The clinical contribution of SPECT/CT with 99mTc-HMPAO-labeled leukocyte scintigraphy in hip and knee prosthetic infections. / Aportación clínica de la SPECT/TC en la gammagrafía con leucocitos marcados con 99mTc-HMPAO en infección de prótesis de cadera y rodilla.

OBJECTIVES: White blood cell scanning with 99mTc-hexamethylpropylene amine oxime (HMPAO) has proven a sensitive and specific imaging method in the diagnosis of suspected prosthesis infection. The aim of this retrospective study was to evaluate the usefulness of SPECT/CT performed simultaneously using a hybrid imaging device of prosthesis infections. MATERIALS AND METHODS: 99mTc-HMPAO scintigraphy was performed on 37 patients (11 men and 26 women; age range 38-84 years; mean age±SD, 65.7±5.6 years). Planar scans were acquired 2.4 and 24hour after injection. SPECT/CT was obtained 4 h after injection, using a dual-head hybrid gama camera coupled with a low-power x-ray tube. In all patients, scintigraphic results were matched with the results of surgery, cultures and clinical follow-up. RESULTS: Seventeen (45,9%) out of 37 patients had prosthesis infection and 20 (54,1%) out of 37 patients had non-infectious prosthesis pathologies with 99mTc-HMPAO scintigraphy and SPECT/CT. The 99mTc-HMPAO scintigraphy was true-positive for infection in 16 of 37 patients and true-negative in 20 of 37 patients. SPECT/CT provided an accurate anatomic localization of all positive foci. With regard to the final diagnosis, SPECT/CT added a significant clinical contribution in 22 of 37 patients (59,4%). Sensitivity, specificity, negative predictive value and positive predictive values were 100%,59.1%,100%,62.5% in planar images with 99mTc-HMPAO scintigraphy and 100%,90.1%,100%,88.2% in the planar+SPECT/CT imaging, respectively. DISCUSSION: Our results indicate that SPECT/CT performed using a hybrid device can improve imaging with 99mTc-HMPAO scintigraphy in patients with suspected osteomyelitis by providing accurate anatomic localization and precise definition of the extent of infection.

Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

Local rhBMP-2 injection after drill-hole injury in rats: does it have systemic effects?

The aim of this study is to investigate the histopathological findings of drill hole healing and interactions of parathyroid hormone (PTH), β-catenin and transcription factor-4 (TCF7L2/Tcf-4) after local application of recombinant human bone morphogenic protein-2 (rhBMP-2). Sprague Dawley rats were used in two groups of ‘femoral cortex hole model’. In the non-treated group, a hole was opened with a 3 mm K-wire in the distal and mid third junction of the right femur. In the treated group, local rhBMP-2 protein was injected into the similar femoral hole. Sterile 18M H2O was injected into the femoral hole at contralateral femur. There was more subperiosteal membranous bone reaction in the group treated with rhBMP-2 injection compared to the non-treated group. This was also proven immunohistochemically in both ipsilateral and contralateral femur with increased anti bone morphogenic protein-2 (anti BMP-2) expression. Moreover, there was an increased subperiosteal reaction at the contralateral femur. Also, in the treated group, PTH expression was increased in cells that form callus, and nuclear beta-catenin expression was increased in chondrocytes of periosteal ossification. Future studies should try to find whether the effects of rhBMP-2 on PTH and Wnt signaling pathway changes with different fracture models, also the systemic effects of local rhBMP-2 application should be investigated.

The first (double) hand transplantation in Turkey.

In September 2010, a bilateral hand allotransplantation was performed on a 28-year-old man who had suffered amputations at the level of 1/3 of the proximal forearm on the right and 1/3 of the distal forearm on the left 2 years previously. This was the first hand transplantation case in Turkey. Preoperative organization, legal difficulties, technical aspects of the operation, and immunosuppressive regimen are detailed herein. The early results of the first composite tissue allograft (CTA) transplantation are also reported. The results were encouraging for all future types of CTA transplantation, including hand and face. Following the early promising outcome of the first case of hand transplantation in Turkey, we have accelerated preparation of regulations for CTA transplantation, including hand and face allotransplantation.

Multiple myeloma presenting as massive ascites.

Ascites is a rare complication of multiple myeloma and may occur either at presentation or more often during the disease course. Most reported cases have been associated with IgA type of myeloma. When it occurs, it is usually associated with extensive liver infiltration with plasma cells, infectious peritonitis or myelomatous peritoneal infiltration. Herein, we describe a case of IgG type multiple myeloma diagnosed by further examinations due to the presence of plasma cells in ascitic fluid.

Homozygous feature of isolated triphalangeal thumb-preaxial polydactyly linked to 7q36: no phenotypic difference between homozygotes and heterozygotes.

Preaxial polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial polydactyly phenotype.

Use of tunnelled catheters in haematological malignancy patients with neutropenia.

This prospective study analysed 83 patients (age 45 +/- 17 years) with haematological neoplasms, implanted with 93 tunnelled catheters, who were neutropenic or developed neutropenia during treatment. Catheters were implanted in the right (n = 82) or left (n = 11) jugular vein by the same surgical team using the same technique. They remained in place for 124 +/- 88 days: 29% were removed due to infection; 18% due to treatment termination and 2% due to mechanical problems. Seventeen patients died with catheters in place. At 30, 60, 90, 120 and 200 days mean catheter duration rates were 82%, 75%, 65%, 60% and 35%, respectively, and freedom from catheter removal due to infection was 92%, 88%, 80%, 77% and 67%, respectively. Patient diagnosis and history of previous catheter infection did not increase catheter infection risk, but patients undergoing stem cell transplantation had an increased infection risk. Tunnelled catheters can be used in high-risk patients with neutropenia. Systemic infections can be managed in most patients without catheter removal.

A patient with diffuse large B-cell non-Hodgkin's lymphoma and AA type amyloidosis.

AA-type amyloidosis is a consequence of a long-standing systemic inflammation and is not associated with a monoclonal protein or clonal bone marrow plasma cells. Proinflammatory cytokines such as interleukin (IL)1, IL-6, and tumor necrosis factor (TNF) stimulate the synthesis of serum amyloid A during inflammation. Although the association of non-Hodgkin's lymphoma (NHL) with AL-type amyloidosis is well known and patients with Hodgkin's lymphoma with AA amyloidosis have been described, AA-type amyloidosis with NHL is extremely infrequent. We report a case of amyloidosis associated with NHL that subsided during R-CHOP chemotherapy.

Bilateral complete avulsion of ocular globes in a Le Fort III maxillofacial fracture: a case report and review of the literature.

PURPOSE: The purpose of this paper is to demonstrate a case of bilateral complete avulsion of the globes following maxillofacial trauma. METHODS: A 23-year-old man with bilateral complete globe avulsion following a maxillofacial trauma. Both globes were luxated out of the orbit and suspended on the skin of the upper lid below the brows. No direct or indirect light reflexes or any eye movements could be noted. Computerized tomography showed complete lacerations of both optic nerves at a level just anterior to the optic canal. There were also multiple fractures corresponding to Le Fort III fracture with Le Fort II components. The brain parenchyma was normal with an exception of brain edema. As the globes were unsuitable for repositioning, both were enucleated. The maxillofacial fractures were immobilized with plates and screws. Although the patient gained consciousness with normal vital signs in the early postoperative period, he died on the ninth day due to Pseudomonas aeruginosa infection, despite invasive antibiotic treatment. DISCUSSION: The optic nerve and the globes are very resistant to mild and moderate trauma. The avulsion of the nerve at the canalicular or more posterior level may demonstrate central nervous system complications resulting in life-threatening conditions. The most critical issue in complete globe avulsions with a transected optic nerve is to rescue the vision. In total transected optic nerves the final eyes could only have had cosmetic benefits. In spite of promising experimental research on optic nerve regeneration, there are unknowns, such as the methods to eliminate the risk of anterior segment ischemia and phthisis bulbi. CONCLUSIONS: Globe avulsions with a complete optic nerve cut remain a challenging problem. More research is required to better understand the pathophysiology of optic nerve repair.

Giant recurrent pyogenic granuloma on the face with satellitosis responsive to systemic steroids.

Pyogenic granuloma is a common benign skin tumour. However, giant recurrent pyogenic granuloma with satellitosis is relatively rare. We present a 52-year-old man who had recurrent gigantic pyogenic granuloma with satellitosis responsive to systemic steroids. Our case of recurrent pyogenic granuloma is interesting because of its clinical presentation, recurrence following surgical excision and its steroid responsiveness. Systemic steroids may be effective in treating recurrent giant pyogenic granulomas during their high-proliferation phase.

The outcome of failed free flaps in head and neck and extremity reconstruction: what is next in the reconstructive ladder?

The indications for free flaps have been more or less clarified; however, the course of reconstruction after the failure of a free flap remains undetermined. Is it better to insist on one's initial choice, or should surgeons downgrade their reconstructive goals? To establish a preliminary guideline, this study was designed to retrospectively analyze the outcome of failed free-tissue transfers performed in the authors hospital. Over the past 8 years (1990 through 1997), 3361 head and neck and extremity reconstructions were performed by free-tissue transfers, excluding toe transplantations. Among these reconstructions, 1235 flaps (36.7 percent) were transferred to the head and neck region, and 2126 flaps (63.3 percent) to the extremities. A total of 101 failures (3.0 percent total plus the partial failure rate) were encountered. Forty-two failures occurred in the head and neck region, and 59 in the extremities. Evaluation of the cases revealed that one of three following approaches to handling the failure was taken: (1) a second free-tissue transfer; (2) a regional flap transfer; or (3) conservative management with debridement, wound care, and subsequent closure by secondary intention, whether by local flaps or skin grafting. In the head and neck region, 17 second free flaps (40 percent) and 15 regional flaps (36 percent) were transferred to salvage the reconstruction, whereas conservative management was undertaken in the remaining 10 cases (24 percent). In the extremities, 37 failures were treated conservatively (63 percent) in addition to 17 second free flaps (29 percent) and three regional flaps (5 percent) used to salvage the failed reconstruction. Two cases underwent amputation (3 percent). The average time elapsed between the failure and second free-tissue transfer was 12 days (range, 2 to 60 days) in the head and neck region and 18 days (range, 2 to 56 days) in the extremities. In a total of 34 second free-tissue transfers at both localizations, there were only three failures (9 percent). However, in the head and neck region, seven of the regional flaps transferred (47 percent) and four cases that were conservatively treated (40 percent) either failed or developed complications that lengthened the reconstruction period because of additional procedures. Six other free-tissue transfers had to be performed to manage these complicated cases. Conservative management was quite successful in the extremities; most patients' wounds healed, although more than one skin-graft procedure was required in 10 patients (27 percent). In conclusion, a second free-tissue transfer is, in general, a relatively more reliable and more effective procedure for the treatment of flap failure in the head and neck region, as well as failed vascularized bone flaps in the reconstruction of the extremities. Conservative treatment may be a simple and valid alternative to second (free) flaps for soft-tissue coverage in extremities with partial and even total losses.

Increased levels of tissue factor pathway inhibitor may reflect disease activity and play a role in thrombotic tendency in Behçet's disease.

Tissue factor pathway inhibitor (TFPI) is a Kunitz-type proteinase inhibitor that has a crucial role in haemostasis and is primarily synthesized in the vascular endothelium. We investigated plasma total TFPI, antiphospholipid antibodies, and some other coagulation and fibrinolytic system parameters in 30 patients with Behçet's disease and 15 controls by the enzyme-linked immunosorbent assay method. TFPI levels were significantly higher in the Behçet's group (119 +/- 57.5 ng/ml) compared with the control group (74.8 +/- 31.5) (P < 0.009). We also noted a statistical significance in TFPI levels between patients with active disease (n:16) (139 +/- 55) and patients without activation (n:14) (96 +/- 53) (P < 0.03), whereas inactive patients lacked any significance when compared with the control group (P < 0.29). Other parameters disclosed no statistical significance between patients and control group except for elevated fibrinogen and plasminogen activator inhibitor-1 levels in the patient group (P < 0.003). Increased levels of TFPI may reflect a defensive mechanism like in other diseases characterized by thrombotic tendency and represent a parameter of disease activity.

Hemophagocytic syndrome associated with inappropiate secretion of antidiuretic hormone in lymphoma and acute myeloblastic leukemia: report of two cases.

Hemophagocytic syndrome (HPS) is a rare clinicopathological disorder characterized by systemic proliferation of phagocytizing histiocytes associated with fever, cytopenias, lymphadenopathy, hepatosplenomegaly, and disseminated intravascular coagulopathy. We present the association of hemophagocytic syndrome associated with inappropriate secretion of antidiuretic hormone (SIADH) in two cases of hematological malignancies; anaplastic large cell lymphoma (ALCL) and acute myeloblastic leukemia (AML M4) In the patient with lymphoma, the diagnosis of lymphoma, HPS and SIADH were concurrent. In the patient with AML, HPS and SIADH were observed while the patient was in hematological remission. Thus it seems that patients with HPS may also carry a risk for the development of SIADH; the relationship with HPS and SIADH should be further investigated.

Effect of Sialic Acid on Platelet Cryopreservation.

Sialic acid is a molecule which is responsible for the net negative surface charge of platelets. We investigated the effect of sialic acid on fresh and cryopreserved platelets. Platelet samples were obtained by platelet apheresis from 8 healthy donors. Platelet suspensions with different sialic acid concentrations (0, 1, 2 and 4 mg/mL) were studied for ADP and ristocetin induced platelet aggregation, basal and ADP induced P-selectin and glycoprotein- Ib/IX expression. Then platelet samples were cryopreserved in 5% DMSO with or without 4 mg/mL sialic acid. After thawing, P-selectin expression was compared with the control group. Six samples were also washed after thawing and P-selectin expression was again compared to unwashed samples. Sialic acid suppressed ADP induced platelet aggregation and P-selectin expression in a dose dependent manner. In cryopreserved samples, P-selectin expression of 4 mg/mL sialic acid containing group was found significantly higher than the control group (p< 0.001). In cryopreserved control group, P-selectin expression of thawedwashed group was significantly higher than thawed-unwashed group (p< 0.05). Our results indicate that sialic acid is not a good cryoprotective agent. Washing procedure after thawing to eliminate DMSO causes significant platelet activation.

Plasma Cell Leukemia: A Report of 5 Cases and Review of the Literature.

Plasma cells are occasionally observed in the peripheral blood of the patients with multiple myeloma. When the number of these circulating cells is significant, the term of plasma cell leukemia is used. We report 5 cases of plasma cell leukemia with poor prognosis with review of the literature.