Teriparatide and clodronate combination as a potential treatment for complex regional pain syndrome type I in delayed consolidation after foot surgery: a case report and review of the literature.

BACKGROUND: Complex regional pain syndrome type I is a pathological condition characterized by an exaggerated response of tissues to low or moderate pain stimuli. The exact pathogenesis and optimal medical treatment for complex regional pain syndrome type I are still not fully understood, although bisphosphonates have shown positive effects in reducing pain. Foot surgery can be complicated by the development of complex regional pain syndrome type I, leading to functional decline and difficulties in weight-bearing. CASE PRESENTATION: The authors present a clinical case involving complex regional pain syndrome type I that developed after surgical foot arthrodesis. The patient, a 42-year-old Caucasian male, did not respond to clodronate treatment but experienced successful outcomes upon the addition of teriparatide, which effectively stimulated the healing of arthrodesis. CONCLUSION: Teriparatide cannot be considered the primary treatment for complex regional pain syndrome due to insufficient solid clinical data. However, when complex regional pain syndrome is associated with or caused by delayed union, teriparatide can be used to address the underlying cause of complex regional pain syndrome.

A local anesthesia without tourniquet for distal fibula hardware removal after open reduction and internal fixation: the safe use of epinephrine in the foot. A randomized clinical study.

Hardware removal after surgical treatment fracture is one of the most common procedures in orthopaedic daily activity. A percentage from 14.5 to 21 of total removal involves the ankle joint. Trying to reduce the important socio-economic impact of this surgical procedure, we thought to perform it using the Wide Awake Local Anaesthesia Without Tourniquet (WALANT), a particular technique presented by D. Lalonde that associated a local anaesthetic drug with epinephrine in order to obtain an effective haemostatic effect despite the lack of a tourniquet. Nowadays, the WALANT efficiency and safety in hand surgery is widely demonstrated in literature but there are no data about its use in lower limb extremity surgeries. Authors performed a randomized study with 60 patients whom underwent distal fibula hardware removal between 2014 and 2016; they were divided into two groups: Group A under loco-regional anaesthesia with tourniquet and Group B under WALANT. We did not find significant differences in term of maximum pain level felt during the anaesthesiologic and surgical procedure. However, the use of WALANT significantly reduced post-operative pain levels. The WALANT procedures also reduced the number of hospitalization days. No differences in term of post-operative complication rates were found. In conclusion, the WALANT can be considered as a suitable option for distal fibula hardware removal in selected patients; it shows important clinical and economic advantages compared to the traditional loco-regional anaesthesia with tourniquet. This study also lays the foundation for the use of the WALANT beyond the field of hand surgery only.

Idiopathic and secondary forms of retroperitoneal fibrosis: a diagnostic approach.

Retroperitoneal fibrosis (RPF) is an uncommon disease characterized by a fibrous reaction that takes place in the peri-aortic retroperitoneum and often entraps the ureters causing obstructive uropathy. RPF is idiopathic in the majority of cases, but can also be secondary to malignancies, infections, drugs, radiotherapy, and rare histiocytic disorders such as Erdheim-Chester disease. Idiopathic RPF is an immune-mediated disease, which can either be isolated, associated with other autoimmune diseases, or arise in the context of a multifocal fibro-inflammatory disorder recently renamed as IgG4-related disease. The differential diagnosis between idiopathic, IgG4-related and secondary RPF is crucial, essentially because the therapeutic approaches - especially of idiopathic vs. secondary RPF - can be dramatically different. This review focuses on the clinical, laboratory and imaging features of the different RPF forms, and also provides an overview of the available treatment options.

The von Hippel-Lindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2.

Functional loss of the von Hippel-Lindau (VHL) tumor suppressor protein (pVHL), which is part of an E3-ubiquitin ligase complex, initiates most inherited and sporadic clear-cell renal cell carcinomas (ccRCC). Genetic inactivation of the TP53 gene in ccRCC is rare, suggesting that an alternate mechanism alleviates the selective pressure for TP53 mutations in ccRCC. Here we use a zebrafish model to describe the functional consequences of pVHL loss on the p53/Mdm2 pathway. We show that p53 is stabilized in the absence of pVHL and becomes hyperstabilized upon DNA damage, which we propose is because of a novel in vivo interaction revealed between human pVHL and a negative regulator of Mdm2, the programmed cell death 5 (PDCD5) protein. PDCD5 is normally localized at the plasma membrane and in the cytoplasm. However, upon hypoxia or loss of pVHL, PDCD5 relocalizes to the nucleus, an event that is coupled to the degradation of Mdm2. Despite the subsequent hyperstabilization and normal transcriptional activity of p53, we find that zebrafish vhl(-/-) cells are still as highly resistant to DNA damage-induced cell cycle arrest and apoptosis as human ccRCC cells. We suggest this is because of a marked increase in expression of birc5a, the zebrafish homolog of Survivin. Accordingly, when we knock down Survivin in human ccRCC cells we are able to restore caspase activity in response to DNA damage. Taken together, our study describes a new mechanism for p53 stabilization through PDCD5 upon hypoxia or pVHL loss, and reveals new clinical potential for the treatment of pathobiological disorders linked to hypoxic stress.

[Catastrophic antiphospholipid syndrome. Communication of 2 forms of presentation]. / Síndrome antifosfolipídico catastrófico. Comunicación de dos formas de presentación.

Antiphospholipid syndrome is characterized by recurrent fetal loss, arterial and venous thromboses, thrombocytopenia and circulating antiphospholipid antibodies. Few patients have a rapidly progressive, fatal outcome. We report two young patients with systemic lupus erythematosus and antiphospholipid antibodies who died after a short course of disease. Although clinical and laboratory findings differed in both patients--small vessel thromboses and microangiopathic hemolytic anemia mimicking thrombotic thrombocytopenic purpura predominated in one of the patients while small and medium size vessel thromboses without hemolysis were present in the other case--autopsy revealed widespread visceral thromboses in both of them, features consistent with a diagnosis of catastrophic antiphospholipid syndrome. This syndrome has not been reported to occur in association with Pneumocistis carinii pneumonia as we describe in one of our patients.

Combination salvage chemotherapy with MIZE (ifosfamide-mesna, idarubicin and etoposide) for relapsing or refractory lymphoma.

In this study, 54 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated in a phase II, multicentric trial with ifosfamide-mesna 1500 mg/m2 IV days 1-3, idarubicin 12 mg/m2 IV day 1 and etoposide 100 mg/m2 IV day 1-3 (MIZE). Overall response was 72%; complete response (CR) and partial response (PR) were 46% and 26% respectively. In Stage I-II pts CR was 59% and in Stage III-IV pts CR was 40.5%. Patients who relapsed from an initial CR had a 64% CR rate when treated with MIZE, in contrast to refractory disease's patients who only had 19% CR (p = 0.004). The group of pts that had an objective response (CR + PR) to front line therapy had a 2 year survival rate of 55% compared with none for refractory disease (p = 0.029) after salvage therapy. Median survival for the entire group was 17.5 months. Better survival was seen in pts who were asymptomatic with low levels of LDH, previous CR, non high-grade histology, and limited disease stage at relapse. Toxicity was mainly hematologic: 91.5% had neutropenia, (56.5% grade III-IV), and 9.5% died from infectious complications. Other clinical toxicities including cardiac toxicity were negligible. MIZE chemotherapy was effective in patients with relapsed and refractory lymphoma and showed limited clinical and cardiac toxicity. Myelosupression was the most frequent single toxicity.

Case report: reactive hemophagocytic syndrome associated with disseminated strongyloidiasis.

The reactive hemophagocytic syndrome is a condition characterized by systemic proliferation of benign hemophagocytic histiocytes, fever, cytopenia, abnormal liver function, and frequently coagulopathy and hepatosplenomegaly. Its occurrence has been documented in association with viral, bacterial, fungal and parasitic infections; a wide spectrum of malignant neoplasms; some miscellaneous disorders; and phenytoin. Disseminated strongyloidiasis is reported in a patients with systemic lupus erythematosus treated with corticosteroids in whom a reactive hemophagocytic syndrome developed and who finally died. This reactive hemophagocytic syndrome is reported for the first time in strongyloidiasis and may not have been recognized in former patients.

Dysfunction of monocytes in Hodgkin's disease by excessive production of PGE-2 in long-term remission patients.

The candidacidal activity and the production of oxygen radicals by monocytes were investigated in untreated and long-term remission patients with Hodgkin's disease (HD). Both groups showed a decreased candidacidal function of monocytes with a chemiluminescence (CL) response significantly lower and delayed with respect to normal controls. Indomethacin at 1 microgram/ml corrected the monocyte deficiency increasing the CL response to normal values and normalizing the kinetics in the untreated patients. However, in patients in remission, the peak was delayed and followed by a significant increase in the production of oxygen radicals compared with untreated patients. A direct linear correlation was found between the percentages of lysed Candida and maximum CL peak of stimulated monocytes. When prostaglandin E2 (PGE-2) levels, measured in supernatants of cultured mononuclear cells, were plotted against the percentages of killed Candida, an inverse linear correlation was found. Therefore, monocytes from HD patients have a dysfunction in the generation of oxygen radicals and a decreased candidacidal activity associated with excessive production of PGE-2. Indomethacin can correct the oxidative metabolism in the untreated patients while in apparently "cured" patients the disorder persists.

A person to person hepatitis A outbreak.

A person to person outbreak of hepatitis A is described: 90 cases of hepatitis A occurred in a small town in Calabria, southern Italy; all cases were under 18 years of age with the highest age-specific incidence rate in the 6-10 year age group. Transmission was identified by tracing close contacts with other incubating or active cases; only eight out of 90 cases were not identified as having a very probable or possible contact with an infecting case. Transmission was high between family members leading to a secondary family attack rate of 51% in children under 16. An enteric disease educational campaign was carried out together with IgG and no cases of hepatitis A were reported in the two years following the investigation.

Normalization of monocyte candidacidal deficiency by cyclooxygenase inhibitors in Hodgkin's disease.

In a previous work, the authors found that the peripheral blood monocytes from patients with Hodgkin's disease (HD) had depressed lytic capability to kill Candida pseudotropicalis and depressed phagocytic function. The aim of this study was to evaluate if cyclooxygenase inhibitors could correct the defective macrophage functions. Fifteen untreated patients with HD and 10 normal subjects were studied. The incubation of the cells from the patients with HD with indomethacin (IM) at 1, 3, and 10 micrograms/ml and with acetylsalicylic acid (ASA) at 20 micrograms/ml increased their previously deficient ability to kill C. pseudotropicalis, reaching values close to those of normal subjects. The oral administration of ASA during 1 week also corrected the monocyte lytic deficiency in the patients' group. Neither the in vitro nor the in vivo treatment with these cyclooxygenase inhibitors had any significant effect on normal subjects' monocytes' lytic function. The drugs did not improve the impaired phagocytic function in patients with HD. These results indicate that the failure of the lytic activity of the monocytes in HD could be associated to an excessive production of PGE2, and the oral administration of inhibitors of the cyclooxygenase activity can correct such abnormality whereas the phagocytic dysfunction is not reverted by them.

Granulopoyesis in vitro para el diagnostico y tratamiento de una anemia aplastica de probable origen inmunologico. / In vitro granulopoiesis for the diagnosis and treatment of aplastic anemia probably of immunologic origin

Se presenta el caso de un paciente de 23 anos de edad, sexo masculino, con anemia aplastica idiopatica de 3 meses de evolucion y manifestaciones hemorragicas e infecciosas, que no habia mejorado con androgenoterapia. Se le realiza cultivo de medula osea y estudio citogenetico que demuestran la existencia de un mecanismo inhibidor de la granulopoyesis, reversible in vitro con GAL y metilprednisona. La administracion de corticoides por via oral lleva a la remision del cuadro hematologico en corto plazo. La correlacion entre el estudio in vitro y la respuesta in vivo a la corticoterapia confirma la importancia de dilucidar los diferentes mecanismos responsables de la aplasia medular donde no siempre el defecto se encuentra en la celula madre

Consumption coagulopathy in acute renal failure induced by hypolipotropic diets.

Weanling male rats fed on a hypolipotropic diet develop acute renal failure whose morphological features vary from focal tubular necrosis to cortical necrosis. We have sequentially studied the hemostatic mechanism in correlation with the morphology of various tissues, mainly renal and hepatic, in choline-deficient rats as well as in three control groups. No important changes were observed in the hemostatic mechanisms before the development of tubular necrosis. Along with tubular necrosis a consumption coagulopathy was found, evidenced mainly by a decrease in the activity of factors V and VIII as well as a prolongation in PTTK and Quick's time and a decrease in platelets. Fibrin degradation products were found in serum and urine and soluble fibrin monomer complexes in the former. Following tubular necrosis thrombi were found in the renal microvasculature. It is possible to speculate that the tubular necrosis induced by choline deficiency could produce an activation of the coagulation system which in turn would lead to thrombosis of the renal microcirculation and cortical necrosis.