Israel Medical Association Journal

Background: Vitamin D insufficiency is associated with autoimmune and chronic inflammatory diseases such as tuberculosis and sarcoidosis. 

Objectives: To evaluate the vitamin D-dependent mechanisms of immunity and autoimmunity in different forms of pulmonary tuberculosis and sarcoidosis.

Methods: We measured the serum levels of 25(OH)D and 1,25(OH)2D, individual autoimmune profiles, plasma concentrations of cathelicidin, several hormones, and production of nine cytokines in patients with short- and long-duration tuberculosis and sarcoidosis.

Results: The level of 25(OH)D was significantly decreased in all patients. Concentration of 1,25(OH)2D was elevated only in sarcoidosis, prolactin content was augmented only in tuberculosis. We saw no expected increase of cathelicidin levels in tuberculosis and sarcoidosis. The individual mean immune reactivity levels of autoantibodies to 24 antigens were significantly lower in tuberculosis and sarcoidosis patients compared to healthy controls. Pronounced deviations from individual mean immune reactivity levels were found for several autoantigens in all patients. The induced production of interferon gamma-γ, interleukin (IL) 2, 17, and 8 by peripheral blood mononuclear cells was significantly increased in patients of both tuberculosis groups, but spontaneous production of tumor necrosis factor-α, IL-2, and IL-6 was lower in the tuberculosis patients than in healthy controls. We registered marked differences in the groups of tuberculosis patients. 

Conclusions: We demonstrated the role of vitamin D deficiency in poor cathelicidin response in  tuberculosis and sarcoidosis. Both diseases are accompanied by significant changes in the autoimmune profile, probably related to the status of vitamin D and cytokine regulation. 

 

Taxanes are often used in the treatment of many types of cancers. Side effects of docetaxel are not as well documented as paclitaxel, but both can cause pulmonary injury. We present a dramatic case of a patient being treated for prostatic adenocarcinoma with docetaxel who presented with interstitial pneumonitis and responded dramatically to the early treatment with corticosteroids. This case is important as it reveals the side effects of docetaxel administration without administration of other chemotherapeutic agents, and it illustrates the importance of early diagnosis and treatment of docetaxel-induced interstitial pneumonitis. Further research into the mechanism of the side effects of docetaxel is warranted.

Background: Radiotherapy to the prostate bed is used to eradicate residual microscopic disease following radical prostatectomy for prostate cancer. Recommendations are based on historical series. 

Objectives: To determine outcomes and toxicity of contemporary salvage radiation therapy (SRT) to the prostate bed. 

Methods: We reviewed a prospective ethics committee-approved database of 229 patients referred for SRT. Median pre-radiation prostate-specific antigen (PSA) was 0.5 ng/ml and median follow-up was 50.4 months (range 13.7–128). Treatment was planned and delivered using modern three-dimensional radiation techniques. Mean bioequivalent dose was 71 Gy (range 64–83 Gy). Progression was defined as two consecutive increases in PSA level > 0.2 ng/ml, metastases on follow-up imaging, commencement of anti-androgen treatment for any reason, or death from prostate cancer. Kaplan-Meier survival estimates and multivariate analysis was performed using STATA. 

Results: Five year progression-free survival was 68% (95%CI 59.8–74.8%), and stratified by PSA was 87%, 70% and 47% for PSA < 0.3, 0.3–0.7, and > 0.7 ng/ml (P < 0.001). Metastasis-free survival was 92.5%, prostate cancer-specific survival 96.4%, and overall survival 94.9%. Low pre-radiation PSA value was the most important predictor of progression-free survival (HR 2.76, P < 0.001). Daily image guidance was associated with reduced risk of gastrointestinal and genitourinary toxicity (P < 0.005). 

Conclusions: Contemporary SRT is associated with favorable outcomes. Early initiation of SRT at PSA < 0.3 ng/ml improves progression-free survival. Daily image guidance with online correction is associated with a decreased incidence of late toxicity.

 

Background: The association between antiphospholipid antibodies (aPL) and multiple sclerosis (MS) has been suggested previously, but prior studies provided contradicting findings. 

Objectives: To characterize the expression profile of eight classic and non-classic aPL in patients diagnosed with MS.

Methods: Using the BioPlex™ 2200 immunoassay, we measured the levels of serum immunoglobulin (Ig)M and IgG isotypes of three classic aPL and five non-classic aPL in 98 subjects with MS and 237 healthy controls. 

Results: Three non-classic aPL were significantly more prevalent among MS patients in comparison to the control group. These antibodies included IgM and IgG against phosphatidylserine-β2GPI (PS-B2), IgG prothrombin complex (PT-PT) and IgM prothrombin (PT). The positive results according to Bonferroni correction are PS-B2 IgG and PT-PT IgG. The remaining aPL profiles did not differ significantly between the two groups.

Conclusions: An association between certain non-classic aPL and MS has been established. The specific role of these autoantibodies in the pathogenesis of the condition remains uncertain.  

 

Background: In the last decade the number of robotic devices and the medical procedures utilizing them increased significantly around the world.

Objective: To evaluate the implementation of robotic surgeries in Israel in various surgical disciplines.

Methods: We conducted a retrospective study accessing information about the annual purchases of robots, the number of physicians trained for their use, and the number of robotic surgeries performed each year, according to indications of surgery and the disciplines of the operating medical staff. The data were taken from the database of Intuitive Surgical Inc.

Results: Six robots were purchased by six medical centers in Israel during the years 2008–2013. There are currently 150 physicians trained to use the robot in one of the simulators of Intuitive Surgical Inc. Of them, 104 are listed as active robotic surgeons. Most of these physicians are urologists, gynecologists, or general surgeons. The number of robotic surgeries increased each year in all fields in which it was implemented. In 2013, 975 robotic surgeries were performed in Israel. Of them, 52% were performed by urologists; 80% of which were radical prostatectomy. 

Conclusions: The use of robotic surgery increased considerably in Israel over recent years, in urology, gynecology, general surgery, and otolaryngology. Despite the lack of conclusive evidence of the advantages of robotic surgery over the laparoscopic approach, the market power and the desire to be at the technological forefront drive many medical centers to purchase the robot and to train physicians in its use.

 

A fundamental challenge for multiple sclerosis (MS) therapy is to promote repair and remyelination beyond their limited spontaneous extent. Glatiramer acetate (GA, Copaxone®), an approved treatment for MS, has been shown to induce immunomodulation as well as neuroprotection in the inflamed central nervous system (CNS) in MS and in its model, experimental autoimmune encephalomyelitis (EAE). Using electron microscopy, immunohistochemistry, and advanced magnetic resonance imaging, we have demonstrated diminished myelin damage in GA-treated mice, in both relapsing-remitting and chronic EAE, even when treatment was applied late after the disease exacerbation, suggesting repair. Furthermore, quantitative analysis indicated significant elevation in remyelinated axons in GA-treated compared to untreated EAE mice. To further prove that GA can promote myelination, we studied its effect in the developing naïve CNS, when injected postnatally. Immunohistochemical and ultrastructural analyses revealed significant increase in the number of myelinated axons, the thickness of the myelin encircling them, and the resulting g-ratios in the spinal cords of GA-injected mice compared to their phosphate-buffered saline-injected littermates. A prominent elevation in the amount of progenitor oligodendrocytes and their proliferation, as well as in mature oligodendrocytes, implied that the effect of GA is linked to the differentiation along the oligodendroglial cascade. Furthermore, a functional advantage in rotating rod test was exhibited by GA-injected mice over their littermates. These cumulative findings indicate that GA treatment affects myelination under inflammatory as well as non-inflammatory conditions, supporting the notion that the repair process in the CNS can be up-regulated by therapy.

Objectives: To describe the exposures experienced by emergency responders to smoke, fire retardants and stress; the utilization of protective equipment; and the frequency of corresponding symptoms during and following the Carmel Forest fire.

Methods: A cohort of 204 firefighters and 68 police who took part in rescue and fire-abating activities during the Carmel Forest fire were recruited from a representative sample of participating stations throughout the country and interviewed regarding their activities during the fire and their coinciding symptoms. Unpaired two-sample t-test compared mean exposures and symptom frequency for firefighters and police. Chi-square estimates of OR and 95% CI are provided for odds of reporting symptoms, incurring injury or being hospitalized for various risk factors.

Results: Of the study participants, 87% reported having at least one symptom during rescue work at the Carmel Forest fire, with eye irritation (77%) and fatigue (71%) being the most common. Occupational stress was extremely high during the fire; the average length of time working without rest was 18.4 hours among firefighters.

Conclusions: Firefighters and police were exposed to smoke and occupational stress for prolonged periods during the fire. Further research is needed on the residual health effects from exposure to forest fires among emergency responders, and to identify areas for improvement in health preparedness.  

Background: Understanding the mechanism and the main components involved in rheumatic mitral regurgitation (MR) associated with dominant pliable mitral stenosis (MS) may improve our ability to repair some mixed rheumatic mitral valve pathologies.

Objectives: To assess mitral valve structural components in pure mitral stenosis versus mitral stenosis associated with mild regurgitation

Methods: Using two-dimensional echocardiography, we performed mitral valve structural analysis in two groups of patients prior to balloon mitral valvuloplasty (BMV). The first group, consisting of 13 females and 2 males (mean age 39 ± 5 years), suffered from pure pliable mitral stenosis (PPMS), while the second group, with 22 females and 2 males (mean age 44 ± 5 years), had mixed mitral valve disease (MMVD) characterized by mild MR in the presence of dominant pliable MS. All echocardiographic measurements relating to the mechanism of MR were undertaken during the systolic phase.

Results: The mean Wilkins scores of the PPMS and MMVD groups were 7 ± 1 and 8 ± 1 respectively (P = 0.004). No significant differences were found between the MMVD group and the PPMS group regarding annular circumference (15.5 ± 1.4 cm vs. 15.4 ± 1.6 cm, P = 0.84), annular diameter (36 ± 4 mm vs. 38 ± 5 mm, P = 0.18), and chordae tendinae length directed to the anterior mitral leaflet (AML) (10 ± 2 mm vs. 11 ± 2 mm, P = 0.137). However, anterior vs. posterior mitral leaflet length during systole was significantly lower in the MMVD than in the PPMS group (2.2 ± 0.5 vs. 2.8 ± 0.4, P = 0.02), whereas the AML thickness at the co-aptation point was greater in the MMVD than in the PPMS group (7 ± 1 vs. 5 ± 1 mm, P = 0.0004).

Conclusions: In rheumatic valves, thickening and shortening of the AML are the main factors determining the appearance of mild MR in the presence of dominant pliable MS.

Background: Many patients present to the emergency department with chest pain. While in most of them chest pain represents a benign complaint, in some patients it underlies a life-threatening illness.

Objectives: To assess the routine evaluation of patients presenting to the ED[1] with acute chest pain via the utilization of a cardiologist-based chest pain unit using different non-invasive imaging modalities.

Methods: We evaluated the records of 1055 consecutive patients who presented to the ED with complaints of chest pain and were admitted to the CPU[2]. After an observation period and according to the decision of the attending cardiologist, patients underwent myocardial perfusion scintigraphy, multidetector computed tomography, or stress echocardiography.

Results: The CPU attending cardiologist did not prescribe non-invasive evaluation for 108 of the 1055 patients, who were either admitted (58 patients) or discharged (50 patients) after an observation period. Of those remaining, 445 patients underwent MDCT[3], 444 MPS[4], and 58 stress echocardiography. Altogether, 907 patients (86%) were discharged from the CPU. During an average period of 236 ± 223 days, 25 patients (3.1%) were readmitted due to chest pain of suspected cardiac origin, and only 8 patients (0.9%) suffered a major adverse cardiovascular event.

Conclusions: Utilization of the CPU enabled a rapid and thorough evaluation of the patients’ primary complaint, thereby reducing hospitalization costs and occupancy on the one hand and avoiding misdiagnosis in discharged patients on the other.
 

[1] ED = emergency department

[2] CPU = chest pain unit

[3] MDCT = multidetector computed tomography

[4] MPS = myocardial perfusion scintigraphy

Background: The incidence of congenital heart defects, reported to be 5–8/1000 in term infants, is not well established in very low birth weight infants.

Objectives: To establish the incidence of congenital heart defects in VLBW[1] infants in the neonatal intensive care unit of our institution.

Methods: A retrospective analysis of the population in the NICU[2] at our institution was performed. VLBW (BW ≤ 1500 g) infants born between 2001 and 2006 who survived more than 48 hours were included in the study. Infants with clinical signs of heart disease underwent echocardiography.

Results: During the study period 437 VLBW live-born infants met the inclusion criteria. Of these, 281 (64.3 %) underwent echocardiography. CHD[3] was detected in 19 infants (4.4%, 95% confidence interval 2.4–5.4%), significantly higher than the incidence of 5–8/1000 in the general population (P < 0.0001). In the subgroup of 154 infants with BW < 1000 g there were 10 (6.5%) with CHD. In the subgroup of 283 infants with BW 100–-1500 g there were 9 (3.2 %, P = 0.19 vs. VLBW) with CHD.

Conclusions:  Our observations show an increased incidence of CHD in VLBW neonates, as compared to the general population. Since not all infants underwent echocardiography, and minor cardiac defects may have been missed in our VLBW infants, the true incidence may be higher than reported here.