Prolonged overall survival following metastasectomy in stage IV melanoma.

BACKGROUND/OBJECTIVES: Current literature supports mixed conclusions regarding the outcomes of metastasectomy in Stage IV melanoma. The objective of this national study was to determine the associations of non-primary site surgery with overall survival (OS) in Stage IV melanoma. METHODS: The National Cancer Database (NCDB) was queried for all Stage IV melanoma cases diagnosed from 2004 to 2015. Cases missing treatment/staging data or undergoing palliative treatment were excluded (remaining n = 14 034). Patients were separated into 'metastasectomy' (n = 4214, 30.0%) and 'non-metastasectomy' (n = 9820, 70.0%) cohorts. Survival outcomes were analysed using Kaplan-Meier and Cox proportional hazards regressions. RESULTS: On univariate analysis, patients with Stage IV melanoma undergoing metastasectomy (median survival: 15.67 month) had greater overall survival compared with those not receiving non-primary surgery (median survival: 7.13 month; 5-year OS 13.2% vs. 5.6%, P < 0.001). M1a patients that underwent non-primary metastasectomy (median survival: 46.36 month) showed greater survival than those that did not (median survival: 15.31 month; P < 0.001). Metastasectomy was undertaken more frequently for cutaneous (M1a) metastasis compared with non-M1a metastasis (34.6% vs. 28.4%, P < 0.001). Of those receiving metastasectomy, 20.3% also received primary site resection, 33.6% radiation, 26.5% chemotherapy and 31.5% immunotherapy. Controlling for covariates on Cox proportional hazard analysis, all metastasectomy patients demonstrated longer survival [Hazard Ratio = 0.519, P < 0.001; CI 95% (0.495-0.545)] as well as when analysing solely M1a metastasectomy patients [Hazard Ratio = 0.546, P < 0.001; CI 95% (0.456-0.653)], lung (M1b) metastasectomy patients [Hazard Ratio = 0.389, P < 0.001; CI 95% (0.328-0.462)] and visceral (M1c) metastasectomy patients [Hazard Ratio = 0.474, P < 0.001; CI 95% (0.434-0.517)]. CONCLUSION: Metastasectomy for Stage IV melanoma is independently associated with improved OS in metastatic cases involving the skin, lung and visceral organs.

Identification and developmental expression of a 5'-3' exoribonuclease from Drosophila melanogaster.

In multicellular organisms, very little is known about the role of mRNA stability in development, and few proteins involved in degradation pathways have been characterized. We have identified the Drosophila homologue of XRN1, which is the major cytoplasmic 5'-3' exoribonuclease in Saccharomyces cerevisiae. The protein sequence of this homologue (pacman) has 59% identity to S. cerevisiae XRN1 and 67% identity to the mouse homologue (mXRN1p) in certain regions. Sequencing of this cDNA revealed that it includes a trinucleotide repeat (CAG)9 which encodes polyglutamine. By directly measuring pacman exoribonuclease activity in yeast, we demonstrate that pacman can complement the yeast XRN1 mutation. Northern blots show a single transcript of approximately 5.2 kb which is abundant only in 0-8-h embryos and in adult males and females. In situ hybridization analysis revealed that the pcm transcripts are maternally derived, and are expressed at high levels in nurse cells. During early embryonic syncytial nuclear divisions, pcm transcripts are homogenously distributed. pcm mRNA is expressed abundantly and ubiquitously throughout the embryo during gastrulation, with high levels in the germ band and head structures. After germ band retraction, pcm transcripts are present at much lower levels, in agreement with the Northern results. Our experiments provide the first example of an exoribonuclease which is differentially expressed throughout development.

[Transient atrioventricular conduction disorder: a potential cause of sudden death in myocarditis due to varicella. A case report]. / Distúrbio transitório da condução atrioventricular: uma causa potencial de morte súbita na miocardite por varicela. Relato de caso.

The case of a patient with varicella skin lesions presenting with heart failure at 4 years of age is described. A transitory atrioventricular conduction disturbance due to myocardial impairment was documented during hospital stay. Despite the clinical improvement with conventional therapy, the patient died from respiratory failure due to a lung infection but with an almost normal electrocardiogram. Necropsy showed myocardial lesions compatible with acute myocarditis. A possible viral specific affinity for the conduction system of the heart is suggested and judged to be a potential cause of death in this disease. Since the actual incidence of varicella myocarditis associated to an atrioventricular conduction disturbance is unknown it seems prudent that every patient with varicella infection should have a cardiac examination during the acute phase of the disease. As the diagnosis of subclinical myocarditis depends essentially on an electrocardiogram, we believe this method should be employed routinely during the acute phase in order to assess myocardial involvement in this disease, which may be a cause of sudden death.

[Etiological profile of bacterial meningitis in a small hospital] / Perfil etiológico das meningites bacterianas em um hospital de pequeno porte.

OBJECTIVE: To determine the etiologic profile of cases of meningitis treated at a small hospital in Ribeirão Preto, State of São Paulo, and to compare it to those reported for other communities.METHODS: a retrospective study was conducted on 103 patients admitted from January 1992 to July 1996 with clinical and laboratory diagnosis of bacterial meningitis. The clinical criteria for diagnosis were based on patient history and physical signs and symptoms, and the laboratory criteria were based on cerebrospinal fluid examination (aspect, cytology, biochemistry, Gram staining, culture and countercurrent immunoelectrophoresis) and blood culture.RESULTS: The etiologic agent was identified in 81.5% of cases: Haemophilus influenzae type b in 32%, Neisseria meningitides in 25.2%, Streptococcus pneumoniae in 8.7%, Staphylococcus aureus and epidermidis in 8.7%, and others agents in 6.9%. CONCLUSIONS: The study showed that the cases of bacterial meningitis treated at the Santa Lydia Hospital of Ribeirão Preto are caused by the same agents detected in other places, with Haemophilus influenzae type b being the predominant one. The study also suggests that when many people are involved in the collection of material for laboratory tests, recovery of the agent may become difficult.

AFLP fingerprinting reveals pattern differences between template DNA extracted from different plant organs.

AFLP (amplified fragment length polymorphism) fingerprinting of cultivars of bread wheat (Triticum aestivum) and some of its wild relatives has allowed the efficient detection of large numbers of polymorphic amplified fragments. While the reproducibility of fingerprints in repeated experiments is high, pattern differences were observed between fingerprints obtained from seed and leaf DNA template from the same wheat accession. These distinct organ specific amplified DNA fragments were shown to be due neither to genotypic mixtures nor to pathogen contamination. They are likely a result of differences in DNA methylation between organs. Even greater numbers of organ specific amplified fragments were observed when fingerprints obtained from the root and shoot of individual seedlings of the wheat relatives Aegilops mutica and Aegilops speltoides were compared. This phenomenon underlines the importance of ensuring that DNA is extracted from physiologically uniform tissue in phylogenetic studies based on AFLP fingerprints. For this purpose, mature seed is a convenient source.

D-2-Hydroxyglutaric aciduria in a patient with a severe clinical phenotype and unusual MRI findings.

We report an infant with intermittent urinary excretion of D-2-hydroxyglutaric (D-2-OHG) acid who died at the age of 10 months from cardiogenic shock due to cardiomyopathy. High urinary concentrations of D-2-OHG and succinic acid, as well as increased levels of lactic acid were detected on three different occasions, whereas a normal urinary profile of organic acids was found on one occasion. The clinical findings of our patient consisted of generalized hypotonia, irritability, developmental delay, generalized tonic seizures, lethargy, cardiomyopathy, and respiratory distress. Cerebral MRI revealed bilateral lesions in the substantia nigra, the periaqueductal area, the medial part of the thalamus, the hypothalamus, the caudate nucleus, putamen and globus pallidus. This pattern is suggestive of a mitochondriopathy. However, respiratory chain enzyme activities were normal in fibroblasts. Exogenous supplementation of D-2-OHG acid strongly inhibited cytochrome-c oxidase activity in fibroblasts from the patient and from normal controls in vitro. The results suggest that our patient has an unusual form of D-2-hydroxyglutaric aciduria (D-2-OHGA), different from the patients published so far, and that the increase of lactic acid and some citric acid cycle intermediates encountered in some patients with D-2-OHGA may be due to a functional defect of the respiratory chain caused by D-2-OHG acid.

Surgical excision of the vegetation as treatment of tricuspid valve endocarditis.

The usual surgical treatment of tricuspid endocarditis is valve replacement or valve excision alone without valve replacement. 'Vegetectomy', i.e. local excision of the vegetation and leaflet repair, has been previously described and can be applied to cases with well-circumscribed vegetations and little or no valve damage. A case of tricuspid valve endocarditis successfully managed by surgical excision of the vegetation is reported.