Waldenström’s macroglobulinemia masquerading as ovarian cancer with peritoneal carcinomatosis,ascites, and elevated CA-125

Waldenström’s macroglobulinemia is a rare hematology malignancy which often presents with “B symptoms,” anemia, and thrombocytopenia. A 46-year-old woman presented with 2 months of abdominal distension accompanied by an unintentional 20-lb weight loss. Her abdominal CT scan demonstrated diffuse carcinomatosis with bilateral ovarian lesions and screening labs revealed a markedly elevated CA-125, suggesting a diagnosis of ovarian cancer. Upon admission for workup, patient was found to have a significant protein gap, later attributed to a markedly elevated IgM. Omental and bone marrow biopsy confirmed the diagnosis of Waldenström’s macroglobulinemia, with elevation in CA-125 thought to be secondary to peritoneal irritation. This patient has since been successfully treated with six cycles of bendamusine and rituximab with no evidence of disease on staging scans and normalization of both CA-125 and IgM. To our knowledge, this is the first documented case of Waldenström’s macroglobulinemia presenting with symptoms classically associated with ovarian cancer and demonstrates the importance of maintaining a broad differential when evaluating patients with abdominal carcinomatosis.     

The Lumbar Ligamentum Flavum Does Not Have Two Layers and Is Confluent with the Interspinous Ligament: Anatomical Study with Application to Surgical and Interventional Pain Procedures

Numerous authors over the years have reported that the lumbar ligamentum flavum has two layers. Our routine cadaveric dissections raised the question whether this understanding is correct, as we always have observed only one layer. Thus, the goal of this cadaveric study was to reevaluate the layers of the ligamentum flavum. Twenty lumbar levels from five fresh-frozen cadaveric specimens were used in this study. After dissection of the lumbar spine, the ligamentum flavum and interspinous ligament were exposed. Each lumbar level was transected through the zygapophyseal joint, and hematoxylin and eosin staining, Masson's trichrome staining and Verhoeff-van Gieson staining were performed. Continuation of the interspinous ligament and ligamentum flavum were observed invariably. There was no evidence of the existence of a two-layered ligamentum flavum. The lumbar ligamentum flavum does not consist of two layers, but is confluent instead with the interspinous ligament that attaches to the zygapophyseal joints. To convey this anatomy better, we suggest describing the lumbar ligamentum flavum as a structure that consists of interlaminar and interspinous parts. Precise knowledge of the ligamentum flavum's anatomy can be of clinical value, particularly when epidural anesthesia or lumbar puncture are performed. Clin. Anat. 32:34–40, 2019. © 2019 Wiley Periodicals, Inc.     

Carnosol induces the osteogenic differentiation of bone marrow-derived mesenchymal stem cells via activating BMP-signaling pathway

Carnosol is a phenolic diterpene phytochemical found in rosemary and sage with reported anti-microbial, anti-oxidant, anti-inflammatory, and anti-carcinogenic activities. This study aimed to investigate the effect of carnosol on the lineage commitment of mouse bone marrow-derived mesenchymal stem cells (mBMSCs) into osteoblasts and adipocytes. Interestingly, carnosol stimulated the early commitment of mBMSCs into osteoblasts in dose-dependent manner as demonstrated by increased levels of alkaline phosphatase activity and Alizarin red staining for matrix mineralization. On the other hand, carnosol significantly suppressed adipogenesis of mBMSCs and downregulated both early and late markers of adipogenesis. Carnosol showed to induce osteogenesis in a mechanism mediated by activating BMP signaling pathway and subsequently upregulating the expression of BMPs downstream osteogenic target genes. In this context, treatment of mBMSCs with LDN-193189, BMPR1 selective inhibitor showed to abolish the stimulatory effect of carnosol on BMP2-induced osteogenesis. In conclusion, our data identified carnosol as a novel osteoanabolic phytochemical that can promote the differentiation of mBMSCs into osteoblasts versus adipocytes by activating BMP-signaling.     

Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans,Saudi Arabia, 2014

Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March–November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case–control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2–4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV.     

IP-10 contributes to the inhibition of mycobacterial growth in an ex vivo whole blood assay

Interferon-γ inducible protein 10 (IP-10), is a potent chemoattractant that promotes migration of monocytes and activated T-cells to inflammation foci. IP-10 is elevated in serum of patients with chronic hepatitis C virus (HCV) and tuberculosis (TB) infections, although it remains to be determined the contribution of IP-10 in restricting Mycobacterium tuberculosis (Mtb) replication. Here, we investigated the impact of IP-10 on mycobacteria replication using the ex vivo model of human whole-blood (WB) assay. In particular, we compared the levels of IP-10 upon infection with different Mtb clinical strains and species of non-tuberculous mycobacteria (NTM) and evaluated how IP-10 may contain bacterial replication. Interestingly, we observed that the inhibition of the host enzyme dipeptidyl peptidase IV (DPP-IV), which inactivates IP-10 through cleavage of two amino acids at the chemokine N-terminus, restricted mycobacterial persistence in WB, supporting the critical role of full length IP-10 in mediating an anti-Mtb response. Addition of recombinant IP-10 expressed in eukaryotic cells enhanced the anti-mycobacterial activity in WB, although no differences were observed when IP-10 containing different proportions of cleaved and non-cleaved forms of the chemokine were added. Moreover, recombinant IP-10 did not exert a direct anti-mycobacterial effect. Our results underscore the clinical relevance of IP-10 in mycobacteria pathogenesis and support the potential outcomes that may derive by targeting the IP-10/CXCR3 pathway as host directed therapies for the treatment of Mtb or NTM infections.