Spatial transcriptomics analysis identifies a tumor-promoting function of the meningeal stroma in melanoma leptomeningeal disease.

Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and patient-matched extra-cranial metastases using spatial transcriptomics in a small number of clinical specimens (nine tissues from two patients) with extensive in vitro and in vivo validation. The spatial landscape of melanoma LMD is characterized by a lack of immune infiltration and instead exhibits a higher level of stromal involvement. The tumor-stroma interactions at the leptomeninges activate tumor-promoting signaling, mediated through upregulation of SERPINA3. The meningeal stroma is required for melanoma cells to survive in the cerebrospinal fluid (CSF) and promotes MAPK inhibitor resistance. Knocking down SERPINA3 or inhibiting the downstream IGR1R/PI3K/AKT axis results in tumor cell death and re-sensitization to MAPK-targeting therapy. Our data provide a spatial atlas of melanoma LMD, identify the tumor-promoting role of meningeal stroma, and demonstrate a mechanism for overcoming microenvironment-mediated drug resistance in LMD.

Ewing's sarcoma in scapula, epidemiology, clinical manifestation, diagnosis and treatment: A literature review.

Background: Ewing's sarcoma (ES) can affect any bone, but its occurrence in the scapula is extremely rare. Only 15 studies investigating this condition exist in the medical literature. Materials and methods: A literature search was conducted in PubMed and Scopus, and studies on ES of scapula published in the English medical literature were retrieved. A total of 15 studies were found and were included in our study. Results: ES prevalence was highest in Asia. Moreover, ES was predominant in males (60%), with a male-to-female ratio of 3:2. ES in 53.3% and 46.6% of the cases were found in the right and left scapula, respectively. The main presentation of patients with ES of scapula was swelling, which was observed in 73.33% of the cases. Of the included studies, 46.6% used plain radiography as the primary investigation method, and 60% used computed tomography for staging and metastasis detection. For definitive diagnosis, 86.6% of the studies used immunohistochemistry markers. Adjuvant chemotherapy was considered in most studies (80%). Neoadjuvant chemotherapy was given in 6 out of 10 cases who underwent surgical treatment. Complications included malignant pleural effusion, respiratory failure, and movement restriction. Conclusion: The scapula is an extremely rare site for ES. Local invasion was found in 63.64% of the cases, whereas pre-metastases were found in 35.71% of the cases. Magnetic resonance imaging was considered to be the best radiological method used to diagnose ES of scapula. Adjuvant chemotherapy, neoadjuvant chemotherapy, and surgery were the main treatments for ES.

Kenny-Caffey syndrome type 1.

Kenny-Caffey syndrome type 1 is a rare hereditary skeletal disorder. We present here a documented case of a 7-month-old girl with the characteristic symptoms of growth retardation, dysmorphic features, and hypoparathyroidism.

Characteristics of epidemic and sporadic strains of Acinetobacter baumannii isolated in Abu Dhabi hospitals.

We compared the antibiotic susceptibility, clonal lineages and resistance genes of singleton Acinetobacter baumannii strains to those of isolates representing repeatedly encountered molecular types in five Abu Dhabi hospitals. One hundred and ten clinically relevant, non-repeat strains were typed by blaOXA-51-like allele sequencing and by PFGE, and selected isolates also by MLST. Resistance was assessed by MIC determinations and by disc diffusion. Genotyping was carried out by PCR, targeting 28 genes. The 80 epidemic strains belonged to worldwide lineages 1, 2 and 7, representing 11 pulsotypes and 9 genotypes, while the 30 sporadic isolates exhibited a high level of genetic variability and, with the exception of a small subgroup, were not associated with any recognized epidemic lineages. All epidemic subtypes carried the ISAba1-linked blaOXA-23 gene, and harboured the int, the blaPER and the armA genes significantly more frequently than their sporadic counterparts. They were all multi-drug resistant, including non-susceptibility to carbepenems, and were often extensively drug resistant, a phenomenon rarely seen among sporadic strains. Epidemic strains represented 78.8 % of intensive care unit isolates, causing more respiratory infections, while sporadic strains were more frequently isolated from wound and soft tissue infections. The study showed that among strains collected at the same time and from the same region, the very heterogeneous, sensitive sporadic strains, with the exception of a few non-susceptible singleton isolates, clearly differed from the highly resistant epidemic ones, which belonged to multiple pulsotypes and genotypes clustered into three worldwide clonal lineages carrying blaOXA-64, blaOXA-66 and blaOXA-69, respectively.

Change in meticillin-resistant Staphylococcus aureus clones at a tertiary care hospital in the United Arab Emirates over a 5-year period.

AIMS: Meticillin-resistant Staphylococcus aureus (MRSA) strains isolated in Tawam Hospital, a tertiary care hospital in the United Arab Emirates, were examined in order to understand the reasons for a doubling of its incidence between 2003 and 2008 while maintaining the same infection control measures. METHODS: All consecutive non-duplicate clinically relevant MRSA isolates recovered between January and December 2003 and between May and October 2008 were studied. The antibiotic susceptibility, pulsed field gel electrophoresis, toxin gene, staphylococcal cassette chromosome mec (SCCmec), spa, agr and multilocus sequence types of the strains were tested. RESULTS: In 2003, typical healthcare-associated (HA-MRSA) genotypes (ST239-MRSA-III, ST22-MRSA-IV and ST5-MRSA-II) represented the majority (61.5%) of the isolates. By 2008 this pattern had changed and clonal types considered as community-associated (CA) MRSA comprised 73.1% of the strains with ST80-MRSA-IV, ST5-MRSA-IV and ST1-MRSA with non-typable SCCmec types being the most frequent. However, further epidemiological investigations showed that only one-third of the CA-MRSA infections were actually acquired in the community, indicating that CA-MRSA clones have entered and spread within the hospital. CONCLUSIONS: The emergence of CA-MRSA clones with subsequent entry to and spread within the hospital has contributed to the increasing incidence of MRSA observed in Tawam Hospital and probably also in other hospitals in the UAE.