Systematic Review of Randomized Controlled Trials of Exercise Interventions Using Digital Activity Trackers in Patients With Cancer.

Background: Exercise can ameliorate cancer- and treatment-related toxicities, but poor adherence to exercise regimens is a barrier. Exercise interventions using digital activity trackers (E-DATs) may improve exercise adherence, but data are limited for patients with cancer. We conducted a systematic review examining the feasibility of E-DATs in cancer survivors and effects on activity level, body composition, objective fitness outcomes, health-related quality of life (HRQoL), self-reported symptoms, and biomarkers. Methods: We identified randomized controlled trials (RCTs) of E-DATs in adult cancer survivors published in English between January 1, 2008, and July 27, 2017. Two authors independently reviewed article titles (n=160), removed duplicates (n=50), and reviewed the remaining 110 articles for eligibility. Results: A total of 12 RCTs met eligibility criteria, including 1,450 patients (mean age, 50-70 years) with the following cancers: breast (n=5), colon or breast (n=2), prostate (n=1), acute leukemia (n=1), or others (n=3). Duration of E-DATs ranged from 4 to 24 weeks, and the follow-up period ranged from 4 to 52 weeks, with retention rates of 54% to 95%. The technology component of E-DATs included pedometers (n=8); pedometers with smartphone application (n=1), Wii Fit (n=1), heart rate monitor (n=1); and a wireless sensor with accelerometer, gyroscope, and magnetometer (n=1). Adherence by at least one measure to E-DATs was >70% in 8 of 8 RCTs. Compared with controls, E-DATs significantly improved patients' step count in 3 of 5 RCTs, activity level in 6 of 9 RCTs, and HRQoL in 7 of 9 RCTs (all P≤05), with no significant changes in biomarkers (eg, interleukin 6, tumor necrosis factor α, C-reactive protein, c-peptide, lipid panel) in 3 RCTs. Duration of E-DAT was not significantly correlated with adherence or study retention. Conclusions: This systematic review shows that E-DATs are feasible to implement in cancer survivors. Future research should examine the optimal type, dose, and schedule of E-DATs for cancer survivors.

Successful reduced-intensity conditioning hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria with aplastic anemia in two children.

Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare cause of bone marrow failure in children. We report two children who presented with pancytopenia, and were diagnosed with PNH with severe aplastic anemia. Both children underwent upfront, successful hematopoietic stem cell transplantation with reduced-intensity conditioning. One patient had a syngeneic donor, and one patient had a 10/10 matched unrelated donor. Neither patient developed graft versus host disease, infections, or recurrent PNH. Reduced-intensity conditioning hematopoietic stem cell transplantation is a reasonable therapy for PNH with marrow failure in children.

Viridans group streptococcal infections among children with cancer and the importance of emerging antibiotic resistance.

Viridans group streptococci (VGS) are major pathogens among children with cancer or receiving hematopoietic stem cell transplantation and are associated with considerable morbidity and mortality rates. The incidence and severity of VGS infections have increased during the past 15 years and account for as many as one third of all bacteremic episodes. Risk factors include severe neutropenia, mucositis, gastrointestinal toxicity, pneumonia, younger age, and high-intensity chemotherapy (especially cytosine arabinoside). VGS no longer can be assumed to be susceptible to penicillin because as many as 37 percent of VGS isolates harbor high levels of resistance (minimum inhibitory concentration >4 microg/mL). Furthermore, resistance to multiple classes of antibiotics, including beta-lactams and fluoroquinolones, has now been documented and is increasing in prevalence. In this article, we present a brief overview of VGS, describe the clinical spectrum of VGS-related diseases in children with cancer, and review the recent data regarding the incidence, clinical significance, and management of emerging antibiotic resistance among VGS.

Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy.

A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. Because the patient was adrenalectomized, extra adrenal androgen production was suspected. Imaging studies including pelvic ultrasound and pelvic magnetic resonance imaging (MRI) were obtained to evaluate for adrenal rest tumors of the ovaries. Abdominal MRI was obtained to evaluate for residual adrenal tissue. A cystic lesion arising from her right ovary suspicious for ovarian neoplasm was noted on pelvic MRI. Right salpingo-oophorectomy was performed and histopathological examination revealed ovarian serous adenocarcinoma, low-grade, and well-differentiated. Tumor marker CA-125 was elevated and additional ovarian cancer staging workup confirmed stage IIIC due to one lymph node positive for carcinoma. The patient then developed a large left ovarian cyst, which led to a complete total abdominal hysterectomy and removal of the left ovary and fallopian tube. Pathology confirmed ovarian serous adenocarcinoma with microscopic focus of carcinoma in the left ovary. After numerous complications, the patient responded well to chemotherapy, CA-125 levels fell and no evidence of carcinoma was observed on subsequent imaging. To our knowledge, this is the first reported case of an ovarian serous adenocarcinoma in a patient with CAH. Although rare, we propose that the ovaries were the origin of androgen production and not residual adrenal tissue. The relationship between CAH and ovarian carcinomas has yet to be established, but further evaluation is needed given the poor survival rate of high-grade serous ovarian carcinoma.

Pneumocystis carinii infection sensitizes lung to radiation-induced injury after syngeneic marrow transplantation: role of CD4+ T cells.

A murine model of bone marrow transplant (BMT)-related lung injury was developed to study how infection sensitizes lung to the damaging effects of total body irradiation (TBI) at infectious and TBI doses that individually do not cause injury. Mice infected with Pneumocystis carinii exhibited an asymptomatic, rapid, and transient influx of eosinophils and T cells in bronchoalveolar lavage fluid (BALF). In contrast, mice infected with P. carinii 7 days before receiving TBI and syngeneic BMT (P. carinii/TBI mice) exhibited severe pulmonary dysfunction, surfactant aggregate depletion, and surfactant activity reductions at 17 days post-BMT. BALF from P. carinii/TBI mice contained a disproportionate initial influx of CD4(+) T cells (CD4(+):CD8(+) ratio of 2.7) that correlated with progressive lung injury (from 8 to 17 days post-BMT). Levels of TNF-alpha in BALF were significantly increased in P. carinii/TBI mice compared with mice given either insult alone, with peak values found at 11 days post-BMT. In vivo depletion of CD4(+) T cells in P. carinii/TBI mice abrogated pulmonary dysfunction and reduced TNF-alpha levels in BALF, whereas depletion of CD8(+) T cells did not affect lung compliance or TNF-alpha. Lung injury was not attributable to direct P. carinii damage, since CD4-depleted P. carinii/TBI mice that exhibited no injury had higher average lung P. carinii burdens than either mice given P. carinii alone or undepleted P. carinii/TBI mice. Together, these results indicate that P. carinii infection can sensitize the lung to subsequent TBI-mediated lung injury via a process dependent on non-alloreactive CD4(+) T cells.

High incidence of penicillin resistance among alpha-hemolytic streptococci isolated from the blood of children with cancer.

OBJECTIVES: To survey the susceptibility profiles to several beta-lactam antibiotics and to identify factors related to resistance among blood isolates of alpha-hemolytic streptococci (AHS) obtained from children with cancer. STUDY DESIGN: All pediatric oncology patients with AHS bacteremia occurring from January 1996 through June 1999 at one cancer center were identified. Isolates were categorized based on the minimum inhibitory concentration as susceptible, intermediate, or resistant to several beta-lactam antibiotics. Demographics and potential factors related to antibiotic resistance were obtained from the medical record. RESULTS: Thirty-eight AHS isolates were obtained from 33 patients. Penicillin susceptibility testing revealed that only 8 (21%) isolates were susceptible, 16 (42%) were intermediate, and 14 (37%) were resistant. All 14 of the penicillin-resistant isolates were also resistant to the 3 cephalosporins tested. Ceftriaxone and ceftazidime were the most active cephalosporins. Antibiotic resistance correlated with the recent use of systemic antibiotics, number of prior infectious episodes, and species type. CONCLUSIONS: Blood culture isolates of AHS obtained from children with cancer are frequently resistant to beta-lactam antibiotics. These results indicate that clinically relevant AHS isolates should be tested for antibiotic susceptibility and that beta-lactam antibiotics may not be optimal empiric therapy for fever and neutropenia in children with cancer who have a high risk of AHS infections.