Clinical Application of Poly(ADP-Ribose) Polymerase (PARP) Inhibitors in Ovarian Cancer.

The treatment of ovarian cancer has remained a clinical challenge despite high rates of initial response to platinum-based chemotherapy. Patients are generally diagnosed at an advanced stage with significant disease burden, which portends to worse survival outcomes. Deficiencies in the homologous recombination (HRD) DNA damage repair (DDR) pathway and mutations in the BRCA1/2 genes have been found in ovarian carcinomas. Moreover, patients with these specific molecular aberrations have demonstrated sensitivity and thus improved response to poly(ADP-ribose) polymerase inhibitor (PARPi) treatment. The results of various clinical trials exploring the use of PARPi in different populations of ovarian cancer patients have shown impressive survival and response outcomes. With expanding indications, the use of PARPi has thus changed the landscape of ovarian cancer treatment. In this chapter, we will describe the different settings of PARPi treatment-frontline maintenance therapy, maintenance therapy for patients with recurrent platinum-sensitive disease, and treatment in the recurrent setting-and discuss treatment considerations and management of toxicities, as well as offer thoughts on future directions.

Targeting the PI3K Pathway in Gynecologic Malignancies.

PURPOSE OF REVIEW: This review explores the PI3K pathway aberrations common in gynecologic malignancies, the relevant therapeutic targets that have been explored to date particularly given their success in endometrial cancers, and predictive biomarkers of response to therapy. RECENT FINDINGS: Landmark trials have been noted involving this pathway, particularly in endometrial cancers. One phase II trial of the potent orally bioavailable mTOR inhibitor, everolimus, in combination with letrozole demonstrated an unprecedented clinical benefit rate (CBR) of 40% and high objective response rate (RR) of 32% in hormone agnostic endometrial cancers. This was followed by GOG 3007 that compared everolimus and letrozole to hormonal therapy yielding similar response rates but double progression-free survival rates. The phosphoinositide 3-kinase (PI3K) signaling pathway is implicated in tumorigenesis given its regulation over cell growth, cellular trafficking, and angiogenesis. In gynecologic malignancies, alterations in PI3K signaling are common. Therefore, developing modulators of the PI3K pathway and identifying molecular markers to predict response are of great interest for these cancer types.

COVID-19 complicating perioperative management of LVAD implantation: A case report and systematic review.

The coronavirus 2019 disease (COVID-19) affected 125 million people worldwide and caused 2.7 million deaths. Some comorbidities are associated with worse prognosis and left ventricular assist device (LVAD) recipients are probably part of this high-risk population. We report a 31-year-old male patient who developed COVID-19 during LVAD implantation. His postoperative period was complicated by severe pneumonia and mechanical ventilation (MV) leading to right ventricular failure (RVF) and inotrope necessity. He experienced multiple complications, but eventually recovered. We present a systematic review of LVAD recipients and COVID-19. Among 14 patients, the mean age was 62.7 years, 78.5% were male. A total of 5 patients (35.7%) required MV and 3 patients (21.4%) died. A total of 2 patients (14.2%) had thromboembolic events. This case and systematic review suggest LVAD recipients are at particular risk of unfavorable outcomes and they may be more susceptible to RVF in the setting of COVID-19, particularly during perioperative period.

Epipericardial fat necrosis as cause of chest pain in patient after heart transplantation.

Epipericardial fat necrosis is an uncommon clinical condition of unknown etiology. It typically presents as acute pleuritic chest pain and should be differentiated from acute pulmonary embolism and acute coronary syndrome. This condition is diagnosed by characteristic chest computed tomography findings of an ovoid mediastinal fatty lesion with intrinsic and surrounding soft-tissue stranding. Treatment of epipericardial fat necrosis includes the administration of anti-inflammatory agents, and symptoms usually resolve within a few days after treatment initiation. This disease entity has rarely been reported since it was first described in 1957. Most current knowledge of epipericardial fat necrosis is based on case reports that describe this condition in previously healthy individuals. We present the case of a 39-year-old woman with a history of heart transplant, who presented with chest pain secondary to epipericardial fat necrosis. Serial computed tomography revealed lesion resolution after appropriate treatment.

Comparison of two Lynch screening strategies in endometrial cancer in a California health system.

OBJECTIVE: Compare detection of Lynch syndrome in endometrial cancer between regions of a health care system with different screening strategies. METHODS: A retrospective study of endometrial cancer (EC) cases from 2 regions of an integrated health care system (Kaiser Permanente Northern (KPNC) and Southern (KPSC) California). Within KPNC, immunohistochemistry tumor screening (IHC) was physician ordered and risk-based; within KPSC, IHC was universal and automated. Clinical risk factors associated with abnormal IHC and Lynch Syndrome (LS) were identified. RESULTS: During the study, there were 2045 endometrial cancers: 1399 in the physician-order group and 646 in the universal testing group. In the physician-order group: among women < age 60, 34% underwent IHC; 9.6% were abnormal, and 3% were possible LS after methylation testing; among women ≥60, 11% underwent IHC, 3% were abnormal and <1% were possible LS. In the universal group, 87% of women age <60 had IHC, 19.4% were abnormal, and 6% were possible LS; Among women age ≥60, 82% underwent IHC, 26% were abnormal, and 2% were possible LS. There were no differences in LS cases between the physician-order group and the universal group in either age strata (<60: 3% vs. 3.6%, p=0.62; ≥60: <1% vs. 1%, p=0.63) Factors associated with LS were younger age (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.04-0.29) and lower body mass index (BMI), (OR 0.38 95% CI 0.18-0.80). CONCLUSIONS: Universal IHC screening did not result in increased LS detection in EC.

Lactic acidosis associated with metformin in patients with moderate to severe chronic kidney disease: study protocol for a multicenter population-based case-control study using health databases.

BACKGROUND: The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis. However, the information available in patients with moderate-severe chronic kidney disease is scarce. METHODS: The ALIMAR-C2 study is a case-control study to assess the association between metformin and lactic acidosis in patients with type 2 diabetes mellitus and moderate-severe chronic kidney disease. The study will be performed with computerized registered electronic health records from eight Spanish hospitals linked to their corresponding primary care health areas from 2010 to 2016, comprising approximately 22.1 million person-years of follow-up. Logistic regression will be used to assess the crude and adjusted risk of lactic acidosis associated with metformin use overall and stratifying by use and dose categories, and chronic kidney disease stage. The overall case fatality rate of lactic acidosis, as well as the case fatality rate stratified by chronic kidney disease stage, will be calculated. DISCUSSION: The ALIMAR-C2 study will provide useful information about the risk of lactic acidosis in type 2 diabetes mellitus patients with renal impairment using metformin.

Next-generation sequencing for the general cancer patient.

Next-generation sequencing is a novel method of DNA sequencing that has become a cornerstone of precision oncology. This sequencing method detects differences in specific DNA sequences between a sample and a reference genome or matched normal DNA. In addition to single-nucleotide variants, other insertions, deletions, copy number changes, and fusions may be drivers of cancer growth, and thus represent therapeutic opportunities. As a result, genomic characterization has been increasingly used to guide treatment decisions, especially in patients with advanced disease. This review discusses the basic technologies involved in next-generation sequencing, the applications of this method, and limitations in the clinical realm.

Head-to-head comparison between the EQ-5D-5L and the EQ-5D-3L in general population health surveys.

BACKGROUND: The EQ-5D has been frequently used in national health surveys. This study is a head-to-head comparison to assess how expanding the number of levels from three (EQ-5D-3L) to five in the new EQ-5D-5L version has improved its distribution, discriminatory power, and validity in the general population. METHODS: A representative sample (N = 7554) from the Catalan Health Interview Survey 2011-2012, aged ≥18, answered both EQ-5D versions, and we evaluated the response redistribution and inconsistencies between them. To assess validity of this redistribution, we calculated the mean of the Visual Analogue Scale (VAS), which measures perceived health. The discriminatory power was examined with Shannon Indices, calculated for each dimension separately. Spanish preference value sets were applied to obtain utility indices, examining their distribution with statistics of central tendency and dispersion. We estimated the proportion of individuals reporting the best health state in EQ-5D-5L and EQ-5D-3L within groups of specific chronic conditions and their VAS mean. RESULTS: A very small reduction in the percentage of individuals with the best health state was observed, from 61.8% in EQ-5D-3L to 60.8% in EQ-5D-5L. In contrast, a large proportion of individuals reporting extreme problems in the 3 L version moved to severe problems (level 4) in the 5 L version, particularly for pain/discomfort (75.5%) and anxiety/depression (66.4%). The average proportion of inconsistencies was 0.9%. The pattern of the perceived health VAS mean confirmed the hypothesis established a priori, supporting the validity of the observed redistribution. Shannon index showed that absolute informativity was higher in the 5 L version for all dimensions. The means (SD) of the Spanish EQ-5D-3L and EQ-5D-5L indices were 0.87 (0.25) and 0.89 (0.22). The proportion of individuals with the best health state within each specific chronic condition was very similar, regardless of the EQ-5D version (≤ 30% in half of the 28 chronic conditions). CONCLUSION: Although the proportion of individuals with the best possible health state is still very high, our findings support that the increase of levels provided by the EQ-5D-5L contributed to the validity and discriminatory power of this new version to measure health in general population, as in the national health surveys.

Constant-Murley Score: systematic review and standardized evaluation in different shoulder pathologies.

PURPOSE: The objective of this study was to evaluate the psychometric properties of the Constant-Murley Score (CMS) in various shoulder pathologies, based on a systematic review and expert standardized evaluations. METHODS: A systematic review was performed in MEDLINE and EMBASE databases. Titles and abstracts were reviewed and finally the included articles were grouped according to patients' pathologies. Two expert evaluators independently assessed the CMS properties of reliability, validity, responsiveness to change, interpretability and burden score in each group, using the EMPRO (Evaluating Measures of Patient Reported Outcomes) tool. The CMS properties were assessed per attribute and overall for each considered group. Only the concept and measurement model was assessed globally. RESULTS: Five individual pathologies (i.e. subacromial, fractures, arthritis, instability and frozen shoulder) and two additional groups (i.e. various pathologies and healthy subjects) were considered. Overall EMPRO scores ranged from 58.6 for subacromial to 30.6 points for instability. Responsiveness to change was the only quality to obtain at least 50 points across all groups, but for frozen shoulder. Insufficient information was obtained in relation to the concept and measurement model and great variability was seen in the other evaluated attributes. CONCLUSIONS: The current evidence does not support the CMS as a gold standard in shoulder evaluation. Its use is advisable for subacromial pathology; but data are inconclusive for other shoulder conditions. Prospective studies exploring the psychometric properties of the scale, particularly for fractures, arthritis, instability and frozen shoulder are needed. LEVEL OF EVIDENCE: Systematic review.

Preoperative Vaginal Metronidazole Decreases the Risk of Pelvic Infections After Radical Robotic Hysterectomy.

OBJECTIVES: Risk factors and infection rates of radical robotic procedures have yet to be described in gynecology. A practice improvement strategy using a solitary dose of vaginal metronidazole the night before surgery was initiated to determine if it decreased the risk of pelvic infection. METHODS: A retrospective chart review of robotic radical hysterectomies for gynecologic malignancy at our institution from April 2010 through April 2016 was performed. Demographic data, operative data, and data on use of metronidazole before surgery were collected. χ Statistical analysis, Student t test, and multivariate analysis were performed to analyze the data. RESULTS: Ninety-four patients met the inclusion criteria, and 46 patients received vaginal metronidazole. Demographic and clinical factors were similar between the 2 groups. The pelvic infection rate was significantly higher in nonusers at 13% (6/46) compared with users at 0% (0/42) (P ≤ 0.05). The genitourinary infection rate was also significantly higher in nonusers at 20% as compared with users at 2.2% (P = 0.02). Operative risk factors found to be associated with pelvic infection included hospital length of stay, blood loss, and metronidazole use. Multivariate regression analysis determined that only vaginal metronidazole had a clinically significant reduction of pelvic and genitourinary infection. DISCUSSION: A single dose of preoperative vaginal metronidazole reduces the risk of pelvic and genitourinary infection after robotic radical hysterectomy.

Economic evaluation of treatments for patients with localized prostate cancer in Europe: a systematic review.

BACKGROUND: Our objective was to assess the efficiency of treatments in patients with localized prostate cancer, by synthesizing available evidence from European economic evaluations through systematic review. METHODS: Articles published 2000-2015 were searched in MEDLINE, EMBASE and NHS EED (Prospero protocol CRD42015022063). Two authors independently selected studies for inclusion and extracted the data. A third reviewer resolved discrepancies. We included European economic evaluations or cost comparison studies, of any modality of surgery or radiotherapy treatments, regardless the comparator/s. Drummond's Checklist was used for quality assessment. RESULTS: After reviewing 8,789 titles, 13 European eligible studies were included: eight cost-utility, two cost-effectiveness, one cost-minimization, and two cost-comparison analyses. Of them, five compared interventions with expectant management, four contrasted robotic with non robotic-assisted surgery, three assessed new modalities of radiotherapy, and three compared radical prostatectomy with brachytherapy. All but two studies scored ≥8 in the quality checklist. Considering scenario and comparator, three interventions were qualified as dominant strategies (active surveillance, robotic-assisted surgery and IMRT), and six were cost-effective (radical prostatectomy, robotic-assisted surgery, IMRT, proton therapy, brachytherapy, and 3DCRT). However, QALY gains in most of them were small. For interventions considered as dominant strategies, QALY gain was 0.013 for active surveillance over radical prostatectomy; and 0.007 for robotic-assisted over non-robotic techniques. The highest QALY gains were 0.57-0.86 for radical prostatectomy vs watchful waiting, and 0.72 for brachytherapy vs conventional radiotherapy. CONCLUSIONS: Currently, relevant treatment alternatives for localized prostate cancer are scarcely evaluated in Europe. Very limited available evidence supports the cost-effectiveness of radical prostatectomy over watchful waiting, brachytherapy over radical prostatectomy, and new treatment modalities over traditional procedures. Relevant disparities were detected among studies, mainly based on effectiveness. These apparently contradictory results may be reflecting the difficulty of interpreting small differences between treatments regarding QALY gains.

Long-acting beta-agonists plus inhaled corticosteroids safety: a systematic review and meta-analysis of non-randomized studies.

BACKGROUND: Although several systematic reviews investigated the safety of long-acting beta-agonists (LABAs) in asthma, they mainly addressed randomized clinical trials while evidence from non-randomized studies has been mostly neglected. We aim to assess the risk of serious adverse events in adults and children with asthma treated with LABAs and Inhaled Corticosteroids (ICs), compared to patients treated only with ICs, from published non-randomized studies. METHODS: The protocol registration number was CRD42012003387 (http://www.crd.york.ac.uk/Prospero). Literature search for articles published since 1990 was performed in MEDLINE and EMBASE. Two authors selected studies independently for inclusion and extracted the data. A third reviewer resolved discrepancies. To assess the risk of serious adverse events, meta-analyses were performed calculating odds ratio summary estimators using random effect models when heterogeneity was found, and fixed effect models otherwise. RESULTS: Of 4,415 candidate articles, 1,759 abstracts were reviewed and 220 articles were fully read. Finally, 19 studies met the inclusion criteria. Most of them were retrospective observational cohorts. Sample sizes varied from 50 to 514,216. The meta-analyses performed (69,939-624,303 participants according to the outcome considered) showed that odds ratio of the LABAs and ICs combined treatment when compared with ICs alone was: 0.88 (95% CI 0.69-1.12) for asthma-related hospitalization; 0.75 (95% CI 0.66-0.84) for asthma-related emergency visits; 1.02 (95% CI 0.94-1.10) for systemic corticosteroids; and 0.95 (95% CI 0.9-1.0) for the combined outcome. CONCLUSIONS: Evidence from observational studies shows that the combined treatment of LABAs and ICs is not associated with a higher risk of serious adverse events, compared to ICs alone. Major gaps identified were prospective design, paediatric population and inclusion of mortality as a primary outcome.

Adaptation and validation of the Spanish version of the Patient-Oriented Prostate Utility Scale (PORPUS).

OBJECTIVE: The Patient-Oriented Prostate Utility Scale (PORPUS) is a combined profile and utility-based quality of life measure for prostate cancer patients. Our objectives were to adapt the PORPUS into Spanish and to assess its acceptability, reliability, and validity. METHODS: The PORPUS was adapted into Spanish using forward and back translations and cognitive debriefing. PORPUS was administered jointly with the SF-36 and the Expanded Prostate Index Composite (EPIC) to 480 Spanish prostate cancer patients treated with radical prostatectomy or radiotherapy. The Spanish PORPUS scores' distribution and reliability were examined and compared with the original instrument. To evaluate construct validity, relationships were assessed between PORPUS and other instruments (testing hypotheses of the original PORPUS study), and among known groups defined by side effect severity. RESULTS: Reliability coefficient was 0.76 (similar to the original PORPUS' 0.81). Spanish PORPUS items presented correlations ranging 0.57-0.88 with the corresponding EPIC domains, as in the original PORPUS study (0.60-0.83). Both PORPUS-P and PORPUS-U showed significant differences and large effect sizes (0.94-1.90) when comparing severe versus no problem groups on urinary, bowel, sexual and hormonal side effects defined by EPIC. CONCLUSIONS: A conceptually equivalent Spanish version was obtained, with high reliability and good construct validity, similar to the original Canadian PORPUS version. It can therefore be used to measure health-related quality of life and utilities in Spanish prostate cancer patients.

Robotic radical stump trachelectomy: Critical steps of a radical procedure without normal anatomical landmarks.

Background: Cervical stump malignancies are an uncommon finding post subtotal hysterectomy. Tumors arise from a primary cervical origin with an incidence of 1-5%. Other described malignancies can include uterine origin, ovarian origin or as metastases from another primary site. A uterine primary is an extremely rare entity and can result from remnant endometrial tissue at the stump apex. Case: 70yo female with a history of remote supracervical hysterectomy for benign indication who presented with postmenopausal spotting. Endocervical curettage of the endocervical stump revealed a grade 2 endometrioid endometrial adenocarcinoma. She was taken to the operating for a robotic radical stump trachelectomy and sentinel lymph node dissection. Conclusions: The surgical video delineates key surgical steps of robotic radical stump trachelectomy including robotic port placement and injection of ICG dye, adhesiolysis and restoration of normal anatomy, opening of the pelvic spaces and exposure of the retroperitoneum, identification and excision of pelvic sentinel lymph nodes, bladder dissection, ureterolysis and ligation of uterine remnant, ureteric tunnel dissection and mobilization of parametrial wing, delineation of a vaginal margin, colpotomy and specimen removal, and vaginal cuff closure.

In Search of Nodular Gastric Antral Vascular Ectasia: A Distinct Entity or Simply Hyperplastic Polyps Arising in Gastric Antral Vascular Ectasia?

CONTEXT.­: Nodular gastric antral vascular ectasia (GAVE) is a reported phenotype of GAVE that has histologic features overlapping with gastric hyperplastic polyps (GHPs), with additional features often seen in flat mucosa of GAVE. OBJECTIVE.­: To determine if nodular GAVE and GHPs are distinct lesions by evaluating the prevalence of features reported in nodular GAVE in GHPs with or without associated GAVE. DESIGN.­: A review of all lesions diagnosed as GHPs between 2014 and 2017 was performed. Slides were analyzed for a number of features including established histologic features of GAVE without knowledge of clinical or endoscopic features. RESULTS.­: A total of 90 polyps were analyzed including 18 from patients with GAVE (20%). GAVE polyps were larger than non-GAVE polyps (average size, 1.3 cm versus 0.68 cm; P < .001), with more common extensive ulceration and associated granulation tissue (61.11% [n = 11] versus 4.17% [n = 3]; P = .004), fibrin thrombi (50% [n = 9] versus 15% [n = 11]; P = .003), moderate to marked vascular ectasia (83% [n = 15] versus 35% [n = 11]; P = .001), and fibrohyalinosis (72% [n = 13] versus 28% [n = 20]; P = .001). All polyps showed foveolar hyperplasia and smooth muscle proliferation. There were no features that were exclusively found in GAVE or non-GAVE cases. CONCLUSIONS.­: Nodular GAVE appears to represent GHPs arising in a background of GAVE, with superimposed features found in flat mucosa of GAVE stomachs. The presence of fibrin thrombi, marked vascular ectasia, fibrohyalinosis, and/or ulceration in a GHP is suggestive but not diagnostic of GAVE, and the absence of these features does not rule out GAVE.

Necropsy findings in heart transplant recipients with or without primary graft dysfunction.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of death in the first year after heart transplant (HT), but pathophysiology and histology are not completely understood. This study describes and compares morphological findings of hearts of patients with and without PGD. METHODS: We included adult patients submitted to HT in a single center who died within the first 14 days after HT and were submitted to necropsy. Clinical and histological data were recorded retrospectively. All heart slides were reviewed by a blinded pathologist. We categorized patients in two groups (PGD and non-PGD) and compared findings between them. RESULTS: Among 322 HTs, 26 patients were included. Median age was 51.5 years, 57.7% were male, 46.1% had non-ischemic cardiomyopathy, 30.8% Chagas cardiomyopathy and 23% ischemic cardiomyopathy. Eleven patients presented PGD, while 15 patients did not. PGD was severe in 72.7% of cases and moderate in 27.3%. PGD group had longer ischemic time (p=0.08), higher incidence of mechanical circulatory support (p=0.004), lower post-transplant biventricular ejection fraction (p=0.005). However, necropsy findings were similar between groups. Necrosis was detected in 80.7% of all cases (p=0.907 comparing groups), taking ≥ 10% of myocardial area in 46.1% of them, and 4 types of necrosis were found either in patients with and without PGD. CONCLUSION: Cardiac pathological findings were similar in HT patients with or without PGD who died within 14 days after the transplant and necrosis was frequent in both groups, raising the hypothesis necrosis is not the cause of cardiac dysfunction in PGD.

Don't SUMP it! Utility of PLAG1 immunocytochemistry in basaloid SUMP subcategory.

BACKGROUND: Basaloid salivary gland neoplasm of uncertain malignant potential (B-SUMP) is an indeterminate diagnostic subcategory, with pleomorphic adenoma (PA) representing the most common benign neoplasm. Pleomorphic adenoma gene 1 (PLAG1) staining is frequently seen in PAs and could aid in distinguishing them from other basaloid neoplasms. The authors evaluated the utility of PLAG1 immunocytochemistry (ICC) in differentiating PAs from other basaloid neoplasms in smears and liquid-based cytology (LBC) specimens. METHODS: In total, 45 B-SUMP cytology aspirates and corresponding surgical excision specimens were identified. PLAG1 immunostaining was performed in all aspirates and surgical excision specimens and was scored as positive (strong/diffuse), equivocal (focal/weak), or negative. RESULTS: PLAG1 ICC was performed directly on 38 smears and seven LBC specimens. PLAG1 was positive in 29 of 45 cases (64%), whereas six of 45 (13%) were equivocal, and 10 of 45 (22%) were negative. PLAG1-positive aspirates included 26 (90%) PAs, two (7%) basal cell adenomas (BCAs), and one (3%) carcinoma ex-PA. PLAG1-equivocal aspirates included four (67%) PAs and two (33%) BCAs, whereas negative aspirates included five (50%) BCAs, four (40%) adenoid cystic carcinomas, and one (10%) metastatic adenosquamous carcinoma. The sensitivity, specificity, positive, and negative predictive values were 87%, 86%, 93%, and 75%, respectively. Diagnostic accuracy was 87%. CONCLUSIONS: PLAG1 ICC is useful when positive (strong/diffuse) and can be reliably performed on smears and LBC specimens. PLAG1 was positive in most PAs and in a small subset of BCAs. Therefore, in the absence of atypical cytologic features, PLAG1-positive tumors could be diagnosed as benign, with a note favoring PA versus BCA. In contrast, PLAG1-negative/equivocal tumors should remain in the B-SUMP category.

Utility of the Milan System for Reporting Salivary Gland Cytopathology in fine needle aspiration cytology of minor salivary gland lesions.

INTRODUCTION: Salivary gland lesions are routinely evaluated by fine-needle aspiration cytology (FNAC) preoperatively. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has standardized salivary gland FNAC reporting. Its application in major salivary glands (MSGs) has been well-established; however, its utility in minor salivary glands (MiSGs) is not well-known. We studied the utility of MSRSGC in MiSG FNAC. MATERIALS AND METHODS: A retrospective search of MiSG FNACs from 2 academic institutions (2006-2023) was performed. FNACs were classified using the MSRSGC. Histologic data were reviewed and recorded. The risk of malignancy (ROM), risk of neoplasia (RON), diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: The series included 43 MiSG FNAC (24 males and 18 females), with a mean age of 55 years (range 10-92). Aspirated sites included the following: palate, buccal space, floor of mouth, lip, tongue, and maxillary sinus. FNACs were classified as nondiagnostic (1), nonneoplastic (3), atypia of undetermined significance (6), benign neoplasm (9), salivary gland neoplasm of uncertain malignant potential (15), suspicious for malignancy, (2) and malignant (7). The risk of neoplasia and risk of malignancy were 87% and 39%. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 100%, respectively. CONCLUSIONS: Milan System for Reporting Salivary Gland Cytopathology offers valuable information for stratifying MiSG lesions. However, the distribution and the range of diagnostic entities encountered differ somewhat from those in MSGs. For instance, mucinous cyst contents may warrant unique consideration in MiSG; while an atypical classification is recommended in MSGs, the high prevalence of mucoceles in MiSG may tilt this group toward benignity.

Atypia of undetermined significance and ThyroSeq v3-positive call rates as quality control metrics for cytology laboratory performance.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends an upper limit of 10% for atypia of undetermined significance (AUS). Recent data suggest that this category might be overused when the rate of cases with molecular positive results is low. As a quality metric, the AUS and positive call rates for this facility's cytology laboratory and each cytopathologist (CP) were calculated. METHODS: A retrospective analysis of all thyroid cytology cases in a 4.5-year period was performed. Cases were stratified by TBSRTC, and molecular testing results were collected for indeterminate categories. The AUS rate was calculated for each CP and the laboratory. The molecular positive call rate (PCR) was calculated with and without the addition of currently negative to the positive results obtained from the ThyroSeq report. RESULTS: A total of 7535 cases were classified as nondiagnostic, 7.6%; benign, 69%; AUS, 17.5%; follicular neoplasm/suspicious for follicular neoplasm, 1.4%; suspicious for malignancy, 0.7%; and malignant, 3.8%. The AUS rate for each CP ranged from 9.9% to 36.8%. The overall PCR was 24% (range, 13%-35.6% per CP). When including cases with currently negative results, the PCR increased to 35.5% for the cytology laboratory (range, 13%-42.6% per CP). Comparison analysis indicates a combination of overcalling benign cases and, less frequently, undercalling of higher TBSRTC category cases. CONCLUSIONS: The AUS rate in the context of PCR is a useful metric to assess cytology laboratory and cytopathologists' performance. Continuous feedback on this metric could help improve the overall quality of reporting thyroid cytology.

Point of care creatinine measurement for diagnosis of renal disease using a disposable microchip.

A point-of-care device for the determination of elevated creatinine levels in blood is reported. This device potentially offers a new and simple clinical regime for the determination of creatinine that will give huge time savings and removal of several steps of determination. The test employs a disposable prefilled microchip and the handheld Medimate Multireader®. By optimizing the analytical conditions it was found that the LOD of the proposed method was 87 µM creatinine, close to the normal human serum levels that are in the range of 60 to 100 µM. A statistical analysis of the residual shows a normal distribution, indicating the absence of systematic errors in the proposed method. The test can be used to distinguish patients with renal insufficiency (creatinine levels >100 µM) from healthy persons. Long-term monitoring could furthermore distinguish between acute renal failure and chronic kidney disease by the rate of creatinine concentration rise.