Erel Joffe

C-reactive protein velocity following antibiotics in patients with chronic obstructive pulmonary disease exacerbation and community acquired pneumonia

INTRODUCTIONnDistinguishing community acquired pneumonia (CAP) from chronic obstructive pulmonary disease (COPD) exacerbation is a challenging task, since fever, productive cough, dyspnea, and leukocytosis are all common features of both conditions. Moreover, chest X-ray might not be sensitive enough. It is therefore quite common for physicians to prescribe unnecessary antibiotics for COPD exacerbation, leading to resistant bacteria and other related adverse affects.nnnAIMnTo study whether CRP levels upon admission and the delta in CRP levels following initiation of antibacterial treatment, could provide an efficient tool for distinguishing CAP from COPD exacerbation.nnnMETHODSnThe study group included 36 COPD exacerbation and 49 CAP patients, admitted to a single Internal Medicine department during the years 2004-2006. All patients were treated with cephalosporins and macrolides upon admission.nnnRESULTSnCRP levels upon admission were significantly higher among CAP patients than among COPD exacerbation patients (111.5+/-104.4 vs. 34.9+/-28.6 mg/l, p<0.0001). CRP levels on the second day of hospitalization, following antibiotic administration to all patients, made a sharp incline in 36.7% of CAP patients compared to only 5.9% of COPD exacerbation patients (p=0.005), and remained unchanged in 61.8% of COPD patients compared to 16.3% of CAP patients (p=0.0006).nnnCONCLUSIONSnCRP levels upon admission and the delta in CRP levels following initiation of antibacterial treatment could provide an efficient tool for distinguishing CAP from COPD exacerbation.

The Value of PET/CT in Detecting Bone Marrow Involvement in Patients With Follicular Lymphoma.

AbstractFollicular lymphoma (FL) is the 2nd most common type of lymphoma diagnosed in the Western World. Bone marrow (BM) involvement is an adverse prognostic factor in FL, routinely assessed by an arbitrary biopsy of the iliac crest. This study was aimed to investigate the role of positron emission tomography/computed tomography (PET/CT) in identifying BM involvement by FL.In this retrospective, single-center study we reviewed the records of consecutive patients with FL at diagnosis or relapse who underwent staging/restaging workup visual assessment of BM uptake was categorized as either normal, diffusely increased, or focally increased. Quantitative BM fluorine-18-fluro-deoxyglucose (FDG) uptake was measured using mean standardized uptake value (BM-SUVmean). The diagnosis of BM involvement was based on either BM histological findings or disappearance of increased uptake at end-treatment PET/CT in patients who responded to treatment.Sixty eight cases with FL were included. Sixteen (23.5%) had BM involvement, 13 (19.1%) had a biopsy proven involvement, and 3 (4.4%) had a negative BM biopsy, but increased medullary uptake that normalized post-treatment. BM FDG uptake in these patients was diffuse in 8 (50%) and focal in 8 (50%). Focal increased uptake was indicative of BM involvement; however, diffuse uptake was associated with 17 false positive cases (32.7%). Overall, visual assessment of BM involvement had a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 48.5%. On a quantitative assessment, BM-SUVmean was significantly higher in patients with BM involvement (SUVmean of 3.7 [1.7–6] vs 1.4 [0.4–2.65], Pu200a<u200a0.001). On receiver operator curve (ROC) analysis, BM-SUVmeanu200a>u200a2.7 had a PPV of 100% for BM involvement (sensitivity of 68%), while BM-SUVmeanu200a<u200a1.7 had an NPV of 100% (specificity of 73%).Visual assessment of PET/CT is appropriate for ruling out BM involvement by FL. Although focal increased uptake indicates marrow involvement, diffuse uptake is nonspecific. SUV measurement improves PET/CT diagnostic accuracy, identifying additional 19% of patients with BM involvement that would have been otherwise missed.

Efficacy and safety of front-line therapy with fludarabine-cyclophosphamide-rituximab regimen for chronic lymphocytic leukemia outside clinical trials: the Israeli CLL Study Group experience

This study aimed to evaluate the efficacy and safety of the fludarabine-cyclophosphamide-rituximab regimen for young physically fit patients with chronic lymphocytic leukemia in the “real-life” setting. We specifically focused on the impact of dose reduction on patient outcomes. The patient cohort consisted of 128 patients with chronic lymphocytic leukemia (≤70 years) treated at 10 Israeli centers with front-line fludarabine-cyclophosphamide-rituximab. We defined reduced chemotherapy as two-thirds or less of the total indicated dose. Patients treated with rituximab were divided into two groups and compared: those who received full dosages of 375 mg/m2 or 500 mg/m2, and patients given less than six cycles with either dose. Overall and clinical complete response rates (92.8% and 70.4%), as well as toxicities and overall survival (median not reached at 6 years), were similar to other reported clinical trials, but progression-free survival was shorter (42.5 months). Almost 50% of patients had some dose reduction of chemotherapy, 21% receiving less than two-thirds of the indicated dose, while close to 30% did not complete six cycles of rituximab. Reduced doses of chemotherapy and rituximab were independently associated with shorter progression-free survival (hazard ratio 3.6, P<0.0001 for reduced chemotherapy; hazard ratio 2.5, P=0.003 for incomplete-treatment with rituximab). Achieving a complete response was associated with longer overall survival but was not linked to the given dose of chemoimmunotherapy. In younger physically fit patients, front-line fludarabine-cyclophosphamide-rituximab therapy in the “real-life” setting achieves long remissions (albeit shorter than in clinical trials) and prolonged overall survival. However, dose reductions are commonly administered and may impact outcome.

The value of electrophysiologic study in decision-making regarding the need for pacemaker implantation after TAVI.

PurposeThe purpose of this study was to evaluate electrophysiologic study (EPS) in risk stratification of relative indications for pacemaker implantation (PMI) after transcatheter aortic valve implantation (TAVI).MethodsWe reviewed files of all patients who had a left bundle branch block (LBBB) and underwent EPS after TAVI between 3/2009 and 5/2015. The indications for EPS were new-onset LBBB and the presence of an old or a new-onset LBBB associated with either PR prolongation after TAVI (∆PR >20xa0ms) or with “slow” atrial fibrillation (<100/min). Pacemakers were implanted when significant infranodal disease was demonstrated. The control group comprised of 55 consecutive patients who underwent TAVI and had an indication for an EPS per our definitions. These patients were discharged without further intervention. All patients were followed during 1xa0year for the composite endpoint of mortality or PMI after hospital discharge.ResultsIndications for EPS were new LBBB (nu2009=u20098, 30.8%), new LBBB + ∆PR >20xa0ms (nu2009=u20099, 34.6%), baseline LBBB + ∆PR >20xa0ms (nu2009=u20097, 26.9%) and new LBBB + slow AF <100xa0bpm (nu2009=u20092, 7.7%). Multilevel conduction disturbances involving the AV node (nu2009=u200919, 73.1%), the His (nu2009=u20093, 11.5%), and the infra-His system (nu2009=u20094, 15.4%) were found. Post discharge, there were 5 (9%) deaths and 3 (5.5%) PMI in the control group compared to none in the EPS group corresponding to event-free survival of 85 and 100%, respectively (pu2009=u20090.04).ConclusionsPatients with LBBB with or without ∆PR >20xa0ms are at a higher risk of mortality and late PMI at 1-year follow-up. EPS can be used to safely identify patients in whom a PMI is needed.

Recurrent hospitalizations with moderate to severe hyponatremia in older adults and its associated mortality

BACKGROUNDnRecurrent hospitalizations with hyponatremia are commonly encountered in older adults admitted to Internal Medicine wards. However, the incidence and the prognostic implication of this phenomenon have never been studied.nnnMETHODSnMedical charts of all older adults (≥75 years) admitted to Internal Medicine wards at a tertiary medical center during 2009-2010 with symptomatic moderate to severe hyponatremia (blood sodium ≤130 meq/l) upon admission were reviewed. The study group included patients with one or more hospitalizations with hyponatremia in the year following the first hospitalization with hyponatremia. The control group included patients with a single hospitalization with hyponatremia. Mortality rates were studied one year following the second hospitalization with hyponatremia in the study group and one year following the single hospitalization with hyponatremia in the control group. Regression analysis was used to study the association between recurrent hospitalizations with hyponatremia and 1-year mortality while controlling for demographics, chronic co-morbidities, albumin serum levels, and the number of hospitalizations.nnnRESULTSnThe cohort included 431 older adults: 301 (69.8%) women; mean age of 84.6±5.6 years. Overall, 120 (27.8%) patients had recurrent hospitalizations with hyponatremia and 125 (29.0%) patients died within a year. 1-Year mortality rates were higher in patients with recurrent hospitalizations with hyponatremia than in patients with a single hospitalization with hyponatremia (42.5% vs. 23.8%; p<0.0001). Regression analysis showed that recurrent hospitalizations with hyponatremia were independently associated with 1-year mortality (odds ratio 1.9; 95% confidence interval 1.1-3.2; p=0.018).nnnCONCLUSIONSnRecurrent hospitalizations with hyponatremia in older adults are common and associated with 1-year mortality.

Primary failure of bortezomib in newly diagnosed multiple myeloma – understanding the magnitude, predictors, and significance

Abstract Botezomib-based induction is highly effective for the treatment of newly diagnosed multiple myeloma (NDMM). We investigated the outcomes of NDMM patients who failed to respond to bortezomib-based induction in a ‘real-life’ clinical setting. In a cohort of 295 consecutive NDMM patients in 3 medical centers, 74 (25%) failed to achieve at least partial response after 4 induction cycles, and were classified as non-responsive. Compared to induction responders, they were older, more frequently anemic, had a higher incidence of del17p and ISS-3, and a worse performance status. In multivariable analysis, bortezomib-based induction failure occurred in 25% of patients and was the strongest independent factor predicting mortality with a 5-fold hazard ratio (95% CI 1.44–8.68). Three-year overall survival in responsive vs. non-responsive patients were 76% vs. 53%, respectively (pu2009<u20090.0001). Survival from time of salvage second-line treatment was significantly shorter among induction non-responders vs. responders (25 months vs. not-reached, pu2009=u20090.024).

Persistently low lymphocyte counts after FCR therapy for chronic lymphocytic leukemia are associated with longer overall survival

Decreased absolute lymphocyte counts (ALCs) following frontline therapy for chronic lymphocytic leukemia may be associated with disease control, even in patients without evidence of minimal residual disease. We studied the prognostic significance of ALCs during the first year following treatment with fludarabine, cyclophosphamide, and rituximab (FCR).

Outcomes of second-line treatment after fludarabine cyclophosphamide and rituximab in patients with chronic lymphocytic leukemia outside clinical trials

To evaluate disease characteristics and long‐term outcomes in patients requiring second‐line treatment following fludarabine, cyclophosphamide, and rituximab (FCR), for relapsed/refractory disease (R/R), or following discontinuation due to toxicities.

Can bone marrow cellularity help in predicting prognosis in myelodysplastic syndromes

To ascertain the relevance of bone marrow cellularity (BMC) to the interpretation of blast percentage (blast%) in MDS prognostication.

Gender differences in mortality among statin users aged 80 years or more

BackgroundLittle is known about the prognosis associated with statin therapy and its gender differences in older adults aged ≥80xa0years.ObjectiveTo study the mortality and survival associated with statin therapy and their gender differences in older adults aged ≥80xa0years.MethodThis was axa0historical prospective study conducted at axa0tertiary medical center. The medical charts of all older adults aged ≥80xa0years who had been admitted to axa0single internal medicine department during 1 year were reviewed. All-cause 3‑year mortality and survival rates following hospital admission in men and in women using statins were investigated.ResultsThe final cohort included 216 patients: 122 (56.5%) women, mean age 85.3xa0± 3.9xa0years. Overall, 66 (53.2%) women and 58 (46.8%) men used statins for 3 years or more following hospital admission. During this time 48 (39.3%) women and 48 (51.1%) men died. The all-cause 3‑year mortality rates were significantly lower only in women who had used statins compared with women who had not used statins (24.2% vs. 57.1%; relative riskxa0= 0.2; 95% confidence interval 0.1–0.5; pxa0< 0.0001). The 3‑year cumulative survival rates were significantly higher in women who had used statins as part of primary as well as secondary cardiovascular prevention (pxa0< 0.0001 and pxa0= 0.014, respectively). Axa0Cox regression analysis showed that statin therapy was independently associated with low 3‑year cumulative mortality rates in women (hazard ratio=0.3; 95% confidence interval=0.1–0.6; pxa0= 0.001).ConclusionIn older adults aged ≥80xa0years, statin therapy is associated with high 3‑year cumulative survival rates only in women.ZusammenfassungHintergrundÜber die mit einer Statintherapie assoziierte Prognose und die Geschlechtsunterschiede bei älteren Menschen (≥80xa0Jahre) ist wenig bekannt.ZielZiel war es, die Mortalitäts- und Überlebensrate sowie die Geschlechtsunterschiede bei einer Statintherapie bei älteren Menschen (≥80xa0Jahre) zu untersuchen.MethodeEine historische prospektive Studie wurde in einem tertiären medizinischen Zentrum durchgeführt. Es erfolgte die Überprüfung der Patientenakten aller älteren Patienten (≥80xa0Jahre), die im 1. Jahr einer einzelnen Abteilung für Innere Medizin zugewiesen wurden. Die 3‑Jahres-Mortalität jeglicher Ursache und die Überlebensraten nach Krankenhauseinweisung bei Männern und Frauen, die Statine einnahmen, wurden untersucht.ErgebnisseIn die finale Kohorte wurden 216xa0Patienten eingeschlossen, davon 122 (56,5%) Frauen (mittleres Alter: 85,3xa0± 3,9xa0Jahre). Insgesamt nahmen 66 (53,2%) Frauen und 58 (46,8%) Männer Statine für 3xa0Jahre oder länger nach einer Krankenhauseinweisung ein. Während dieser Zeit starben 48 (39,3%) Frauen und 48 (51,1%) Männer. Die 3‑Jahres-Mortalitätsrate jeglicher Ursache war nur bei Frauen, die Statine einnahmen, signifikant geringer als bei Frauen, die keine Statine einnahmen (24,2% vs. 57,1%; relatives Risiko: 0,2; 95% Konfidenzintervall [CI] 0,1–0,5; pxa0< 0.0001). Die kumulative Überlebensrate war signifikant höher bei Frauen, die als Teil der kardiovaskulären Primär- und Sekundärprävention Statine einnahmen (pxa0< 0,0001 bzw. pxa0= 0,014). Eine Cox-Regressionsanalyse zeigte, dass eine Statintherapie unabhängig mit einer geringeren 3‑Jahres-Mortalitätsrate bei Frauen assoziiert war (Hazard-Ratio 0,3; 95% CI 0,1–0,6; pxa0= 0,001).SchlussfolgerungBei älteren Menschen (≥80xa0Jahre) ist eine Statintherapie nur bei Frauen mit einer hohen kumulativen 3‑Jahres-Überlebensrate assoziiert.