Treatment of iatrogenic femoral artery injuries with ultrasound-guided compression.

Iatrogenic injuries of the groin are becoming more common after increasingly sophisticated vascular intervention. These injuries are accurately detected by duplex and color Doppler ultrasonography. Recent treatment of these lesions by ultrasound-guided compression repair (UGCR) has been described. During a 1-year period we identified 18 femoral artery injuries, including 17 pseudoaneurysms and one arteriovenous fistula. Three of the pseudoaneurysms thrombosed spontaneously before attempted treatment. The remaining 15 lesions underwent a trial of UGCR. Successful closure was accomplished in 10 patients (56%). Seven of these lesions were successfully treated during the initial session, and thrombosis was accomplished after repeat compression in three additional lesions. Three patients who were given anticoagulants had a failed UGCR, but their pseudoaneurysms thrombosed after administration of anticoagulants was discontinued. Two patients had failed UGCR and required operation. Seven (88%) of eight patients who were not given anticoagulants were successfully treated. In contrast only two (29%) of seven patients given therapeutic doses of anticoagulant medication were successfully treated by the technique. There was no statistical difference between mean pseudoaneurysm diameter, mean width and length of pseudoaneurysm neck, or depth of pseudoaneurysm neck from skin surface in patients in whom successful initial closure was achieved when compared with those patients in whom the initial attempt failed. UGCR is a safe, simple, noninvasive technique that can be used to treat many femoral artery injuries that traditionally were treated with surgery. The technique can be applied by any laboratory that has the necessary ultrasonography equipment and is currently the method of choice for treating uncomplicated iatrogenic femoral artery injuries at our institution.     

The role of surveillance cultures in patients likely to develop chemotherapy-induced mucositis

 Mucositis can be the major dose-limiting toxicity during the adminstration of certain types of chemotherapy, especially 5-fluorouracil, methotrexate and doxorubicin. Infection probably plays a role after initial inflammatory changes occur in the mucous membranes of the mouth after chemotherapy, especially if the patient becomes neutropenic. The issues addressed in this paper following a review of the literature are whether surveillance cultures can be helpful to avoid mucositis or at least predict who will be at risk for its development and whether this will be a help in decisions on the antimicrobial treatment that should be given if mucositis develops. Bacterial, fungal and viral causes of mucositis have been identified. The simplest to deal with is viral, since if herpes simplex is identified it should be treated with acyclovir; in the case of allogeneic bone marrow transplants acyclovir is usually given prophylactically. Fungal organisms almost certainly play a part; especially if a Candida species, particularly Candida tropicalis, is identified in surveillance cultures, it is probably important. The significance of bacterial pathogens in surveillance cultures is more difficult to sort out except for Pseudomonas aeruginosa, which almost always predicts for eventual systemic infection, especially bacteraemia. The poor overall predictive value (both positive and negative) for surveillance cultures and their significant expense do not support their routine use in 1997.     

Non-opioid analgesia improves pain relief and decreases sedation after gastric bypass surgery

PURPOSE: Several non-opioid drugs have been shown to provide analgesia during and after surgery. We compared sevoflurane anesthesia with fentanyl analgesia to sevoflurane and non-opioid drug treatment for gastric bypass surgery and recovery. METHODS: Thirty obese patients (body mass index > 50 kg.m(-2)) undergoing gastric bypass were randomized to receive sevoflurane anesthesia with either fentanyl or a non-opioid regimen including ketorolac, clonidine, lidocaine, ketamine, magnesium sulfate, and methylprednisolone. Morphine use by patient-controlled analgesia (PCA) pump and pain score measured by visual analogue scale were determined in the postanesthesia care unit (PACU) and for the first 16 hr after surgery. Sedation was evaluated in the PACU. Investigators assessing patient outcomes were blinded to the study group. RESULTS: Fentanyl treated patients were more sedated in the PACU compared to the non-opioid group. Non-opioid treated patients required 5.2 +/- 2.6 mg.hr(-1) morphine by PCA during their stay in the PACU while patients anesthetized with fentanyl used 7.8 +/- 3.3 mg.hr(-1) (P < 0.05). Fentanyl and non-opioid treated patients showed no difference in pain score one or 16 hr after surgery. CONCLUSION: Our results show that non-opioid analgesia produced pain relief and less sedation during recovery from gastric bypass surgery compared to fentanyl.     

Forsaken Pharmaceutical: Glasdegib in Acute Myeloid Leukemia and Myeloid Diseases

Advancements in the understanding of the pathogenesis of acute myeloid leukemia (AML) have led to the introduction and approval of a number of novel drugs in AML. Glasdegib, an oral hedgehog pathway inhibitor, was approved in 2018 in combination with low-dose cytarabine for the treatment of newly diagnosed AML in patients unfit for intensive chemotherapy. In this review, we discuss the preclinical rationale for glasdegib, important clinical trials that led to glasdegib’s approval, and future trials of glasdegib in AML and other myeloid diseases. Notably, 2 large randomized, placebo-controlled phase 3 trials (AML BRIGHT 1019) are currently recruiting patients with newly diagnosed AML to evaluate glasdegib in combination with intensive chemotherapy or azacitidine, depending on the patient’s ability to tolerate induction chemotherapy. While glasdegib and low-dose cytarabine have been eclipsed by venetoclax and hypomethylating agent combinations for newly diagnosed AML in the United States, we discuss other areas where glasdegib may still have an opportunity to improve outcomes in this devastating disease.     

Cefoperazone compared with ampicillin plus tobramycin for severe biliary tract infections.

In a prospective, randomized, multicenter study, the efficacy and safety of cefoperazone and the combination ampicillin-tobramycin as initial therapy for patients with severe acute biliary tract infections were compared. Of 77 patients initially entered in the study, definite severe biliary tract infection was confirmed in 67. Sixty-four patients completed treatment. At the end of treatment, 35 of 36 (97%) patients given cefoperazone and 23 of 28 (82%) given ampicillin-tobramycin were cured of their infection (P = 0.07). Pathogens were recovered from the bile in 32 patients; microbiological cures were observed in 18 of 19 (94%) patients receiving cefoperazone and 8 of 13 (62%) receiving ampicillin-tobramycin (P = 0.03). Thirteen patients had septicemia. None (0%) of the eight septicemic patients from the cefoperazone group, but two of five (40%) from the ampicillin-tobramycin group, were clinical failures. Of the isolated pathogens, 51% were resistant to ampicillin, while the resistance rate was 4% for tobramycin and 1% for cefoperazone (P less than 0.001). Biliary concentrations of cefoperazone were maintained at high levels--236 +/- 87 micrograms/ml up to 12 h after administration. Even in the presence of severe obstruction, cefoperazone levels in the bile and gallbladder wall were above MICs for most pathogens. Cefoperazone may be considered as an excellent alternative in the therapy of severe biliary tract infections.     

Persistence of Atrial Fibrillation After Its Induction-Importance of the Duration and Dispersion of Atrial Refractoriness and Electrical Remodeling

BACKGROUND: The electrophysiologic mechanisms of the persistence of atrial fibrillation (AF) after its initiation are not well understood. Therefore, the electrophysiologic characteristics of the right atrium were evaluated in an acute, pacing-induced model of AF in the pig in order to identify parameters associated with persistence of AF. METHODS AND RESULTS: AF was induced by rapid atrial pacing in 30 anesthetized, open-chest, juvenile pigs. Sustained (S) AF was defined as that lasting >10 minutes, nonsustained (NS) AF <10 minutes but >30 seconds, and no (N) AF <30 seconds. Activation mapping and programmed stimulation (S1S1 = 200 ms) was performed at 56 electrodes on the right atrial free wall, to determine ERP (mean and minimum), dispersion of refractoriness (ERPdisp, ELEdisp), conduction velocity (CV), wavelength, AF cycle length (mean of 10 beats), and AF cycle length/time (electrical remodeling). SAF was induced in 10 pigs, NSAF in 9, and NAF in 11. AF cycle length was shorter in SAF and/vs NS vs NAF (P <.001). Mean ERP (107 +/- 9 and/vs 122 +/- 5 vs 142 +/- 9, p <.001) and wavelength (7 +/- 1 and/vs 9 +/- 1 vs 11 +/- 1, P <.001) were shorter in SAF and/vs NSAF vs NAF. Minimum ERP was shorter in SAF and NSAF vs NAF (P <.001). CV at cycle lengths of 200 and 150 msec was not different between groups. Dispersion of ERP was greater in SAF and/vs NSAF vs NAF (8 +/- 1 and/vs 11 +/- 1 vs 19 +/- 4, P <.001). CONCLUSIONS: Persistence of AF correlated with shorter ERP and wavelength, and greater dispersion of ERP and electrical remodeling. There was no correlation with CV.     

Ectopic supernumerary kidney: Another cause of a pelvic mass

Ectopic supernumerary pelvic kidney is a rare cause of a pelvic mass in the adolescent populations. We present a case of an ectopic supernumerary pelvic kidney, found incidentally, on a computed axial tomographic (CT) examination.     

Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis

Heparanase is an endoglycosidase that cleaves heparan sulfate side chains of proteoglycans, resulting in disassembly of the extracellular matrix underlying endothelial and epithelial cells and associating with enhanced cell invasion and metastasis. Heparanase expression is induced in carcinomas and sarcomas, often associating with enhanced tumor metastasis and poor prognosis. In contrast, the function of heparanase in hematological malignancies (except myeloma) was not investigated in depth. Here, we provide evidence that heparanase is expressed by human follicular and diffused non-Hodgkin''s B-lymphomas, and that heparanase inhibitors restrain the growth of tumor xenografts produced by lymphoma cell lines. Furthermore, we describe, for the first time to our knowledge, the development and characterization of heparanase-neutralizing monoclonal antibodies that inhibit cell invasion and tumor metastasis, the hallmark of heparanase activity. Using luciferase-labeled Raji lymphoma cells, we show that the heparanase-neutralizing monoclonal antibodies profoundly inhibit tumor load in the mouse bones, associating with reduced cell proliferation and angiogenesis. Notably, we found that Raji cells lack intrinsic heparanase activity, but tumor xenografts produced by this cell line exhibit typical heparanase activity, likely contributed by host cells composing the tumor microenvironment. Thus, the neutralizing monoclonal antibodies attenuate lymphoma growth by targeting heparanase in the tumor microenvironment.Heparanase is an endo-β-d-glucuronidase capable of cleaving heparan sulfate (HS) side chains at a limited number of sites, releasing saccharide products with appreciable size (4–7 kDa) and biological potency. Enzymatic degradation of HS leads to disassembly of the extracellular matrix (ECM) and correlates with the metastatic potential of tumor-derived cells, attributed to enhanced cell dissemination as a consequence of HS cleavage and remodeling of the ECM and basement membrane underlying epithelial and endothelial cells (1, 2). Heparanase expression is induced in human cancer, most often associating with reduced patients’ survival postoperation, increased tumor metastasis, and higher vessel density (3–5). In addition, heparanase up-regulation is associated with tumors larger in size (3, 5). Likewise, heparanase over-expression enhanced (6, 7), whereas local delivery of anti-heparanase siRNA inhibited (8), the growth of tumor xenografts. These results imply that heparanase function is not limited to tumor metastasis but is engaged in progression of the primary lesion, thus critically supporting the intimate involvement of heparanase in tumor progression and encouraging the development of heparanase inhibitors as anticancer therapeutics (9–12). As a consequence, heparanase inhibitors are currently evaluated in phase 1 clinical trials (13).Heparanase activity is similarly implicated in the progression of multiple myeloma (14–16), but its significance in other hematologic malignancies has not yet been characterized. Lymphomas are a heterogeneous group of cancers that arise from developing lymphocytes and produce tumors predominantly in lymphoid structures (i.e., bone marrow), but also in extranodal tissues. Collectively, lymphomas constitute the fifth most common cancer in North America, with more than 90% of the patients being affected by lymphomas of B-cell origin (17). Despite overall improvements in outcomes of lymphoma, ∼30–40% of patients have disease that is either refractory or relapses after standard therapy (18). Therefore, a better understanding of the molecular pathobiology of lymphomas is needed for the development of new therapeutic approaches. Here, we provide evidence that heparanase is expressed by B-lymphomas and that heparanase inhibitors restrain tumor growth. Furthermore, we describe the development of novel heparanase-neutralizing monoclonal antibodies (mAbs) that attenuate lymphoma growth by targeting heparanase in the tumor microenvironment.     

Increased somatic complaints and health-care utilization in children: effects of parent IBS status and parent response to gastrointestinal symptoms

OBJECTIVES: Irritable bowel syndrome (IBS) runs in families. The aims of this study were (i) to exclude biased perception by a mother with irritable bowel as the explanation for increased gastrointestinal (GI) symptoms in their children, (ii) to determine whether non-GI as well as GI symptoms run in families, and (iii) to determine whether parent IBS status and solicitous responses to illness exert independent effects on children's symptom reports, medical clinic visits, and school absences. METHODS: Two hundred and eight mothers with irritable bowel and their 296 children (cases: average age 11.9 yr; 48.6% male) and 241 nonirritable bowel mothers and their 335 children (controls: 11.8 yr; 49.0% male) were interviewed. Other factors assessed were stress, mother's and child's psychological symptoms, child's perceived competence, pain coping style, age, and sex. Children were interviewed apart from their parents. RESULTS: Case children independently reported more frequent stomach aches (F(591) = 9.22; p= 0.0025) and non-GI symptoms (F(562) = 21.03; p < 0.001) than control children. Case children also had more school absences (F(625) = 26.53; p < 0.0001), physician visits for GI symptoms (F(602) = 8.09; p= 0.005), and non-GI clinic visits (F(602) = 27.92; p < 0.001) than control children. Children whose mothers made solicitous responses to illness complaints independently reported more severe stomach aches (F(590) = 11.42; p < 0.001), and they also had more school absences for stomach aches (F(625) = 5.33; p < 0.05), but solicitous behavior did not significantly impact non-GI symptom reporting, clinic visits, or school absences. Differences between cases and controls remained significant after adjusting for potential moderators. CONCLUSIONS: (i) Frequent GI complaints in children whose mothers have irritable bowel are not explained by the mother's biased perceptions; (ii) children of mothers with irritable bowel have more non-GI as well as GI symptoms, disability days, and clinical visits; (iii) and parent IBS status and solicitous responses to illness have independent effects on the child's symptom complaints.