Yakir Rottenberg

Loneliness, Health, and Longevity

BACKGROUND Objective measures of loneliness and poor social contacts are associated with negative health outcomes. However, the influence of subjective loneliness among elderly persons is poorly documented. We hypothesized that loneliness among persons aged 70-90 years is associated with subsequent decline in health, function, and longevity. METHODS Mortality data for subjects aged 70-90 years were obtained; subjective loneliness, health, comorbidity, depression, and functional status were assessed through the Jerusalem Longitudinal Cohort Study (1990-2010), a prospective longitudinal study. A representative sample of 407, 661, and 1,113 participants born 1920-1921 were assessed at home at ages 70, 78, and 85, respectively. Participants were asked how often they felt lonely, with answers dichotomized to never versus rarely/often/very often. In the age group of 70, 78, and 85, we excluded 67, 141, and 408 depressed participants from the study sample, which, thus, comprised 340, 520, and 705 participants, respectively. RESULTS At age 70, 78, and 85, prevalence of loneliness was 27.9% (n = 95), 23.8% (n = 124), and 24% (n = 169), respectively. The only factor consistently associated at all ages with increased likelihood of loneliness was not being married. After adjusting for baseline variables, we found no association between loneliness and subsequent deterioration 7 years later in functional status, mood, cognition, chronic pain, or rising comorbidity between ages 70 and 78 or 78 and 85. Loneliness was not associated with mortality among the participants aged 70-78, 78-85, and 85-90. We repeated all data analysis, without excluding depressed participants, without any change in overall findings. CONCLUSIONS Our findings do not support the hypothesis that subjective loneliness is associated with increased morbidity or mortality from age 70 to 90.

Tissue microarray-based study of patients with lymph node-positive breast cancer shows tyrosine phosphorylation of signal transducer and activator of transcription 3 (tyrosine705-STAT3) is a marker of good prognosis.

BackgroundAlthough lymph node-positive breast cancers are associated with poorer prognosis, individual patients may have different clinical outcomes. Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signalling pathways. The goal of this study was to determine the prognostic value of phosphorylated (tyrosine705)-STAT3 in node-positive breast cancer patients.MethodsImmunohistochemical analysis of Phospho-STAT3 was performed on a tissue microarray of breast cancer specimens. The expression pattern of Phospho-STAT3 was correlated with survival outcome, and clinical and pathological parameters.ResultsOut of 125 interpretable tumours, positive Phospho-STAT3 nuclear expression was seen in 35 (28%) of tumours. There was no significant relationship between Phospho-STAT3 expression and clinical-pathological parameters including age, hormonal receptor status, grade and tumour size. Interestingly positive tumours had a significantly improved disease-free survival at 5 years (p=0.035). Additionally, positive Phospho-STAT3 nuclear expression was correlated with significantly improved survival at both 5 years (p=0.023) and 10 years (p=0.026). Finally, in multivariate analyses Phospho-STAT3 was found to be an independent prognostic marker of overall survival in node-positive breast cancer patients.ConclusionThese findings support the role of Phospho-STAT3 as an important independent prognostic marker in node-positive breast cancer patients.

Handgrip Strength in Old and Very Old Adults: Mood, Cognition, Function, and Mortality

To determine the trajectory of handgrip strength (HGS) from age 70 to 90 and its association with mood, cognition, functional status, and mortality.

Prevalence of Pain With Advancing Age Brief Report

BACKGROUND The epidemiology of chronic pain with advancing age remains poorly established. Although most studies have examined somatic (musculoskeletal and joint) pain, visceral pain (such as headache and abdominal pain) has warranted less attention. We present longitudinal data from age 70 to 90 years concerning chronic musculoskeletal/joint pain, abdominal pain, and headache. METHODS Data was collected by the Jerusalem Longitudinal Study, which is a prospective study of a representative sample from the 1920-1921 birth-cohort living in West Jerusalem. Participants underwent comprehensive assessment at home in 1990, 1998, 2005, and 2010, at ages 70 (n = 460), 78 (n = 763), 85 (n = 1149), and 90 years (n = 394), respectively, and were directly questioned concerning the presence and location of pain. RESULTS The overall prevalence of pain of any kind at ages 70, 78, 85, and 90 years was 73% (n = 336/460), 81.1% (n = 619/763), 56.3% (n = 647/1149), and 31.2% (n = 123/394), respectively. Pain at younger ages only was associated with female gender, lower educational status, functional dependence, physical inactivity, increased body mass index, loneliness, depression, and poor self-rated health. At ages 70, 78, 85, and 90 years, chronic neck/back pain was present among 41.5%, 58.9%, 30.1%, and 14.6% of participants, respectively; chronic joint pain was present among 43.0%, 60.6%, 45.2%, and 25.2%, respectively. In contrast abdominal pain was less common and disappeared among the oldest old: 14.7%, 13.9%, 1.7%, and 1.5%, respectively, with a similar pattern for headache: 43.3%, 33.5%, 2.1%, and 1.3%. While pain was reported at ≥2 sites by 42.3% and 54.6% at ages 70 and 78 years, respectively, by ages 85 and 90 years, pain was most frequently reported at only 1 site. CONCLUSIONS Visceral pain (headache and abdominal pain) completely disappeared among the oldest old, in contrast to a far smaller decline in somatic (musculoskeletal and joint) pain.

Depression and Health Service Utilization From Age 70 to 85: The Jerusalem Longitudinal Study

BACKGROUND Health service utilization rises with age, and yet, its determinants are poorly understood. Our objective was to examine the association between depression and health service utilization from age 70-85. METHODS A representative sample (born 1920-1921) from the Jerusalem Longitudinal Cohort Study (1990-2010) was assessed at age 70, 78, and 85 for depression (using the Brief Symptoms Inventory); emergency room (ER) visits, and hospitalization in the previous year; social, functional, and medical domains. RESULTS We examined 414, 674, and 1118 subjects at ages 70, 78, and 85, among whom prevalence of depression was 16.2%, 21.1%, and 36.7%, respectively. ER visits and hospitalization were higher among depressed subjects. We adjusted for sex as well as financial status (social model); physical activity, going outdoors, functional status (functional model); and diabetes, ischemic heart disease, hypertension, cancer, dementia, chronic pain, and smoking (medical model). Depressed subjects were more likely to report increased ER visits, after adjustment in social, functional or medical models at age 78 (odds ratio [OR], 2.1, 95% confidence interval [CI], 1.3-3.3; OR, 1.8, 95% CI, 1.1-2.9; OR, 2.0, 95% CI, 1.26-3.26), and at age 85 (OR, 1.7, 95% CI, 1.33-2.3; OR, 1.4, 95% CI, 1.04-1.81; and OR, 1.4, 95% CI, 1.1-1.94), respectively. Aside from the social model at age 85 (OR, 1.5, 95% CI, 1.1-2.0), depression was not associated with increased likelihood of hospitalization. CONCLUSIONS Depression at ages 78 and 85 is consistently associated with increased ER visits and should be considered among older people presenting to the ER.

Prediagnostic self-assessed health and extent of social networks predict survival in older individuals with cancer: A population based cohort study

OBJECTIVES To assess the association between social networks on survival after cancer diagnosis in a population-based sample of elderly Israelis (>60 yo) living in the community in 1985 and followed for up to 20 years. MATERIALS AND METHODS We conducted a historical prospective study, using baseline measurements from a 1985 survey of a representative sample of community-dwelling population. Five distinct social networks were defined using information regarding number and intensity of social contacts: traditional-family (reference category), friends and neighbors, narrow-family, diverse, and attenuated. Cancer was ascertained through the Israel Cancer Registry, and mortality through the Population Registry after 20 years of follow-up. RESULTS The final study population included 676 participants diagnosed with cancer after 1985. Persons in the diverse network showed a lower risk of death (HR=0.74, 95% CI: 0.56-0.98) after adjusting for age, sex, smoking and self-assessed health. On the other hand, poor self-rated health at baseline (HR=1.39, 95% CI: 1.10-1.74 poor vs. all other categories of self-assessed health) was associated with increased risk of death. After excluding cancers amenable to early detection (breast, prostate, and colon) a borderline significant decreased risk of death following a diagnosis of cancer (HR=0.72, 95% CI: 0.52-1.01) was found. CONCLUSION There is evidence of a significant protective association between diverse social networks present before a cancer diagnosis and survival after the onset of disease. Social support from a variety of sources may be an important element in improving cancer survival in older individuals.

Blood donors with positive direct antiglobulin tests are at increased risk for cancer.

BACKGROUND: Positive direct antiglobulin tests (DATs) have been associated with both autoimmunity and lymphoproliferative disorders. However, it is unknown whether DAT+ in healthy blood donors is associated with an increased risk of malignancies.

Gemcitabine-induced supraventricular tachycardia

The superior toxicity profile is one of the major reasons for the widespread use of gemcitabine in cancer treatment. Bone marrow suppression is the most common side effect, while non-hematological events are relatively infrequent. Cardiac toxicity is a rare complication and cardiac arrhythmia is even rarer. We report the case of a 67-year-old woman with metastatic breast cancer without a history of cardiac arrhythmia or ischemic heart disease who developed supraventricular tachycardia. The symptoms had started immediately after gemcitabine treatment. The arrhythmia responded poorly to common treatment and was eventually controlled by oral propranolol five days after admission. The present case suggests that supraventricular tachycardia may be triggered by gemcitabine even without underlying significant heart disease and may be resistant to conventional therapy.

The changing face of cancer in the elderly: Only a demographic change?

The cancer burden of the elderly is high and has increased over time. One reason for this is increased longevity. Increasing age-specific rates of cancer in this age-group may also explain this phenomenon. Two age-groups were examined, older than 65 years and those younger than 65. The age-specific rates for all cancers combined among the Jewish population in Israel were identified via the Israel Cancer Registry during the years 1973-2002. Comparing the years 1973-1977 and 1998-2002, the age-specific rates for all cancers combined increased by about 35% in both age-groups. The most prominent increase was in prostate cancer in men (176% in the older group, p<0.01 and 368% in the younger group, p=0.01) followed by breast cancer in women (64% in the older group, p<0.01 and 50% in the younger group, p<0.01). In the years 1993-2002 a shift toward stabilization and even a decrease in incidence has been noted in some of the cancers, mainly in people aged 65 years and older. These data do not support the hypothesis that the overall change in the cancer burden in the aged could be explained by differences in the risk of developing cancer between these two age-groups.

Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients

Abstract Molecular portraits of numerous tumors have flooded oncologists with vast amounts of data. In parallel, effective inhibitors of central pathways have shown great clinical benefit. Together, this promises potential clinical benefits to otherwise end-stage cancer patients. Here, we report a clinical service offering mutation detection of archived samples using the ion Ampliseq cancer panel coupled with clinical consultation. A multidisciplinary think tank consisting of oncologists, molecular-biologists, genetic counselors, and pathologists discussed 67 heavily pretreated, advanced cancer patient cases, taking into account mutations identified using ion Ampliseq cancer panel, medical history, and relevant literature. The team generated a treatment plan, targeting specific mutations, for 41 out of 64 cases. Three patients died before results were available. For 32 patients, the treating oncologists chose not to include the panel recommendation in the treatment plan for various reasons. Nine patients were treated as recommended by the panel, 5 with clinical benefit, and 4 with disease progression. This study suggests that routine use of massive parallel tumor sequencing is feasible and can judiciously affect treatment decisions when coupled with multidisciplinary team-based decision making. Administration of personalized based therapies at an earlier stage of disease, expansion of genetic alterations examined, and increased availability of targeted therapies may lead to further improvement in the clinical outcome of metastatic cancer patients.