An atypical presentation of CNS tuberculosis manifesting with meningoencephalitis and tuberculoma in a New York taxi driver.

Mycobacterium Tuberculous (MTb) meningitis is a rare manifestation of extrapulmonary tuberculosis (Tb) but remains the most common form of Central Nervous System (CNS) manifestation of tuberculosis. It is associated with significant morbidity and mortality yet difficult to diagnose given the low sensitivity and specificity of diagnostic testing with cerebral spinal fluid (CSF) analysis which typically shows CSF findings of lymphocytic pleocytosis, elevated protein, and low glucose and is confirmed by acid fast bacillus (AFB) culture. Here, we describe a case of severe meningoencephalopathy in the setting of disseminated tuberculosis with atypical radiological findings of tuberculoma.

Aero to the heart: A case of aortic valve endocarditis caused by Aerococcus Urinae in an elderly woman.

Aerococcus urinae (A. urinae) is an infrequent cause of infective endocarditis (IE) and few cases have been reported especially in older women. As of this publication, there are 31 reported cases of IE caused by aerococcus urinae, and of these, 4 are of women, 3 of which are aged > 75 years. Here, we describe a case of A. urinae endocarditis in an 80-year-old woman presenting with worsening fatigue. A diagnosis of native aortic valve endocarditis was established based on characteristic findings of aortic valvular vegetation on transesophageal echocardiogram along with isolation of A. urinae on blood cultures.

Recurrent herpes simplex virus mimicking vulvar carcinoma in patient with Human Immunodeficiency Virus: A case report.

Patients with human immunodeficiency virus (HIV) are at increased risk for developing other gynecologic conditions, including herpes simplex virus (HSV) and vulvar intraepithelial neoplasia (VIN)/carcinoma. We describe the case of a woman with a history of microinvasive vulvar squamous cell carcinoma who presented with hypertrophic ulcerated vulvar and peri-anal masses concerning for malignancy. This case highlights the need to maintain a high index of suspicion for malignancy and herpes simplex virus, even with negative polymerase chain reaction (PCR) test, as well as the difficulty of treating this often-resistant lesion.

Combination antibiotic therapy for treatment of a patient with infected prosthesis and peri-prosthetic abscess due to Klebsiella pneumoniae harboring New Delhi Metallo (NDM) beta-lactamase.

Treatment options for patients infected with multi-drug resistant gram-negative bacteria harboring metallo-beta-lactamases (MBLs) requires precision therapy. We present the case of a 20 year-old male with a right distal femoral peri-prosthetic abscess with presumed infected hardware and osteomyelitis in whom four multi-drug resistant gram negative bacteria were isolated. The rapid identification of an MBL producing organism, novel combination of therapy, and prompt infection prevention enforcement and education led to appropriate treatment of our patient as well as prevention of spread of organisms during and after hospitalization. This case illustrated successful management of multiple challenges faced by patients infected and/or harboring extensively resistant bacteria.

Streptococcus pseudoporcinus: Case Reports and Review of the Literature.

Streptococcus pseudoporcinus is a beta-hemolytic Gram-positive, catalase-negative, nonmotile coccus arranged in short chains, usually found in the female genitourinary tract and differentiated from Streptococcus porcinus in 2006. Only two human infections associated with this organism have been reported to date: one in a patient with a first digit wound infection and another with lower extremity cellulitis. We describe two novel cases of Streptococcus pseudoporcinus causing endocarditis in one and pneumonia with empyema in another, illustrating the potential of these bacteria to cause severe invasive and life-threatening disease.

Changing pattern of recurrences in patients with early HER2-positive breast cancer receiving neoadjuvant chemotherapy in the era of dual anti-HER2 therapy.

BACKGROUND: Over the last 10 years, there has been a major treatment revolution for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We aimed to explore the outcome of different neoadjuvant chemotherapy in a tertiary breast cancer centre with early HER2-positive breast cancer as well as factors associated with pathological complete response (pCR) and recurrence-free survival (RFS). The pattern of recurrence was also studied. METHODS: This retrospective study analysed the outcome of neoadjuvant chemotherapy during the period 2005 to 2016 in a tertiary referral centre in Hong Kong. Patients were divided into three groups according to the neoadjuvant chemotherapy they received: chemotherapy only (Chemo), chemotherapy plus trastuzumab (Chemo-H) and chemotherapy plus double anti-HER2 therapy (Chemo-DH). RESULTS: There were 226 cases analysed during the study period. The rate of pCR was 5%, 26% and 60% in Chemo, Chemo-H and Chemo-DH groups, respectively (Chemo vs pooled Chemo-H/DH: p<0.0001; Chemo-H vs Chemo-DH: p<0.0001). This was accompanied by a trend of increased rate of breast conservation therapy in Chemo-DH cohort (p=0.046). Use of double anti-HER2 therapy, older age (>50 years) and hormone receptor negativity were associated with more pCR. pCR was associated with better RFS. Among those with recurrence, the proportion of patients with brain as the only site of recurrence increased remarkably with more efficacious anti-HER2 treatment (0% in Chemo, 8% in Chemo-H, 67% in Chemo-DH). CONCLUSION: pCR remains an important predictive factor for improved RFS. In the era of dual anti-HER2 neoadjuvant therapy, brain-only recurrence poses a challenge to disease surveillance and treatment.

Sentinel Lymph Node Biopsy in Early Breast Cancer: Magnetic Tracer as the Only Localizing Agent.

BACKGROUND: The combined use of radioisotope and blue dye is the gold standard in sentinel lymph node (SLN) localization in early breast cancer. Superparamagnetic iron oxide (SPIO) has recently emerged as a non-inferior new tracer in sentinel lymph node mapping with fewer disadvantages. This study represents the first and the largest cohort of superparamagnetic iron oxide application in Asian population. METHODS: Retrospective analysis of a prospectively maintained database was performed from August 2016 to December 2017. All patients with SLN localization by SPIO were included in this study. RESULTS: A total of 328 breast cancer patients with 333 SLNB procedures were included in this study. Median age was 54 years (range 32-86). Median tumor size was 1.9 cm (range 0.1-12 cm).There were 138 breast-conserving surgeries and 195 mastectomies. All patients received injection of SPIO 1 day prior to operation. A total of 329 successful sentinel lymph node biopsy (SLNB) procedures were undertaken with 1514 sentinel lymph nodes (SLNs) identified. One hundred and fifty-three (10.1%) of the SLNs were positive for malignancy. There were 54 patients with macrometastases, 26 with micrometastases and 24 with isolated tumor cells. Sixty-seven patients underwent subsequent axillary dissection. Four patients failed sentinel lymph node identification with SPIO. The success rate of SPIO in sentinel lymph node localization was 98.8%. CONCLUSION: SPIO represents a feasible alternative in sentinel lymph node mapping with comparably high nodal detection rate.

Statistical assessment of bi-exponential diffusion weighted imaging signal characteristics induced by intravoxel incoherent motion in malignant breast tumors.

BACKGROUND: The purpose of this study is to statistically assess whether bi-exponential intravoxel incoherent motion (IVIM) model better characterizes diffusion weighted imaging (DWI) signal of malignant breast tumor than mono-exponential Gaussian diffusion model. METHODS: 3 T DWI data of 29 malignant breast tumors were retrospectively included. Linear least-square mono-exponential fitting and segmented least-square bi-exponential fitting were used for apparent diffusion coefficient (ADC) and IVIM parameter quantification, respectively. F-test and Akaike Information Criterion (AIC) were used to statistically assess the preference of mono-exponential and bi-exponential model using region-of-interests (ROI)-averaged and voxel-wise analysis. RESULTS: For ROI-averaged analysis, 15 tumors were significantly better fitted by bi-exponential function and 14 tumors exhibited mono-exponential behavior. The calculated ADC, D (true diffusion coefficient) and f (pseudo-diffusion fraction) showed no significant differences between mono-exponential and bi-exponential preferable tumors. Voxel-wise analysis revealed that 27 tumors contained more voxels exhibiting mono-exponential DWI decay while only 2 tumors presented more bi-exponential decay voxels. ADC was consistently and significantly larger than D for both ROI-averaged and voxel-wise analysis. CONCLUSIONS: Although the presence of IVIM effect in malignant breast tumors could be suggested, statistical assessment shows that bi-exponential fitting does not necessarily better represent the DWI signal decay in breast cancer under clinically typical acquisition protocol and signal-to-noise ratio (SNR). Our study indicates the importance to statistically examine the breast cancer DWI signal characteristics in practice.

The Impact of the Oncotype DX Breast Cancer Assay on Treatment Decisions for Women With Estrogen Receptor-Positive, Node-Negative Breast Carcinoma in Hong Kong.

BACKGROUND: The Oncotype DX Breast Cancer Assay is validated to assess risk of distant recurrence and likelihood of chemotherapy (CT) benefit in estrogen receptor-positive ESBC in various populations. In Hong Kong, > 80% of breast cancers are early stage breast cancer (ESBC) and > 60% of these women receive CT. This prospective study measured changes in CT type and recommendations, as well as physician impression of assay impact in a homogenous Chinese population. METHODS: Consecutive patients with estrogen receptor-positive, T1-3 N0-1mi M0 ESBC were offered enrollment. After surgery, physicians discussed treatment options with patients, then ordered the assay, then reassessed treatment recommendation considering assay results. Changes in treatment recommendation, CT utilization, physician confidence, and physician rating of influence on their treatment recommendations were measured. RESULTS: A total of 146 evaluable patients received pre- and post-testing treatment recommendations. CT recommendations (including changes in intensity of CT) were changed for 34 of 146 patients (23.3%; 95% confidence interval, 16.7%-31.0%); change in intensity occurred in 7 of 146 (4.8%). There were 27 changes in treatment recommendations of adding or removing CT altogether (18.5% change; 95% confidence interval, 12.6%-25.8%). CT recommendations decreased from 52.1% to 37.7%, a net absolute reduction of 14.4% (P < .001; 27.6% net relative reduction). Pre-assay, 96% of physicians agreed/strongly agreed that they were confident in their treatment recommendation; post-assay, 90% of physicians agreed/strongly agreed with the same statement. Thirty percent of physicians agreed/strongly agreed that the test had influenced their recommendation, similar to the proportion of changed recommendations. CONCLUSIONS: The Oncotype DX Assay appears to influence physician ESBC adjuvant treatment recommendations in Hong Kong.

Risk factors and natural history of breast cancer in younger Chinese women.

AIM: To investigate the age differences in the risk factors, clinicopathological characteristics and patterns of treatment of female breast cancer patients. METHODS: Seven thousand one hundred and fifty-two women with primary breast cancer from the Hong Kong Breast Cancer Registry were recruited after receiving patients' consent, they were asked to complete standardized questionnaires which captured their sociodemographic characteristics and risk factors associated with breast cancer development. Among them, clinicopathological data and patterns of treatment were further collected from medical records of 5523 patients with invasive breast cancers. Patients were divided into two groups according to the age at diagnosis: younger (< 40 years old) vs older patients (≥ 40 years old) for subsequent analyses. RESULTS: Analysis on the sociodemographic characteristics and exposure to risk factors were performed on 7152 women with primary breast cancer and the results revealed that younger patients were more likely to have unhealthy lifestyles; these include a lack of exercise (85.4% vs 73.2%, P < 0.001), having high stress in life (46.1% vs 35.5%, P < 0.001), having dairy/meat-rich diets (20.2% vs 12.9%, P < 0.001), having alcohol drinking habit (7.7% vs 5.2%, P = 0.002). Younger patients were also more likely to have hormone-related risk factors including nulliparity (43.3% vs 17.8%, P < 0.001) and an early age at menarche (20.7% vs 13.2%, P < 0.001). Analyses on clinicopathological characteristics and patterns of treatment were performed on 5523 women diagnosed with invasive breast cancer. The invasive tumours in younger patients showed more aggressive pathological features such as having a higher percentage of grade 3 histology (45.7% vs 36.5%, P < 0.001), having a higher proportion of tumours with lymphovascular invasion (39.6% vs 33.2%, P = 0.003), and having multifocal disease (15.7% vs 10.3%, P < 0.001); they received different patterns of treatment than their older counterparts. CONCLUSION: Younger patients in Hong Kong are more likely to encounter risk factors associated with breast cancer development and have more aggressive tumours than their older counterparts.

Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy.

BACKGROUND: Although invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity. METHODS: The clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed. RESULTS: Two hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p <0.001) and more often postmenopausal (p <0.03) than HK patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p <0.002); yet despite this, ILC tumors were as likely as IDC to present with nodal metastases (p >0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p <0.0005), ILC tumors failed to demonstrate any such inverse relationship (p >0.6). CONCLUSION: These data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.

Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer's disease.

Alzheimer's disease (AD), the most common dementia, is characterized by potentially neurotoxic aggregation of Aß peptide and tau protein, and their deposition as amyloid plaques and neurofibrillary tangles (NFTs). Tau aggregation also occurs in other common neurodegenerative diseases. Frontotemporal dementia (FTD) can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation, which may cause neuronal dysfunction and deposition of NFTs. 17-allylamino-17-demethoxygeldanamycin (17-AAG) is a potent inhibitor of heat shock protein 90 (Hsp90), a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins. 17-AAG binds to Hsp90 and enhances degradation of Hsp90 client protein. We sought to determine whether 17-AAG can reduce Aß and tau pathology in the brains of AD and FTD model mice expressing Aß or P301L mutant tau, respectively. Mice were randomized to receive 25, 5, or 0 mg/kg 17-AAG thrice weekly from age eight to 11 months. Analysis was performed by rotarod test on motor function, on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections, and on mortality. A high dose of 17-AAG tended to decrease NFTs in male mice (p = 0.08). Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.

Benefit of ultrasonography in the detection of clinically and mammographically occult breast cancer.

OBJECTIVE: The purpose of this study was to evaluate the performance of high-resolution ultrasonography in the detection of clinically and mammographically occult breast cancer. MATERIALS AND METHODS: From September 2003 to November 2006, a total of 1485 patients were confirmed to have in situ or invasive breast cancer in Hong Kong Sanatorium and Hospital Breast Care Centre. All patients underwent mammography (MMG) and/ or sonography (USG) evaluation. Patients' age and size of tumor detected by USG alone were compared with those detected by MMG. RESULTS: Altogether, 222 patients (17%) had positive imaging findings on USG only, among which 22 (13%) patients had nonpalpable tumors. Performing USG increased the cancer detection rate among clinically and mammographically occult breast lesions by 14.3%. The mean size of the tumors detected only by USG was 1.98 cm, which was not significantly different from the mean size of tumor detected by MMG (1.46) (p = 0.23). This remains true in the group of patients with nonpalpable tumors (1.36 vs. 1.46 cm, p = 0.88). The sensitivity of USG is 91%, which is significantly higher than that of MMG (78%) (p = 0.001). This remains true in patients age <40 or > or = 40, tumor grading I toIII, and LVI +/- cases. However, MMG had higher sensitivity in the group of patients with nonpalpable tumors (73% vs. 62%, p = 0.01) and noninvasive cancers (72% vs. 69%, p = 0.01). CONCLUSIONS: The use of high-resolution USG may lead to detection of a significant number of occult cancers that are no different in size from nonpalpable mammographically detected lesions.

Experience of stereotactic breast biopsy using the vacuum-assisted core needle biopsy device and the advanced breast biopsy instrumentation system in Hong Kong women.

BACKGROUND: Stereotactic breast biopsy of non-palpable lesions using the vacuum-assisted core needle biopsy (CNB) device and the large core excision biopsy system is a reliable biopsy method when compared with open biopsy. Its use in Western countries is well accepted. This study aimed to assess the feasibility and results of using these systems to perform stereotactic biopsy in Asian women. METHODS: A total of 114 patients with non-palpable mammographic lesions underwent stereotactic breast biopsy using the vacuum-assisted CNB device and the large core excision biopsy system between November 1999 and December 2002. The indications for biopsy were mammographic abnormalities considered indeterminate or suspicious that were not palpable or visible on ultrasound. The methods adopted for biopsy in Asian women were reviewed and the results including the final pathology, complications, scarring and acceptance by patients were recorded. RESULTS: Stereotactic breast biopsy was performed using the vacuum-assisted CNB device in 107 patients and the large core excision biopsy system in seven patients. Of those who underwent biopsy using the vacuum-assisted CNB device, 15 (14%) had moderate to severe bleeding during the procedure and seven (6.5%) had severe bruising afterwards. Carcinoma was detected in 31 of the 114 patients (27.2%). CONCLUSION: Although Asian women in general have smaller and denser breasts than their Western counterparts, stereotactic breast biopsy using the vacuum-assisted CNB device and the large core excision biopsy system was feasible with modification of the individual steps during the procedure. Our results are comparable with those published previously and the procedure was well accepted by patients.