Dysfunction In Survivors Research Articles

Identification and management of late dysfunction in survivors of head and neck cancer: Implementation and outcomes of an interdisciplinary quality of life (IQOL) clinic

Identifying and treating late dysfunction in survivors of head and neck cancer (HNC) is important; however, an effective way to do so is not established. A quality improvement initiative altering our HNC survivorship clinic to include surveillance by rehabilitation providers was undertaken. The nature of dysfunction identified, along with the number and type of referrals to ancillary/support services were collected and compared to baseline. The baseline, single-provider, clinic evaluated 61 patients and referred 2 (3%) to ancillary/support services. Fifty-seven patients were evaluated in the interdisciplinary clinic, with 36 (63%) referred to at least one ancillary/support service for new/progressive dysfunction. Of 59 referrals made, 22 (37%) were for dysphagia, 17(29%) were for neck/shoulder dysfunction, and 28 (47%) were attended by the patient. Many HNC survivors exhibit late dysfunction appropriate for referral to ancillary/support services. A survivorship clinic including surveillance by rehabilitation specialists may optimize identification of dysfunction.

Bacterial sepsis increases hippocampal fibrillar amyloid plaque load and neuroinflammation in a mouse model of Alzheimer's disease

BackgroundSepsis, a leading cause for intensive care unit admissions, causes both an acute encephalopathy and chronic brain dysfunction in survivors. A history of sepsis is also a risk factor for future development of dementia symptoms. Similar neuropathologic changes are associated with the cognitive decline of sepsis and Alzheimer's disease (AD), including neuroinflammation, neuronal death, and synaptic loss. Amyloid plaque pathology is the earliest pathological hallmark of AD, appearing 10 to 20 years prior to cognitive decline, and is present in 30% of people over 65. As sepsis is also more common in older adults, we hypothesized that sepsis might exacerbate amyloid plaque deposition and plaque-related injury, promoting the progression of AD-related pathology. MethodsWe evaluated whether the brain's response to sepsis modulates AD-related neurodegenerative changes by driving amyloid deposition and neuroinflammation in mice. We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in APP/PS1–21 mice, a model of AD-related β-amyloidosis. We performed CLP or sham surgery at plaque onset (2 months of age) and examined pathology 2 months after CLP in surviving mice. ResultsSepsis significantly increased fibrillar amyloid plaque formation in the hippocampus of APP/PS1–21 mice. Sepsis enhanced plaque-related astrocyte activation and complement C4b gene expression in the brain, both of which may play a role in modulating amyloid formation. CLP also caused large scale changes in the gut microbiome of APP/PS1 mice, which have been associated with a pro-amyloidogenic and neuroinflammatory state. ConclusionsOur results suggest that experimental sepsis can exacerbate amyloid plaque deposition and plaque-related inflammation, providing a potential mechanism for increased dementia in older sepsis survivors.

NF-κB Blockade by NEMO Binding Domain Peptide Ameliorates Inflammation and Neurobehavioral Sequelae After Cranial Radiation Therapy in Juvenile Mice

Cranial radiation therapy (CRT) is a common treatment for pediatric brain tumor patients. However, side effects include significant neurobehavioral dysfunction in survivors. This dysfunction may in part be caused by inflammation, including increased production of tumor necrosis factor alpha (TNFα) and its receptor TNFR1, which can activate the nuclear factor kappa light-chain enhancer of activated B cells (NF-κB). The TNFα blockade abrogates this inflammatory response, although it presents immunologic risks. Thus, modulation of pathway subsets may be preferable. Here, we test whether inhibition of NF-κB activation using an NF-κB essential modulator binding domain (NBD) peptide mitigates CRT-induced neuroinflammation and improves behavioral outcomes. Male C57BL/6J 28-day old mice were randomized to saline (sham), 5 Gy whole-brain CRT, or CRT + NBD-peptide. Brain tissue was collected after 4 hours or 3 months for Western blot or immunohistochemistry. The cortex, corpus callosum (CC), and dentate gyrus were variably imaged for NF-κB-p65, IκBα, proliferation, apoptosis, necroptosis, TNFα, TNFR1, IBA-1, doublecortin, CD11c, and GFAP. Neurobehavioral changes were assessed by open field and elevated plus maze tests 3 months post-CRT. NF-κB expression increased in whole and nuclear fractions 4 hours after CRT and was abrogated by NBD treatment. Cell death increased and proliferation decreased after CRT, including within neuronal progenitors, with some loss mitigated by NBD. Increased levels of TNFα, IBA-1, and GFAP were found in the CC and cortex months after CRT and were limited by NBD. The anti-NF-κB peptide also improved neurobehavioral assessments, yielding improvements in anxiety and exploration. Results suggest a role for NF-κB modulation by NBD peptide in the reduction of neuroinflammation and mitigation of behavioral complications after pediatric radiation therapy.

Impaired phagocytic function in CX3CR1+ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in old mice.

Skeletal muscle dysfunction in survivors of pneumonia disproportionately affects older individuals in whom it causes substantial morbidity. We found that skeletal muscle recovery was impaired in old compared with young mice after influenza A virus‐induced pneumonia. In young mice, recovery of muscle loss was associated with expansion of tissue‐resident skeletal muscle macrophages and downregulation of MHC II expression, followed by a proliferation of muscle satellite cells. These findings were absent in old mice and in mice deficient in Cx3cr1. Transcriptomic profiling of tissue‐resident skeletal muscle macrophages from old compared with young mice showed downregulation of pathways associated with phagocytosis and proteostasis, and persistent upregulation of inflammatory pathways. Consistently, skeletal muscle macrophages from old mice failed to downregulate MHCII expression during recovery from influenza A virus‐induced pneumonia and showed impaired phagocytic function in vitro. Like old animals, mice deficient in the phagocytic receptor Mertk showed no macrophage expansion, MHCII downregulation, or satellite cell proliferation and failed to recover skeletal muscle function after influenza A pneumonia. Our data suggest that a loss of phagocytic function in a CX3CR1+ tissue‐resident skeletal muscle macrophage population in old mice precludes satellite cell proliferation and recovery of skeletal muscle function after influenza A pneumonia.

Early evidence of pulmonary dysfunction in survivors of childhood Hodgkin lymphoma

Survivors of childhood Hodgkin lymphoma (HL) are at risk for pulmonary late effects, but whether survivors also experience pulmonary dysfunction early off therapy is not well understood. We determined the incidence of pulmonary dysfunction in children/adolescents with HL at entry into survivorship, as well as risk factors related to this outcome. Survivors in clinical remission and with a pulmonary function test (PFT) obtained 2–6 years off therapy were included. Seventy-five of 118 subjects met eligibility criteria (mean age at diagnosis: 13 years, mean time off therapy: 40 months). Survivors of HL had a higher than expected incidence of pulmonary dysfunction at entry into survivorship (40/75 [53%] had an abnormal DLCO and/or a restrictive or obstructive impairment). Evidence for diffusion impairment was associated with female sex (odds ratio [OR] = 3.19, p = .04). Longitudinal follow-up studies are needed to determine if early evidence of pulmonary dysfunction predicts risk for later onset pulmonary outcomes.

Cardiac Monitoring for Thoracic Radiotherapy: Survey of Practice Patterns in the United States

American Society of Clinical Oncology (ASCO)'s 2017 Guideline on Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers identified patients receiving thoracic radiation (TRT) ≥ 30 Gy (heart in field) at increased risk for developing radiation induced heart disease (RIHD). ASCO encouraged clinicians to actively screen and monitor for baseline modifiable cardiac risk factors and therapy-induced cardiotoxicity in this high-risk population, which would include a majority of lung and esophageal patients obtaining definitive TRT. Further, coronary artery calcium (CAC) is an independent risk factor for adverse cardiac events that can be mitigated with preventative medical therapy. CAC is easily identified on non-contrast thoracic CT simulation scans, yet it is unclear whether ROs are aware of the clinical implications of CAC seen on simulation scans. We sought to assess ROs practice patterns, experiences, and perceptions of cardiac screening and monitoring for TRT patients. A 28-question survey was emailed to United States ROs 3 times from September 2018 to January 2019. Responses were collected on Survey Monkey and descriptive statistics were used to report results. Of the 162 respondents from 42 states, 94% treat non-breast thoracic cancers to doses ≥ 45 Gy with heart in the field, 51% practice in academic settings, and 62% have an average of 1-5 thoracic cancer patients actively on treatment. While 22% have access to a Cardio-Oncology program, 81% were not aware of the ASCO cardiac monitoring guidelines. Only 24% agreed with these guidelines, whereas 41% thought they should be more specific and 35% were not sure. The most significant reported barrier to cardiac monitoring in asymptomatic patients was lack of strong evidence for type and timing of cardiac monitoring tests (69%). The majority (56%) did not monitor cardiac changes after RT. When monitoring, 38% prefer ECHO, yet 72% were unsure or had no preference as to which type of ECHO to order. While 62% agreed that RIHD could occur in any section of the heart in the RT field and that the earliest expected time-point that cancer survivors would be symptomatic from RIHD was <2years (27%), 2-5 years (41%) or 5-10 yrs (26%), 72% would NOT reduce tumor coverage and 67% would NOT reduce RT dose in order to minimize RT heart dose since the priority was cancer control. If CAC was evident on CT sim scans, 68% had never thought about what actions to take or did not take any actions, whereas 38% would refer to internist or cardiologist. Only 7% reported having ongoing clinical trials for cardiac monitoring at their centers. This survey highlights a critical gap in knowledge about cardiac monitoring and potentially missed opportunities for preventive medical management in a high risk population that may have competing life-threatening cardiac risks. Future studies focusing on timing and detection of RIHD may elucidate the utility of cardiac monitoring for TRT patients.

A Retrospective Evaluation of Risk of Peripartum Cardiac Dysfunction in Survivors of Childhood, Adolescent and Young Adult Malignancies.

Long-term survivors of childhood, adolescent and young adult (AYA) malignancies with past exposure to potentially cardiotoxic treatments are at risk of peripartum cardiac dysfunction. Incidence and risk factors for peripartum cardiac dysfunction and maternal cardiac outcomes in this population were investigated. Eligible long-term survivors were aged <30 years at cancer diagnosis, with ≥1 pregnancy occurring ≥5 years after diagnosis. “Peripartum” cardiac events were defined as occurring within pregnancy or ≤5months after delivery. Cardiac events were classified “symptomatic” or “subclinical”. “Peripartum cardiomyopathy” (PPCM) was defined as symptomatic dysfunction without prior cardiac dysfunction. Of 64 eligible women, 5 (7.8%) had peripartum cardiac events: 3 symptomatic, 2 subclinical. Of 110 live births, 2 (1.8%, 95% CI 0.2–6.4) were defined as PPCM: Significantly greater than the published general population incidence of 1:3000 (p < 0.001), representing a 55-fold (95% CI 6.6–192.0) increased risk. Risk factor analyses were hypothesis-generating, revealing younger age at cancer diagnosis and higher anthracycline dose. Postpartum, cardiac function of 4 women (80%) failed to return to baseline. In conclusion, peripartum cardiac dysfunction is an uncommon but potentially serious complication in long-term survivors of paediatric and AYA malignancies previously treated with cardiotoxic therapies. Peripartum cardiac assessment is strongly recommended for at-risk patients.

Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer.

Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer.

The frequency and the diagnosis of pituitary dysfunction after traumatic brain injury.

Clinical research studies over the last 15years have reported a significant burden of hypopituitarism in survivors of traumatic brain injury (TBI). However, debate still exists about the true prevalence of hypopituitarism after head injury. We have reviewed the literature describing the frequency of post-traumatic hypopituitarism and discuss the factors which may explain the variable frequency of the reported deficits in clinical studies including research methodology and the natural history of the disease. Pituitary hormone perturbations in the acute phase following injury are frequent but are difficult to attribute to traumatic pituitary damage due to physiological hormonal changes in acute illness, the confounding effect of medications, other co-morbidities and lack of appropriate control subjects. Nevertheless, a small number of studies have emphasised the clinical importance of acute, dynamic disturbance of the hypothalamic-pituitary-adrenal axis. There is a much larger evidence base examining the frequency of hypopituitarism in the chronic, recovery phase following head injury. These studies report a very broad prevalence of long-term pituitary hormone dysfunction in survivors of TBI. However, systematic review suggests the prevalence to be between 27 and 31%. Survivors of head injury are at risk of pituitary hormone dysfunction and we suggest an approach to the diagnosis of post-traumatic hypopituitarism in routine clinical practice.

New insight into the intraventricular pressure gradient as a sensitive indicator of diastolic cardiac dysfunction in patients with childhood cancer after anthracycline therapy.

Cardiac dysfunction due to cardiotoxicity from anthracycline chemotherapy is a leading cause of morbidity and mortality in survivors of childhood cancer. The intraventricular pressure gradient (IVPG) of the left ventricle (LV) is the suction force of blood from the left atrium to the LV apex during early diastole and is a sensitive indicator of diastolic function. We assessed IVPG as a new indicator of the cardiac dysfunction in survivors of childhood cancer after anthracycline therapy. We performed a prospective echocardiographic study on 40 survivors of childhood cancer aged 6-26years who received anthracycline therapy (group A) and 53 similar-age normal controls (group N). The subjects were divided into the younger groups, N1 and A1 (age < 16years); older groups, N2 and A2 (age ≥ 16years). IVPG was calculated using color M-mode Doppler imaging of the mitral inflow using Euler's equation. Total IVPG was divided into the basal and mid-to-apical IVPG to demonstrate more clearly the mechanisms of the LV diastolic suction force. The total anthracycline dose was 16.2-600.0mg/m2 (median 143.5mg/m2). Total IVPG significantly decreased in group A2 compared with that in group N2 (0.39 ± 0.07 vs. 0.29 ± 0.11mmHg/cm; p = 0.010). The mid-to-apical IVPG significantly decreased in groups A1 and A2 compared with that in groups N1 and N2, respectively (N1 vs. A1: 0.20 ± 0.05 vs. 0.16 ± 0.05mmHg/cm, p = 0.036; N2 vs. A2: 0.21 ± 0.06 vs. 0.14 ± 0.06mmHg/cm, p = 0.001). Basal IVPG, E wave, and E/e' were not significantly different between patients and normal controls. The total and mid-to-apical IVPG, especially mid-to-apical IVPG, could be sensitive new indicators in survivors of childhood cancer after anthracycline therapy.

Predicting Long-term Cognitive Dysfunction in Survivors of Critical Illness with Plasma Inflammatory Markers: a Retrospective Cohort Study.

Persistent inflammation in intensive care unit (ICU) survivors is associated with higher long-term mortality and poorer mobility. However, it is unknown if inflammatory markers are associated with other dysfunctions observed in survivors of critical illness. Thus, it was investigated if plasma levels of interleukin (IL)-6 and IL-10 at hospital discharge were associated with long-term functional and cognitive performance after ICU discharge. Adult patients admitted for >48h to a 20-bed mixed ICU in a University Hospital had blood collected within 48h before hospital discharge to measure IL-6 and IL-10 levels. After a median time of 48months, cognitive status was determined by the Mini-Mental State Examination (MMSE), and functional status was determined by the Barthel Index. Patients at the higher 25th percentile of both IL-6 and IL-10 had a worse long-term cognitive performance, but not worse functional status, even when adjusted for confounders after long-term follow-up. In conclusion, elevated circulating IL-6 and IL-10 concentrations at hospital discharge were associated with long-term cognitive dysfunction in ICU survivors.

Two-Dimensional Speckle Tracking Echocardiography-Derived Strain Measurements in Survivors of Childhood Cancer on Angiotensin Converting Enzyme Inhibition or Receptor Blockade.

Speckle tracking echocardiography (STE)-derived strain indices are believed to detect early cardiac dysfunction in survivors of childhood cancer and have potential to identify patients who may benefit from early heart failure treatment. However, effects of heart failure treatment on STE-derivedstrain measurements in this population are unknown. The aim of this study was to assess STE-derivedstrain measurements in survivors of childhood cancer treated with angiotensin converting enzyme inhibition or receptor blockade (ACEi/ARB). Two-dimensional speckle tracking analysis was retrospectively performed on echocardiograms from childhood cancer survivors before and during therapy with ACEi/ARB. Global left ventricular longitudinal and circumferential strain (GLS and GCS) and strain rates (LSR and CSR) were assessed and correlated with conventional echocardiographic measures of function. In 22 childhood cancer survivors (median age: 14.8, range 6.4-21.6years), mean GLS (-13.83 ± 0.74% to -15.94 ± 0.74%, p = 0.002), GCS (-18.79 ± 1.21% to -20.74 ± 0.84%, p = 0.027), LSR (-0.78 ± 0.04 to -0.88 ± 0.04s-1, p = 0.022), and CSR (-1.08 ± 0.07 to -1.21 ± 0.06s-1, p = 0.027) improved on therapy. Improvement in GLS was maintained for greater than 1 year on ACEi/ARB (p = 0.02). Measures of strain and strain rate correlated with standard echocardiographic measures of function and were reproducible. These findings support the use of ACEi/ARB to treat post-chemotherapy-related cardiovascular changes in childhood cancer survivors, provide proof-of-concept that STE-derived strainand strain rate may be used to reliably monitor cardiac function during therapy, and support continued investigation into the clinical benefit of strain measurements in this population.

Neuropsychological and self-reporting outcomes following rehabilitation of cognitive dysfunction in survivors of breast cancer: A pilot study involving survivor-partner dyads.

Neuropsychological and self-reporting outcomes following rehabilitation of cognitive dysfunction in survivors of breast cancer: A pilot study involving survivor-partner dyads.

Fulminant myocarditis: Characteristics, treatment, and outcomes.

Myocarditis is an inflammatory disease of the myocardium with a broad spectrum of clinical presentations, ranging from mild symptoms to severe heart failure. The course of patients with myocarditis is heterogeneous, varying from partial or full clinical recovery in few days to advanced low cardiac output syndrome requiring mechanical circulatory support or heart transplantation. Fulminant myocarditis (FM) is a peculiar clinical condition and is an acute form of myocarditis, whose main characteristic is a rapidly progressive clinical course with the need for hemodynamic support. Despite the common medical belief of the past decades, recent comprehensive data, including a recent registry that compared FM with acute non-FM, highlighted that FM has a poor inhospital outcome, often requires advanced hemodynamic support, and may result in residual left ventricular dysfunction in survivors. This review aimed to provide an updated practical definition of FM, including essentials in the diagnosis and management of the disease. Finally, the outcome of FM was critically revised according to the current published registries focusing on the topic.

Pituitary dysfunction in survivors of Russell's viper snake bite envenomation: A prospective study.

Endocrinal insufficiency caused by vasculotoxic snake envenomation is under-recognized and is mostly confined to a specific geographic area. We conducted a prospective study to determine the prevalence and pattern of pituitary-target gland insufficiencies caused by snake envenomation. The hormonal evaluation of patients who had suffered from vasculotoxic snake envenomation was done at baseline and at 6 months of follow-up. Those patients with a documented hormonal insufficiency underwent magnetic resonance imaging (MRI) of the hypothalamo-pituitary area. The severity of envenomation was assessed by the acute physiology and chronic health evaluation II (APACHE-II) score, the sepsis-related organ failure assessment (SOFA) score, and the snake bite severity score (SBSS) for all patients. Seventy-six patients were seen during the study period, of which 60 were available for a repeat hormonal evaluation at 6 months, with the majority of patients belonging to the middle age group (mean age, 37.6 ± 14.9 years). The mean lag period at presentation was 32 ± 20 h. Thirty-five patients (46.1%) had coagulopathy, 20 patients (26.3%) had acute kidney injury (AKI), and 8 of 76 patients (10.5%) needed renal replacement therapy (RRT) in the form of hemodialysis. Six patients (out of 41 with vasculotoxic bites) developed chronic hypopituitarism, which was in continuation with the acute hypopituitarism that they developed. Growth hormone and glucocorticoid deficiencies were the most common endocrinopathies observed. The occurrence of hypopituitarism was observed only in patients with a vasculotoxic snake bite (due to Russell's viper); coagulopathy, renal insufficiency, or any of the scoring tools did not predict the occurrence of hypopituitarism. Acute asymptomatic and chronic symptomatic or asymptomatic hypopituitarism are important sequelae of viper bite in a small proportion of patients and can occur in the presence of normal pituitary imaging. Routine prospective pituitary hormone screening should be done in all patients within the first 6 months of envenomation by the vasculotoxic snakebite as chronic pituitary dysfunction can often occur in these patients.

The effect of antegrade pulmonary blood flow following a late bidirectional Glenn procedure.

The effect of antegrade pulmonary blood flow (APBF) has never been studied in the bidirectional Glenn (BDG) procedure performed late. Records of 112 consecutive patients who had a BDG procedure during a 10-year period were reviewed retrospectively. The patients were divided into 2 groups based on whether APBF occurred following the BDG procedure (APBF group, n = 81) or not (non-APBF group, n = 31). The median age at the BDG procedure was 6.16 ± 3.93 years in the APBF group and 6.12 ± 4.40 years in the non-APBF group. Demographics and pre- and intraoperative variables were comparable for both groups. Follow-up data were obtained for patients at the BDG stage and for those who had undergone the Fontan completion. Both oxygen saturation levels (81.72 ± 1.976% vs 78.32 ± 2.344%, P < 0.01) and pulmonary pressure (13.59 ± 1.376 mmHg vs 12.90 ± 0.978 mmHg, P = 0.012) were higher in the APBF group immediately after the BDG procedure. Both the duration of chest tube drainage and the total length of stay were longer in the APBF group. The pre-Glenn measurements showed a mean McGoon ratio of 1.68 ± 0.114 in the APBF group and 1.67 ± 0.098 in the non-APBF group (P = 0.474). The McGoon ratios measured before the Fontan procedure were also comparable (1.669 ± 0.726 vs 1.685 ± 0.669, P = 0.576). At the pre-Fontan measurement, there was no significant difference in mean pulmonary artery pressures between the groups (13.72 ± 1.368 vs 13.50 ± 1.265, P = 0.653). Fifty-nine patients underwent the Fontan completion (43 from the APBF group and 16 from the non-APBF group) procedure with a median of 1.2 (APBF group) and 1.4 (non-APBF group) years after the BDG procedure. No significant differences between groups were observed in arterial oxygen saturation levels, incidence of systemic atrioventricular valve regurgitation or ventricular dysfunction in survivors at the last follow-up visit. The BDG procedure can be safely performed at a relatively older age (∼6 years). APBF increases oxygen saturation but also prolongs pleural effusion and hospital stay. Medium-term outcomes and the Fontan completion rate in the APBF and the non-APBF groups are comparable. Further large studies and long-term follow-up are needed to clarify the effect of APBF in patients who have the late BDG.

Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline Summary.

Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline Summary.

Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline.

Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.

Hypothalamic-Pituitary Axis Dysfunction in Survivors of Childhood CNS Tumors: Importance of Systematic Follow-Up and Early Endocrine Consultation.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. An 11-year-old male with a history of metastatic tectal plate low-grade glioma who was diagnosed at age 2.8 years transferred his care to the long-term follow-up clinic. He completed treatment with multiagent chemotherapy-carboplatin, vincristine, temozolomide, procarbazine, lomustine, and thioguanine-at age 4.5 years and did not require radiotherapy. At primary diagnosis, he presented with hydrocephalus that required ventriculoperitoneal shunt placement, with a subsequent shunt revision at age 6 years. Residual metastatic tumors in the third and fourth ventricles and in the suprasellar region remained stable for more than 5 years. The patient achieved normal developmental milestones and was not taking medications. He was offered screening for hypothalamic-pituitary axis (HPA) dysfunction because of his suprasellar lesion. His height was at the 25th percentile for chronological age, with decline from the 50th percentile noted during the preceding 18 months ( Fig 1 , point c). Pubertal stage was Tanner 4 for pubic hair and penile size, which contrasted with small testes (4.5 mL). Pubic hair and voice changes were noticed 2 to 3 years before this visit. Plasma testosterone level was consistent with Tanner 4 (255 ng/dL = 8.9 nmol/L). An x-ray of the left hand revealed a notably advanced bone age of 15.5 years. Plasma free T4, thyroid-stimulating hormone (TSH), and 8 am cortisol levels were normal. The patient was referred to the endocrinology clinic where he was diagnosed with growth hormone deficiency and was started on replacement therapy. He reached his final adult height of 144.1 cm at age 13.3 years ( Fig 1 , point d).

Targeted CBT May Be Best for Treating Cognitive Problems in Cancer Survivors

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessTargeted CBT May Be Best for Treating Cognitive Problems in Cancer SurvivorsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:2 Sep 2016https://doi.org/10.1176/appi.pn.2016.8b7AbstractMany cancer survivors find themselves dealing with deficits in concentration and working memory even years after their chemotherapy has concluded.Thanks to advances in cancer therapy, cancer survivors are leading longer, fuller lives. As the population of cancer survivors has grown, however, it has become increasingly clear that some will experience long-term cognitive effects of cancer therapy—a condition commonly known as “chemobrain.”“Most patients will report cognitive issues during the chemotherapy process, but as these are potent agents, feeling weak, confused, or disoriented is not surprising,” said Tim Ahles, Ph.D., a behavioral psychologist at Memorial Sloan-Kettering Cancer Center who has dedicated himself to understanding the cancer-cognition connection. Ahles noted that evidence also indicates hormonal therapies and radiation for cancer may also compromise cognition.“If these problems were limited to the short term, it might not be a big issue,” he continued. “However, cancer survivors are still showing signs of cognitive impairment years after their last treatment.”Although older patients with cancer might be expected to show some degree of age-related cognitive decline (such as loss of episodic memory), Ahles noted that chemotherapy-induced problems most often affect attention, working memory, and processing speed. In addition, these deficits typically do not get progressively worse as would be expected with an age-related disorder. A recent study from St. Jude Children’s Research Hospital also found higher exposure to a chemotherapy drug was associated with long-term executive dysfunction in survivors of pediatric cancer (Psychiatric News, July 1).Ahles thinks that chemotherapy agents may compromise the brain’s ability to distinguish relevant information from irrelevant information, which might explain why cancer survivors experience symptoms that resemble attention-deficit/hyperactivity disorder (ADHD). Because most chemotherapy drugs cannot cross the blood-brain barrier, however, the exact mechanism by which they exert their effects is unknown (with brain tumors being an exception). Treating cognitive issues with cancer patients and survivors can be challenging. While many cancer patients and survivors experiencing chemotherapy-induced cognitive problems are given stimulants such as methylphenidate or modafinil, it remains unclear whether this is the best approach for all patients, who may be in a weakened state due to ongoing chemotherapy. Cognitive therapies can also be used to treat chemotherapy-induced cognitive dysfunction, but this approach also presents challenges.As Robert Ferguson, Ph.D., an assistant professor of medicine at the University of Pittsburgh Cancer Institute Biobehavioral Oncology Program told Psychiatric News, an important component of cognitive-behavioral therapy (CBT) is to educate patients about their disorder, so they can be more aware of their behaviors and actively work to change them.“But we don’t really have that luxury when discussing cancer-related cognition problems, because our understanding of what these chemotherapies are doing is still quite limited,” he said.He noted that while many cancer survivors are older adults, the distinct manifestation of chemotherapy-induced problems means that applying existing CBT programs for dementia may not be appropriate. At the same time, ADHD-tailored cognitive therapies, which often require intensive training to get patients to improve their attention and working memory skills, may not be a good fit either. Such cognitive training is time consuming, Ferguson said, “and cancer survivors have already given up a lot of their time. They want to get back to their regular lives as quickly as possible.”To assist cancer survivors with cognitive dysfunction, Ferguson and colleagues at the University of Maine (where he was prior to joining Pittsburgh) have been working on a CBT therapy known as Memory and Attention Adaptation Training (MAAT).MAAT, which was designed to be administered over the course of just one month, focuses on teaching patients compensatory skills to manage cognitive issues; such strategies include encouraging patients to make schedules or softly talk through tasks as they are being performed. A few years back Ferguson carried out a small clinical study in 40 breast cancer survivors and found that MAAT did provide modest benefits for some elements of cognitive function, as well as anxiety related to their cognitive problems. In a more recent study, Ferguson found cancer survivors also reported cognitive improvements following MAAT by videoconference. (Patients could participate in the program at home, which Ferguson noted was another important consideration for cancer survivors.)While Ferguson noted that more research is needed to determine the long-term effects of MAAT on larger populations of cancer survivors, he said he believes MAAT may serve as a simple way to offer them a strategy for coping with cognitive challenges. ■An abstract of “A Randomized Trial of Videoconference-Delivered Cognitive Behavioral Therapy for Survivors of Breast Cancer With Self-Reported Cognitive Dysfunction” can be accessed here. “Development of CBT for Chemotherapy-Related Cognitive Change: Results of a Waitlist Control Trial” is available here. ISSUES NewArchived