High Body Mass Index is Associated with Shorter Retention of Tumor Necrosis Factor-Alpha Blocker Treatment in Rheumatoid Arthritis.

PURPOSE: To evaluate the association between body mass index (BMI) and tumor necrosis factor α (TNF-α) blockers retention in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: This prospective cohort study analyzed data about patients with RA who initiated TNF blockers from the Israeli registry of inflammatory diseases from 2011 to 2019. Patients were grouped by BMI: normal (BMI <24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), obese (BMI 30-34.9 kg/m2) and morbid obese (BMI ≥35 kg/m2). Treatment cessation due to inefficacy was defined as an "event" and therapy with a drug above 3 months was defined as a "course." Kaplan-Meier survival curve was used to describe drug survival. Event-free survival was calculated using Cox regression with a hazard ratio and confidence interval of 95%. RESULTS: The final analysis included 521 RA patients (80% females) treated with etanercept, infliximab, adalimumab or golimumab. Eight hundred and eighteen treatment initiations were included in the final analysis, 334 (41%) in the normal weight group, 261 (32%) in the overweight, 144 (17%) in the obese and 79 (10%) in the morbid obesity group. Three hundred and twenty-six (40%) treatment initiations were with etanercept, 215 (26%) with adalimumab 197 (24%) with infliximab, and 80 (10%) with golimumab. BMI was inversely associated with drug survival. Morbid obese patients were more likely to discontinue treatment compared with normal weight patients HR 2.28 (95% CI 1.67-3.10, p<0.01). This association remained significant for each drug type (except for golimumab) in a subgroup analysis. Adalimumab switch rate was higher compared to etanercept with HR =1.51 (95% CI 1.20-1.91, p<0.01), no other significant differences were noted between the other drugs. CONCLUSION: Morbid obese RA patients have lower TNF-α blocker retention compared to normal weight patients.

The presence of a bulky mediastinal mass of 7 cm or greater in diameter confers an adverse prognosis to patients with advanced Hodgkin lymphoma in case of negative interim PET/CT.

In the PET-adapted therapy era, a bulky mediastinal mass (BMM) is not considered a risk factor in patients with advanced-stage Hodgkin lymphoma (HL). The current retrospective study aimed to estimate the prognostic significance of BMM presence and size for disease-free survival (DFS) and determine the most accurate mass size cutoff (among 5 cm, 7 cm, 10 cm) to predict inferior DFS in such patients. The study included 196 advanced-HL patients treated at Rambam (n = 121) and Memorial Sloan Kettering Cancer Center (n = 75) between 2002 and 2016. At a median follow-up of 66.5 (1-222) months, 36 relapses occurred. In multivariate analysis, only the cutoff of 7 cm predicted inferior DFS and PFS (p < 0.007 and <0.038, respectively) in interim PET/CT (PET-2) negative (79%) patients. This study identifies the BMM size cutoff of 7 cm in any plane as most precise in predicting adverse prognosis in PET-2-negative patients with advanced-stage HL. More aggressive initial chemotherapy than ABVD improves such prognosis.

The epidemiology of Staphylococcus aureus bacteraemia in Israeli children: Community- vs hospital-acquired or healthcare related infections.

AIM: Incidences of Staphylococcus aureus bacteraemia (SAB) in Israeli children are unknown. The characteristics of SAB in children have not been evaluated. METHODS: SAB from children aged ≤18 years old, admitted to a tertiary hospital in Israel during 2002-2015, were included. The proportional rate of SAB was calculated per 1000 admissions. SAB were classified as community acquired (CA), hospital acquired (HA) and healthcare related (HCR). Patients' characteristics, antibiotic susceptibility and outcomes were assessed in each group. RESULTS: The rate of SAB was stable, 1.48 per 1000 admissions. HA, CA and HCR-SAB comprised 53%, 25% and 22%, respectively. Only 27/185 (14.6%) were caused by methicillin-resistant S aureus (MRSA): 22%, 6% and 5% of HA, CA and HCR-SAB, respectively. Central venous catheter, recent surgery, immunodeficiency and age <6 years were the main risk factors for HA and HCR-SAB (adjusted OR: 68.9, 7.5, 5.8 and 5.5, respectively). Treatment duration for CA was >21 days: and for HA and HCR, 14-20 days. All-cause in-hospital mortality and 30-day mortality were documented in 10 (5%) and 3 (2%) episodes, respectively. CONCLUSION: The rate of SAB; the proportions of CA, HA and HCR-SAB; and the proportion of MRSA was stable over the years. MRSA was mainly in HA-SAB. Thirty-day mortality was rare.

The cultural expression of spiritual distress in Israel.

BACKGROUND: Although spiritual distress is present across cultures, the ways in which patients experience it vary between cultures. Our goal was to examine the cultural expression and key indicators of spiritual distress in Israel. METHODS: We conducted a structured interview of 202 oncology outpatients in a cross-sectional study. Self-diagnosis of spiritual distress, which is a demonstrated gold standard for identifying its presence, was compared with the Facit-Sp-12 and a number of other items (from the Spiritual Injury Scale and newly developed Israeli items) hypothesized as Israeli cultural expressions of spiritual distress, demographic and medical data, and patient desire to receive spiritual care. RESULTS: Significant variation was found between Israeli cultural expression of spiritual distress and that found in studies from other countries. Key expressions of spiritual distress in this study included lack of inner peace, grief, and an inability to accept what is happening. Items related to faith were not significant, and loss of meaning showed mixed results. Patients requesting spiritual care were more likely to be in spiritual distress. No demographic or medical data correlated with spiritual distress. CONCLUSIONS: Specially designed interventions to reduce spiritual distress should address the expressions of the distress specific to that culture. Studies of the efficacy of spiritual care can examine the extent of spiritual distress in general or of its specific cultural expressions.

Prevalence of Iron Deficiency and Iron Deficiency Anemia in Strenuously Training Male Army Recruits.

OBJECTIVES: The objectives of our study were to determine the effect of strenuous physical training on the prevalence of iron deficiency anemia (IDA), iron deficiency (ID) with normal hemoglobin (Hb), and anemia without ID. METHODS: Our study was a prospective observational study. We followed 115 healthy male recruits in the Israel Defense Forces elite units during 15 months of training. Blood samples were collected at recruitment and at 6-, 9- and 15-month follow-ups. RESULTS: Upon recruitment, anemia (Hb < 14 g/dL), ID, and ID anemia (IDA) were diagnosed in 28, 31, and 9% of individuals, respectively. Sixty-three subjects (54%) were followed for 6 months; 9 of them (14%) developed new-onset IDA. Among them, the prevalence of anemia rose from 19 to 52%, and ID from 33 to 35%. At the 15-month follow-up, 29% had developed new-onset IDA and 65% showed evidence of ID. CONCLUSION: We report a high prevalence of anemia, ID, and IDA among young healthy males participating in prolonged strenuous training programs. These findings can be partly explained by the physiological changes associated with strenuous physical activity. Further investigations aiming to develop specific diagnostic guidelines for this unique population are warranted.

Prognostic significance of heparanase expression in primary and metastatic breast carcinoma.

High levels of heparanase are detected in many types of tumors, associated with bad prognosis. Typically, heparanase levels are evaluated in a biopsy taken from the primary lesion, whereas its expression by the resulting metastases is most often unresolved. This becomes critically important as anti-heparanase compounds enter advanced clinical trials. Here, we examined the expression of heparanase in pairs of primary and the resulting distant metastases of breast carcinoma. Interestingly, we found that heparanase expression in the metastatic lesion does not always reflect its expression in the primary tumor. Accordingly, in some cases, the primary lesion was stained positive for heparanase while the metastasis stained negative, and vice versa. Heparanase discordance occurred in 38% of the patients, higher than that reported for hormone receptors, and was associated with bad prognosis. Thus, examination of heparanase levels in the tumor metastases should be evaluated for most efficient precision medicine applying heparanase inhibitors. Furthermore, we found that in stage I breast cancer patients strong heparanase staining is associated with shorter overall survival. Thus, heparanase levels can assist in the diagnosis and in determining the necessity and type of treatment in early stage breast cancer.

Modification of initial therapy in early and advanced Hodgkin lymphoma, based on interim PET/CT is beneficial: a prospective multicentre trial of 355 patients.

This multicentre study evaluated 5-year progression-free (PFS) and overall survival (OS) in early and advanced Hodgkin lymphoma (HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles (PET-2). Between September 2006 and August 2013, 359 patients aged 18-60 years, were recruited in nine Israeli centres. Early-HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy (ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced-HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET-2-negative patients further received ABVD ×4; PET-2-positive patients received EB ×4 and ISRT to residual masses. With a median follow-up of 55 (13-119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early-HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced-HL, the PFS was 81% and 68%, respectively (P = 0·08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early-HL, even with additional ABVD and ISRT. Advanced-HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients.

Distinguishing Between Spiritual Distress, General Distress, Spiritual Well-Being, and Spiritual Pain Among Cancer Patients During Oncology Treatment.

CONTEXT: Spiritual distress is present in approximately 25% of oncology patients. OBJECTIVES: We examined the extent to which this measure is identical to a variety of other measures, such as spiritual well-being, spiritual injury, spiritual pain, and general distress. METHODS: Structured interview of oncology outpatients over 12 months, approached nonselectively. The presence or absence of spiritual distress was compared against spiritual pain and two spiritual well-being tools: Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12-Item Scale (FACIT-Sp-12) and the Spiritual Injury Scale (SIS). We also examined whether a general distress visual analogue scale sufficed to identify spiritual distress. Other questions concerned demographic and clinical data. RESULTS: Of 416 patients approached, 202 completed the interview, of whom 23% reported spiritual distress. All measures showed significant correlation (receiver operating characteristic, area under the curve: SIS 0.79; distress thermometer [DT] 0.68; FACIT-Sp-12 0.67), yet none were identical with spiritual distress (sensitivity/specificity: SIS 64%/79%; spiritual pain 72%/76%; DT 41%/76%; FACIT-Sp-12 57%/72%). Of the FACIT-Sp-12 subscales, only peace correlated with spiritual distress. A significant predictor of spiritual distress was patients' self-evaluation of grave clinical condition (odds ratio 3.3; 95% CI 1.1-9.5). Multivariable analysis of individual measure items suggests an alternative three-parameter model for spiritual distress: not feeling peaceful, feeling unable to accept that this is happening, and perceived severity of one's illness. CONCLUSION: The DT is not sufficient to identify spiritual distress. The peace subscale of FACIT-Sp-12 is a better match than the measure as a whole. The SIS is the best match for spiritual distress, although an imperfect one.

Biopsy of breast cancer metastases: patient characteristics and survival.

BACKGROUND: Discordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival. METHODS: The medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival. RESULTS: Of 409 patients suspected of having MBC, 165 (40%) had a biopsy, and 34% of these had discordant HR or HER2 status when compared to the initial diagnosis. In multivariate analysis, having a biopsy was associated with: recurrence in years 2010-2014, disease-free interval of > =3 years, stage 0-IIA at presentation, suspected locoregional recurrence, being HR+/HER2-, or missing HR/HER2 at diagnosis. A similar multivariate analysis revealed that having a biopsy was associated with improved survival (HR = 0.67, p = 0.002). The association of biopsy and improved survival was noted in specific subgroups: patients with missing HR and HER2 data at initial diagnosis (p = 0.001), those without metastases in liver, lung or brain (p = 0.001), and being younger than 70 years old at recurrence (p < 0.001). CONCLUSIONS: Specific clinical factors were associated with biopsy at the time of suspected recurrence. Having a biopsy was associated with reduced mortality.

Do Wound Cultures Give Information About the Microbiology of Blood Cultures in Severe Burn Patients?

BACKGROUND: Blood stream infection (BSI) and the subsequent development of sepsis are among the most common infection complications occurring in severe burn patients. This study was designed to evaluate the relationship between the burn wound flora and BSI pathogens. METHODS: Documentation of all bacterial and fungal wound and blood isolates from severe burn patients hospitalized in the burn unit and intensive care unit was obtained from medical records retrieved retrospectively from a computerized, hospital-wide database over a 13-year period. All data were recorded in relation to the Ryan score. RESULTS: Of 195 severe burn patients, 88 had at least 1 BSI episode. Transmission of the same pathogen from wound to blood was documented in 30% of the patients, with a rising BSI frequency as the Ryan score increased. There were a total of 263 bacteremic episodes in 88 study patients, 44% of blood isolates were documented previously in wound cultures, and transmission of the same pathogen from wound to blood was noted in 65% of bacteremic patients. CONCLUSIONS: When there is clinical suspicion of sepsis, appropriate empirical systemic antibiotic therapy should be broad spectrum and should rely on the susceptibility of the organisms from recent cultures of the burn wound surface, until the blood cultures results are completed.

The effect of complementary and alternative medicine on quality of life, depression, anxiety, and fatigue levels among cancer patients during active oncology treatment: phase II study.

BACKGROUND: During the past decade, there has been growing interest in complementary and alternative medicine (CAM) among cancer patients and it is being integrated more frequently within conventional cancer centers. The long-term effect of mind-body therapies on quality of life (QoL), depression, anxiety, and fatigue was tested prospectively in this study. PATIENTS AND METHODS: Cancer patients who received six weekly sessions of CAM during their oncological treatments participated in the study. The Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI) and QoL-EORTC-C30 were completed during the intervention and follow-up period. RESULTS: Over a two-year period, 163 patients entered the study, 135 of whom completed all six CAM sessions. An improvement was demonstrated in the median of BFI from 4.8 to 3.9 (p < 0.001), HADS-Anxiety from 8 to 7 (p < 0.001) and HADS-Depression from 7 to 6 (p < 0.001) after 12 weeks. In addition, the median of global QoL improved from 50 to 67 (p < 0.001), and a significant improvement was noticed in several parameters on the functioning and symptoms scales of the QoL-EORTC-C30. CONCLUSION: Cancer patients who completed six weekly sessions of CAM improved significantly on measured outcomes, regardless of their demographic characteristics.

Malnutrition in surgical wards: a plea for concern.

Background. Malnutrition in hospitalized patients is underdiagnosed, with 30 to 60% of patients admitted being malnourished. The objective of this study was to investigate the nutritional status of patients in a general surgery ward and to define the correlation between the risk of malnutrition and the hospital course and clinical outcome. Study design. The study group included 100 consecutive patients admitted to a general surgery ward who were ambulant and could undergo the Malnutrition Universal Screening Tool (MUST). Results. Thirty-two patients (33%) had aMUST score of 2 or higher, and were therefore defined at high-malnutrition risk. The patients at risk had longer hospitalization and worse outcome. The length of stay of the malnourished patients was significantly longer than that of patients without malnutrition risk (18.8 +/- 11.5 vs. 7 +/- 5.3 days, P = .003). Mortality in the high-risk group was higher overall, in hospital, and after six months and one year of followup. Conclusions. Medical personnel must be aware that malnutrition afflicts even patients whose background is not suggestive of malnutrition. Best results are achieved when cooperation of all staff members is enlisted, because malnutrition has severe consequences and can be treated easily.