Israel Medical Association Journal

Background: Functional mitral and tricuspid regurgitation (fMR and fTR, respectively) portend increased morbidity and mortality among heart failure (HF) patients.

Objectives: To characterize acute decompensated valvular HF (VHF) as a novel HF category, defined by presence of either more than moderate fTR or more than moderate fMR with left ventricular ejection fraction (LVEF) ≤ 50%.

Methods: Patients with VHF were prospectively enrolled over a 6-month period and compared to acute decompensated heart failure (ADHF) patients without significant fTR or fMR. We used a standardized diuretic protocol when indicated, and appropriate inpatient guideline-directed medical therapy was initiated.

Results: Among 322 patients admitted with ADHF, 83 (26%) met VHF criteria with mean age 66 ± 13 years, 43 (52%) males, and median LVEF of 30% (20–55). Of 61 patients in whom the diuretic protocol was initiated, 59 (97%) had an adequate response (i.e., > 100 cc/hour for at least 6 hours). VHF patients had longer length of hospitalization (8 [5–13] vs. 5 [3–8] days, P < 0.001), and higher rates of 90–day heart replacement therapy (HRT) or death (hazard ratio 2.52, 95% confidence interval (1.13–5.64); P = 0.024).

Conclusions: Over a quarter of ADHF patients can be newly categorized as VHF patients, distinguished by prolonged hospitalization and worse 90-day mortality / HRT rate. The initial response rate to a standardized diuretic protocol was high.

Reversible cerebral vasoconstriction syndrome (RCVS) comprises a group of conditions characterized by reversible vasoconstrictions of cerebral arteries. Clinical manifestations include sudden-onset severe headaches with or without additional neurologic signs and symptoms [1].

The incidence of RCVS is 2.7 cases per million adults. It predominantly affects women, and about 9% of all RCVS cases occur during the postpartum period [2,3]. Other possible precipitating factors, such as subarachnoid hemorrhage, ischemic stroke, intracranial hemorrhage, and exposure to vasoactive drugs, have also been reported in association with RCVS [2]. The exact pathophysiology of RCVS is not well understood, although hormonal influences have been suggested as possible contributing factors.

Alkalosis-induced cerebral vasoconstriction is described but not well understood. Hyperventilation is commonly used in neurologic patients to decrease intracranial pressure and cerebral blood flow. Hyperventilation causes cerebral vasoconstriction directly by hypocapnia and may indirectly affect through alkalosis.

We present a case of RCVS in a postpartum patient admitted to the intensive care unit (ICU) with severe metabolic alkalosis necessitating hemodialysis.

Background: Although 5-amino-salycilic acids (5-ASA) are often used with corticosteroid treatment in moderate-to-severe ulcerative colitis, the value of continuing/initiating 5-ASA in this clinical setting has not been explored. 

Objectives: To investigate the impact of a combination 5-ASA+corticosteroid therapy on the outcome of hospitalized patients with acute moderate-severe ulcerative colitis. 

Methods: We conducted a retrospective study of patients hospitalized with moderate-severe ulcerative colitis in two centers, Israel and South Korea. Patients were classified into those who received 5-ASA and corticosteroids and those who received corticosteroids alone. Analysis was performed for each hospitalization event. The primary outcome was the rate of treatment failure defined as the need for salvage therapy (cyclosporin-A/infliximab/colectomy). The secondary outcomes were 30 days re-admission rates, in-hospital mortality rates, time to improvement, and length of hospitalization. 

Results: We analyzed 209 hospitalization events: 151 patients (72%) received 5-ASA+corticosteroids and 58 (28%) corticosteroids alone. On univariate analysis the combination therapy group had a lower risk for treatment failure (11% vs. 31%, odds ratio 0.28, 95% confidence interval 0.13–0.59, P = 0.001). However, this difference disappeared on multivariate analysis, which showed pre-admission oral corticosteroid treatment to be the most significant factor associated with the need for salvage therapy. 

Conclusions: A signal for possible benefit of a combination 5-ASA and corticosteroids therapy was found, but was confounded by the impact of pre-admission corticosteroid treatment. 

 

We describe a unique E3, the F-box protein, Ufo1, of yeast. Ufo1 recruits the mating switch endonuclease, Ho, to the SCF complex for ubiquitylation. In addition to the F-box and WD40 protein-protein interaction domains found in all F-box proteins, Ufo1 has a unique domain comprising multiple copies of the ubiquitin-interacting motif. Ufo1 interacts with the UbL-UbA protein, Ddi1, via its UIMs[1], and this is required for turnover of SCF ^Ufo1 complexes. This is a novel function for an UbL-UbA protein. Deletion of the genomic UFO1 UIMs is lethal and our data indicate that Ufo1ΔUIM acts as a dominant negative leading to inhibition of the SCF pathway of substrate degradation and to cell cycle arrest. Furthermore, we found that Ddi1 is required for the final stages of degradation of Ho endonuclease. In the absence of Ddi1, Ho does not form a complex with the 19S RP and is stabilized. Stabilization of Ho leads to perturbation of the cell cycle and to the formation of multi-budded cells. Our experiments uncover a novel role for the ubiquitin-proteasome system in maintenance of genome stability.