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עמוד בית
Sun, 24.11.24

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April 2014
Tania Sezin MSc, Emily Avitan-Hersh MD, Margarita Indelman MSc, Roni Moscona MD, Edmond Sabo MD, Rina Katz MSc, Shimon Pollack MD and Reuven Bergman MD
 Background: Human amnion membrane (HAM) was suggested to be a superior antigenic substrate for immunoblotting in detecting autoantibodies of autoimmune bullous skin diseases.

Objectives: To determine the properties of HAM as an antigenic substrate for the detection of autoantibodies in pemphigus vulgaris and bullous pemphigoid.

Methods: Immunomapping and tandem liquid chromatography mass spectrometry were used to delineate the antigenic structure of HAM in 25 pemphigus patients, 41 pemphigoid patients, and 36 controls. Immunoblotting and indirect immunofluorescence were used to study the diagnostic utility of HAM, and the results were compared to those of indirect immunofluorescence on monkey esophagus, immunoblotting using normal human skin, and enzyme-linked immunosorbent assay (ELISA).

Results: Immunomapping demonstrated the presence of all the antigens known to be targeted in autoimmune bullous skin diseases, in both normal human skin and HAM, except for the absence of BP230, and low threshold levels of Dsg1, Dsg3 and Dsc3 in HAM. HAM indirect immunofluorescence demonstrated anti-basement membrane zone antibodies in 48.7% of the pemphigoid patients, and anti-intercellular space antibodies in 72.0% of the pemphigus patients. HAM immunoblotting did not demonstrate anti-BP230 antibodies, but detected anti-BP180 antibodies in 53.6% of the pemphigoid patients. It did not demonstrate anti-Dsg1 and/or anti-Dsg3 antibodies in any of the pemphigus patients. These results were inferior to those of ELISA and monkey esophagus indirect immunofluorescence.

Conclusions: Compared to other studied methods, HAM does not offer advantages in detecting autoantibodies in bullous pemphigoid and pemphigus vulgaris. 

Arie Apel MD, Meirav Kedmi MD, Etai Levi MD, Miriam Berkowicz MD, Yaron Davidovitz MD, Abraham Kneller MD, Elena Ribakovsky MD, Avichai Shimoni MD, Arnon Nagler MD MSc and Abraham Avigdor MD
 Background: Acute lymphocytic leukemia (ALL) is a rare disease with a poor outcome in adults. Over the years different protocols have been developed with the aim of improving the outcome. The German study group protocols (GMALL), which are the most frequently used in our institutions, changed significantly between the periods 1989–93 and 1999–2003.

Objectives: To investigate whether the change in protocols over the years resulted in an outcome difference at two hospitals in Israel.

Methods: We thoroughly reviewed the records of 153 patients from Sheba Medical Center and Soroka Medical Center, of whom 106 comprised the study group. The patients were divided into two groups according to the treatment protocol used: 40 patients with the 1989/93 protocol and 66 with the 1999/2003 protocol. Outcome was analyzed for the two groups.

Results: We found a significant difference in disease-free survival (DFS) between the two groups for B cell-ALL (B-ALL) patients who achieved complete remission after induction. There was no difference in overall survival. We did not find any difference in outcome for T cell-ALL patients or for CD20-positive patients.

Conclusions: In our retrospective analysis, GMALL 99/2003 led to a better DFS for B-ALL patients who were in complete remission after induction. This is possibly related to the differences in medications between the protocols, but may also be due to better supportive care. Despite the proven advantage of the newer protocols regarding overall survival, in our experience there was no other significant difference between the two regimens. 

Eyal Kramer MD, Oscar Herman MD, Jacob Frand MD, Lior Leibou MD, Letizia Schreiber MD and Hananya Vaknine MD
 Background: Basal cell carcinoma (BCC) is the most common malignancy in humans. Several factors have been associated with the biological behavior of these tumors, including histopathologic type, depth of tumor invasion, perineural invasion, and the expression of several biologic markers including Ki67, a proliferative marker. Previous studies assessing the relationship between the proliferative fraction, as expressed by Ki67, and the histologic variants of BCC as well as its association with the tendency to recur, failed to illustrate significant statistical correlation.

Objectives: To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables.

Methods: In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up.  Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histologic analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion.

Results: Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes.

Conclusions: The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histologic subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

George Habib MD MPH, Munir Nashashibi MD and Sara Gips MD
Background: Computed tomography pulmonary angiography (CTPA) is considered the method of choice for diagnosing pulmonary embolism (PE). In most patients with impaired renal function, ventilation-perfusion (V/Q) scanning is the preferred modality.

Objectives: To evaluate the predictive value of V/Q scanning in patients with impaired renal function.

Methods: We assessed all patients with impaired renal function who underwent V/Q scanning. The patients studied included those who also had CTPA (group 1) and those who did not (group 2). We recorded the results of V/Q scanning, chest X-rays, CTPA, D-dimer levels, ultrasound of deep veins, and clinical probability for PE (Wells' score) in group 1. CTPA results were considered true results. Anticoagulant treatment was documented in all the patients.

Results: Of the 45 patients in group 1, 12 (22%) had positive CTPA for PE. The positive predictive value (PPV) for patients with high probability results on V/Q scanning for PE was 30%. Restricting results to D-dimer levels ≥ 1000 ng/ml added little to this value. Restricting results to Wells’ score ≥ 7 resulted in 72% PPV. The negative predictive values for low or moderate probability were ~79 % and ~67% respectively. Of the 95 patients in group 2, all those with high probability for PE were treated with anticoagulants.

Conclusions: Patients with impaired renal function and high probability for PE on V/Q scanning had very low PPV for PE. Due to the lack of CTPA studies, patients with high probability for PE on V/Q scanning were treated with anticoagulants.

Maitseo Kuno Nwako-Mohamadi MBChB BAO MSc, Vidushi Madan MD, Matthew N. Tanko MBBS FMCPath (Nig) and Sandro Vento MD
March 2014
Firas Abu Akar, Revital Arbel, Zvi Benninga, Mushira Aboo Dia and Bettina Steiner-Birmanns
All victims of violence encountered in our emergency rooms and clinics need to be recognized and documented as such. Although there has been progress in the implementation of rules concerning (domestic) violence against women, children and the elderly, the management of cases where patients have been subjected to violence while under the custody of legal enforcement agencies, or patients who have been victims of torture, is still not sufficiently standardized. We describe the Istanbul Protocol of the United Nations, an excellent tool that can help physicians and health professionals recognize and treat cases of torture or institutional violence.

February 2014
Salman Zarka, Masad Barhoum, Tarif Bader, Itay Zoaretz, Elon Glassberg, Oscar Embon and Yitshak Kreiss
Yoav Rosenthal, Amir Arami, Yona Kosashvili, Nir Cohen, Eli Sidon and Steven Velkes
Background: Bisphosphonates reduce the overall risk of fractures among patients with osteoporosis, and this beneficial effect is long-lasting. However, since bisphosphonates inhibit bone remodeling, they may enhance the formation and propagation of micro-cracks over time and patients may therefore be prone to atypical fatigue fractures, mainly in the subtrochanteric region and femoral shaft.

Objectives: To present two cases of subtrochanteric fractures related to bisphosphonate treatment and review of the current literature.

Conclusions: Despite the overall beneficial effect of bisphosphonates, further research is required to prevent this significant complication. 

Noam Rosen, Roy Gigi, Amir Haim, Moshe Salai and Ofir Chechik
Background: Above-the-knee amputations (AKA) and below-the-knee amputations (BKA) are commonly indicated in patients with ischemia, extensive tissue loss, or infection. AKA were previously reported to have better wound-healing rates but poorer rehabilitation rates than BKA.

Objectives: To compare the outcomes of AKA and BKA and to identify risk factors for poor outcome following leg amputation.

Methods: This retrospective cohort study comprised 188 consecutive patients (mean age 72 years, range 25–103, 71% males) who underwent 198 amputations (91 AKA, 107 BKA, 10 bilateral procedures) between February 2007 and May 2010. Included were male and female adults who underwent amputations for ischemic, infected or gangrenotic foot. Excluded were patients whose surgery was performed for other indications (trauma, tumors). Mortality and reoperations (wound debridement or need for conversion to a higher level of amputation) were evaluated as outcomes. Patient- and surgery-related risk factors were studied in relation to these primary outcomes.

Results: The risk factors for mortality were dementia [hazard ratio (HR) 2.769], non-ambulatory status preoperatively (HR 2.281), heart failure (HR 2.013) and renal failure (HR 1.87). Resistant bacterial infection (HR 3.083) emerged as a risk factor for reoperation. Neither AKA nor BKA was found to be an independent predictor of mortality or reoperation.

Conclusions: Both AKA and BKA are associated with very high mortality rates. Mortality is most probably related to serious comorbidities (renal and heart disease) and to reduced functional status and dementia. Resistant bacterial infections are associated with high rates of reoperation. The risk factors identified can aid surgeons and patients to better anticipate and possibly prevent severe complications.

Edward Koifman, Paul Fefer, Ilan Hay, Micha Feinberg, Elad Maor and Victor Guetta
Background: Percutaneous edge-to-edge mitral valve repair using the MitraClip® system has evolved as a new tool in the treatment of mitral regurgitation (MR).

Objectives: To present our initial experience with MitraClip implantation in 20 high risk patients at Sheba Medical Center.

Methods: Twenty high surgical risk patients with symptomatic significant MR underwent MitraClip implantation. Clinical and echocardiographic parameters were recorded at baseline and at follow-up.

Results: The patients’ mean age was 76 years and 65% were male. Coronary artery disease was present in 85% and 45% had previous bypass surgery. Renal failure was present in 65%, atrial fibrillation in 60%, and 30% had an implantable cardioverter defibrillator/cardiac resynchronization therapy device. Mean left ventricular ejection fraction was 36%. Grade III-IV MR was present in all patients with the vast majority suffering from functional MR secondary to ventricular remodeling. New York Heart Association (NYHA) class was III-IV in 90%. Patients were followed for a mean of 231 days. Acute reduction of MR grade to ≤ 2 was accomplished in 19 of the 20 patients (95%) with a 30 day mortality of 5%. At follow-up MR was reduced to ≤ 2 in 64% of patients, and NYHA class improved in 70% of patients. An additional 2 patients (11%) died during follow-up.

Conclusions: MitraClip implantation is feasible and safe in high risk highly symptomatic patients with significant MR. Acute and mid-term results are comparable to similar high risk patient cohorts in the literature. Continued surveillance and longer follow-up are needed to elucidate which patients are most likely to benefit from the procedure.

Itai Gat, Mordechai Dulitzki, Eyal Schiff, Eyal Sivan and Michal J. Simchen
Background: Homozygous carriers of factor V Leiden (FVL) have an up to 80-fold increased risk of venous thrombosis, but the risk of obstetric complications in FVL homozygosity is unclear.

Objectives:
To compare obstetric and thromboembolic complications among factor V Leiden (FVL) homozygous and heterozygous carriers treated with prophylactic dose anticoagulation during pregnancy.

Methods:
In this retrospective case-control study we performed a chart review for the years 2004–2010 of homozygous and heterozygous FVL carriers who were treated with low molecular weight heparin (LMWH) at a dose of 0.6 mg/kg/day during pregnancy. Adverse outcomes included thromboembolic and obstetric complications. A composite adverse obstetric outcome was defined as the presence of at least one of the following: late intrauterine fetal demise, severe intrauterine growth restriction (< 5th percentile), preeclampsia, placental abruption. Pregnancy outcomes of homozygous and heterozygous FVL carriers were compared.

Results:
We compared the pregnancies of 13 homozygous FVL women with those of 82 heterozygous FVL carriers. Thromboembolic events occurred only in heterozygous FVL controls. Gestational age and birth weight were similar. The composite adverse obstetric outcome rate was higher for homozygous compared with heterozygous FVL carriers (23.1% vs. 11%, respectively), although not statistically significant. A trend for prematurity among homozygous FVL patients was evident, with 2/13 women (15.3%) in the homozygous FVL group giving birth before 34 weeks gestation, compared with only 2/82 (2.3%) in the heterozygous group.

Conclusions:
Pregnancy outcome was similar for homozygous and heterozygous FVL carriers on LMWH thromboprophylaxis. The overall likelihood of thromboembolic complications was low. Thromboprophylaxis may decrease the risk for placental and thromboembolic complications in homozygous FVL patients to a similar level as in heterozygotes.
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