Cognitive impairment in hodgkin lymphoma survivors.

Cancer-related cognitive impairment (CRCI) is commonly reported post-chemotherapy in adults with solid tumours. Hodgkin lymphoma (HL) mostly affects young adults. Data regarding CRCI in HL survivors (HLS) are scarce. The current study aimed to objectively assess CRCI incidence and characteristics in HLS. HLS, who completed first-line (chemotherapy ± radiation) therapy and remained in complete remission for 6 months to 5 years from therapy end, were evaluated. Age- and education-matched healthy individuals served as controls (n = 14). Test results were compared to population norms and healthy controls. Study participants completed self-reported questionnaires evaluating fatigue, depression, anxiety, quality of life and cognitive function. Subjects underwent neurocognitive evaluation, assessing processing speed, memory, attention, executive functions and intelligence domains. The present study included 51 HLS with a median age of 28 years, mean education of 14·5 ± 2·5 years. Complaints related to cognitive deterioration and fatigue were significantly more severe and frequent in HLS compared to healthy controls. Objective neurocognitive evaluation demonstrated that 30% of HLS were impaired in ≥2 cognitive domains. In conclusion, the present study demonstrates that fatigue and cognitive impairment, predominantly in executive functions and memory, constitute frequent and alarming findings in HLS. These adverse effects can persist and exert an impact on all aspects of life.

A 14-Year Experience in the Management of Patients with Acquired Immune Thrombotic Thrombocytopenic Purpura in Northern Israel.

Acquired idiopathic thrombotic thrombocytopenic purpura (I-TTP) is a life-threatening microangiopathic disorder usually treated with therapeutic plasma exchange (TPE). The current study assessed the role of rituximab in the treatment of complicated I-TTP. The sequence of TTP events was compared in a group of I-TTP patients treated with TPE and a cohort of refractory or relapsed patients who also received rituximab. This retrospective evaluation included 45 I-TTP patients, treated between January 2000 and October 2013, who underwent at least 3 TPE procedures and were followed up until December 2013 or death. Thirty-one patients with an uncomplicated course received TPE only. Fourteen patients had a complicated course due to either a primary refractory/exacerbated disease (n = 5) or relapse (n = 9) and received rituximab together with TPE. The median number of TPE procedures performed in the first TTP episode in the uncomplicated cohort and groups with primary refractory or relapsed TTP was 11, 27 and 45, respectively. The relapse rates per follow-up year in the uncomplicated I-TTP, primary refractory and relapsed I-TTP groups were 0.18, 0.2 and 0.6 episodes, respectively. After rituximab therapy this rate dropped to 0.2 per year in the relapsed subgroup. In conclusion, about a quarter of patients with I-TTP had a complicated course and experienced a major benefit from rituximab in terms of effectiveness and safety.

Hodgkin lymphoma patients in first remission: routine positron emission tomography/computerized tomography imaging is not superior to clinical follow-up for patients with no residual mass.

There is no consensus regarding optimal follow-up mode for Hodgkin lymphoma (HL) patients that achieve complete remission following chemotherapy or combined chemo- and radiation therapy. Several studies demonstrated high sensitivity of positron emission tomography/computerized tomography (PET/CT) in detecting disease progression; however, these techniques are currently not recommended for routine follow-up. This retrospective study conducted in two Israeli (N = 291) and one New Zealand academic centres (N = 77), compared a group of HL patients, followed-up with routine imaging every 6 months during the first 2 years after achieving remission, once in the third year, with additional dedicated studies performed due to symptoms or physical findings (Group I) to a group of patients without residual masses who underwent clinically-based surveillance with dedicated imaging upon relapse suspicion (Group II). Five-year overall survival (OS) was 94% and median time to relapse was 8·6 months for both modes. Relapse rates in Groups I and II were 13% and 9%, respectively. During the first 3 years of follow-up, 47·5 and 4·7 studies were performed per detected relapse in Groups I and II, respectively. The current study demonstrated no benefit in either progression-free survival (PFS) or OS in HL patients followed by routine imaging versus clinical follow-up. The cost was 10 times higher for routine imaging.

Early-onset plasmapheresis and LDL-apheresis provide better disease control for pediatric homozygous familial hypercholesterolemia than HMG-CoA reductase inhibitors and ameliorate atherosclerosis.

Plasmapheresis (PA) and low-density lipoprotein apheresis (LDL-A) were assessed in five children with homozygous familial hypercholesterolemia (HFH) previously receiving statins. LDL-A required smaller extracorporeal blood volumes. Mean HDL-cholesterol reduction post-procedure was 32% and 60% with LDL-A and PA, respectively. Non-HDL-C reduction was 64% and 69%, respectively. Pre-procedural LDL-C decreased significantly with weekly versus biweekly LDL-A. Carotid intimal media thickness (IMT) studies demonstrated disappearance of atheromatous lesions and normal ITM in 4/5 patients. Echocardiography revealed normal aortic valves, coronary orifices and supra-valvular area in all patients. Apheresis is effective in pediatric HFH. It may be started in patients weighing 14 kg.

Mechanical ventilation for older medical patients in a large tertiary medical care center.

BACKGROUND: The development of technologies for the prolongation of life has resulted in an increase in the number of older ventilated patients in internal medicine and chronic care wards. Our study aimed to determine the factors influencing the outcomes of older ventilated medical patients in a large tertiary medical center. METHODS: We performed a prospective observational cohort study including all newly ventilated medical patients aged 65 years and older over a period of 18 months. Data were acquired from computerized medical records and from an interview of the medical personnel initiating mechanical ventilation. RESULTS: A total of 554 patients underwent mechanical ventilation for the first time during the study period. The average age was 79 years, and 80% resided at home. Following mechanical ventilation, 8% died in the emergency room, and the majority of patients (351; 63%) were hospitalized in internal medicine wards. In-hospital mortality was 64.1%, with 48% dying during the first week of hospitalization. Overall 6-months survival was 26%. We found that a combination of age 85 years and older, functional status prior to ventilation, and associated morbidity (diabetes with target organ injury and/or oncological solid organ disease) were the strongest negative predictors of survival after discharge from the hospital. CONCLUSION: Mechanical ventilation at older age is associated with poor survival and it is possible to identify factors predicting survival. In the midst of the COVID-19 pandemic, the findings of this study may help in the decision-making process regarding mechanical ventilation for older people.

Recognizing severe fatigue and decline in quality of life in Hodgkin lymphoma survivors.

Hodgkin lymphoma (HL) is common in young adults and considered curable in most patients. Young HL survivors (HLS) are at risk of long-term adverse effects. Our study aimed to assess various fatigue and quality of life (QoL) complaints, and their correlations with treatment. Self-reported questionnaires assessing fatigue (MFI-20) and QoL-related issues (EORTC-QOL-C-30) were used to examine HLS aged 18-65 who completed first-line chemotherapy ± radiotherapy (RT) and were in complete remission for at least six months post-therapy. The cohort included 120 HLS (median age 32 years), assessed between 6 months and 15 years post-treatment. About 28% presented with severe fatigue and severely reduced QoL. Higher fatigue levels were associated with four cycles of the ABVD + RT. Young HLS experience high levels of persistent physical fatigue, emotional distress, and cognitive decline that are insufficiently investigated. Assessment of these complaints is essential and further investigation may provide tailored solutions for a better QoL for HLS.

Addition of high-dose methotrexate to standard treatment for patients with high-risk diffuse large B-cell lymphoma contributes to improved freedom from progression and survival but does not prevent central nervous system relapse.

Combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is regarded as standard care for diffuse large B-cell lymphoma (DLBCL) and upfront intensification of therapy is still controversial. The current study aimed to dertermine whether the addition of high-dose methotrexate (HDMTX) affects long-term outcomes and could also prevent central nervous system (CNS) relapse. Medical records of 480 patients with DLBCL treated between 1994 and 2013 at Rambam and Hadassah medical centers in Israel were reviewed; 130 (27%) had received HDMTX. Patients receiving HDMTX generally had higher International Prognostic Index (IPI) and CNS-IPI scores. HDMTX addition significantly improved progression free and overall survival (p = .001) and this advantage was maintained in multivariate analysis (HR for OS 0.3; 95% CI 0.19-0.47; p < .0001). Thirty-one (6.5%) patients had CNS relapse and in these cases high CNS-IPI, but not HDMTX treatment, was independently associated with CNS relapse (HR 1.2; 95% CI 1.2-11.5; p = .02). In conclusion, the addition of HDMTX to CHOP/RCHOP independently and significantly improved prognosis of patients with high-risk DLBCL, irrespective of their risk for CNS relapse.

Hyperthyroxinemia at birth: a cause of idiopathic neonatal hyperbilirubinemia?

BACKGROUND: Some neonates develop idiopathic hyperbilirubinemia (INHB) requiring phototherapy, yet with no identifiable causes. We searched for an association between abnormal thyroid levels after birth and INHB. METHODS: Of 5188 neonates, 1681 (32.4%) were excluded due to one or more risk factors for hyperbilirubinemia. Total thyroxine (TT4) and thyroid stimulating hormone values were sampled routinely at 40-48 hours of age and measured in the National Newborn Screening Program. RESULTS: Of the 3507 neonates without known causes for hyperbilirubinemia, 61 (1.7%) developed INHB and received phototherapy. Univariate analyses found no significant association between mode of delivery and INHB (vacuum-delivered neonates were a priori excluded). Nonetheless, in cesarean-delivered (CD) neonates, two variables had significant association with INHB: TT4 ≥ 13 µg/dL and birth at 38-38.6 weeks. In vaginally delivered (VD) born neonates, INHB was associated with weight loss > 7.5% up to 48 hours of age. Multivariate logistic regression analysis showed a strong effect of mode of delivery on possible significant association with INHB. In CD neonates, such variables included: TT4 ≥ 13 µg/dL [P = 0.025, odds ratio (OR) 5.49, 95% confidence interval (CI) 1.23-24.4] and birth at 38-38.6 weeks (P = 0.023, OR 3.44, 95% CI 1.19-9.97). In VD neonates, weight loss > 7.5% (P = 0.019, OR 2.1, 95% CI 1.13-3.83) and 1-min Apgar score < 9 (P < 0.001, OR 3.8, 95% CI 1.83-7.9), but not TT4, showed such an association. CONCLUSIONS: INHB was significantly associated with birth on 38-38.6 week and TT4 (≥ 13 µg/dL) in CD neonates, and with a weight loss > 7.5% in VD neonates. We herein highlight some acknowledged risk factors for neonatal hyperbilirubinemia, and thus minimize the rate of INHB.

Natural history of dementia associated with lacunar infarctions.

BACKGROUND: Lacunar stroke (VaD-L) is the most common stroke subtype associated with vascular dementia (VaD). OBJECTIVE: To evaluate the rate of cognitive and behavioral changes in patients with probable VaD-L. METHODS: We measured rates of change on the Mini-Mental State Examination (MMSE), Digit Span, Logical Memory, Controlled Oral Word Association Test, CERAD battery and the Neuropsychiatric Inventory (NPI) of 77 [age at entry 65.9+/-8.1 (mean+/-standard deviation) years] patients with probable VaD, periventricular white matter and basal ganglia lacunae, longitudinally studied for 25.7+/-11 months. RESULTS: Mean number of follow-up visits was 2.6. Overall annual vascular event rate was 0.25. VaD-L in mildly and moderately impaired patients is characterized by progressive cognitive and behavioral decline. The rate of cognitive and behavioral progression depends on the occurrence of vascular episodes (VE) during the course of the illness [(-1.1) MMSE and (+4.0) NPI points annually without VE vs. (-2.0) and (+10.3) points following VE]. The rates of progression are a function of the severity of the cognitive and behavioral impairment. Impaired cognition is associated with impaired behavior. A subgroup of VaD-L patients runs a progressively deteriorating course despite the absence of clinically apparent new vascular episodes. CONCLUSION: VaD-L is characterized by cognitive and behavioral decline in 83% of the patients. The rate of decline is determined mainly by the severity of the cognitive and behavioral impairment at baseline and by the occurrence of new vascular episodes.

Malnutrition in cardiac surgery: food for thought.

BACKGROUND: Undernourished patients treated in general surgery departments suffer from prolonged and complicated hospitalizations, and higher mortality rates compared with well nourished patients. Pivotal information regarding patients' nutritional status and its effect on clinical outcome is lacking for cardiac surgery patients. We investigated the prevalence of malnutrition risk and its association with 30-day hospital mortality and postoperative complications. METHODS AND RESULTS: Four hundred and three patients who underwent cardiac surgery during 2008 and were screened with the Malnutrition Universal Screening Tool (MUST) on admission were enrolled. Univariate and multivariate logistic regression analyses compared the association of high and low risk for malnutrition with length of hospitalization (LOS), in-hospital and 30-day mortality, and postoperative complications. Almost 20% of the patients were found to be at high risk for malnutrition. Univariate analyses revealed higher in-hospital mortality rates (p = 0.03) and greater incidence of LOS and antibiotic treatment longer than 21 days (p = 0.002 and p = 0.04, respectively), vasopressor treatment longer than 11 days (p = 0.02), and positive blood cultures (p = 0.02) in patients belonging to the high-risk MUST group. Incorporation of the MUST in a multivariate model with the European System for Cardiac Operative Risk Evaluation (EuroSCORE) significantly improved postoperative complications prediction, as well as in-hospital and 30-day mortality, compared with the EuroSCORE alone. CONCLUSIONS: Malnutrition is prevalent in patients undergoing cardiac surgery, associated with higher postoperative mortality and morbidity. Preoperative MUST screening has emerged as highly relevant for enabling early diagnosis of patients at malnutrition risk, predicting postoperative mortality and morbidity, thus promoting well timed treatment. Prospective studies are needed to explore whether intervention can decrease malnutrition risk.

Prospective evaluation of the dosing regimen of vancomycin in children of different weight categories.

BACKGROUND: Pharmacokinetics (PK), pharmacodynamics and optimal dosing of vancomycin in obese children is not known. Higher trough levels of vancomycin may improve outcomes. This prospective study evaluated the appropriateness of twice-daily regimen for the adherence to guidelines, among obese and non obese children. METHODS: Children receiving vancomycin, (20 mg/kg BID) were included. Patients were divided into 3 groups. Adequacy was defined as trough level ≥ 10mg/L and AUC/MIC > 400. An alternative-dosing regimen was calculated based on individual PK parameters. RESULTS: Seventy-seven pairs (trough, peak) were taken from 51 children. Mean trough level was 3.36 ± 2.58, only 3% fell in therapeutic range, no statistical difference was observed between obese, normal weight or underweight groups. One child had an AUC/MIC > 400. All children recovered. CONCLUSION: PK properties of all weight groups were similar. More frequent and higher doses are needed to achieve the goals of current guidelines.

Progression of dementia associated with lacunar infarctions.

BACKGROUND: Lacunar stroke (L) is the most common stroke subtype associated with vascular dementia (VaD-L). OBJECTIVE: To evaluate the cognitive and behavioral course in patients with probable VaD-L. METHODS: We longitudinally measured rates of change on MMSE, digit span, logical memory, Controlled Oral Word Association, CERAD battery and neuropsychiatric inventory (NPI) in 77 patients (age at entry 69 +/- 8.1 years) with probable VaD-L for 25.75 +/- 11 months. RESULTS: The mean number of follow-up visits was 2.6 +/- 0.67 (range 2-4). Time interval between any two consecutive visits was at least 5 months (range 5-41). MMSE deteriorated by 1.44+/- 1.8 points annually and NPI increased by 6.01 +/- 13.7 points annually (p < 0.0001). The rates of cognitive and behavioral decline were predominantly influenced by the cognitive state at entry into the study and the occurrence of new vascular episodes during follow-up [(-0.95 +/- 1.7) MMSE and (+2.02 +/- 14.1) NPI points annually without vascular episodes vs. (-2.09 +/- 1.6) and (+11.3 +/- 11.4) points following vascular episodes (p < 0.0001)]. Impaired cognition was associated with impaired behavior (p < 0.001). VaD-L patients without additional vascular episodes at follow-up have a progressively deteriorating course as well (p < 0.0001). CONCLUSION: VaD-L is characterized by cognitive and behavioral decline. The rate of decline is determined mainly by the severity of the cognitive and behavioral impairment at baseline and by the occurrence of new vascular episodes.