Rare KIT (CD117) expression in multiple myeloma abrogates the usefulness of imatinib mesylate treatment

Background: Imatinib mesylate blocks the tyrosine kinase activity of KIT (CD117) and is an effective treatment for gastrointestinal stromal tumors. In multiple myeloma, KIT expression has been detected by flow cytometry in about 33% of specimens, but no previous immunohistochemical assessment has yet been made of the expression pattern of KIT. Materials and methods: We performed immunohistochemical analyses of 100 patients, including 72 with multiple myeloma (MM), 8 with lymphoplasmacytic lymphoma (LPL), 10 with monoclonal gammopathy of undetermined significance (MGUS) and 10 with reactive plasmocytosis. One KIT-positive MM was sequenced using polymerase chain reaction analysis. Results: In MM, only 2 cases (2.8%) were KIT positive. The great majority of the cases (97, 2%) did not express the KIT receptor tyrosine kinase. No mutation of the c-kit gene was detected. Conclusions: KIT expression is a rare event in MM and not detectable in MGUS and LPL. Therefore, treatment with imatinib is unlikely to be effective in these patient

Psychosocial and obstetric determinants of women signalling distress during Edinburgh Postnatal Depression Scale (EPDS) screening in Sydney, Australia

Background and objectives: The perinatal period presents a high-risk time for development of mood disorders. Australia-wide universal perinatal care, including depression screening, make this stage amenable to population-level preventative approaches. In a large cohort of women receiving public perinatal care in Sydney, Australia, we examined: (1) the psychosocial and obstetric determinants of women who signal distress on EPDS screening (scoring 10-12) compared with women with probable depression (scoring 13 or more on EPDS screening); and (2) the predictive ability of identifying women experiencing distress during pregnancy in classifying women at higher risk of probable postnatal depression. Methods: We analysed routinely collected perinatal data from all live-births within public health facilities from two health districts in Sydney, Australia (N = 53,032). Perinatal distress was measured using the EPDS (scores of 10-12) and probable perinatal depression was measured using the EPDS (scores of 13 or more). Logistic regression models that adjusted for confounding variables were used to investigate a range of psychosocial and obstetric determinants and perinatal distress and depression. Results: Eight percent of this cohort experienced antenatal distress and about 5 % experienced postnatal distress. Approximately 6 % experienced probable antenatal depression and 3 % experienced probable postnatal depression. Being from a culturally and linguistically diverse background (AOR = 2.0, 95% CI 1.8-2.3, P < 0.001), a lack of partner support (AOR = 2.9, 95% CI 2.3-3.7) and a maternal history of childhood abuse (AOR = 1.9, 95% CI 1.6-2.3) were associated with antenatal distress. These associations were similar in women with probable antenatal depression. Women who scored 10 to12 on antenatal EPDS assessment had a 4.5 times higher odds (95% CI 3.4-5.9, P < 0.001) of experiencing probable postnatal depression compared with women scoring 9 or less. Conclusion: Antenatal distress is more common than antenatal depressive symptoms and postnatal distress or depression. Antenatal maternal distress was associated with probable postnatal depression. Scale properties of the EPDS allows risk-stratification of women in the antenatal period, and earlier intervention with preventively focused programs. Prevention of postnatal depression could address a growing burden of illness and long-term complications for mothers and their infants

Discrepancy of target sites between clinician and cytopathological reports in head neck fine needle aspiration: Did I miss the target or did the clinician mistake the organ site?

The diagnostic accuracy of fine needle aspiration cytology (FNAC) of head and neck lesions is relatively high, but cytologic interpretation might be confusing if the sample is lacking typical cytologic features according to labeled site by physician. These errors may have an impact on pathology search engines, healthcare costs or even adverse outcomes. The cytology archive database of multiple institutions in southern Iran and Australia covering the period 2001–2011, were searched using keywords: salivary gland, head, neck, FNAC, and cytology. All the extracted reports were reviewed. The reports which showed discordance between the clinician’s impression of the organ involved and subsequent fine needle biopsy request, and the eventual cytological diagnosis were selected. The cytological diagnosis was confirmed by histology or cell block, with assistance from imaging, clinical outcome, physical examination, molecular studies, or microbiological culture. The total number of 10,200 head and neck superficial FNAC were included in the study, from which 48 cases showed discordance between the clinicians request and the actual site of pathology. Apart from the histopathology, the imaging, clinical history, physical examination, immunohistochemical study, microbiologic culture and molecular testing helped to finalize the target organ of pathology in 23, 6, 7, 8, 2, and 1 cases respectively. The commonest discrepancies were for FNAC of “salivary gland” [total: 20 with actual final pathology in: bone (7), soft tissue (5), lymph node (3), odontogenic (3) and skin (2)], “lymph node” [total: 12 with final pathology in: soft tissue (3), skin (3), bone (1) and brain (1)], “soft tissue” [total: 11 with final pathology in: bone (5), skin (2), salivary gland (1), and ocular region (1)] and “skin” [total: 5 with final pathology in: lymph node (2), bone (1), soft tissue (1) and salivary gland (1)]. The primary physician requesting FNAC of head and neck lesions are incorrect in their clinical impression of the actual site in nearly 0.5 percent of cases, due to the overlapping clinical and imaging findings or possibly due to inadequate history taking or physical examination

Intimate partner violence identified through routine antenatal screening and maternal and perinatal health outcomes

Background: This study investigated the association between intimate partner violence (IPV) identified on routine prenatal screening and perinatal outcomes for mother and infant. Methods: Routinely collected perinatal data for a cohort of all women and their infants born in public health facilities in Sydney (Australia) over the period 2014-2016 (N = 52,509) were analysed to investigate the risk of adverse maternal and perinatal outcomes associated with a history of IPV. The association between an affirmative response on prenatal IPV screening and low birth weight (LBW) < 2.5 kg, preterm birth < 37 weeks, breastfeeding indicators and postnatal depressive symptoms (PND) was investigated in a series of logistic regression models. Results: IPV was associated with an increased risk of PND (OR = 2.53, 95% CI 1.76-3.63), not breastfeeding at birth (OR = 1.65, 95% CI 1.30-2.09), non-exclusive breastfeeding at discharge (OR = 1.66, 95% CI 1.33-2.07) and first post-natal visit (OR = 1.54, 95% CI 1.24-1.91). Self-reported fear of a partner was strongly associated with an increased risk of PND (OR = 3.53, 95% CI 2.50-5.00), and also LBW (OR = 1.58, 95% CI 1.12-2.22), preterm birth (OR = 1.38, 95% CI 1.08-1.76), lack of early initiation of breastfeeding (OR = 1.67, 95% CI 1.28-2.17), non-exclusive breastfeeding at discharge from hospital (OR = 1.60, 95% CI 1.24-2.06) and at the first post-natal visit (OR = 1.27, 95% CI 0.99-3.04). Conclusions: IPV reported at the time of pregnancy was associated with adverse infant and maternal health outcomes. Although women may be disinclined to report IPV during pregnancy, universal, routine antenatal assessment for IPV is essential for early identification and appropriate management to improve maternal and newborn health

ETV4 and ETV5 drive synovial sarcoma through cell cycle and DUX4 embryonic pathway control

Synovial sarcoma is an aggressive malignancy with no effective treatments for patients with metastasis. The synovial sarcoma fusion SS18-SSX, which recruits the SWI/SNF-BAF chromatin remodeling and polycomb repressive complexes, results in epigenetic activation of FGF receptor (FGFR) signaling. In genetic FGFR-knockout models, culture, and xenograft synovial sarcoma models treated with the FGFR inhibitor BGJ398, we show that FGFR1, FGFR2, and FGFR3 were crucial for tumor growth. Transcriptome analyses of BGJ398-treated cells and histological and expression analyses of mouse and human synovial sarcoma tumors revealed prevalent expression of two ETS factors and FGFR targets, ETV4 and ETV5. We further demonstrate that ETV4 and ETV5 acted as drivers of synovial sarcoma growth, most likely through control of the cell cycle. Upon ETV4 and ETV5 knockdown, we observed a striking upregulation of DUX4 and its transcriptional targets that activate the zygotic genome and drive the atrophy program in facioscapulohumeral dystrophy patients. In addition to demonstrating the importance of inhibiting all three FGFRs, the current findings reveal potential nodes of attack for the cancer with the discovery of ETV4 and ETV5 as appropriate biomarkers and molecular targets, and activation of the embryonic DUX4 pathway as a promising approach to block synovial sarcoma tumors

Perinatal distress and depression in culturally and linguistically diverse (CALD) Australian women : the role of psychosocial and obstetric factors

Perinatal distress and depression can have significant impacts on both the mother and baby. The present study investigated psychosocial and obstetric factors associated with perinatal distress and depressive symptoms among culturally and linguistically diverse (CALD) Australian women in Sydney, New South Wales. The study used retrospectively linked maternal and child health data from two Local Health Districts in Australia (N = 25,407). Perinatal distress was measured using the Edinburgh Postnatal Depression Scale (EPDS, scores of 10–12) and depressive symptoms, with EPDS scores of 13 or more. Multivariate multinomial logistic regression models were used to investigate the association between psychosocial and obstetric factors with perinatal distress and depressive symptoms. The prevalence of perinatal distress and depressive symptoms among CALD Australian women was 10.1% for antenatal distress; 7.3% for antenatal depressive symptoms; 6.2% for postnatal distress and 3.7% for postnatal depressive symptoms. Antenatal distress and depressive symptoms were associated with a lack of partner support, intimate partner violence, maternal history of childhood abuse and being known to child protection services. Antenatal distress and depressive symptoms were strongly associated with postnatal distress and depressive symptoms. Higher socioeconomic status had a protective effect on antenatal and postnatal depressive symptoms. Our study suggests that current perinatal mental health screening and referral for clinical assessment is essential, and also supports a re-examination of perinatal mental health policy to ensure access to culturally responsive mental health care that meets patients’ needs

Effectiveness of Protease Inhibitor Monotherapy versus Combination Antiretroviral Maintenance Therapy: A Meta-Analysis

The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs