Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management.

Idiopathic thrombocytopenic purpura (ITP) is characterized by a low platelet count, which is the result of both increased pla- telet destruction and insufficient platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modu- lation have been identified. Conventional treatments for ITP aim at reducing platelet destruction, either by immunosuppression or splenectomy. Two new thrombopoietic agents,AMG 531 and eltrombopag, have been used in clinical trials to stimulate platelet production in ITP patients not responsive to standard treatments. These new molecules bear no structural resemblance to thrombopoietin, but still bind and activate the thrombopoietin receptor. This review will focus on the pathophysiology and treatment of ITP in adults, highlighting recent advances in both fields

Expectations and outcomes when moving from open to laparoscopic adrenalectomy: Multivariate analysis

Various authors have suggested that laparoscopic adrenalectomy (LA) leads to better surgical outcomes than open surgery. The debate is still open, however, and indications and limitations of minimally invasive surgery have not been completely established. The objective of our study was to compare surgical outcomes of LA and open adrenalectomy (OA), using multivariate analysis to adjust for potential confounding factors (e.g., size of the lesion, histology). Between 1995 and June 2000 at "Careggi" Hospital in Florence, Italy patients with an indication for adrenalectomy were treated laparoscopically if the lesion was 2 hours, blood loss greater than or equal to 500 ml) between patients operated on through a traditional approach and those who underwent LA. On the other hand, patients operated on laparoscopically have a significantly higher probability than the OA group of experiencing a better recovery from surgery (i.e., require less postoperative analgesics and return to normal activities earlier). The results of the present study show that, although LA does not add much benefit in terms of expected intraoperative outcomes, it dramatically speeds patients' recovery from surgery. The two approaches are complementary and should both be integrated into the technical background of all endocrine surgeons

Epilepsy with auditory features: A heterogeneous clinico-molecular disease

Objective: To identify novel genes implicated in epilepsy with auditory features (EAF) in phenotypically heterogeneous families with unknown molecular basis. Methods: We identified 15 probands with EAF in whom an LGI1 mutation had been excluded. We performed electroclinical phenotyping on all probands and available affected relatives. We used whole-exome sequencing (WES) in 20 individuals with EAF (including all the probands and 5 relatives) to identify single nucleotide variants, small insertions/deletions, and copy number variants. Results: WES revealed likely pathogenic variants in genes that had not been previously associated with EAF: a CNTNAP2 intragenic deletion, 2 truncating mutations of DEPDC5, and a missense SCN1A change. Conclusions: EAF is a clinically and molecularly heterogeneous disease. The association of EAF with CNTNAP2, DEPDC5, and SCN1A mutations widens the phenotypic spectrum related to these genes. CNTNAP2 encodes CASPR2, a member of the voltage-gated potassium channel complex in which LGI1 plays a role. The finding of a CNTNAP2 deletion emphasizes the importance of this complex in EAF and shows biological convergence

Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions

Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation

New records of rare species in the Mediterranean Sea (October 2021)

This Collective Article presents information about 27 taxa belonging to five Phyla (one Ochrophyta, one Cnidaria, three Arthropoda, two Mollusca and twenty Chordata) and extending from the Western Mediterranean Sea to the Levantine Sea and theBlack Sea (Sea of Marmara). The new records were reported from 11 countries as follows: Algeria: occurrence of the Africanstriped grunt Parapristipoma octolineatum; Spain: new records of eight uncommon fish species (Gadella maraldi, Hypleurochilusbananensis, Lobotes surinamensis, Parapristipoma octolineatum, Selene dorsalis, Sphoeroides marmoratus, Tetragonuruscuvieri, and Trachyrincus scabrus) from the Spanish Mediterranean; Italy: new record of the football octopus Ocythoe tuberculatafrom the Southern Tyrrhenian Sea; a rare sighting of a juvenile phase of a moray eel of the genus Gymnothorax, tentativelyidentified as Gymnothorax cf. unicolor in the Ligurian Sea; first record of adult Facciola’s sorcerer Facciolella oxyrhynchus inthe Adriatic Sea; occurrence of the tope shark Galeorhinus galeus in the Northern Adriatic Sea; Libya: first confirmed recordof the pen shell Pinna rudis; first documented record of the palaemonid shrimp Brachycarpus biunguiculatus; first record of thefish Sudis hyalina; Malta: new records of Grant’s rockling, Gaidropsarus granti; multiple concomitant reports of the rare hydromedusanspecies Aequorea forskalea; Croatia: a record of the skipjack tuna Katsuwonus pelamis in the Southern Adriatic Sea;Albania: new record of the bigeye thresher shark Alopias superciliosus; Greece: confirmation of the rare brown alga Sargassumflavifolium occurrence in the Eastern Mediterranean Sea; first record of the scaleless dragonfish Bathophilus nigerrimus; Turkey:first occurrence of the calanoid copepod Pteriacartia josephinae in the Aegean Sea; first documented record of the Cremona’s seaslug Placida cremoniana for the easternmost Mediterranean Sea; new record of the yellow-headed goby Gobius xanthocephalusin the Sea of Marmara; Cyprus: first record of the Liechtenstein’s goby Corcyrogobius liechtensteini; an individual of the Yellowfintuna Thunnus albacares captured with handline by an artisanal fisher; Lebanon: an individual of the Black marlin Istiompaxindica captured in a gill ne

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma 3 cm, located between 115 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane i

A Controversy That Has Been Tough to Swallow: Is the Treatment of Achalasia Now Digested?

Esophageal achalasia is a rare neurodegenerative disease of the esophagus and the lower esophageal sphincter that presents within a spectrum of disease severity related to progressive pathological changes, most commonly resulting in dysphagia. The pathophysiology of achalasia is still incompletely understood, but recent evidence suggests that degeneration of the postganglionic inhibitory nerves of the myenteric plexus could be due to an infectious or autoimmune mechanism, and nitric oxide is the neurotransmitter affected. Current treatment of achalasia is directed at palliation of symptoms. Therapies include pharmacological therapy, endoscopic injection of botulinum toxin, endoscopic dilation, and surgery. Until the late 1980s, endoscopic dilation was the first line of therapy. The advent of safe and effective minimally invasive surgical techniques in the early 1990s paved the way for the introduction of laparoscopic myotomy. This review will discuss the most up-to-date information regarding the pathophysiology, diagnosis, and treatment of achalasia, including a historical perspective. The laparoscopic Heller myotomy with partial fundoplication performed at an experienced center is currently the first line of therapy because it offers a low complication rate, the most durable symptom relief, and the lowest incidence of postoperative gastroesophageal reflux

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

In lung cancer, DNA content abnormalities have been described as a heterogeneous spectrum of impaired tumour cell DNA histogram patterns. They are merged into the common term of aneuploidy and probably reflect a high genotypic instability. In non-small-cell lung cancer, the negative effect of aneuploidy has been a subject of controversy inasmuch as studies aimed at determining the survival–DNA content relationship have reported conflicting results. We made a meta-analysis of published studies aimed at determining the prognostic effect of aneuploidy in surgically resected non-small-cell lung cancer. 35 trials have been identified in the literature. A comprehensive collection of data has been constructed taking into account the following parameters: quality of specimen, DNA content assessment method, aneuploidy definition, histology and stage grouping, quality of surgical resection and demographic characteristics of the analysed population. Among the 4033 assessable patients, 2626 suffered from non-small-cell lung cancer with aneuploid DNA content (overall frequency of aneuploidy: 0.65; 95% CI: (0.64–0.67)). The DerSimonian and Laird method was used to estimate the size effects and the Peto and Yusuf method was used in order to generate the odds ratios (OR) of reduction in risk of death for patients affected by a nearly diploid (non-aneuploid) non-small-cell lung cancer. Survivals following surgical resection, from 1 to 5 years, were chosen as the end-points of our meta-analysis. Patients suffering from a nearly diploid tumour benefited from a significant reduction in risk of death at 1, 2, 3 and 4 years with respective OR: 0.51, 0.51, 0.45 and 0.67 (P< 10−4for each end-point). 5 years after resection, the reduction of death was of lesser magnitude: OR: 0.87 (P = 0.08). The test for overall statistical heterogeneity was conventionally significant (P< 0.01) for all 5 end-points, however. None of the recorded characteristics of the studies could explain this phenomenon precluding a subset analysis. Therefore, the DerSimonian and Laird method was applied inasmuch as this method allows a correction for heterogeneity. This method demonstrated an increase in survival at 1, 2, 3, 4 and 5 years for patients with diploid tumours with respective size effects of 0.11, 0.15, 0.20, 0.20 and 0.21 (value taking into account the correction for heterogeneity;P< 10−4for each end-point). Patients who benefit from a surgical resection for non-small-cell lung cancer with aneuploid DNA content prove to have a higher risk of death. This negative prognostic factor decreases the probability of survival by 11% at one year, a negative effect deteriorating up to 21% at 5 years following surgery. © 2001 Cancer Research Campaign http://www.bjcancer.co