Israel Medical Association Journal

Idiopathic pulmonary arterial hypertension (IPAH) is an isolated small-vessel disease comprising vasoconstriction, remodeling and thrombosis of small pulmonary arteries. However, there is evidence that IPAH[1] does not respect anatomic boundaries and might extend into large vessels such as large central thrombi. On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH) represents a distinct category of pulmonary hypertension as it is thought to be due to an occlusion of the major pulmonary arteries following a thromboembolic event. However, it is currently evident that in most patients, there is a concomitant small-vessel disease. The involvement of both small and large vessels in both IPAH and CTEPH[2] together with a high incidence of silent thromboembolic events might create difficulties in identifying the true cause of pulmonary hypertension. An accurate diagnosis of the cause determines the management and prognosis. Patients with CTEPH can potentially be offered curative surgery in the form of pulmonary endarterectomy; however, oxygen, vasodilators, anticoagulation, and lung transplantation are more feasible options for IPAH.

Background: Coronary CT angiography is an accurate imaging modality; however, its main drawback is the radiation dose. A new technology, the "step and shoot," which reduces the radiation up to one-eighth, is now available.

Objectives: To assess our initial experience using the "step-and-shoot" technology for various vascular pathologies.

Methods: During a 10 month period 125 consecutive asymptomatic patients (111 men and 14 women aged 25–82, average age 54.9 years) with various clinical indications that were appropriate for step-and-shoot CCTA[1] (regular heart rate < 65 beats/minute and body weight < 115 kg) were scanned with a 64-slice multidetector computed tomography Brilliance scanner (Philips, USA). The preparation protocol for the scan was the same as for the regular coronary CTA. All examinations were interpreted by at least one experienced radiologist and one experienced interventional cardiologist. The quality of the examinations was graded from 1 (excellent imaging quality of all coronary segments) to 4 (poor quality, not diagnostic). There were 99 patients without a history of coronary intervention, 13 after coronary stent deployment (19 stents), and 3 after coronary artery bypass graft.

Results: Coronary interpretation was obtained in 122 examinations (97.6%). The imaging quality obtained was as follows: 103 patients scored 1 (82.4%), 15 scored 2 (12%), 4 scored 3 (3.2%) and 3 scored 4 (2.4%). The grades were unrelated to cardiac history or type of previous examinations. Poor image quality occurred because of sudden heart rate acceleration during the scan (one patient), movement and respiration (one patient), and arrhythmia and bad scan timing (in one). Two patients were referred to percutaneous coronary intervention based on the CCTA findings, which correlated perfectly.

Conclusions: Step-and-shoot CCTA is a reliable technique and CCTA algorithm comparable to the regular CCTA. This technique requires the lowest radiation dose, as compared to other coronary imaging modalities, that can be used for all CCTA indications based on the inclusion criteria of low (> 65 bpm) and stable heart rate.

Background: In many hospitals a chest X-ray is performed routinely at each patient’s admission. There are scant data regarding its usefulness in contemporary patient populations, which are characterized by patients’ increasing age, severity of illness, and different comorbidities.

Methods: We studied consecutive patients admitted during a 2 month period to a single department of medicine, where hospital policy mandates performing a CXR[1] on admission or soon after. Two senior clinicians who were not involved in the care of these patients assessed the discharge summaries for a clinical indication to perform CXR on admission, as well as its contribution to patient management (major positive, major negative, minor positive, or no contribution). Logistic regression analysis was performed with the SPSS 12 software program.

Results: The study population comprised 675 patients whose mean age was 64.5 ± 17.2 years. Their presenting complaints included chest pain (18%), dyspnea (12%), weakness (10.5%), fever (9%), abdominal pain (8%) and neurologic complaints (7.5%). Physical examination of the chest was normal in 585 (87%) of the cases and abnormal in 87 (13%). Examination of the heart was normal in 518 (77%) and abnormal in 129 (19%). In 19.6% (130 cases) CXR was not performed. Of the 545 CXRs done, 260 (48%) were normal. In only 128 (23.5%) did the admission CXR make a major positive contribution to diagnosis or treatment. In 61 (11.2%) it provided a minor positive contribution and in 153 (28.1%) a major negative contribution. In 184 patients (33.8%) the CXR did not affect either diagnosis or management. It made a major positive contribution to management in patients for whom there was an indication for performing the X-ray (odds ratio 10.3, P < 0.0005) and in those with a relevant finding on physical examination (OR[2] 1.63, P = 0.110). For a major negative contribution of the CXR to management (i.e., ruling out clinically important possibilities), the clinical indication was also very important (OR 72.9, P < 0.005). When patients with either a clinical indication for performing a CXR or an abnormal chest examination were excluded, 329 patients remained (60% of the 545 who had a CXR) in only 12 of them (3.6%) did the routine admission CXR contribute to patient management.

Conclusions: A routine admission CXR has a significant impact on patient management only in those patients in whom there are relevant findings on physical examination or a clear clinical indication for performing the test. There is no need to routinely order CXR on admission to hospital.

[1] CXR = chest X-ray

[2] OR = odds ratio

Background: An accurate preoperative definition of tumor and lymph node status is needed for reaching the correct decision regarding rectal cancer treatment. Transrectal ultrasonography is the most commonly used diagnostic modality for the local staging of rectal cancer.

Objectives: To determine the accuracy of TRUS[1] in the staging of rectal cancer.

Methods: We conducted a retrospective study on 95 patients evaluated by TRUS. The rectum was subdivided into two parts (lower and upper).

Results: Sixty patients underwent radical surgery. Of these, 34 received no preoperative chemo-irradiation owing to µT1, µT2 tumor or the patient’s choice (neo-adjuvant treatment was suggested to patients with adenocarcinoma that proved to be µT3). The overall accuracy rate was 80% for T stage. Overstaging was found in 13.3% and understaging in 6.7%.The N-stage was correctly assessed in 70%. The overall accuracy rate for tumors was 73.9% in the lower part and 90.9% in the upper. A trend towards a lower accuracy rate for low-lying tumors compared to high-located rectal tumors was found (P = 0.532), which did not reach statistical significance.

Conclusions: TRUS gave better results for T1 and T3 stage rectal tumors but was inaccurate for stage T2, indicating the possible need for local excision in order to base the final treatment for T2 tumors on pathologic staging.
[1] TRUS = transrectal ultrasonography
 

Background: The best therapeutic alternative for patients suffering from in-stent restenosis after drug-eluting stent implantation remains to be elucidated.

Objective: To characterize the pattern, treatment and outcomes of DES[1]-related in-stent restenosis in patients treated at our institution.

Methods: We determined the incidence and major adverse clinical events in 71 consecutive patients with DES failure among 2473 patients who were treated with 2548 drug-eluting stents between 2004 and 2007. We analyzed the clinical data, procedural parameters and clinical outcomes.

Results: The type and number of stents implanted were as follows: Cypher (n=1808), Endeavor (421) and Taxus (319) of these, 53 (2.9%), 10 (2.4%), and 8 (2.5%) patients respectively presented with restenosis. The mean time to restenosis was 11.3 ± 9.9 months. Patients’ mean age was 65 ± 11 years 75% were male, and 68% had diabetes mellitus. Unstable angina was the clinical presentation in 52 (73%). At 6 months, 3 patients had developed myocardial infarction (4.2%), repeat restenosis at follow-up was diagnosed in 8 patients (11.3%), the overall major adverse clinical events rate was 18.3% (13 patients), and 2 patients died (2.8%).

Conclusions: Drug-eluting stent-related restenosis is relatively infrequent but remains a clinical challenge. It occurs more frequently in complex lesion subsets, but the overall intermediate-term prognosis is tolerable.  

[1] DES = drug-eluting stent

Background: Hypocalcaemia following thyroid and parathyroid surgery is a well-recognized potential complication.

Objectives: To determine the utility of intraoperative quick parathormone assay in predicting severe hypocalcemia development following parathyroidectomy for a single-gland adenoma causing primary hyperparathyroidism.

Methods: A retrospective cohort study was performed. IO-QPTH[1] values were measured at time 0 (T0) before incision, and 10 (T10) and 30 minutes (T30) following excision of the hyperfunctioning gland. Percent decrease in IO-QPTH at 10 minutes (T10), maximum percent decrease of IO-QPTH value, and lowest actual IO-QPTH value obtained at surgery were used to determine any correlation with the development of postoperative hypocalcemia requiring treatment.

Results: Percent decrease in IO-QPTH at 10 minutes, maximum percent decrease in IO-QPTH and lowest IO-QPTH value did not correlate with the lowest postoperative calcium levels measured 18 hours after surgery (r = 0.017, P = 0.860 r = 0.018, P = 0.850 and r = 0.002, P = 0.985 respectively). For the purposes of our analysis, patients were subdivided into three groups. Group 1 comprised 68 patients with normal calcium levels (serum Ca 8.6¨C10.3 mg/dl) Group 2 had 28 patients with hypocalcemia (8.1¨C8.6 mg/dl) Group 3 included 12 patients with severe hypocalcemia (calcium level ¡Ü 8.0 mg/dl) requiring calcium supplementation due to symptoms of hypocalcemia. There was no difference between the three groups in the lowest IO-QPTH value (P = 0.378), percent decrease in IO-QPTH (P = 0.305) and maximum percent decrease in IO-QPTH (P = 0.142).

Conclusions: IO-QPTH evaluation was not useful in predicting the group of patients susceptible to develop severe postoperative hypocalcemia.  

[1] IO-QPTH = intraoperative quick parathormone

Background: Patients with severe persistent asthma despite GINA 2002 step 4 treatment are at risk for asthma-related morbidity and mortality. This study constitutes the Israeli arm of the international INNOVATE study.

Objectives: To determine the efficacy and safety of Xolair® as an add-on treatment in patients with severe persistent asthma.

Methods: Asthma patients (age 12–75 years) not controlled with high dose inhaled corticosteroids and long-active beta-2 agonists were randomized to receive either Xolair® or placebo for 28 weeks in a double-blind study in two Israeli centers.

Results: Thirty-three patients, 20 females and 13 males, mean age 54 ± 11.7 years, were included in the Israeli arm of the INNOVATE study. There were neither major adverse events nor withdrawals from the study. Xolair® (omalizumab) significantly reduced the rate of clinically significant asthma exacerbations (55% reduction) and all asthma-related emergency visits (53% reduction).
Conclusions: In patients with severe persistent difficult-to-treat asthma, despite regular treatment with LABA[1] and inhaled corticosteroids (GINA 2002 step 4), Xolair® is a safe and effective treatment

Objectives: To investigate the incidence of splenic emboli treated in a single general internal medicine department over the last 3 years.

Methods: We examined the records of a 35 bed internal medicine department in a hospital in the center of Israel.

Results: Over a period of 3 years 13 patients admitted to one internal medicine department developed acute abdominal pain and areas of hypoperfusion in the spleen on contrast computed tomography imaging. The patients were treated with anticoagulants, their course was benign and there were no long-term sequelae.

Conclusions: Embolus to the spleen is not rare in an internal medicine department. Diagnosis can be easily made by contrast CT scanning and treatment with anticoagulants results in a good prognosis. 

Objectives: To determine whether reliable data could be obtained at lower cost.

Methods: The study sample consisted of 50 patients with mild to severe stable COPD]1[. All underwent pulmonary function test and the cardiopulmonary exercise test, 6 minute walk and 15 step exercise oximetry test as part of their regular follow-up visit. Functional capacity was graded according to each test separately and the functional capacities obtained were correlated.

Results: The results showed that most of the patients had severe COPD according to pulmonary function tests (mean forced expiratory volume in the first second 46.3 ± 19.9% of predicted value). There was a good correlation between the cardiopulmonary exercise test and the 6 minute walk functional capacity classes (r = 0.44, P = 0.0013). We did not find such correlation between the 15 step exercise oximetry test and the cardiopulmonary exercise test (r = 0.07, P = 0.64).

Conclusions: The study shows that the 6 minute walk is a reliable and accurate test in the evaluation of functional capacity in COPD patients.

Background: Left main coronary artery disease is considered a surgical indication in most centers. However, in some cases prohibited from surgery or in patients with prior bypass grafting, there is a need for percutaneous coronary intervention in LMCA[1] disease scenarios.

Objectives: To assess the clinical outcomes among patients undergoing stent-based LMCA angioplasty.

Methods: We identified 34 consecutive patients who underwent PCI[2] in LMCA at our institution. Procedural data and clinical outcomes were obtained for all patients.

Results: The mean age was 71 ± 12 years. There were 27 elective and 7 emergent procedures performed on 23 “protected” LMCA and 11 “unprotected” LMCA. In emergent procedures, the prevalence of cardiogenic shock (29% vs. 0%, P = 0.04) in patients with prior coronary bypass (29% vs. 8.5%, P = 0.007) was significantly higher compared to elective cases. Procedural success in emergent procedures was significantly lower than in elective procedures (71 vs. 100%, P = 0.04). In emergent versus elective procedures, the in-hospital mortality rate was higher (43 vs. 0%, P = 0.006). The rate of cumulative major adverse cardiac events at 1 and 6 months was 43% and 71% in emergent cases versus 0% and 33% in elective cases (P < 0.05 for both comparisons). In patients with “unprotected” LMCA the overall major cardiac events at 1 month was higher compared to “protected” LMCA patients (27 vs. 0%, P = 0.02). Multivariate analysis revealed emergent procedure as an independent predictor for mortality and adverse cardiac events (odds ratio 6.7; 95% confidence interval 1.2–36; P = 0.02).

Conclusions: Percutaneous interventions in LMCA are feasible and relatively safe in carefully selected cases. Procedural outcomes and clinical prognosis is highly dependent on the nature of disease prior to angioplasty (e.g., elective vs. emergent procedure) as well as on protection of the LMCA by patent grafts.

Background: Transcobalamin II is a serum transport protein for vitamin B₁₂. Small variations in TC-II[1] affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B₁₂ deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes.

Objectives: To study 23 members of a four-generation family with hereditary vitamin B₁₂ deficiency and neurologic disorders.

Methods: Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members.

Results: Partial TC-II deficiency was found in 19 subjects. Apo TC- II (free TC-II unbound to vitamin B₁₂) and total unsaturated B₁₂ binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B₁₂) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B₁₂ levels but were not anemic. Low serum B₁₂ levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B₁₂ injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency.

Conclusions: We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances – despite normal serum vitamin B₁₂ levels. Low serum UBBC[2] and apo TC-II should confirm the diagnosis. Early vitamin B₁₂ therapy may prevent irreversible neurologic damage.