Impact of health literacy on diabetes outcomes: a cross-sectional study from Lahore, Pakistan.

OBJECTIVES: To evaluate the functional health literacy of patients with type 2 diabetes in Lahore and its impact on glycaemic control. STUDY DESIGN: A six-month cross-sectional study. METHODS: Health literacy in 204 patients with diabetes was evaluated using a validated questionnaire (Short Test of Functional Health Literacy [s-TOFHLA]). RESULTS: The frequency distribution among various age groups (P = 0.003), education levels (P = 0.0005), socio-economic status levels (P = 0.0005) and glycated haemoglobin (HbA1C) levels (P = 0.0005) differed significantly with health literacy level. The majority of patients with diabetes (86.1%) with poor glycaemic control (HbA1C >9%) had inadequate health literacy and were more likely to have retinopathy (odds ratio = 13.1, P = 0.003). Health literacy levels were not significantly different when compared for antidiabetic therapies (P = 0.234). Significant associations were observed between predictors of glycaemic control (s-TOFHLA score [P = 0.0005], education status [P = 0.0005] and disease risks [P = 0.005]) and HbA1C, level. However, after adjusting for basic characteristics, only s-TOFHLA score had a significant association with HbA1C level (P = 0.001). CONCLUSIONS: These data suggest that inadequate health literacy is potentially associated with poor glycaemic control, and microvascular and macrovascular complications, particularly retinopathy. As such, educational and training programmes should be introduced to improve functional health literacy of patients with diabetes for better glycaemic control.

The ATHENA HPV study underrepresents "other" high-risk HPV genotypes when compared with a diverse New York City population.

OBJECTIVE: Persistent infection with oncogenic high risk HPV (hrHPV) types causes virtually all cases of cervical cancer. HPV 16 and 18 have been targeted for individual genotyping and vaccination because of their presence in 71% of invasive cervical cancers worldwide. Montefiore Medical Center, Bronx, New York serves a population known for ethnic and racial diversity. Given this diversity it is possible that HPV genotypes not individually detected by current testing are causing significant disease. METHODS: We conducted a retrospective analysis of liquid based cervicovaginal cytology and Cobas HPV results reported between October 5, 2015 and March 30, 2016. This included 20 483 samples from patients aged 16-95 (average age 42), with racial distribution including: African-American 32.4%, Other (includes denied, unknown, mixed, Hispanic) 52.1%, Caucasian 14.5%, Asian 0.7%, American Indian/Alaskan Native 0.3%. In all, 14 938 samples (72.9%) were submitted for clinically requested COBAS 4800 HPV testing, which separately reports HPV 16, 18 and a pool of 12 other hrHPV. RESULTS: A total of 3180 (21.5%) tested hrHPV positive. The percentage of patients with cytologic diagnosis of HSIL (high-grade squamous intraepithelial lesion) that were positive only for HPV 16 was 19.4% vs 1.8% for all cytologic diagnoses. However, only one of the HSIL cases was HPV 18 positive along with other hrHPV (OHR). Surprisingly, a majority (64.5%) was positive for only OHR. CONCLUSIONS: Further evaluation is needed to determine if this pool of other hrHPV includes individual genotypes that in our population carry a higher risk of persistence and progression to cancer.

SurePath Specimens Versus ThinPrep Specimen Types on the COBAS 4800 Platform: High-Risk HPV Status and Cytology Correlation in an Ethnically Diverse Bronx Population.

OBJECTIVE: To compare the cytologic preparations of 130 cervical specimens (from women of various ethnicities at high risk for human papillomavirus [HPV] infection) using the SurePath (SP) collection system with specimens gathered using the ThinPrep (TP) system, as processed on the Cobas 4800 analyzer, to determine which collection method more accurately identifies HPV infection. METHODS: In our prospective study, specimens were collected from 130 women of various ethnicities residing in or near Bronx County, NY. The SP-collected specimen was first processed for cytologic findings; if clinical HPV testing was requested on that specimen, it was tested using Hybrid Capture II (HC2) methodology. We tested the remnant SP-collected cell concentrate using the Cobas analyzer. Then, the TP-collected and SP-collected specimens were tested in the same run on that analyzer, and the results were compared. We also compared the results with the concurrent cytologic findings. RESULTS: The results were concordant for overall HR-HPV status in 93.8% of cases. Also, a statistically significant lower cycle threshold value was observed with Cobas testing of specimen concentrates tested via the BD SurePath Pap Test (P = .001), suggesting higher sensitivity compared with specimens tested via the ThinPrep Pap Test. CONCLUSION: Cobas 4800 HPV testing of SP-collected specimen concentrates yields comparable results to TP-collected specimen concentrates. Based on the limited data that we derived, SP collection may be a more favorable methodology than TP collection for HPV testing of individuals at high risk in our ethnically diverse, urban patient population.

The value of manipulation of displaced distal radius fractures in the emergency department.

The aim of this study was to report the success of maintaining reduced distal radius fractures with cast immobilisation and analyse risk factors for redisplacement. A retrospective analysis of distal radius fracture manipulated between April 2011 and 2013 was conducted. Age, gender, fracture classification, ulna fracture, dorsal comminution and volar alignment were recorded. Reduction and redisplacement were measured using Sarmiento's modification of Lidstrom's system. 110 patients were included ; mean age 62.8 years and 83.4% female. The AO classification was used to grade initial fractures A2 (44%), A3 (25%), C1 (20%) and C2 (10%). 86.4% of cases were improved following manipulation, although 48.4% redisplaced and 27.4% required surgical intervention. The radial length (60%) was harder to maintain than dorsal alignment (44%) in cases of redisplacement. Successful alignment of the volar cortices was associated with a statistically significant reduction in redisplacement (p = 0.024). Manipulation of distal -radius fractures is initially beneficial but half of cases redisplace.

A comparison of magnetic resonance arthrography and arthroscopic findings in the assessment of anterior shoulder dislocations.

OBJECTIVE: The aim of this study is to establish the sensitivity and specificity of MRA in the investigation of patients with traumatic anterior shoulder dislocations. MATERIALS AND METHODS: A retrospective analysis of consecutive patients undergoing both magnetic resonance arthrography and arthroscopic assessment after a traumatic anterior shoulder dislocation between January 2011 and 2014 was performed. Demographic data were collected from electronic records. Images were interpreted by 8 musculoskeletal radiologists and patients were treated by 8 consultant orthopaedic surgeons. Arthroscopic findings were obtained from surgical notes and these findings were used as a reference for MRA. The sensitivity, specificity, and positive predictive value were calculated for the different injuries. RESULTS: Sixty-nine patients underwent both an MRA and shoulder arthroscopy during the study period; however, clinical notes were unavailable in 9 patients. Fifty-three patients (88 %) were male, the mean age was 28 years (range 18 to 50) and 16 subjects (27 %) had suffered a primary dislocation. The overall sensitivity and specificity of MRA to all associated injuries was 0.9 (CI 0.83-0.95) and 0.94 (CI 0.9-0.96) retrospectively. The lowest sensitivity was seen in osseous Bankart 0.8 (CI 0.44-0.96) and superior labral tear (SLAP) lesions 0.5 (CI 0.14-0.86). The overall positive predictive value was 0.88 (CI 0.76-0.91) with the lowest values found in rotator cuff 0.4 (CI 0.07-0.83) and glenohumeral ligament (GHL) lesions 0.29 (CI 0.05-0.7). CONCLUSION: Magnetic resonance angiography has a high sensitivity when used to identify associated injuries in shoulder dislocation, although in 8 patients (13 %) arthroscopy identified an additional injury. The overall agreement between MRA and arthroscopic findings was good, but the identification of GHL and rotator cuff injuries was poor.

Cytogenetic studies of spontaneous miscarriages: a seven year study to compare significance of primary vs. secondary culture methods for assessment of fetal karyotype yield and maternal cell contamination.

Primary in-situ culture (PIC) and secondary trypsinized culture (STC) are the two currently used methods for culturing chorionic villi in order to cytogenetically evaluate products of conception (POC) from spontaneous miscarriages. We compare these culture techniques in our laboratory over a period of seven years to evaluate fetal karyotype yield and maternal cell contamination. Data from a total of 2077 cases from 1992-1999 was entered into a data entry program created in Epi Info version 6. Analysis, using the chi square test of significance, was performed in the same program. Our data demonstrated a statistically significant excess of normal female karyotype detected by the STC method and a statistically significant excess of abnormal karyotypes detected by the PIC method. We attribute these findings to the greater risk of maternal cell contamination with the STC method. We conclude that the PIC method is more accurate in detecting the fetal karyotype and the STC method has a higher risk of maternal cell contamination. We suggest that the PIC method should be adopted as the method of choice when evaluating POC by culturing chorionic villi.

Tyrosine kinase activation in breast carcinoma with correlation to HER-2/neu gene amplification and receptor overexpression.

The HER-2/neu oncogene encodes a transmembrane receptor with intrinsic tyrosine kinase activity. A pilot study was performed to investigate downstream effects of HER-2/neu (or related growth factor receptor) activation by identifying phosphorylated tyrosine. Fifty-four breast carcinomas were evaluated for HER-2/neu overexpression by the HercepTest (Dako, Carpinteria, CA) and the monoclonal CB11 antibody (Ventana, Tucson, AZ). Phosphotyrosine (an indication of tyrosine kinase activity) was detected by an antiphosphotyrosine mouse monoclonal antibody (Upstate Biotechnology, Lake Placid, NY). The gene amplification status was evaluated in 50 of the 54 cases by fluorescence in situ hybridization (FISH) using the Ventana gene probe. The HER-2/neu oncogene amplification was detected in 28% (14 of 50) of cases. Of the 14 cases showing oncogene amplification, tyrosine kinase activity was detected in 9 (64.2%) cases. There was moderate agreement between HER-2/neu gene amplification and tyrosine kinase activity (kappa = 0.43). Immunohistochemical staining of 3+ (with both HercepTest and CB11) showed better agreement with HER-2/neu oncogene amplification and increased tyrosine kinase activity than 2+ immunohistochemical staining. Overall, oncogene amplification and overexpression correlated with increased tyrosine kinase activity, supporting the mechanism of tyrosine kinase activation by HER-2/neu amplification and overexpression. However, 7 cases showing increased tyrosine kinase activity did not show gene amplification or 3+ receptor expression (by either HercepTest or CB11), raising the possibility of other growth factor receptors operating via the tyrosine kinase pathway. There was no apparent correlation between tyrosine kinase activity and hormone receptor status (estrogen or progesterone). Increased tyrosine kinase activity is more commonly associated with higher-grade tumors and thus may correlate with aggressive biologic behavior in breast carcinoma. The results of this pilot study suggest that a larger-scale investigation into downstream activation of tyrosine kinase and correlation to clinical outcome or response to Herceptin therapy may identify subsets of patients whose clinical response or outcome may be predicted by tyrosine kinase activation.

De novo translocation (8;12) and frontofacionasal dysplasia in a newborn boy.

We describe a newborn boy one of triplets, whose karyotype was 46,XY, t(8;12)(q22;q21). Prenatal diagnosis of multiple craniofacial anomalies had been made. Following delivery, the patient was thought to exhibit findings consistent with a diagnosis of frontofacionasal dysostosis. We hypothesize that one of the break points of this translocation may involve a gene essential to craniofacial development.

Prenatal diagnosis and clinical features of an individual with tetrasomy 18p and trisomy 18q mosaicism.

Prenatal diagnosis and clinical follow up of a patient with mosaicism for anomalies of chromosome 18 are reported. The fetus appeared on ultrasound to have multiple anomalies, including clubbed feet, abnormal hand positioning, edema of the scalp, cleft palate, and polyhydramnios. The karyotype on amniocytes was 47,XY,+i(18p). Postnatally, the peripheral blood karyotype was 46,XY,+i(18q), whereas the skin fibroblast karyotype was 47,XY,+i(18p). The infant had many features consistent with those previously described in cases of tetrasomy 18p and some that were consistent with trisomy 18q.

Reproduction in a patient with trisomy 8 mosaicism: case report and literature review.

We describe a patient with trisomy 8 mosaicism followed through a sixth pregnancy and discuss issues in phenotypic and genotypic variability, the risk for neoplasia, and reproductive risks.

A five-year experience with fragile X testing. Setting laboratory standards of practice and a cost-effective protocol.

During the years 1990-1994, our center tested 652 patients, with a broad range of referral indications, for fragile X syndrome using either cytogenetic analysis alone (Protocol 1) or more recently, a combination of DNA analysis and routine karyotyping (protocol 2). The overall positive rate for fragile X was 3.1% with an incidence of other chromosomal abnormalities (OCAs) of 3.2%. Breakdown of cases using each testing protocol along with percent positives is: [table: see text] Use of Protocol 2 yielded only definitive fragile X results, while more than half of the "positives" using Protocol 1 were equivocal. Historically this has been problematic for both the laboratory and physician since interpretation is often dependent on an equally equivocal clinical picture. Protocol 2 eliminates these diagnostic dilemmas without compromising detection of other chromosomal abnormalities, the incidence of which appears to be unaffected by testing method used. The overall incidence of OCA of 3.2% underscores the value of routine karyotyping in this referral group and likely reflects the phenotypic variability of fragile X and its clinical overlap with other chromosomal abnormalities. We believe that a fragile X testing protocol combining routine karyotyping with definitive molecular technology represents the most cost-effective diagnostic approach to this clinically challenging patient population.

Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22.

Ring chromosomes are found in most dermatofibrosarcoma protuberans (DFSPs), and recent reports demonstrate that portions of the DFSP ring chromosomes derive from chromosome 17. In this study we characterized ring chromosomes in three DFSPs using a combined approach of karyotyping, chromosome painting, and comparative genomic hybridization. Chromosome painting demonstrated that the ring chromosomes in each DFSP were composed of discontinuous, interwoven sequences from chromosomes 17 and 22. Amplification of chromosomes 17 and 22 sequences was confirmed in each of these cases by comparative genomic hybridization, and over-representation of chromosomes 17 and 22 sequences was also demonstrated by comparative genomic hybridization in 1 of 2 cytogenetically unremarkable DFSPs. We conclude that amplification of chromosomes 17 and 22 sequences, in ring form, is a characteristic aberration in DFSP.

Chromosome aberrations in desmoid tumors. Trisomy 8 may be a predictor of recurrence.

Cytogenetic analyses of short-term cultures revealed clonal chromosome aberrations in 6 of 13 desmoid tumors. These aberrations included two consistent events, trisomy 8 (n = 4) and trisomy 20 (n = 3), which have not been reported previously in desmoid tumors. Because trisomy 8 was found in two recurrent desmoid tumors, we used fluorescent in situ hybridization (FISH) methodology to evaluate chromosome 8 in 25 paraffin-embedded and frozen desmoid specimens. The FISH studies demonstrated that both patients with cytogenetic trisomy 8 at the time of recurrence also had had trisomy 8 in primary tumors 4 years earlier. The proportion of trisomy 8 cells in these cases did not change substantially between original diagnosis and recurrence. The FISH studies also revealed trisomy 8 in one recurrent desmoid tumor which had been cytogenetically unremarkable and revealed trisomy 8 in one recurrent desmoid that had not been karyotyped. Four of six patients with trisomy 8 had been followed for more than 1 year, and the desmoid tumors in each of these 4 patients recurred. By contrast, recurrence was noted in only 2 of 17 patients whose desmoid tumors lacked trisomy 8. Our findings demonstrate that trisomy 8 and trisomy 20 are nonrandom aberrations in desmoid tumors. Trisomy 8 appears to be associated with an increased risk of recurrence.

Translocation t(8;13)(p11;q11-12) in stem cell leukemia/lymphoma of T-cell and myeloid lineages.

An unusual hematologic neoplasia has been described recently in which the predominant clinical features include T-cell lymphoma, myeloid hyperplasia, and eosinophilia. The multilineage involvement in this disorder suggests transformation of a primitive stem cell. Abnormal karyotypes have been described in three such cases, including one case with t(8;13)(p11.2;q12) and a second case with t(8;13)(p23;q14). We report translocation of chromosomes 8 and 13 in lymph node karyotypes from two patients with this syndrome. Fluorescence in situ hybridization confirmed an identical translocation, t(8;13)(p11;q11-12), in lymphoma cells from each patient. The translocation breakpoints are of particular interest because the FLT3 receptor tyrosine kinase gene has been mapped 13q12. FLT3 is expressed highly in hematopoietic progenitor cells and in myeloid and lymphoid acute leukemias.

Fluorescent in situ hybridization assessment of chromosome 7 copy number in uncultured lung and kidney cells.

Trisomy 7 is common in cells cultured from nonneoplastic lung and kidney tissues, but the frequency of trisomy 7 in uncultured lung and kidney has not been determined. In this study, we used fluorescent in situ hybridization (FISH) to assess chromosome 7 copy number in uncultured interphase nuclei from lung and kidney specimens. All specimens had low level mosaicism for trisomy 7(1.5-5.25%), but control experiments indicated a potential wide margin of error in quantifying these events.

Clonal rearrangement of chromosome band 6p21 in the mesenchymal component of pulmonary chondroid hamartoma.

Pulmonary chondroid hamartomas (PCH) are biphasic benign tumors that contain both mesenchymal and epithelial populations. In this report we describe two PCH in which clonal translocations at chromosome band 6p21 were demonstrated in mesenchymal cells. One of these had a unique translocation, t(6;14)(p21;q24), that was also found in one of two PCH karyotyped previously. The t(6;14) has not been described in other varieties of benign or malignant neoplasia. The 6p21 aberrations are of particular interest because break points in this chromosomal region appear to be characteristic of endometrial polyps. Endometrial polyps, like PCH, are biphasic benign tumors in which mesenchymal clonality has been demonstrated.