From Refractory Ascites to Dilutional Hyponatremia and Hepatorenal Syndrome: Current Options for Treatment

Cirrhosis is associated with high morbidity rates due to complications of portal hypertension. Ascites is the most frequent complication in patients with cirrhosis, and refractory ascites will develop in approximately 10 % of patients during follow-up. Currently, the first-line treatment for patients with refractory ascites is large-volume paracentesis with albumin supplementation. In more advanced stages of the disease, dilutional hyponatremia may develop as the result of nonosmotic hypersecretion of vasopressin. Although vaptans have shown promising results as a potential pharmacologic approach to treating hypervolemic hyponatremia, their results on long-term efficacy and safety in patients with cirrhosis are not conclusive. Moreover, because of concerns regarding side effects, the US Food and Drug Administration recently removed the indication of tolvaptan for use in patients with cirrhosis. Finally, in late stages of the disease, intense renal vasoconstriction occurs and leads to the development of hepatorenal syndrome. The treatment of choice for patients with hepatorenal syndrome is vasoconstrictor drugs followed by liver transplantation.     

Methicillin-resistant Staphylococcus aureus meningitis in adults: a multicenter study of 86 cases

Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is an uncommon disease, and little is known about its epidemiology, clinical features, therapy, and outcome. We performed a multicenter retrospective study of MRSA meningitis in adults. Eighty-six adult patients were included and the following data were obtained: underlying diseases, clinical presentation, analytical and microbiologic data, response to therapy, and outcome.There were 56 men (65%) and the mean age was 51.5 years; 54 of them (63%) had severe comorbidities. There were 78 cases of postoperative meningitis and 8 of spontaneous meningitis. The infection was nosocomial in 93% (80/86) of the cases. Among the 78 patients with postoperative meningitis, the most common predisposing conditions were cerebrospinal fluid (CSF) devices (74%), neurosurgery (45%), CSF leakage (17%), and head trauma (12%). Most patients had fever (89%), altered mental status (68%), headache (40%), and meningeal signs (29%). The most common CSF findings were pleocytosis (90%), elevated protein level (77%), and hypoglycorrhachia (30%). CSF Gram stain and blood cultures were positive in 49% (32/65) and 36% (16/45) of cases, respectively. An associated MRSA infection and polymicrobial meningitis appeared in 33% (28/86) and 23% (20/86) of cases, respectively. Antimicrobial therapy was given to 84 patients. Most of them received vancomycin (92%) either as monotherapy (64%) or in combination with other antibiotics (28%), for a median of 18 days. Overall 30-day mortality was 31% (27/86). Multivariate study identified 2 independent factors associated with mortality: spontaneous meningitis (odds ratio [OR], 21.4; 95% confidence interval [CI], 2.3-195.4; p = 0.007), and coma (OR, 9.7; 95% CI, 2.2-42.3; p = 0.002).In conclusion, MRSA is a relatively uncommon but serious disease. Although most cases are nosocomial infections appearing in neurosurgical patients, spontaneous meningitis may present as a community-onset infection in patients with severe comorbidities requiring frequent contact with the health care system. Most patients have a favorable response to vancomycin, but the beneficial effect of combined and intraventricular therapy, or alternative drugs, remains unclear. MRSA meningitis is associated with a high mortality, and the presence of spontaneous infection and coma are the most important prognostic factors.     

Clofarabine-based chemotherapy for relapsed/refractory adult acute lymphoblastic leukemia and lymphoblastic lymphoma. The Spanish experience

The present study reports the Spanish PETHEMA group experience in 31 heavily pretreated relapsed/refractory acute lymphoblastic leukemia (ALL) and lymphoma (LL) patients treated with clofarabine-based regimens. The complete remission (CR) rate was 31% (median CR duration of 3 months [range 2–28]) and the overall survival probability at 1 year was 10% (95%CI 4–16%). Responses were seen in B and T lineage diseases and in patients with adverse cytogenetics. Hematological and infectious grade >3 toxicities were found in 100 and 67% of the patients, respectively, with 7 (23%) treatment-related deaths. Other organ toxicities were infrequent. Clofarabine-based chemotherapy regimens might induce CRs in ALL and LL patients, but hematological toxicity and infections may limit their use in heavily pretreated patients.     

Degree of mucositis and duration of neutropenia are the major risk factors for early post-transplant febrile neutropenia and severe bacterial infections after reduced-intensity conditioning

Background and objectives: Whether the intensity of the conditioning regimen affects febrile neutropenia (FN) and severe bacterial infections (SBIs) is not well established. We analyzed the risk factors (RFs) for the development of FN and SBI in the first 100 d post‐transplant in 195 consecutive adult recipients of a reduced‐intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC‐allo). Materials and methods: The RIC regimens consisted of fludarabine plus melphalan (62%) or busulphan (38%) (FluMel or FluBu). SBIs include pneumonia, urinary tract infections, and bacteremia. Results: FN occurred in 141 patients (72%), always in the first 30 d post‐allo‐RIC. However, a SBI occurred in only 27 patients (14%) during this early post‐transplant period (P < 0.02) and NCI CTC grade III–IV mucosal damage in the first 10 d post‐transplantation (P = 0.03). RFs identified to SBI by multivariate analysis included corticosteroid therapy before day +100 (P < 0.01), mycophenolate mofetil‐based graft‐versus‐host disease (GVHD) prophylaxis (P < 0.01), and previous SBI before day +30 (P < 0.01). The rate of SBI from day +30 to +100 varied according to the number of RFs; thus, the rate of SBI was 1% in patients without any RF, 17% in patients with one RF, 29% with one RFs, and 53% in those with all three RFs. Conclusions: After an RIC‐allo, FN and early SBI occurred mostly in patients with severe mucositis and early‐onset neutropenia, while postengraftment high‐dose steroid therapy for acute GVHD was the major RF.     

Drug dosage recommendations in patients with chronic liver disease

Chronic liver diseases (CLD) alter the kinetics of drugs. Despite dosage adjustment is based on Child-Pugh scores, there are no available recommendations and/or algorithms of reference to facilitate dosage regimens. A literature review about dose adjustment of the drugs from the hospital guide -which are included in the list of the WHO recommended drugs to be avoided or used with caution in patients with liver disease- was carried out. The therapeutic novelties from the last few years were also included. In order to do so, the summary of product characteristics (SPC), the database DrugDex-Micromedex, the WHO recommendations and the review articles from the last 10 years in Medline were reviewed. Moreover, the kinetic parameters of each drug were calculated with the aim of establishing a theoretical recommendation based on the proposal of Delcò and Huet. Recommendations for 186 drugs are presented according to the SPC (49.5%), DrugDex-Micromedex (26.3%) and WHO (18.8%) indications; six recommendations were based on specific publications; the theoretical recommendation based on pharmacokinetic parameters was proposed in four drugs. The final recommendations for clinical management were: dosage modification (26.9%), hepatic/analytical monitoring of the patient (8.6%), contraindication (18.8%), use with caution (19.3%) and no adjustment required (26.3%). In this review, specific recommendations for the practical management of patients with chronic liver disease are presented. It has been elaborated through a synthesis of the published bibliography and completed by following a theoretical methodology.     

Immediate and delayed postoperative morbidity in functional and non-functioning pituitary adenomas

Neurosurgery is the most widely used definite treatment for pituitary tumors, while medical treatments are a good option to improve symptoms, which tend to recur when drugs are stopped. The aim of this study was to assess postsurgical morbidity of secreting pituitary adenomas (adrenocorticotropin hormone -ACTH- and growth hormone -GH- secreting) and non-functioning (NF) adenomas, operated between January 2002 and May 2009. We retrospectively reviewed the data of 94 patients who were operated by the same neurosurgeons and compared the immediate (1st month) and delayed (1st year) complications between the three groups of adenomas. Forty had immediate post-operative complications (42% of NF, 37% of GH-secreting and 48% of ACTH-secreting adenomas). The most frequent complications were transient diabetes insipidus (23%), cerebrospinal fluid leaks (7%), sinusitis and meningitis (2%). Patients with Cushing's disease showed a tendency to have more transient diabetes insipidus and sinusitis compared to NF adenomas (P = 0.071). Ten patients had delayed complications during the first post-operative year (7% of NF, 11% of GH-secreting and 15% of ACTH-secreting), with a greater incidence of arthromyalgias and acute carpal tunnel syndrome in ACTH-secreting adenomas, compared with the other groups (P < 0.05). We conclude, that although ACTH-secreting adenomas are mostly microadenomas (78%) and affect younger patients, they are associated with a greater number of immediate and delayed complications during the first postoperative year (mainly invalidating arthromyalgias and acute carpal tunnel syndrome) compared with larger GH-secreting and NF adenomas, probably related to acute glucocorticoid deprivation after successful surgery.