The prevalence and predictors of discharge opioid overprescribing in opioid-naïve patients after breast, gynecologic, and head and neck cancer surgery: a prospective cohort study.

PURPOSE: The management of pain following cancer-related surgeries involves the use of opioid analgesics. Nevertheless, there is little evidence characterizing the utility and prescription patterns of opioids after these procedures. Our primary aim was to identify patients from three types of cancer surgery who were overprescribed with opioids. The secondary aim was to determine the potential predictors of overprescribing in the same period. METHODS: We conducted the study at a single cancer referral hospital. Opioid-naïve patients with breast, gynecologic, or head and neck cancer were studied. Patients were considered opioid-naïve if they had a history of opioid use ≤ 30 mg oral morphine equivalent daily dose for less than seven days in the preceding three months before surgery. We recruited eligible participants by convenience sampling on the wards until at least 102 patients were included in the final analysis. After discharge, we followed up on the participants on day 7 via telephone using a structured proforma including questions to identify the last date and amount of opioid dose taken. The equivalent days of opioid use were calculated by their 24-hr use before discharge and the number of doses prescribed for discharge. Our primary outcome was the prevalence of overprescribing in the three surgical specialties defined as the number of patients taking less than 50% of discharge opioids within the first seven days after discharge. We examined the predictors on incidents of overprescribing using multivariable Poisson regression as the secondary outcome. RESULTS: We recruited 119 patients, and 107 patients were included in the final analysis. There were 59/107 (55%) patients found to be overprescribed with opioids. At discharge, they exhibited lower mean numerical rating scale pain scores, lower mean pain severity scores, higher equivalent days of opioids prescribed, and not used opioids in the last 24 hr before discharge. The incidence of overprescribing was 2.4 times greater for patients prescribed with opioids without 24-hr opioid use (relative risk [RR], 2.38; 95% confidence interval [CI], 1.30 to 4.35; P = 0.005). Similarly, the incidence of overprescribing was 1.7 times greater for patients who had opioids 24 hr before discharge and were supplied with opioids for five equivalent days or more at the time of discharge (RR, 1.67; 95% CI, 1.09 to 2.56; P = 0.02). CONCLUSION: Our study shows that the majority of recruited patients undergoing breast, gynecologic, or head and neck cancer surgery were overprescribed opioids. Individualized assessments on patients' 24-hr opioid requirements before discharge and supplying for less than five days are important considerations to reduce overprescribing in opioid-naïve patients after cancer surgery.

RéSUMé: OBJECTIF: La prise en charge de la douleur à la suite d'interventions chirurgicales liées au cancer passe par l'utilisation d'analgésiques opioïdes. Néanmoins, il existe peu de données probantes caractérisant l'utilité et les habitudes de prescription des opioïdes après ces interventions. Notre objectif principal était d'identifier les patient·es de trois types de chirurgie du cancer auxquel·les des opioïdes avaient été surprescrits. L'objectif secondaire était de déterminer les prédicteurs potentiels de surprescription au cours de la même période. MéTHODE: Nous avons mené cette étude dans un seul hôpital de référence pour le cancer. La patientèle naïve aux opioïdes atteinte de cancer du sein, gynécologique ou de la tête et du cou a été étudiée. Les patient·es étaient considéré·es comme naïfs ou naïves aux opioïdes si leurs antécédents d'utilisation d'opioïdes étaient inférieurs ou égaux à une dose quotidienne équivalente à 30 mg de morphine orale pendant moins de sept jours au cours des trois mois précédant la chirurgie. Nous avons recruté les participant·es éligibles par échantillonnage de commodité dans les services jusqu'à ce qu'au moins 102 personnes soient incluses dans l'analyse finale. Après le congé, nous avons fait un suivi téléphonique auprès des participant·es le 7e jour à l'aide d'un formulaire structuré comprenant des questions visant à identifier la dernière date et la dose d'opioïdes prise. Les jours équivalents de consommation d'opioïdes ont été calculés en fonction de leur utilisation dans les 24 heures précédant le congé et du nombre de doses prescrites pour le congé. Notre critère d'évaluation principal était la prévalence de la surprescription dans les trois spécialités chirurgicales, définie comme le nombre de patient·es prenant moins de 50 % des opioïdes reçus au congé dans les sept premiers jours suivant le congé. Nous avons examiné les prédicteurs d'incidents de surprescription en utilisant la régression de Poisson multivariée comme critère d'évaluation secondaire. RéSULTATS: Nous avons recruté 119 patient·es, et 107 patient·es ont été inclus·es dans l'analyse finale. Une surprescription d'opioïdes a été observée pour 59 patient·es sur 107 (55 %). À leur congé, ces personnes présentaient des scores de douleur moyens plus faibles sur l'échelle d'évaluation numérique, des scores moyens de gravité de la douleur plus faibles, des jours équivalents d'opioïdes prescrits plus élevés et n'avaient pas utilisé d'opioïdes dans les 24 heures précédant le congé. L'incidence de surprescription était 2,4 fois plus élevée chez les patient·es à qui l'on avait prescrit des opioïdes sans utilisation d'opioïdes dans les 24 heures (risque relatif [RR], 2,38; intervalle de confiance [IC] à 95 %, 1,30 à 4,35; P = 0,005). De même, l'incidence de surprescription était 1,7 fois plus élevée chez les patient·es qui avaient reçu des opioïdes 24 heures avant le congé et qui avaient reçu des opioïdes pendant cinq jours équivalents ou plus au moment du congé (RR, 1,67; IC 95 %, 1,09 à 2,56; P = 0,02). CONCLUSION: Notre étude montre qu'il y a eu surprescription d'opioïdes pour la majorité des patient·es recruté·es bénéficiant d'une chirurgie de cancer du sein, gynécologique ou de la tête et du cou. Des évaluations individualisées des besoins en opioïdes des patient·es dans les 24 heures avant leur congé et une administration pendant moins de cinq jours sont des considérations importantes pour réduire la surprescription chez les personnes naïves aux opioïdes après une chirurgie oncologique.

A temperature-dependent virus-binding assay reveals the presence of neutralizing antibodies in human cytomegalovirus gB vaccine recipients' sera.

Human cytomegalovirus (HCMV) remains an important cause of mortality in immune-compromised transplant patients and following congenital infection. Such is the burden, an effective vaccine strategy is considered to be of the highest priority. The most successful vaccines to date have focused on generating immune responses against glycoprotein B (gB) - a protein essential for HCMV fusion and entry. We have previously reported that an important component of the humoral immune response elicited by gB/MF59 vaccination of patients awaiting transplant is the induction of non-neutralizing antibodies that target cell-associated virus with little evidence of concomitant classical neutralizing antibodies. Here we report that a modified neutralization assay that promotes prolonged binding of HCMV to the cell surface reveals the presence of neutralizing antibodies in sera taken from gB-vaccinated patients that cannot be detected using standard assays. We go on to show that this is not a general feature of gB-neutralizing antibodies, suggesting that specific antibody responses induced by vaccination could be important. Although we can find no evidence that these neutralizing antibody responses are a correlate of protection in vivo in transplant recipients their identification demonstrates the utility of the approach in identifying these responses. We hypothesize that further characterization has the potential to aid the identification of functions within gB that are important during the entry process and could potentially improve future vaccine strategies directed against gB if they prove to be effective against HCMV at higher concentrations.

From the archives of MD Anderson Cancer Center: Sporadic Burkitt lymphoma with a complex karyotype and SOX11 expression.

Burkitt lymphoma (BL) is a mature B-cell neoplasm arising from germinal center B-cells. There are three epidemiological variants of which the sporadic variant is most prevalent in developed countries representing 1-2 % of all lymphomas in adults. Patients usually present with bulky abdominal masses and ~ 30 % have bone marrow involvement. BL is characterized by a germinal center B-cell immunophenotype and usually has a simple karyotype. Here we report an unusual case of sporadic BL in a 44-year-old man and we use this case to review sporadic BL in adults. The patient presented with a cecal mass and bone marrow involvement. Biopsy of the cecal mass and bone marrow evaluation showed infiltration by intermediate-size lymphoma cells positive for monotypic kappa, CD10, CD19, CD20, CD22, CD38 bright, CD43, CD45, Bcl6 and ROR1, and negative for CD11c, CD23, CD30, CD44, CD200 and Bcl2. As expected, the lymphoma cells were strongly positive for MYC and Ki-67 showed a proliferation rate of nearly 100 %, but the cells were also positive for SOX11 and cytoplasmic LEF1. Conventional chromosomal analysis revealed t(8;14) as part of a complex karyotype. Based on our literature review, and is shown in this case, sporadic BL in adults shows some differences with the classic description of BL in children. We also discuss the differential diagnosis of BL.

IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that is potentially pathogenic in immunosuppressed individuals and pregnant females during primary infection. The HCMV envelope glycoprotein B (gB) facilitates viral entry into all cell types and induces a potent immune response. AD-2 epitope is a highly conserved linear neutralizing epitope of gB and a critical target for antibodies; however, only 50% of sero-positive individuals make IgG antibodies to this site and IgA responses have not been fully investigated. This study aimed to compare IgG and IgA responses against gB and the AD-2 epitope in naturally exposed individuals and those receiving a recombinant gB/MF59 adjuvant vaccine. Thus, vaccination of sero-positive individuals improved pre-existing gB-specific IgA and IgG levels and induced de novo gB-specific IgA and IgG responses in sero-negative recipients. Pre-existing AD-2 IgG and IgA responses were boosted with vaccination, but de novo AD-2 responses were not detected. Naturally exposed individuals had dominant IgG responses towards gB and AD-2 compared with weaker and variable IgA responses, although a significant IgA binding response to AD-2 was observed within human breastmilk samples. All antibodies binding AD-2 contained kappa light chains, whereas balanced kappa/lambda light chain usage was found for those binding to gB. V region-matched AD-2-specific recombinant IgG and IgA bound both to gB and to AD-2 and neutralized HCMV infection in vitro. Overall, these results indicate that although human IgG responses dominate, IgA class antibodies against AD-2 are a significant component of human milk, which may function to protect neonates from HCMV.

Magnetic Domain Wall Based Synaptic and Activation Function Generator for Neuromorphic Accelerators.

Magnetic domain walls are information tokens in both logic and memory devices and hold particular interest in applications such as neuromorphic accelerators that combine logic in memory. Here, we show that devices based on the electrical manipulation of magnetic domain walls are capable of implementing linear, as well as programmable nonlinear, functions. Unlike other approaches, domain-wall-based devices are ideal for application to both synaptic weight generators and thresholding in deep neural networks. Prototype micrometer-size devices operate with 8 ns current pulses and the energy consumption required for weight modulation is ≤16 pJ. Both speed and energy consumption compare favorably to other synaptic nonvolatile devices, with the expected energy dissipation for scaled 20 nm devices close to that of biological neurons.

Laboratory diagnosis for thalassemia intermedia: Are we there yet?

BACKGROUND: Differentiation between thalassemia major and thalassemia intermedia at presentation is not uniformly characterized, for which an absolute criteria needs to be developed. This study investigated the primary and secondary genetic modifiers to develop a laboratory finding by forming different genetic mutational combinations seen among thalassemia intermedia patients and comparing them with thalassemia major. METHODS: This cross-sectional study analyzed 315 thalassemia intermedia patients. One hundred and five thalassemia major patients were recruited on the basis of documented evidence of diagnosis and were receiving blood transfusion therapy regularly. Various mutational combinations were identified, and comparison was performed between thalassemia intermedia and major using statistical software STATA 11.1. RESULTS: The mean age of the total population was 5.9 ± 5.32 years of which 165 (52%) were males. Of the two groups (thalassemia intermedia and thalassemia major), IVSI-5, IVSI-1, and Fr 8-9 were more prevalent among the thalassemia intermedia cohort. When comparison was performed between the thalassemia intermedia and thalassemia major patients, it showed significant results for the presence of Xmn-1 polymorphism. CONCLUSION: The presence of IVSI-5 homozygous with Xmn-1, IVSI-5 heterozygous with Xmn-1, Cd 30 homozygous with or without Xmn-1 and IVSI-1 homozygous or heterozygous either with or without Xmn-1 prove to be strong indicators towards diagnosis of thalassemia intermedia.

Current-Induced Domain Wall Motion in a Compensated Ferrimagnet.

Owing to the difficulty in detecting and manipulating the magnetic states of antiferromagnetic materials, studying their switching dynamics using electrical methods remains a challenging task. By employing heavy-metal-rare-earth-transition-metal alloy bilayers, we experimentally study current-induced domain wall dynamics in an antiferromagnetically coupled system. We show that the current-induced domain wall mobility reaches a maximum at the angular momentum compensation point. With experiment and modeling, we further reveal the internal structures of domain walls and the underlying mechanisms for their fast motion. We show that the chirality of the ferrimagnetic domain walls remains the same across the compensation points, suggesting that spin orientations of specific sublattices rather than net magnetization determine Dzyaloshinskii-Moriya interaction in heavy-metal-ferrimagnet bilayers. The high current-induced domain wall mobility and the robust domain wall chirality in compensated ferrimagnetic material opens new opportunities for high-speed spintronic devices.

The Spatial Resolution Limit for an Individual Domain Wall in Magnetic Nanowires.

Magnetic nanowires are the foundation of several promising nonvolatile computing devices, most notably magnetic racetrack memory and domain wall logic. Here, we determine the analog information capacity in these technologies, analyzing a magnetic nanowire containing a single domain wall. Although wires can be deliberately patterned with notches to define discrete positions for domain walls, the line edge roughness of the wire can also trap domain walls at dimensions below the resolution of the fabrication process, determining the fundamental resolution limit for the placement of a domain wall. Using a fractal model for the edge roughness, we show theoretically and experimentally that the analog information capacity for wires is limited by the self-affine statistics of the wire edge roughness, a relevant result for domain wall devices scaled to regimes where edge roughness dominates the energy landscape in which the walls move.

Expression of aberrant antigens in hematological malignancies: A single center experience.

BACKGROUND AND OBJECTIVE: Aberrant phenotype is a phenomenon of abnormal expression or loss of expression of cell specific lineage marker not associated with specific cell type. Aberrant phenotype expression due to genetic defects may be associated with unfavorable outcome. It can be used to determine minimal residual disease status. The purpose of the study was to find out the occurrence of aberrant phenotypes in leukemia/lymphoma patients. METHODS: One milliliter peripheral blood or bone marrow samples were analyzed on FACS Calibur flowcytometer. The cells were lysed and stained following standard protocol. Data was acquired and analyzed by CellQuest-Pro software. The Antigenic expression was rated as positive when the percentage of positive blast cells was ≥ 20%. In that manner, aberrant phenotype was considered positive when 20% of blast cells show expression of markers. RESULTS: Of a total 145 cases analyzed, 26 were acute myeloid leukemia, 71 of acute lymphoblastic leukaemia, 48 were of Chronic Lymphoid leukemia on the basis of morphological features and confirmed by flow cytometry. Overall, 19% (28) cases showed aberrant expression of antigens. In 32% (9/28) AML patients, CD5, CD7, CD64dim, CD10, CD117, CD25 and TdT were expressed while in 25% (7/28) ALL patients CD33, CD13, HLA-DR and CD3 were detected. Among chronic leukemia, all aberrant expressions were seen in cases of B-CLL (10/28) only; with CD11c, CD3 and CD10 as the aberrantly expressed markers. CONCLUSION: Variability in aberrant phenotype expression was observed in different types of acute and chronic leukemia patients with no prognostic implications on treatment response.

Room-Temperature Spin-Orbit Torque Switching Induced by a Topological Insulator.

The strongly spin-momentum coupled electronic states in topological insulators (TI) have been extensively pursued to realize efficient magnetic switching. However, previous studies show a large discrepancy of the charge-spin conversion efficiency. Moreover, current-induced magnetic switching with TI can only be observed at cryogenic temperatures. We report spin-orbit torque switching in a TI-ferrimagnet heterostructure with perpendicular magnetic anisotropy at room temperature. The obtained effective spin Hall angle of TI is substantially larger than the previously studied heavy metals. Our results demonstrate robust charge-spin conversion in TI and provide a direct avenue towards applicable TI-based spintronic devices.

Analysis of dental erosion induced by different beverages and validity of equipment for identifying early dental erosion, in vitro study.

OBJECTIVE: To understand early dental erosion induced by different beverages and the equipment for its detection. METHODS: The study was conducted at the University Malaya Medical Centre, Kuala Lumpur, Malaysia, from June to September 2014, and comprised single-rooted, unpolished teeth divided into six groups. Electron micrographs and other baseline readings for further analyses were taken before and after the exposure to different beverages. The teeth were exposed to the beverages using a modified Nordini's artificial mouth model. The positioning of the teeth on the motorised stage of the equipment was standardised. RESULTS: Of the several beverages used, CocaCola had the lowest pH value of 2.53, while tap water had the highest pH of 5.4. Deionised distilled water, which was used as a reference, had a pH near to neutral /alkaline of 7.3. The fluoride content ranged between 9.38ppm in tea and 0.005ppm in orange juice. Teeth exposed to beverages with low pH and considerably high fluoride underwent slight remineralisation (roughness increase 8% from tea), while beverages with no fluoride content and low pH roughened the enamel surface (Coca Cola roughened upto 37%). Quantitative analyses of tooth erosion, micro-hardness, surface-roughness, and surface-height showed that all beverages exhibited positive erosive effect on the tooth enamel surface (p<0.005). CONCLUSIONS: CocaCola was found to be the most erosive agent among both hot and cold beverages (37%), while coffee was more erosive among the hot beverages (29%).

PD-L1 Expression in Ampullary Adenocarcinoma.

INTRODUCTION: Ampullary adenocarcinoma is a rare neoplasm often treated by the complex Whipple's procedure. Several histological factors predict poor prognosis including pancreatobiliary morphology, presence of lymphovascular, perineural invasion and local or distant metastasis. Systemic therapy with gemcitabine, 5-fluorouracil regimens are given with variable benefits. Immunotherapy checkpoint inhibitors have shown beneficial anti-tumor effects in several carcinomas, the most remarkable being in non-small cell lung cancer. Administration of these novel drugs is based on immunohistochemical expression (which may or may not be indicative of response to therapy) along with meticulous decision making by the multidisciplinary team. Immunohistochemistry (IHC) is an effective means of immune marker demonstration and has been used in various tumor types for predictive and prognostic purposes. METHODS: PD-L1 IHC (clone E1L3N) was applied in 101 cases of ampullary adenocarcinoma. Tumor infiltrating lymphocytes were also evaluated. The immunoreactivity was assessed and categorized into following staining thresholds: <1%, <5%, <10% and ≥10% for tumor cells (membranous and/or cytoplasmic staining pattern), and 5% and 10% cut-offs for immune cells. RESULTS: We found that at a 10% cut-off, 73.3% (74/101) patients were men (P = .006) older than 50 years of age (P < .001) presenting with a tumor measuring <3 cm (P = .001). It was significantly associated with intestinal differentiation (P = .004) and grade 1 tumors (P = .001). Twelve patients presented with recurrence as well (P = .03). CONCLUSION: In the context of ampullary adenocarcinoma, this study highlights the positivity observed with the PD-L1 IHC clone E1L3N at different thresholds, with the particularly stronger associations being evident at a 10% cut-off.

TP53 mutation is frequent in mantle cell lymphoma with EZH2 expression and have dismal outcome when both are present.

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and p53 mutant pattern by immunohistochemistry. Comparative analysis disclosed that EZH2 expression correlates with high Ki-67 proliferation rate irrespective of TP53 mutation. Aggressive histology is associated with EZH2 expression or TP53 mutation, possibly via independent mechanisms. p53 mutant pattern is due to TP53 mutation. MCL patients with EZH2 expression or TP53 mutation show inferior outcome and when both are present, patients have dismal outcome.

Association of knowledge, attitudes, and behaviors for colon cancer screening in Hispanic patients.

PURPOSE: The purpose of our cross-sectional study was to examine the association between sociodemographic, knowledge, attitude and behavior factors with colon cancer screening among low-income Hispanic patients from an urban family medicine clinic in San Antonio, Texas. METHODS: Using random stratified sampling, 804 patients were surveyed with 274 Hispanic patients meet the eligibility criteria for colon cancer screening (aged > or = 50 years). A 10-page self-administered questionnaire in Spanish or English completed in the clinic waiting room included self-reported colonoscopy, sociodemographic characteristics, health status, knowledge, attitudes, and behaviors toward colon cancer screening. Associations between colonoscopy and patient characteristics were assessed using logistic regression. RESULTS: 62% of patients reported having been tested for colonoscopy. Older Hispanics (age mean=59 + 6.1 SD) were more likely to have a colonoscopy than younger Hispanics (age mean = 56 +/- 4.8 SD) (P < .001). Bivariate analysis showed that patients who discussed colon cancer risk with their doctor (P = .001), did not smoke (P = .004), or encouraged family members or friends to be tested for colon cancer (P < .001) were more likely to be screened. Multiple variable logistic regression analysis showed that older age, having cancer, discussing the risk factors with their doctor, and encouraging family members or friends to get tested were significant predictors for colonoscopy testing in Hispanics. CONCLUSIONS: Colonoscopy screening in a sample of low-income Hispanic patients differed by age and health experience. Intervention programs that increase colon cancer screening in Hispanics patients should concentrate on those aged < 60. Patient education for knowledge, positive attitude, and behaviors may improve colon cancer screening.

Classic congenital adrenal hyperplasia: A delayed presentation.

Congenital adrenal hyperplasia (CAH) is a rare congenital disorder, which in cases of female genotype may result in virilization. Specific enzyme deficiencies in adrenocorticoid hormones biosynthetic pathway lead to excess androgen production causing virilization. Classic type presents early in infant life as salt losing or simple virilizing type, whereas non classic form presents late at puberty or in adult life. Depending on the type of classic CAH, type of adrenocorticoid deficiency, extent of virilization & genotype, surgical corrective procedures, glucocorticoid & mineralocorticoid replacement therapy are the mainstay of management. We present here a case of classic congenital adrenal hyperplasia of simple virilizing type, which presented later in childhood.

Utility of morphologic assessment of bone marrow biopsy in diagnosis of lysosomal storage disorders.

Introduction: Lysosomal storage disorders (LSDs) are rare disorders and pose a diagnostic challenge for clinicians owing to their generalized symptomatology. In this study, we aim to classify LSDs into two broad categories, namely, Gaucher disease (GD) and Niemann-Pick/Niemann-Pick-like diseases (NP/NP-like diseases) based on the morphology of the storage cells in the bone marrow (BM) aspiration smears and trephine biopsy sections. Materials and Method: This retrospective study includes 32 BM specimens morphologically diagnosed as LSDs at our institute, in the last 10 years. Subsequently, they were subclassified into GD and NP/NP-like diseases. Further, we have compared and analyzed the clinical, hematological, and biochemical parameters for the two groups of LSDs. Results: Based on BM morphology, 59.4% (n = 19) cases were diagnosed as NP/NP-like diseases and 40.6% (n = 13) cases as GD. Abdominal distension and failure to thrive were the most common clinical manifestations in both groups of LSDs. Anemia and thrombocytopenia were frequently seen in either of the LSDs. On the assessment of metabolic profile, elevated total/direct bilirubin and liver enzymes were more commonly seen in NP/NP-like diseases when compared with GD. Conclusion: We have classified LSDs into GD and NP/NP-like diseases based on the morphology of the storage cells in the BM specimen. The hallmark findings on BM biopsy annexed with the comparative features of the two proposed categories can aid the clinician in clinching the diagnosis. Formulation of such a methodology will prove instrumental for patient care in an underresourced setting.

Non-Small Cell Lung Cancer: Targetable Variants in Concurrent Tissue and Liquid Biopsy Testing in a North Indian Cohort.

OBJECTIVES: Testing for EGFR, ALK, ROS1 and MET alterations in paired tissue and plasma samples of treatment-naïve patients of NSCLC and correlating their status with overall survival. MATERIALS AND METHODS: One hundred treatment-naïve patients were recruited after obtaining informed consent. Ten ml of blood was collected within a period of two weeks from histological diagnosis, prior to the start of any treatment. DNA & RNA extraction was done from formalin-fixed paraffin embedded (FFPE) tissue and total cell-free nucleic acid extraction was done from plasma samples. EGFR mutation, ALK, ROS1 and MET rearrangements were tested by ARMS (Amplification Refractory Mutation System) PCR. All statistical analyses were conducted in R version 4.1.1. RESULTS: A total of 61 cases showed molecular alterations in tissue samples which included EGFR mutations (47), ALK rearrangements (12), ROS1 fusion (2). MET alteration was not detected. Forty-three cases showed EGFR mutations in plasma, 26 of which were concurrently positive in tissue. Concordance observed was 62%. ALK-EML4 rearrangement, ROS1 fusion and MET were not detected in plasma samples. Sensitivity and specificity for detection of EGFR mutation in plasma were 55.3% and 67.9% respectively. Univariate Cox regression analysis showed a positive association between EGFR mutation in tissue and overall survival (HR = 0.4; 95% CI: 0.2-0.7; p = 0.003) and improved overall survival in those who received targeted therapy (HR = 0.29; 95% CI: 0.1-0.8; p = 0.02). CONCLUSION: Concurrent testing in tissue and liquid biopsy in NSCLC increased the detection of EGFR mutations (47% to 64%). This has substantial implications in deciding treatment and administration targeted therapy and the consequent overall survival.

Severe obstetric morbidity and its outcome in patients presenting in a tertiary care hospital of Karachi.

OBJECTIVE: To determine the frequency, types (disease states) and outcome of severe obstetric morbidity in patients presenting at a public-sector tertiary care hospital. METHODS: The cross-sectional study was conducted at the Obstetrics and Gynaecology Unit II, Civil Hospital, Karachi, from April to September 2010. Consecutive cases of severe obstetric morbidity (near-miss), as defined by specific criteria, presenting in emergency were included. They were categorised into six groups: haemorrhage, hypertensive disorders in pregnancy, sepsis, ruptured uterus, anaemia, and a miscellaneous group encompassing morbidities not falling in the aforementioned groups. Obstetric near-miss (ONM) cases were described by disease-specific criteria. Primary outcome measures were frequency of near-miss in each disease specific group, type (disease state) of near miss in a group, maternal outcome measures i.e. hospital stay >7 days, hysterectomy, urinary/faecal fistula, morbidity due to management intervention and maternal death. Maternal near-miss ratio and mortality to near-miss ratio were calculated. Secondary outcome measures were ventilator support for >24 hours, and intensive care admission for >48 hours. RESULTS: There were 1508 deliveries during the study period from which 130 patients met the inclusion criteria. Among the 130 enrolled patients, obstetric near-miss (survivors) were 111. Among the total of 1442 livebirths, the maternal near-miss ratio was calculated to be 76.97/1000 livebirths. Nineteen maternal deaths resulted in the near-miss to mortality ratio of 5.8:1. Haemorrhage (34.2%) was the most frequent group, followed by hypertensive disorders (29.1%) and ruptured uterus (11.53%). Case fatality rates of sepsis (35%) and miscellaneous (30%) groups were the highest. Hysterectomy rates were 3.60% and hospital stay > 7 days stood at 31.33%. The intensive care admission rate was 42.34%. CONCLUSION: Haemorrhage, hypertensive disorders and ruptured uterus were the leading causes of obstetric near-miss, whereas sepsis, acute fatty liver of pregnancy and peripartum cardiomyopathy resulted in the highest case fatalities.

Frequency Of CD34 Expression In Acute Lymphoblastic Leukaemia And Its Correlation With Clinicopathological Characteristics: A Single Centre Experience From Pakistan.

Background: This study was carried out to determine the frequency of CD34 positivity in acute lymphoblastic leukaemia (B-ALL) in our population and to report its association with the clinicopathological profile at the time of diagnosis. Methods: The cross-sectional study was conducted at National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan, from March 2020 till December 2020.Newly diagnosed patients were selected, from both genders and all age groups. Relevant history and findings of physical examination were recorded. Immunohistochemistry was done on trephine biopsy and molecular studies were carried on bone marrow aspirates or peripheral blood samples. Results: Out of 105 patients enrolled, 67 (63.8%) were males, with a male to female ratio (M: F) 1.8:1. Of the total patients, 62 (59.04%) were above 15 years of age. CD34 was expressed in 73 (69.5%) cases. Lymphadenopathy, splenomegaly, and hepatomegaly were separately noted in context to CD 34 expression in 22 (66.6%), 24 (64.8%), and 14 (58.3%) patients, respectively. CNS disease was seen in a total of 3(2.75%) subjects, in which 2 (66.6%) of the patients had CD34 expression. Total 81 patients in our study fall into the high-risk group out of which CD 34 expression was seen in 58(71.6%) subjects. Cytogenetic analysis, BCR-ABL p190, and MLL gene rearrangement were investigated in all participants. Cytogenetic analysis revealed an abnormality in 20 (19%) cases out of which 13 (17.8%) cases were from CD34 positive group. Conclusion: Our study reported CD34 expression in more than two-thirds of cases. High-risk disease was significantly associated with CD34 expression.

Perinatal outcome and near-miss morbidity between placenta previa versus abruptio placentae.

OBJECTIVE: To compare perinatal outcome and near-miss morbidities between placenta previa versus abruptio placentae in patients of antepartum haemorrhage (APH). STUDY DESIGN: Cross-sectional, analytical study. PLACE AND DURATION OF STUDY: Gynaecology Unit II, Civil Hospital, Karachi, from August 2007 to July 2009. METHODOLOGY: Patients with APH diagnosed as placenta previa and abruptio placentae who delivered after 24 weeks of pregnancy were selected from labour room. Outcome measures were birth weight, neonatal intensive care admission, stillbirth, perinatal mortality rates, near-miss, surgical intensive care admission, postpartum haemorrhage, hysterectomy, massive transfusion, renal failure, coagulopathy and maternal death. Stillbirth was defined as a fetus weighing≥500 gm showing no sign of life after birth. Near-miss was defined as severe organ dysfunction which if not treated appropriately, could result in death. Descriptive statistics were calculated and chi-square was applied with significance level<0.05. RESULTS: Stillbirths and perinatal mortality rates were significantly higher in abruptio placentae, 52.97% versus 18.18% and 534/1000 versus 230/1000 (p<0.01). Near-miss cases were also significantly higher in abruptio placentae, 22.27% verus 11.18% (p<0.01). Hypovolemic shock and coagulation failure were also significantly higher in abruptio placentae (p<0.05). CONCLUSION: Abruptio placentae carry significantly higher perinatal mortality and near-miss morbidity than placenta previa.