Early autologous and allogeneic peripheral blood stem cell transplantation for adult patients with acute B and T cell precursor neoplasms: a 12-year single center experience.

Adult acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a rare and heterogeneous malignancy characterized by uncontrolled proliferation of B or T cell precursor cells. Here, we retrospectively analyzed the outcome of early autologous stem cell transplantation in standard-risk patients in first complete remission (n=24) and of allogeneic transplantation in high and highest risk, and relapsed/refractory patients (n=35). The 10-year overall survival after autologous transplantation was 45%. The 10-year overall survival after allogeneic transplantation was 58%. The cumulative incidence of relapse was 29% after allogeneic and 67% after autologous transplantation. The cumulative incidence of non-relapse mortality was 0% after autologous and 12% after allogeneic transplantation. This retrospective single center analysis in a limited number of standard-risk patients clearly demonstrates that early autologous transplantation in first complete remission leads to an acceptable long-term outcome with a short overall treatment duration of less than 6 months compared with more than 2 years with conventional chemotherapy. More sensitive and standardized methods to detect minimal residual disease (MRD) will further help to identify those patients more accurately who are most likely to benefit from such a short and intensive treatment strategy (i.e., MRD negative standard-risk patients) or those who require early targeted therapy (e.g., blinatumomab) in case of MRD positivity. Early allogeneic transplantation results in long-term survival/cure in nearly two-thirds of all high and highest risk, and relapsed/refractory patients.

Autologous stem cell transplantation following simultaneous liver and kidney transplantation in severe amyloid light chain amyloidosis associated with multiple myeloma: a case report.

INTRODUCTION: The involvement of vital organs in multiple myeloma (MM) with systemic amyloid light-chain (AL) amyloidosis can lead to acute organ failure. In this case, the fear of recurrence or progression of multiple myeloma often excludes those patients from undergoing organ transplantation. Nevertheless, clinically fit patients might benefit from a different therapeutic approach. This case presentation might highlight this particular unmet need and strengthen a different treatment approach. CASE PRESENTATION: To our knowledge, we present the first case of successful simultaneous liver and kidney transplantation, followed by autologous stem cell transplantation in a 60-year-old Caucasian male patient suffering from MM (Durie-Salmon stage IIB; ISS-stage: III, RISS stage: III) with primary AL amyloidosis. Chemotherapy treatment led to end-stage kidney disease requiring dialysis. Liver failure also occurred after at least three cycles of CyBorD (bortezomib, cyclophosphamide, and dexamethasone) of induction therapy with a good hematologic response. Over three years after the initial diagnosis, the patient is reportedly showing an excellent quality of life and a complete remission. DISCUSSION AND CONCLUSION: We conclude that kidney and liver transplantation followed by autologous stem cell transplantation can be a treatment option for a selected group of patients with MM if AL amyloidosis is leading. In the end, the remission assessment by IMWG response criteria displayed a complete remission of MM together with complete reconstitution of organ functions (liver & renal function) as long as upfront clinical evaluation excludes significant cardiac involvement and other severe co-morbidities.

Clavicle Trauma: From Acromioclavicular Joint Injuries to Distal Clavicle Fractures and Midshaft Fractures in Contact Athletes.

Injuries to the clavicle and its articulations (the acromioclavicular and sternoclavicular joints) are becoming increasingly common. Conventional treatment has been dominated by nonsurgical techniques; however, the active patient was often left with substantial residual disability that was underreported. It is now recognized that surgical intervention may be advantageous in specific patients, especially athletes. Surgeons should consider pathophysiology, indications, and surgical techniques to best manage these injuries.

Current treatment concepts of Philadelphia-negative MPN.

Since William Dameshek has described the concept of "myeloproliferative disorders (MPD)" by identifying common clinical characteristics (i.e. hemorrhage, thrombosis and leukemic transformation) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), the advent of molecular biology has provided substantial molecular insight into the pathobiology of myeloproliferative neoplasia (MPN). Recently, the description of the gain-of-function mutation of JAK2 (JAK2V617F) has been identified in classical Philadelphia (Ph)-negative MPN, thus providing a rational target for novel innovative treatment strategies. In addition, molecular characterization of atypical Ph-negative MPN (e.g. the KITD816V mutation in mastocytosis and PDGF-receptor rearrangements in hypereosinophilic syndromes/chronic eosinophilic leukemia) complement the molecular knowledge of this heterogeneous disease family. Currently, clinical studies testing various JAK2-inhibitors in PV, ET as well as in primary and secondary myelofibrosis (MF) are under way. Interestingly, first data indicate that despite marked clinical activity in terms of spleen size reduction and improvement of constitutional symptoms, these inhibitors might not sufficiently reduce disease burden. Thus, alternative and well established treatment strategies, such as inhibition of thrombocyte aggregation by low dose aspirin, cytotoxics (e.g. hydroxyurea), immuno- and stroma-modifying therapy with interferon, tyrosine kinase inhibitors and, in selected cases, allogeneic stem cell transplantation are still important treatment options for patients suffering from MPN, which will be discussed in detail in this review.

New approaches to diagnosis and arthroscopic management of partial-thickness cuff tears.

Partial-thickness cuff tears (PTCTs) are increasingly recognized as a source of pain and athletic impairment, especially in overhead athletes. 1,2 Improvements in diagnostic imaging have enhanced the ability to detect and quantify partial cuff disease, and arthroscopic advances have led to novel techniques by which partial cuff tears can be repaired. 2-6 Despite increasing recognition and improved understanding of this condition, the natural history, clinical evaluation, and management of partial tears remain elusive. This is because of the disparity between the extent of partial cuff tearing and the wide variability in clinical impairment and the frequent overlay of concomitant labral and subacromial pathology. When should operating on an athlete with a partial cuff tear be considered? What percentage of cuff tear justifies repair rather than debridement? Does this threshold vary according to the athlete or sport? And if the partial tear is repaired, what can be expected in terms of return to activity, particularly in a high-level thrower? The purpose of this manuscript is to provide an overview of partial cuff tears and their evaluation and management.

Lisfranc injury in a national hockey league player: a case report.

Tarsometatarsal joint dislocations and fracture-dislocations are uncommon injuries most frequently resulting from high-energy trauma as encountered in crush injuries, falls, and motor vehicle accidents. Although less common in athletes, this injury is being recognized with greater frequency and may carry a poor prognosis for return to high levels of competition. These injuries present a considerable challenge to orthopedic surgeons caring for athletes because of the prolonged period of recovery often required [ 1,2,5,6,12]. The literature contains descriptions of this injury in football players, gymnasts, tennis players, and track and field athletes [2,5,9]. To our knowledge, no report of such a Lisfranc injury to a hockey player has been described. This is a case report of a National Hockey League player that sustained a Lisfranc injury requiring surgical stabilization, but was able to return to elite hockey play.

Factors predictive of outcome after use of the Ponseti method for the treatment of idiopathic clubfeet.

BACKGROUND: The nonoperative technique for the treatment of idiopathic congenital talipes equinovarus (clubfoot) described by Ponseti is a popular method, but it requires two to four years of orthotic management. The purpose of this study was to examine the patient characteristics and demographic factors related to the family that are predictive of recurrent foot deformities in patients treated with this method. METHODS: The cases of fifty-one consecutive infants with eighty-six idiopathic clubfeet treated with use of the Ponseti method were examined retrospectively. The patient characteristics at the time of presentation, such as the severity of the initial clubfoot deformity, previous treatment, and the age at the initiation of treatment, were examined with use of univariate logistic regression analysis modeling recurrence. Demographic data on the family, including annual income, highest level of education attained by the parents, and marital status, as well as parental reports of compliance with the use of the prescribed orthosis, were studied in relation to the risk of recurrence. RESULTS: The parents of twenty-one patients did not comply with the use of orthotics. Noncompliance was the factor most related to the risk of recurrence, with an odds ratio of 183 (p < 0.00001). Parental educational level (high-school education or less) also was a significant risk factor for recurrence (odds ratio = 10.7, p < 0.03). With the numbers available, no significant relationship was found between gender, race, parental marital status, source of medical insurance, or parental income and the risk of recurrence of the clubfoot deformity. In addition, the severity of the deformity, the age of the patient at the initiation of treatment, and previous treatment were not found to have a significant effect on the risk of recurrence. CONCLUSION: Noncompliance and the educational level of the parents (high-school education or less) are significant risk factors for the recurrence of clubfoot deformity after correction with the Ponseti method. The identification of patients who are at risk for recurrence may allow intervention to improve the compliance of the parents with regard to the use of orthotics, and, as a result, improve outcome. LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.

Complications of treatment of acromioclavicular and sternoclavicular joint injuries.

Although common, AC joint injuries and their treatments are not benign. The injury itself and both nonsurgical and surgical treatments may result in complications yielding persistent pain, deformity, or dysfunction. Sternoclavicular joint injuries are far less common and are typically the result of higher energy trauma. As such, the associated complications may be more serious. Familiarity with the potential complications of these injuries can help the treating physician to develop strategies to minimize their incidence and sequelae.

Structure and function of the ion channel ICln.

Normal function of organs and cells is tightly linked to the cytoarchitecture. Control of the cell volume is therefore vital for the organism. A widely established strategy of cells to counteract swelling is the activation of chloride and potassium channels, which leads to a net efflux of salt followed by water - a process termed regulatory volume decrease. Since there is evidence for swelling-dependent chloride channels (IClswell) being activated also during pathological processes, the identification of the molecular entity underlying IClswell is of utmost importance. Several proteins are discussed as the channel forming IClswell, i.e. phospholemman, p-glycoprotein, CLC-3 and ICln. In this review we would like to focus on the properties of ICln, a protein cloned from a Madin Darby canine kidney (MDCK) cell library whose expression in Xenopus laevis oocytes resulted in a nucleotide sensitive outwardly rectifying chloride current closely resembling the biophysical properties of IClswell.

ICln, an ion channel-forming protein associated with cell volume regulation.

It is not resolved whether the anionic channel involved in volume regulation after cell swelling comprises one or more subunits. Moreover, it remains to be determined which of the different proteins cloned so far, for which an involvement in cell volume regulation has been postulated, is the ideal candidate. In this review, we consider the role of the ICln protein, cloned from MDCK cells, in cell volume regulation.

Vasculopathy of small muscular arteries in pediatric patients after bone marrow transplantation.

Bone Marrow Transplant (BMT) is a critical therapeutic intervention for a variety of diseases occurring in the pediatric patient. Complications of allogeneic BMT include graft-versus-host disease (GVHD), infection, drug toxicity, thrombotic microangiopathy, and veno-occlusive disease. With solid organ transplantation, chronic vascular rejection has emerged as a major factor limiting long-term survival of the graft. We present a vasculopathy of small muscular arteries in 6 patients after allogeneic BMT. Cases include 4 boys and 2 girls ranging in age from 4 months to 13 years with full or partial human leukocyte antigen matching. Five of the 6 transplants were from related donors. The vasculopathy occurred 13 to 418 days after transplant and was noted in surgical specimens (2) and at autopsy (4). It was seen in the gastrointestinal tract and lung in 3 cases each. Vascular changes in small muscular arteries include concentric intimal or medial hyperplasia with luminal narrowing, prominent myxoid change, extravasated red blood cells, and presence of some foamy histiocytes with no evidence of thrombotic microangiopathy. Vasculopathy contributed to intestinal compromise requiring surgical intervention 3 times in 1 patient, and diffuse alveolar damage with hemorrhage in another. All 6 patients are dead. The cause of this unusual vasculopathy present in patients after BMT is likely to be multifactorial, involving effects of irradiation, chemotherapy, cyclosporine, and GVHD. Together these may create a negative synergy which produces an obliterative arteriopathy that should be recognized as a pathological entity and may be a harbinger of a poor prognosis.

Picosecond absorption studies on rhodopsin and isorhodopsin in detergent and native membrane.

Picosecond transient absorption spectra of rhodopsin and isorhodopsin were measured at room temperature with a double-beam laser spectrophotometer after excitation at 355 nm. Photolysis studies were performed on rhodopsin solubilized in two different detergents (digitonin and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate). The resulting rhodopsin/bathorhodopsin absorption difference spectra were measured at times from 35 ps to 250 ns following photoexcitation. Rhodopsin and isorhodopsin in native disk membrane were studied after suspension in 75% glycerol. Isorhodopsin was prepared by photoisomerizing rhodopsin in disk membrane at 77 K. Transient spectra obtained from the visual pigments in native membrane were of a quality approaching that obtained from detergent-solubilized rhodopsin. The batho intermediate derived from isorhodopsin was spectrally the same as that generated by rhodopsin photolysis and was produced with a quantum yield higher than had been predicted on the basis of other studies.

Ranitidine in the treatment of acute upper gastrointestinal haemorrhage--a comparative study. Preliminary report.

50 patients with acute gastrointestinal bleeding (GIB) were randomly allocated to treatment with i.v. Ranitidine 50 mg b.d., or to a standard conservative therapy. When possible i.v. administration was replaced by oral ranitidine 150 mg b.d. for a total of up to 10 days. Three subgroups included gastric ulcer, duodenal ulcer and haemorrhagic gastritis. The criteria were: the need for blood replacement, comparison of the endoscopic appearance before and after therapy, and the final outcome of treatment, including the need for surgery. Ranitidine appeared to be superior to the standard treatment, the advantages being due largely to the gastric ulcer cases.