD age, 59.0 5.6 years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% 95% CI, 6.95%-7.21% and 6.94% 95% CI, 6.82%-7.06%, respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% 95% CI, 0.65%-0.73%) and 1451 men in the control group (0.78% 95% CI, 0.73%-0.82%) died of prostate cancer (rate ratio RR, 0.92 95% CI, 0.85-0.99; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score GS ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% 95% CI, 23.0%-23.4%) and 50 336 deaths in the control group (23.3% 95% CI, 23.1%-23.5%) (RR, 0.97 95% CI, 0.94-1.01; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment.
In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small.
isrctn.org Identifier: ISRCTN92187251.
To identify clinical variables of pneumonia in children with acute leukemia that predicted respiratory failure and mortality.
A retrospective chart review of children with acute leukemia admitted to ...the hospital with the diagnosis of pneumonia or ARDS from March 1991 to April 1994.
Lucile Salter Packard Children's Hospital at Stanford, a 168-bed teaching hospital and regional tertiary referral center for children in northern California.
During this study period, 20% of the 174 admissions of children with acute leukemia had pneumonia at the time of admission or during the course of the hospitalization for a total of 36 admissions. The mean age of these children was 9.2±1.1 years.
Eleven percent of the children with pulmonary infiltrates in one quadrant on the chest x-ray film at the onset of pneumonia and 53% of the children with pulmonary infiltrates in more than one quadrant at the onset of pneumonia died. Fifteen percent of the children without sepsis at the onset of pneumonia and 70% of the children with sepsis at onset died. Eighteen percent of the children without shock at the onset of pneumonia and 75% of the children with shock at the onset died. None of the children died who required ≤3 L/min of O2 to maintain SO2 ≥95%, but 79% of the children who required >3L/min O2 died. Using the criteria “>3 L/min O2 by nasal cannula to maintain SO2 ≥95%” to identify the nonsurvivors had a sensitivity of 100% and specificity of 88%. This specificity was not increased by combining the criteria “O2 requirements at any time” and “the extent of pulmonary infiltrates at the onset of pneumonia.” All children who required mechanical ventilatory support for respiratory failure had previously received >3 L/min O2 by nasal cannula to maintain SO2 ≥95% for 37.8±12.9 h (range 3 to 96 h). Nine of the 10 children in our study who received mechanical ventilation died.
In children with acute leukemia and pneumonia, the amount of O2 required to maintain SO2 ≥95% may identify those who are likely to develop respiratory failure hours before mechanical ventilatory support is needed. The ability to identify children at risk for respiratory failure is not increased by combining the risk factors “oxygen requirements” and “extent of pulmonary infiltrates at the onset of pneumonia.” Finally, only 10% of the children who required mechanical ventilatory support survived.
We have investigated prospectively the efficacy of two nonpharmacologic relaxation techniques in the therapy of anxiety. A simple, meditational relaxation technique (MT) that elicits the changes of ...decreased sympathetic nervous system activity was compared to a self-hypnosis technique (HT) in which relaxation, with or without altered perceptions, was suggested. 32 patients with anxiety neurosis were divided into 2 groups on the basis of their responsivity to hypnosis: moderate-high and low responsivity. The MT or HT was then randomly assigned separately to each member of the two responsivity groups. Thus, 4 treatment groups were studied: moderate-high responsivity MT; low responsivity MT; moderate-high responsivity HT; and low responsivity HT. The low responsivity HT group, by definition largely incapable of achieving the altered perceptions essential to hypnosis, was designed as the control group. Patients were instructed to practice the assigned technique daily for 8 weeks. Change in anxiety was determined by three types of evaluation: psychiatric assessment; physiologic testing; and self-assessment. There was essentially no difference between the two techniques in therapeutic efficacy according to these evaluations. Psychiatric assessment revealed overall improvement in 34% of the patients and the self-rating assessment indicated improvement in 63% of the population. Patients who had moderate-high hypnotic responsivity, independent of the technique used, significantly improved on psychiatric assessment (p = 0.05) and decreased average systolic blood pressure from 126.1 to 122.5 mm Hg over the 8-week period (p = 0.048). The responsivity scores at the higher end of the hypnotic responsivity spectrum were proportionately correlated to greater decreases in systolic blood pressure (p = 0.075) and to improvement by psychiatric assessment (p = 0.003). There was, however, no consistent relation between hypnotic responsivity and the other assessments made, such as diastolic blood pressure, oxygen consumption, heart rate and the self-rating questionnaires. The meditational and self-hypnosis techniques employed in this investigation are simple to use and effective in the therapy of anxiety.
Changes in the management of torso gunshot wounds (TGSWs) have evolved in recent years as a result of differences between military and civilian injuries and increasing interest in avoiding ...nontherapeutic invasive procedures. The objective of this study was to establish the utility and accuracy of computed tomography (CT) in the evaluation of selected patients with TGSWs.
Retrospective review for a 6-year period of patients who sustained TGSWs and underwent CT solely for the purpose of trajectory determination. Patients had complete physical examinations and plain radiographic evaluations by a dedicated group of in-house trauma surgeons. When trajectory was indeterminate after evaluation, CT was performed. In some cases, CT was used when trajectory was determined to be intracavitary but organ injury was believed to be unlikely or amenable to nonoperative management.
Fifty TGSW patients underwent 52 computed tomographic scans. Abdominal/pelvic CT was performed in 37 patients, and thoracic CT was performed in 15 patients. All patients were stable and none sustained complications attributable to CT or delay in therapy. Twenty of 37 abdominal/pelvic computed tomographic scans excluded transabdominal or pelvic trajectory. Seventeen of 37 scans proved transabdominal or pelvic trajectory; nine laparotomies were performed, and eight patients were observed. Nine of 15 thoracic computed tomographic scans excluded transmediastinal trajectory. Six of 15 scans suggested vascular proximity and prompted further workup, which was positive in two cases.
CT of selected TGSW patients is safe and may reduce the incidence of invasive diagnostic procedures. A prospective evaluation of CT for TGSW patients is warranted.
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