Maher Deeb

Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience

Enzyme replacement therapy is the standard of care for symptomatic Gaucher disease. Velaglucerase alfa is a human beta-glucocerebrosidase produced in a well-characterized human cell line. A 9-month phase 1/2 open-label, single-center trial and ongoing extension study were conducted to evaluate safety and efficacy of velaglucerase alfa. Twelve symptomatic adult type 1 Gaucher patients (intact spleens) received velaglucerase alfa (60 U/kg per infusion) during phase 1/2. An extension study was offered to patients completing the trial; step-wise dose reduction (to 30 U/kg per infusion) was instituted. Eleven patients completed phase 1/2; 10 entered the extension; 9 patients reached 39 months of extension. No drug-related serious adverse events or withdrawals, and no antibodies were observed. Home therapy was successfully implemented during the extension. Statistically significant improvements (P < .004) were noted in mean percentage change from baseline to 9 months and baseline to 48 months for hemoglobin (+19.2%, +21.7%, respectively), platelet counts (+67.6%, +157.8%, respectively), normalized liver volume (-18.2%, -42.8%, respectively), and normalized spleen volume (-49.5%, -79.3%, respectively). These significant clinical changes and safety profile led to phase 3 trials and highlight the potential of velaglucerase alfa as alternative therapy for type 1 Gaucher disease. The extension trial is registered at http://www.clinicaltrials.gov as NCT00391625.

Permanent pacemaker implantation following cardiac surgery: indications and long-term follow-up.

Background: Conduction disturbances requiring permanent pacemaker implantation after heart surgery occur in about 1.5% of patients. Early pacemaker implantation may reduce morbidity and postoperative hospital stay. We reviewed our experience with patients undergoing surgery to try and identify predictors for pacemaker requirements and patients who will remain pacemaker dependent.

Aortic Valve Replacement: Choice Between Mechanical Valves and Bioprostheses

Abstract  Background: The choice between a mechanical or bioprosthetic valve replacement device is not always clear, although patient age is most often the determining factor. We reviewed our experience with patients undergoing aortic valve replacement (AVR) in order to assess and compare long‐term outcomes between patients receiving a mechanical valve and those receiving a bioprosthesis. Methods: Three hundred fifty‐two patients underwent AVR with or without coronary artery bypass between 1993 and2004: 189 received a mechanical valve and 163 a bioprosthesis. Events included: late mortality, thrombo‐embolic events, stroke, bleeding events, valve thrombosis, endocarditis, reoperation, and coronary catheterization. Results: Patients in the bioprosthesis group were older (71 ± 11 vs. 65 ± 13) than in the mechanical group (p < 0.0001). There was no difference in operative mortality (6.8%) or morbidity. Follow‐up (61 ± 40 months) was available in 87%. For mechanical valves and bioprostheses, respectively: 3‐, 5‐, and 10‐year survival was 92%, 86%, and 69% versus 90%, 86%, and 71% (p = n.s.); and event‐free survival was 79%, 68%, and 41% versus 79%, 68%, and 44% (p = n.s.). Five patients (3%) in each group required re‐replacement of their aortic valve (p = n.s.). Coronary artery disease requiring bypass surgery did not affect long‐term survival. Age at operation and renal failure were the only predictors for late mortality. Conclusions: Survival and event‐free survival are similar for patients receiving a mechanical or biological aortic valve substitute. Selection of a valve replacement device should be based on life expectancy, patient preference, ability to take anticoagulants, lifestyle, risk of bleeding, and risk of reoperation. Patient age alone should not be the determining factor.

Does coronary endarterectomy increase the risk of coronary bypass

Abstract  Background: With increased incidence of angioplasty and stent implantation, patients referred for coronary bypass (CABG) typically have more advanced and diffuse coronary disease. Thus, more patients may require endarterectomy in order to achieve complete revascularization. We compared our results in patients undergoing CABG with or without coronary endarterectomy. Methods: Between 1993 and 1999, 2372 patients underwent isolated CABG in our department. A retrospective analysis was performed to compare patients requiring coronary endarterectomy of the LAD (group 1, n #88), endarterectomy of arteries other than the LAD (group 2, n #143), to those not requiring endarterectomy (group 3, n # 2071). Patients undergoing CABG without the use of cardiopulmonary bypass were excluded. Group 1 had a higher incidence of proximal LAD stenosis (p #0.001) than group 3, while group 2 had a higher incidence of peripheral vascular disease (p #0.02), preoperative Ml (p # 0.03) and LV dysfunction (p = 0.001). Results: Operative mortality was 10% in group 1 (p < 0.001) and 4% in group 2 (p #IMS) compared to 3% in group 3. Incidence of perioperative Ml was 12% in group 1 (p # 0.001) and 8% in group 2 (p # 0.001) compared to 2% in group 3. Conclusions: Patients requiring endarterectomy of the LAD are at increased risk of operative mortality. This was not true for patients requiring endarterectomy of arteries other than the LAD. In both groups there was an increased risk of perioperative myocardial infarction.

Ectopic pancreatic pseudocyst and cyst presenting as a cervical and mediastinal mass - case report and review of the literature

Ectopic pancreas in the mediastinum is extremely rare. We are reporting on a case of a twenty two year old woman who presented to our clinic with a large cervical mass. The CT scan revealed a cystic lesion in the anterior mediastinum. The patient underwent surgical resection by cervical approach. A Cystic mass with pseudocysts, cysts and complete pancreatic tissue were found in pathology. There were no signs of pancreatitis or malignancy. No recurrence was observed after a follow up of four years. We reviewed the case reports describing this rare condition in the medical literature.We conclude that the possibility of ectopic pancreatic tissue should be included in the differential diagnosis of anterior mediastinal cystic mass, though as a remote possibility. Surgery is probably needed for the diagnosis and treatment. Posterior mediastinal pseudocyst is a different entity associated with acute pancreatitis. In those cases surgery is not recommended. Our third conclusion is that pancreatic tissue should be actively sought, if a structure resembling a pseudocyst is found in an unexpected location.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1849369005957671

Gaucher Disease Spectrum of Sonographic Findings in the Liver

Objective. Our large tertiary clinic for patients with Gaucher disease has used sonography as the preferred modality to monitor hepatosplenomegaly in hundreds of patients for more than 18 years. With the advent of specific enzyme replacement therapy (ERT), sonographic monitoring of changes in both hepatomegaly and the echogenicity of the hepatic tissue may highlight features that are amenable to ERT. Methods. All patients (500) seen at presentation and at annual or semiannual routine visits have undergone sonographic examinations by a single senior radiologist (I.H.‐H.). Results. Thirty‐nine patients (7.8%) had sonographic evidence of hepatic disease (21 male and 18 female; age range, 18–90 years); 26 (66.7%) of these received ERT, and 10 (25.6%) were splenectomized. Conclusions. Liver findings are relatively rare. Among 500 patients, there was no instance of computed tomographic findings that had not been previously shown by sonography. Radiologists should be acquainted with the variable sonographic spectrum of the Gaucher liver. If hepatic lesions are small, hyperechoic, and slowly evolving, one may surmise that they are due to Gaucher cell accumulation. However, special attention should be paid to progressive deterioration and irregularities in liver texture because other metabolic processes and cancers must be ruled out.

Uniportal video-assisted thoracic surgery: the Middle East experience

BACKGROUND The application of uniportal video-assisted thoracic surgery (VATS) for both minor and major thoracic procedures is gaining widespread use across the globe. Believing its advantages, both in superb surgical results and less morbidity, our center has the privilege to be one of the first centers in the Middle East to introduce this surgical technique into our standard practice. This study presents our initial experience using this technique in 192 procedures and demonstrates the results of postoperative pain level in a sample of 90 patients. METHODS In a retrospective study of prospectively collected data, 192 uniportal VATS procedures were analyzed between November 2013 and June 2016. The level of early post-operative pain (postoperative days 1-4) was analyzed in the first 90 cases between November 2013 and March 2015. Uniportal technique was used for a wide array of procedures: blebectomies, pleurectomies, wedge resections, anatomical major lung resections, mediastinal tumors, empyema drainage and decortications. RESULTS The mean age of patients was 49.6 years, and 72 patients were females (37%). Thirty-five (18.2%) patients underwent anatomical resections with conversion to thoracotomy in three patients (8%). Six (3%) patients had air leak >4 days. The average chest drain duration was 3.25 days. The average length of stay was 4.2 days. Postoperative pain level was low in the first 4 days following the surgery and 30 days mortality was 0%. CONCLUSIONS Uniportal VATS surgery is a safe and established technique with a minimal invasive thoracic surgery. Excellent results with minimal morbidity, short hospital stay and low postoperative pain are amongst its strong points. Thoracic surgeons experienced in thoracic surgical approaches can safely perform uniportal VATS.

Lung coin lesions due to Echinococcal disease (2004:7b).

A 17-year-old Arab boy had been suffering from a nonproductive cough for several weeks. There was no past history of illness. The patient was afebrile, his physical examination was unremarkable and laboratory profile revealed no abnormality. Chest radiography was performed (Fig. 1), followed by chest computed tomography (CT; Fig. 2a–d). CT showed two well-defined, round coin lesions with a diameter of 1.5 cm and 1 cm in the right lung and a left upper lobe lesion measuring 0.8 cm (Fig. 2a–c). In addition to that, a cystic lesion was noted in the right lobe of the liver (Fig. 2d and Fig. 3). The presumptive diagnosis was echinococcal disease of the liver and the lungs. However, the echinococcal antibody test was negative. The patient underwent resection of the right lung lesions. Pathological examination revealed echinococcal cysts (Fig. 4).