Israel Medical Association Journal

Background: Pulmonary infiltrates (PIs) detected in patients with non-Hodgkin lymphoma (NHL) may present a diagnostic challenge due to their wide differential diagnosis, including infection, pulmonary lymphoma and immunochemotherapy-associated pulmonary toxicity.

Objectives: To characterize therapy-associated PIs by positron emission tomography/computed tomography (PET/CT) imaging.

Methods: We conducted a historical analysis of fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) PIs in NHL patients treated with combined immunochemotherapy including rituximab. Incidence of PIs, radiological features, patients’ characteristics, underlying NHL type, rituximab/chemotherapy dosing schedules, and symptoms were recorded. Therapy-associated PIs were defined as new or worsening PIs appearing after treatment onset, without evidence of active pulmonary lymphoma or infection.

Results: Among 80 patients who met the pre-specified criteria, therapy-associated PIs were identified in 17 (21%), 6 of whom had accompanying symptoms. Increased FDG uptake was observed in nine, and PI resolution in six. The incidence of PIs was higher in females and in patients with aggressive lymphoma, at advanced stages, and in those who had received treatment consisting of a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 14 days (R-CHOP-14).

Conclusions: This characterization of therapy-associated PIs may support the clinician managing NHL patients. Further prospective studies are needed to establish the role of each therapeutic component and the natural history of this phenomenon.

Background: Syncope prognosis varies widely: 1 year mortality may range from 0% in the case of vasovagal events up to 30% in the presence of heart disease. 

Objectives: To assess the outcomes and prognosis of patients with implantable cardiac defibrillator (ICD) and indication of primary prevention and compare patients presenting with or without prior syncope.

Methods: We reviewed the charts of 75 patients who underwent ICD implantation with the indication of primary prevention and history of syncope and compared them to a control group of 80 patients without prior syncope. We assessed the number of ventricular tachycardia (VT), ventricular fibrillation (VF), shock, anti-tachycardia pacing (ATP), and death in each group during the follow-up.

Results: Mean follow-up was 893 days (810–976, 95% confidence interval) (no difference between groups). Patients with prior syncope had a higher ejection fraction (EF) (35.5 ± 12.6 vs. 31.4 ± 8.76, P = 0.02), more episodes of VT (21.3% vs. 3.8%, P = 0.001) and VF (8% vs. 0%, P = 0.01) and also received more electric shocks (18.7% vs. 3.8%, P = 0.004) and ATP (17.3% vs. 6.2%, P = 0.031). There were no differences in inappropriate shocks (6.7% vs. 5%, P = 0.74), in cardiovascular mortality (cumulative 5 year estimate 29.9% vs. 32.2% P = 0.97) and any death (cumulative 5 year estimate 38.1% vs. 48.9% P = 0.18) during the follow-up.

Conclusions: Syncopal patients before ICD implantation seem to have more episodes of VT/VF and shock or ATP. No mortality differences were observed

 

The identification and prompt diagnosis of Horner syndrome (HS) is essential for preventing permanent damage. HS may arise when a lesion presents anywhere along the three-neuron oculosympathetic pathway that begins at the posterior-lateral nuclei of the hypothalamus all the way through to the orbit. We present four cases and review the literature to familiarize the reader with the identification, diagnosis and treatment of Horner syndrome. The four patients, three adults and one child, were followed for at least 6 months following the initial diagnosis (range 6–18 months). There was partial resolution in three of the four cases, while the fourth resolved completely. There are numerous causes of HS, some of them iatrogenic. While iatrogenic cases of HR are rare in both adults and children, HS is seen more often following surgical procedures. Prompt recognition of the syndrome and correction of the offending agent may prevent permanent damage to the neuronal pathway. It is therefore recommended that practitioners be aware of the risks for development of iatrogenic HS and the signs for early detection.

Background: The prevalence and etiology of nephrolithiasis vary, depending on geography, gender and ethnicity. 

Objectives: To analyze the demographic data of return nephrolithiasis patients in a tertiary care center.

Methods: We retrospectively reviewed our prospective registry database of return patients seen at our outpatient clinic for nephrolithiasis. Data included gender, age at first visit, age at first stone event, body mass index (BMI), self-reported hypertension, diabetes mellitus (DM), and hyperlipidemia. All patients were seen at least twice and had undergone a metabolic workup. 

Results: A total of 260 return patients were seen during the period 2010–2015. The male:female ratio was 3.1:1. Mean age at the first stone event was 44.1 years. Median time elapsed since the first stone event to medical evaluation was 5 years (interquartile range 1–12 years). Hypertension was reported by 33.1% of the patients, DM by 23.5% and hyperlipidemia by 30.4%. All three diseases were reported by 11.5% of patients. The metabolic abnormalities detected were hypocitraturia (60%), low urine volume (LUV) (60%), hypercalciuria (40.8%), hyperoxaluria (24.2%), hyperuricosuria (16.5%) and hyperuricemia (13.5%). Stone compositions from most to least frequent were calcium-oxalate (81%), calcium-phosphate (11.9%) and uric acid (7.1%). We also found that 24.6% were obese (BMI ≥ 30 kg/m2) and showed higher rates of hypertension, DM, hyperlipidemia, hyperuricemia and hyperuricosuria compared with non-obese patients. Significantly higher rates of obesity and LUV were detected in females compared with males. Patients over age 45 had lower rates of hyperuricemia compared with patients ≥ 45 years old (P = 0.038).

Conclusions: Factors related to nephrolithiasis can potentially differ among populations and countries. Our findings emphasize the significance of individualized national health programs to address local issues.

 

Background: Atrial fibrillation (AF) is a common complication of coronary artery bypass graft (CABG) surgery, occurring in 20%–40% of patients, mostly during the first week after surgery. It is associated with increased morbidity and mortality, but data are limited. 

Objectives: To assess the correlation between new-onset in-hospital AF following CABG and long-term AF, cerebrovascular accident (CVA), or death.

Methods: We conducted an analysis of 161 consecutive patients who underwent isolated CABG surgery in a tertiary center during the period 2002–2003. 

Results: Patients’ mean age was 72 years, and the majority were males (77%). Approximately half of the patients experienced prior myocardial infarction, and 14% had left ventricular ejection fraction < 40%. Postoperative AF (POAF) occurred in 27% of the patients. Patients were older and had larger left atrium diameter. POAF was strongly correlated with late AF (OR 4.34, 95%CI 1.44–13.1, P = 0.01) during a mean follow-up of 8.5 years. It was also correlated with long-term stroke but was not associated with long-term mortality. 

Conclusions: POAF is a common complication of CABG surgery, which is correlated with late AF and stroke. Patients with POAF should be closely monitored to facilitate early administration of anticoagulant therapy in a high risk population upon recurrence of AF. 

 

Background: Legg-Calvé-Perthes disease (LCPD) is an idiopathic hip osteonecrosis prevalent in children < age 15 years. The etiology remains incompletely understood, partly because of multiple potential environmental risk factors and partly because of lack of genetic markers. It has been hypothesized that hyperactivity may induce mechanical stress and/or vascular damage at a fragile joint. 

Objectives: To assess children with LCPD for markers of attention deficit hyperactivity disorder (ADHD) relative to their unaffected comparably aged siblings to exclude the contribution of hyperactive behavior versus environmental and/or genetic factors in LCPD. 

Methods: All children followed in the Pediatric Orthopedic Clinic, and their comparably aged siblings, were recruited. ADHD was assessed using the TOVA computerized test and DSM-IV criteria. Quality of life and sleep disorders as ancillary tests were assessed using the Child Health Questionnaire (Parent Form 50), Pediatric Outcomes Data Collection Instrument, and Pediatric Daytime Sleepiness Scale.

Results: Sixteen children with LCPD (age 9.1 ± 3.3, 75% males) were compared with their closest-aged siblings (age 9.3 ± 2.6, 30% males). Mean TOVA scores of children with LCPD (-3.79 ± 2.6) and of their non-LCPD siblings (-3.6 ± 4.04) were lower relative to the general population (0 ± 1.8, P < 0.0001). Both group means were in the ADHD range (≤ -1.8) implying that 73% of this LCPD cohort and 53% of their non-LCPD siblings performed in the ADHD range, relative to 3.6% incidence expected in the general population (P < 0.0001). Other test results were similar in both groups. 

Conclusions: Our findings in a small cohort of children with LCPD and their comparably aged siblings do not support an association between LCPD and ADHD. ADHD markers were equally high in the LCPD children and siblings. 

 

Background: Trauma is the leading cause of childhood morbidity and mortality. Abdominal bleeding is one of the common causes of mortality due to trauma. Angiography and embolization are well recognized as the primary treatments in certain cases of acute traumatic hemorrhage in adults; however, evidence is lacking in the pediatric population. 

Objectives: To assess the safety and efficacy of transcatheter arterial embolization (TAE) for blunt and penetrating abdominal and pelvic trauma in the pediatric age group.

Methods: Three children with blunt abdominal trauma and one child with iatrogenic renal injury (age 4–13 years) were managed with TAE for lacerated liver (one patient), pelvic fractures (one patient) and renal injuries (two patients). The first two patients, victims of road accidents, had multisystem injuries and were treated by emergency embolization after fluid resuscitation in the Emergency Department (ED). The other two patients had renal injuries: a 4 year old boy with blunt abdominal trauma was diagnosed on initial computed tomography with an unexpected Wilms tumor and was treated with embolization 1 day after admission due to hemodynamic deterioration caused by active arterial tumor bleeding. The following day he underwent successful nephrectomy. The other patient was 13 year old boy with nephrotic syndrome who underwent renal biopsy and developed hemodynamic instability. After fluid resuscitation, he underwent an initial negative angiography, but second-look angiography the following day revealed active bleeding from an aberrant renal artery, which was then successfully embolized.

Results: In all four patients, TAE was diagnostic as well as therapeutic, and no child required surgical intervention for control of bleeding.

Conclusions: We propose that emergency transcatheter angiography and arterial embolization be considered following resuscitation in the ED as initial treatment in children with ongoing bleeding after blunt abdominal trauma or iatrogenic renal injury. Implementation of this policy demands availability and cooperation of the interventional radiology services. 

 

Background: Laparoscopy has gradually become the gold standard for the treatment of non-palpable testicles (NPT), with different success and complication rates. 

Objectives: To evaluate outcomes of the one-stage laparoscopic orchiopexy for NPT in our department.

Methods: We retrospectively evaluated the medical files of patients who underwent laparoscopic orchidopexy with the identical technique. Only patients with at least one year follow-up were included. At follow-up we assessed the age (at surgery), follow-up time, laterality of testes, postoperative complications, testicular size and testicular localization. 

Results: Thirty-six consecutive patients, median age 16 months, underwent one-stage laparoscopic orchiopexy. Sixteen patients (44.4%) had peeping testis type, in 13 patients (36.1%) the testicle was located within 2 cm from the internal ring and in the remaining 7 patients (19.4%) it was detected > 2 cm from the internal ring. In six children (16.7%) dividing the spermatic vessels was performed in one stage with laparoscopic orchiopexy. In the remaining 30 patients (83.7%) a laparoscopic one-stage procedure was performed with preservation of the spermatic vessels. Testicular atrophy was observed in 2 cases (5.6%), and 6 patients (16%) had a relatively small testicle compared to the contralateral normal testicle at follow-up. Two patients (5.6%) presented with testicle positioning at the entrance area into the scrotum. None of the patients demonstrated hernia recurrence at follow-up. There was no difference in surgical outcome in children who had surgery with preservation of the spermatic vessels versus those who underwent orchiopexy with division of the spermatic vessels in one stage. 

Conclusions: Laparoscopic transection of the testicular vessels appeared to be safe in boys with high abdominal testes that did not reach the scrotum after laparoscopic high retroperitoneal dissection. 

 

Background: Pregnant women with acute abdominal pain pose a diagnostic challenge. Delay in diagnosis may result in significant risk to the fetus. The preferred diagnostic modality is magnetic resonance imaging (MRI), since ultrasonography is often inconclusive, and computed tomography (CT) would expose the fetus to ionizing radiation

Objectives: To describe the process in setting up an around-the-clock MRI service for diagnosing appendicitis in pregnant women and to evaluate the contribution of abdominal MR in the diagnosis of acute appendicitis.

Methods: We conducted a retrospective study of consecutive pregnant women presenting with acute abdominal pain over a 6 year period who underwent MRI studies. A workflow that involved a multidisciplinary team was developed. A modified MRI protocol adapted to pregnancy was formulated. Data regarding patients' characteristics, imaging reports and outcome were collected retrospectively. 

Results: 49 pregnant women with suspected appendicitis were enrolled. Physical examination was followed by ultrasound: when positive, the patients were referred for MR scan or surgery treatment; when the ultrasound was inconclusive, MR scan was performed. In 88% of women appendicitis was ruled out and surgery was prevented. MRI diagnosed all cases with acute appendicitis and one case was inconclusive. The overall statistical performance of the study shows a negative predictive value of 100% (95%CI 91.9–100%) and positive predictive value of 83.3% (95%CI 35.9–99.6%).

Conclusions: Creation of an around-the-clock imaging service using abdominal MRI with the establishment of a workflow chart using a dedicated MR protocol is feasible. It provides a safe way to rule out appendicitis and to avoid futile surgery in pregnant women.

Background: Although 5-amino-salycilic acids (5-ASA) are often used with corticosteroid treatment in moderate-to-severe ulcerative colitis, the value of continuing/initiating 5-ASA in this clinical setting has not been explored. 

Objectives: To investigate the impact of a combination 5-ASA+corticosteroid therapy on the outcome of hospitalized patients with acute moderate-severe ulcerative colitis. 

Methods: We conducted a retrospective study of patients hospitalized with moderate-severe ulcerative colitis in two centers, Israel and South Korea. Patients were classified into those who received 5-ASA and corticosteroids and those who received corticosteroids alone. Analysis was performed for each hospitalization event. The primary outcome was the rate of treatment failure defined as the need for salvage therapy (cyclosporin-A/infliximab/colectomy). The secondary outcomes were 30 days re-admission rates, in-hospital mortality rates, time to improvement, and length of hospitalization. 

Results: We analyzed 209 hospitalization events: 151 patients (72%) received 5-ASA+corticosteroids and 58 (28%) corticosteroids alone. On univariate analysis the combination therapy group had a lower risk for treatment failure (11% vs. 31%, odds ratio 0.28, 95% confidence interval 0.13–0.59, P = 0.001). However, this difference disappeared on multivariate analysis, which showed pre-admission oral corticosteroid treatment to be the most significant factor associated with the need for salvage therapy. 

Conclusions: A signal for possible benefit of a combination 5-ASA and corticosteroids therapy was found, but was confounded by the impact of pre-admission corticosteroid treatment. 

 

Mechanical thrombectomy with stent retrievers is now the reference therapy for acute ischemic stroke (AIS) in the anterior circulation in association with thrombolysis. We conducted an extensive systematic review and meta-analysis to evaluate the clinical and angiographic outcomes of stent-retriever thrombectomy in patients with acute anterior circulation stroke. Available literature published to date on observational studies and three randomized trials (MR CLEAN, ESCAPE, and EXTEND-IA) involving the stent-retriever device were reviewed. Successful recanalization and favorable clinical outcome were defined by a TICI ≥ 2b and modified Rankin Scale score of ≤ 2 at 90 days following AIS, respectively. A total of 2067 patients harboring an anterior circulation stroke were treated with a stent retriever: 433 patients from 3 randomized trials involving the device and 1634 patients from observational studies. Mean NIH Stroke Scale score on admission was 16.6, and mean time from onset to recanalization was 300 minutes. Successful recanalization was achieved in 82% (95%CI 77–86, 31 studies). The 90 day favorable outcome was achieved in 47% (95%CI 42–5.2, 34 studies) with an overall mortality rate of 17% (95%CI 13–20, 31 studies). Symptomatic intracerebral hemorrhage was identified in 6% (95%CI 4–8, 32 studies). In patients with AIS caused by a proximal intracranial occlusion of the anterior circulation, stent-retriever thrombectomy is safe and restores brain reperfusion in four of five treated patients, allowing favorable clinical outcome in one of two AIS patients with large vessel occlusion. 

Immune function is the most basic physiological process in humans and indeed throughout the animal kingdom. Interestingly, the vast majority of textbooks of physiology do not include a chapter on immunity. Our species survival is dependent on the diversity of the immune response and the ability for antigen presentation and effector mechanisms to be enormously promiscuous. As physicians, we are likely all too aware of how brief our life span is and the myriad of diseases and events that shorten it. It is not surprising that we question where our life comes from and our relationship within the universe. Many hypotheses have been offered regarding the likelihood that intelligent life exists elsewhere. We propose that such issues be discussed in the context of basic biologic observations on earth, such as the sight of a dense flock of tens of thousands of starlings maneuvering in rapid twists and turns at dusk before settling in trees for the night. The mathematical likelihood for life elsewhere was proposed by Frank Drake in a classic equation whose 'thesis' has stimulated the search for alien civilizations and the nature of life. A fundamental gap in this equation is the presence of a diverse immune response, a feature essential for survival of Life, presumably also extra-terrestrially.