BRAF plus MEK-targeted drugs: a new standard of treatment for BRAF-mutant advanced melanoma

BRAF plus MEK-targeted drugs have out-performed BRAF inhibitor monotherapy in three randomized phase 3 studies, and such combinations have become a new standard of treatment for BRAF-mutant advanced melanoma. With an overall response rate of about 70%, no other therapy in melanoma has shown a better response rate in late-phase clinical trials than combined BRAF and MEK inhibitors; the rapid kinetics of response make them the ideal front-line treatment for symptomatic, BRAF-mutant advanced melanoma patients. Nevertheless, the development of mechanisms of resistance limits the duration of response to such treatment in the majority of cases, with only about 20% of patients treated with the combination being progression-free at 3 years. The aim of this review is to report the efficacy and safety outcomes of the combination of BRAF plus MEK inhibitors compared with BRAF inhibitor monotherapy and immunotherapy, as well as to discuss future perspectives to improve outcomes based on current clinical and translational research studies.     

Delayed hyperbaric oxygen treatment after acute carbon monoxide poisoning

Journal of Neurology -     

Nasal seromucinous hamartoma (microglandular adenosis of the nose): a morphological and molecular study of five cases

Five cases of nasal seromucinous hamartoma were studied and their clinical, morphological, immunohistochemical and molecular data are reported. The patients, three females and two males, ranged in age from 49 to 66 years (mean 56 year, SD ± 7.91). All lesions were located in the nasal cavity. In four cases where follow-up was obtained, no recurrence was evident. In all cases, numerous small seromucinous tubules, embedded in a cellular stroma, were present in the lamina propria. Tubules were lined by one layer of cuboidal cells which displayed luminal phenotype positive for lysozyme and EMA in four, and S100 protein in all cases. Collagen IV and laminin positive basal lamina outlined the tubules which lacked basal cells. Stromal spindle cells present among tubules were immunoreactive for calponin in all cases and for alpha-smooth muscle actin in four cases. DNA mutation analysis of mitochondrial D-loop region was performed by direct sequencing in order to verify the mutation rate of these lesions. The tubules of the five seromucinous hamartomas showed a higher mutation rate especially in heteroplasmy (0.52% homoplasmy, 2.02% heteroplasmy) in comparison to normal seromucinous glands which exhibited a lower mutation frequency (0.83%). This is considered a sign of a low cellular proliferation rate consistent with a benign process. It is concluded that nasal seromucinous hamartomas are benign glandular proliferations that may resemble microglandular adenosis of the breast. Their distinction from benign and malignant mimics is discussed.     

A new microbiological problem in intensive care units: environmental contamination by MRSA with reduced susceptibility to glycopeptides

The present study evaluated the percentage of methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to glycopeptides in four intensive care units (ICU) by means of environmental sampling of air and representative surfaces. The total bacterial count was taken and possible S. aureus strains were subsequently isolated. To assess methicillin resistance, an antibiogram was performed on the colonies that were positive to the coagulase test. A standard E-test was then carried out on the colonies that developed, in order to evaluate glycopeptide resistance, and any heterogeneous resistance was confirmed by means of a macromethod E-test.

The antibiogram performed on the colonies of S. aureus revealed that 85.7% of all air samples were positive for MRSA, and that 64.3% of all the samples proved to be heterogeneously resistant to glycopeptides. Methicillin resistance was recorded in 41.0% of surface samples, and 32.5% of all samples proved positive for hGISA.     

Dural sinus thrombosis in spontaneous intracranial hypotension

Dural sinus thrombosis (DST) is rarely associated with spontaneous intracranial hypotension (SIH). Engorgement of the venous system, caused by the CSF loss that occurs in SIH, is considered to favour the thrombosis, although signs of both SIH and DST are usually seen simultaneously at the first diagnostic MRI. We observed two patients with SIH and DST. Changes in pattern of headaches and MRI findings demonstrated that DST followed SIH. In SIH, the velocity of the blood flow in the dural sinuses may be reduced because of dilatation of the venous system which compensates the CSF loss. Other possible mechanisms seem unlikely on the grounds of both clinical presentation and MRI studies. Received in revised form: 6 December 2005     

Imaging aspects of the diagnosis of sarcoidosis

Sarcoidosis is a systemic granulomatous disorder of unknown aetiology with a wide spectrum of radiological appearances and almost invariably pulmonary involvement. Lung involvement accounts for most of the morbidity and much of the mortality associated with sarcoidosis. Imaging contributes significantly to the diagnosis and management of patients with sarcoidosis. In typical cases, chest radiography may be sufficient to establish the diagnosis with little margin of error and CT is not necessary. However, CT can play a critical role in several clinical settings: atypical clinical and/or radiographic findings; normal or near-normal chest radiograph but clinical suspicion of sarcoidosis; and detection of complications. Moreover, in many patients, CT findings are atypical and unfamiliar to most radiologists (e.g. sarcoidosis mimicking other lung diseases and vice versa), and in these cases histological confirmation of the diagnosis is recommended. CT is also useful in assessing disease extent and may help to discriminate between reversible and irreversible lung disease, thus providing critical prognostic information. This review concentrates on the more difficult imaging aspects of sarcoidosis, in particular differential diagnosis and disease complications. Key points ?Sarcoidosis is characterized by a wide spectrum of radiological appearances. ?In typical cases, imaging substantially contributes to the diagnosis of sarcoidosis. ?CT plays a critical role in atypical and complicated cases. ?CT may discriminate between reversible and irreversible lung disease.     

Vaginal cuff dehiscence after hysterectomy: a multicenter retrospective study

Objective

This study estimates the incidence of vaginal cuff dehiscence resulting from different approaches to hysterectomy.

Study design

This multicentric study was carried out retrospectively. We retrospectively analyzed 8635 patients; 37% underwent abdominal hysterectomy, 31.2% vaginal hysterectomy, and 31.8% laparoscopic hysterectomy. All the hysterectomies were considered, vaginal evisceration was registered and analyzed for time of onset, trigger event, presenting symptoms, details of prolapsed organs and type of repair surgery. Continuous variables were compared using the one-way analysis of variance between groups as all data followed a Gaussian distribution, as confirmed by the Kolmogorov–Smirnov test. Differences among subgroups were assessed using the Tukey–Kramer multiple comparisons test. Categorical variables were compared with two tailed Chi-square tests with Yates correction or Fisher's exact test, as appropriate. Pearson's linear correlation was used to verify linear relationships between the dehiscence interval and patient's age at surgery.

Results

Thirty-four patients (0.39%) experienced vaginal evisceration. The laparoscopic route was associated with a significantly higher incidence of dehiscence (p < 0.05). No differences were found between the 6027 patients (69.8%) who had closure of the vaginal cuff and the 2608 (30.2%) who had an unclosed cuff closure technique.

Conclusion

Vaginal evisceration after hysterectomy is a rare gynecological surgical complication. Sexual intercourse before the complete healing of the vaginal cuff is the main trigger event in young patients, while evisceration presents as a spontaneous event in elderly patients. Surgical repair can be performed either vaginally or laparoscopically with similar outcomes.