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Diagnostic Cytopathology Jun 2022In this era of personalized medicine, targeted immunotherapies like immune checkpoint inhibitors (ICI) blocking the programmed death-1 (PD-1)/program death ligand-1... (Review)
Review
In this era of personalized medicine, targeted immunotherapies like immune checkpoint inhibitors (ICI) blocking the programmed death-1 (PD-1)/program death ligand-1 (PD-L1) axis have become an integral part of treating advanced stage non-small cell lung carcinoma (NSCLC) and many other cancer types. Multiple monoclonal antibodies are available commercially to detect PD-L1 expression in tumor cells by immunohistochemistry (IHC). As most clinical trials initially required tumor biopsy for PD-L1 detection by IHC, many of the currently available PD-1/PD-L1 assays have been developed and validated on formalin fixed tissue specimens. The majority (>50%) of lung cancer cases do not have a surgical biopsy or resection specimen available for ancillary testing and instead must rely primarily on fine needle aspiration biopsy specimens for diagnosis, staging and ancillary tests. Review of the literature shows multiple studies exploring the feasibility of PD-L1 IHC on cytological samples. In addition, there are studies addressing various aspects of IHC validation on cytology preparations including pre-analytical (e.g., different fixatives), analytical (e.g., antibody clone, staining platforms, inter and intra-observer agreement, cytology-histology concordance) and post-analytical (e.g., clinical outcome) issues. Although promising results in this field have emerged utilizing cytology samples, many important questions still need to be addressed. This review summarizes the literature of PD-L1 IHC in lung cytology specimens and provides practical tips for optimizing analysis.
Topics: B7-H1 Antigen; Biomarkers, Tumor; Biopsy, Fine-Needle; Humans; Immunohistochemistry; Lung Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 35293692
DOI: 10.1002/dc.24955 -
European Journal of Neurology Jun 2022Neurosarcoidosis can affect all parts of the nervous system of which myelitis is relatively frequent. The aim of this study was to describe clinical characteristics,... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Neurosarcoidosis can affect all parts of the nervous system of which myelitis is relatively frequent. The aim of this study was to describe clinical characteristics, treatment and prognosis of patients with myelitis attributable to neurosarcoidosis.
METHODS
We performed a retrospective cohort study and a systematic review and meta-analysis of neurosarcoidosis-associated myelitis.
RESULTS
Myelitis was identified in 41 of 153 (27%) neurosarcoidosis patients seen at our clinic from 2015 to 2020. Classification of neurosarcoidosis was definite in three (7%), probable in 29 (71%) and possible in nine patients (22%). The median (interquartile range) age at onset was 49 (41-53) years and 20 of the patients were female (49%). The presenting symptoms included muscle weakness in 31 of 41 patients (78%), sensory loss in 35 (88%) and micturition abnormalities in 30 (75%). Spinal magnetic resonance imaging showed longitudinally extensive myelitis in 27 of 36 patients (75%) and cerebrospinal fluid examination showed an elevated leukocyte count in 21 patients (81%). Initial treatment consisted of glucocorticoids in 38 of 41 patients (93%), with additional methotrexate or azathioprine in 21 of 41 patients (51%) and infliximab in 10 of 41 patients (24%). Treatment led to remission, improvement or stabilization of disease in 37 of 39 patients (95%). Despite treatment, 18 of 30 patients (60%) could not walk independently at the end of follow-up (median 36 months). A review of the literature published between 2000 and 2020 identified 215 patients with comparable clinical characteristics and results of ancillary investigations.
CONCLUSION
Sarcoidosis-associated myelitis is observed in 27% of neurosarcoidosis patients. Although treatment often led to a decrease in disease activity, residual neurological deficits leading to loss of ambulation occurred frequently.
Topics: Central Nervous System Diseases; Female; Humans; Magnetic Resonance Imaging; Male; Myelitis; Retrospective Studies; Sarcoidosis
PubMed: 35189010
DOI: 10.1111/ene.15295 -
BMJ Open Ophthalmology 2022To demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.
Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review.
OBJECTIVE
To demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.
METHODS AND ANALYSIS
Retrospective chart review on patients with advanced cutaneous melanoma who developed AIR after initiating immunotherapy. Complete ophthalmic examination and relevant ancillary testing were performed on each patient. The presence of AIR-associated anti-retinal antibodies was confirmed by western blot and/or immunohistochemical staining. Ophthalmic and systemic outcomes after treatment for AIR were followed over time. A systematic review of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Case 1 developed photopsia and nyctalopia with electroretinographic findings characteristic for melanoma-associated retinopathy 1 week after initiating ipilimumab/nivolumab immunotherapy. Case 2 experienced new severe bilateral visual field loss associated with anti-retinal and anti-optic nerve antibodies while on maintenance nivolumab immunotherapy. Case 3 developed decreased visual acuity due to acute exudative polymorphous vitelliform maculopathy within 2 weeks of initiating ipilimumab/nivolumab immunotherapy. All patients had concurrent extraocular immune-related adverse events in addition to the presence of anti-retinal antibodies on serological testing. 14 published cases of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma were identified and reviewed.
CONCLUSIONS
Immune checkpoint inhibition can trigger the development of AIR with varied clinical manifestations in patients with advanced cutaneous melanoma. This study highlights the need for close monitoring in cutaneous melanoma patients receiving immunotherapy who develop new visual symptoms with or without funduscopic changes, as well as the potential role for screening of patients prior to initiating immunotherapy.
Topics: Antibodies, Monoclonal, Humanized; Autoimmune Diseases; Humans; Immunologic Factors; Immunotherapy; Ipilimumab; Melanoma; Nivolumab; Retinal Diseases; Retrospective Studies; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35047671
DOI: 10.1136/bmjophth-2021-000889 -
Langenbeck's Archives of Surgery Mar 2022Giant parathyroid adenoma (GPA) can present with severe biochemical derangement similar to the clinical presentation of parathyroid carcinoma (PC). This study aims to...
PURPOSE
Giant parathyroid adenoma (GPA) can present with severe biochemical derangement similar to the clinical presentation of parathyroid carcinoma (PC). This study aims to present the current evidence on surgical management of GPAs in primary hyperparathyroidism.
METHODS
A systematic review of the literature on GPAs was conducted following the PRISMA guidelines. Data on clinical, biochemical, preoperative diagnostic, and surgical methods were analysed.
RESULTS
Sixty-one eligible studies were included reporting on 65 GPAs in eutopic, ectopic mediastinal, and intrathyroidal locations (61.5%, 30.8%, and 7.7%, respectively). A palpable neck mass was present in 58% of GPAs. A total of 90% of patients had symptoms including fatigue, skeletal pain, pathological fracture, nausea, and abdominal pain. Ninety percent of patients had significant hypercalcaemia (mean 3.51 mmol/L; range: 2.59-5.74 mmol/L) and hyperparathyroidism with PTH levels on average 14 times above the upper limit of the normal reference. There was no correlation between the reported GPA size and PTH nor between GPA weight and PTH (p = 0.892 and p = 0.363, respectively). Twenty-four percent had a concurrent thyroidectomy for suspicious features, intrathyroidal location of GPA, or large goitre. Immunohistochemistry such as Ki-67, parafibromin, and galectin-3 was used in 18.5% of cases with equivocal histology. Ninety-five percent of GPAs were benign with 5% reported as atypical adenomas.
CONCLUSION
The reported data on GPAs are sparse and heterogeneous. In GPAs with suspicious features for malignancy, en bloc resection with concurrent thyroidectomy may be considered. In the presence of equivocal histological features, ancillary immunohistochemistry is advocated to differentiate GPAs from atypical adenomas and PCs.
Topics: Adenoma; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Parathyroid Hormone; Parathyroid Neoplasms
PubMed: 35039921
DOI: 10.1007/s00423-021-02406-3 -
American Journal of Preventive Medicine Apr 2022Current evidence has revealed the beneficial effects of mobile health applications on systolic and diastolic blood pressure. However, there is still no solid evidence of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Current evidence has revealed the beneficial effects of mobile health applications on systolic and diastolic blood pressure. However, there is still no solid evidence of the underlying factors for these outcomes, and hypertension treatment is performed mainly by medication intake. This study aims to analyze the impacts of health applications on medication adherence of patients with hypertension and understand the underlying factors.
METHODS
A systematic review and meta-analysis were conducted considering controlled clinical trials published, without year filter, through July 2020. The searches were performed in the electronic databases of Scopus, MEDLINE, and BVSalud. Study characteristics were extracted for qualitative synthesis. The meta-analysis examined medication-taking behavior outcomes using the generic inverse-variance method to combine multiple variables.
RESULTS
A total of 1,199 records were identified, of which 10 studies met the inclusion criteria for qualitative synthesis, and 9 met the criteria for meta-analysis with 1,495 participants. The analysis of mean changes revealed significant improvements in medication adherence (standardized mean difference=0.41, 95% CI=0.02, 0.79, I=82%, p=0.04) as well as the analysis of the values measured after follow-up (standardized mean difference=0.60, 95% CI=0.30, 0.90, I=77%, p<0.0001). Ancillary improvements were also identified, such as patients' perceived confidence, treatment self-efficacy and self-monitoring, acceptance of technology, and knowledge about the condition and how to deal with health issues.
DISCUSSION
There is evidence that mobile health applications can improve medication adherence in patients with hypertension, with broad heterogeneity between studies on the topic. The use of mobile health applications conceivably leads to ancillary improvements inherent to better medication adherence.
Topics: Blood Pressure; Humans; Hypertension; Medication Adherence; Mobile Applications; Telemedicine
PubMed: 34963562
DOI: 10.1016/j.amepre.2021.11.003 -
The Journal of Orthopaedic and Sports... May 2022To summarize the content, development, and delivery of education interventions in clinical trials for people with knee osteoarthritis (OA). (Review)
Review
Knee Osteoarthritis Education Interventions in Published Trials Are Typically Unclear, Not Comprehensive Enough, and Lack Robust Development: Ancillary Analysis of a Systematic Review.
OBJECTIVE
To summarize the content, development, and delivery of education interventions in clinical trials for people with knee osteoarthritis (OA).
DESIGN
Ancillary analysis of a systematic review.
LITERATURE SEARCH
MEDLINE, EMBASE, SPORTDiscus, CINAHL, and Web of Science were searched from inception to April 2020.
STUDY SELECTION CRITERIA
Randomized controlled trials involving patient education for people with knee OA.
DATA SYNTHESIS
Content of education interventions was matched against a predefined topic list (n = 14) and categorized as accurate and clear, partially accurate/lacks clarity, or not reported. We examined whether education interventions included skill development or stated learning objectives and if they were developed based on theory, previous research, or codesign principles. Delivery methods and mode(s) were also identified. Data were summarized descriptively.
RESULTS
Thirty-eight education interventions (30 trials) were included. Interventions lacked comprehensiveness (median topics per intervention = 3/14, range = 0-11). Few topics were accurately and clearly described (10%, 13/136). Sixty-one percent (n = 23/38) of interventions targeted skill development, and 34% (n = 13/38) identified learning objectives. Forty-two percent (n = 16/38) were based on theory; 45% (n = 17/38) were based on research for chronic conditions, including 32% (n = 12/38) based on OA. Eleven percent of interventions (n = 4/38) were codesigned. Education was typically facilitated through face-to-face sessions (median = 9, range = 0-55), supplemented with telephone calls and/or written materials.
CONCLUSION
Education interventions for people with knee OA lacked comprehensiveness plus accurate and clear descriptions of topics covered. Most interventions failed to identify learning objectives and were not based on theory, previous research, or codesign principles. .
Topics: Humans; Osteoarthritis, Knee
PubMed: 34905960
DOI: 10.2519/jospt.2022.10771 -
Revista Colombiana de Obstetricia Y... Sep 2021To report the case of a patient diagnosed with ectopic mammary tissue in the vulva, and to conduct a literature review of the diagnosis, treatment and prognosis of this...
OBJECTIVE
To report the case of a patient diagnosed with ectopic mammary tissue in the vulva, and to conduct a literature review of the diagnosis, treatment and prognosis of this condition in that location.
MATERIALS AND METHODS
A 49-year-old patient who presented with a painful vulvar mass to a private intermediate complexity center in Bogotá, Colombia. The lesion was assessed on ultrasound and then surgically excised; histopathology showed ectopic mammary tissue with absence of malignancy. A search was conducted in the PubMed, Embase, Cochrane, LILACS and Scielo databases using the keywords “Vulva,” “Breast” and “Ectopic.” Case reports and case series of women with histopathology-confirmed mammary tissue in the vulva were included.
RESULTS
Overall, 184 titles were identified and, of these, 94 were ultimately included, for a total of 126 cases, with 57.9% being benign tumors, 95% in women under 50 years of age, and 42.06% being malignant tumors, 92% in women over 50 years of age. Diagnosis was made on the basis of the clinical findings, with ancillary diagnostic imaging, tumor markers and immunohistochemistry in some cases. Local excision was performed in 91% of cases with benign pathology and in 43% of cases with malignant pathology, with the diagnostic method being therapeutic.
CONCLUSIONS
Ectopic mammary tissue in the vulva must be considered as part of the differential diagnosis of vulvar masses, prognosis being different in pre and postmenopausal women. Further studies are needed to enhance the characterization of this condition and define the ideal course of treatment in terms of relapse and survival.
Topics: Adult; Breast; Choristoma; Diagnosis, Differential; Female; Humans; Middle Aged; Vulva; Vulvar Diseases
PubMed: 34851570
DOI: 10.18597/rcog.3593 -
Frontiers in Physiology 2021Many reports describe statistical approaches for estimating interindividual differences in trainability and classifying individuals as "responders" or "non-responders."... (Review)
Review
Many reports describe statistical approaches for estimating interindividual differences in trainability and classifying individuals as "responders" or "non-responders." The extent to which studies in the exercise training literature have adopted these statistical approaches remains unclear. This systematic review primarily sought to determine the extent to which studies in the exercise training literature have adopted sound statistical approaches for examining individual responses to exercise training. We also (1) investigated the existence of interindividual differences in trainability, and (2) tested the hypothesis that less conservative thresholds inflate response rates compared with thresholds that consider error and a smallest worthwhile change (SWC)/minimum clinically important difference (MCID). We searched six databases: AMED, CINAHL, EMBASE, Medline, PubMed, and SportDiscus. Our search spanned the aerobic, resistance, and clinical or rehabilitation training literature. Studies were included if they used human participants, employed standardized and supervised exercise training, and either: (1) stated that their exercise training intervention resulted in heterogenous responses, (2) statistically estimated interindividual differences in trainability, and/or (3) classified individual responses. We calculated effect sizes (ES) to examine the presence of interindividual differences in trainability. We also compared response rates ( = 614) across classification approaches that considered neither, one of, or both errors and an SWC or MCID. We then sorted response rates from studies that also reported mean changes and response thresholds ( = 435 response rates) into four quartiles to confirm our ancillary hypothesis that larger mean changes produce larger response rates. Our search revealed 3,404 studies, and 149 were included in our systematic review. Few studies ( = 9) statistically estimated interindividual differences in trainability. The results from these few studies present a mixture of evidence for the presence of interindividual differences in trainability because several ES values lay above, below, or crossed zero. Zero-based thresholds and larger mean changes significantly (both < 0.01) inflated response rates. Our findings provide evidence demonstrating why future studies should statistically estimate interindividual differences in trainability and consider error and an SWC or MCID when classifying individual responses to exercise training. [website], identifier [registration number].
PubMed: 34819869
DOI: 10.3389/fphys.2021.665044 -
The Indian Journal of Medical Research Jul 2021In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the... (Review)
Review
BACKGROUND & OBJECTIVES
In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the standardization of the management protocol for the same. In addition, there also exists diversity in the views about the clinical diagnosis, ancillary investigations and clinical parameters. The objective of the present study was to evaluate the reported outcomes of surgical interventions for the management of LSCD.
METHODS
A systematic review of published literature on limbal stem cell transplantation (LSCT) was performed using Ovid Medline, Embase and PubMed for a duration of 2009 to 2019. Original studies including prospective, retrospective case series and randomized controlled trials, articles in English language, articles with access to full text and studies with more than or at least 10 patients were included in this review. Data related to clinical and visual outcomes were evaluated, and pool estimates of different surgeries were calculated using random-effects model and individually using Pearson's Chi-square test.
RESULTS
A total of 1133 abstracts were evaluated. Finally, 17 studies were included for the analysis. Among these 17 studies, direct limbal lenticule transplantation was performed in five studies, of which autologous tissue from the fellow eye [conjunctival limbal autograft (CLAU)], allograft from a cadaver/live donor [keratolimbal allograft (KLAL)/conjunctival limbal allograft (CLAL)] and combination of CLAU plus KLAL were done in one, three and one studies, respectively. The ex vivo expanded cultivated limbal epithelial transplantation (CLET) was reported in six studies and simple limbal epithelial transplantation (SLET) in four studies. Two were comparative studies comparing CLET and CLAL (living-related CLAL) with cadaveric KLAL, respectively. Outcome analysis of the included studies showed significant heterogeneity. Calculated pool rate for various types of surgeries was calculated. The pool estimate for CLAL was 67.56 per cent [95% confidence interval (CI), 41.75-93.36; I=83.5%, P=0.002]. For KLAL, this value was 63.65 per cent (95% CI, 31.38-95.91; I=92.4%, P=0.000). Pool estimate for CLET was 78.90 per cent (95% CI, 70.51-87.28; I=73.6%, P=0.001). Corresponding values for SLET were 79.08 per cent (95% CI, 74.10-84.07; I=0.0%, P=0.619). CLAU and combination of CLAU plus KLAL were done in one study each; hence, statistical analysis could not be done. The functional outcome in terms of gain in visual acuity post-operatively was better in KLAL (P<0.005) and SLET group as compared to CLET group.
INTERPRETATION & CONCLUSIONS
The present analysis suggests that though the anatomical success rates were almost identical between SLET, CLET, CLAL, and KLAL procedures, the functional success rates were better following KLAL and SLET procedures as compared to CLET. Decision for LSCT for cases of ocular burns based on either clinical judgement of the surgeon or individual diagnosis remains a suitable option.
Topics: Corneal Diseases; Humans; Limbus Corneae; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Stem Cell Transplantation; Stem Cells; Transplantation, Autologous
PubMed: 34782530
DOI: 10.4103/ijmr.IJMR_1139_18 -
JAMA Network Open Nov 2021The use of magnetic resonance imaging (MRI) in pretreatment planning of ductal carcinoma in situ (DCIS) remains controversial. Understanding changes in short-term...
Patient-Reported Testing Burden of Breast Magnetic Resonance Imaging Among Women With Ductal Carcinoma In Situ: An Ancillary Study of the ECOG-ACRIN Cancer Research Group (E4112).
IMPORTANCE
The use of magnetic resonance imaging (MRI) in pretreatment planning of ductal carcinoma in situ (DCIS) remains controversial. Understanding changes in short-term health-related quality of life associated with breast MRI would allow for a more complete comparative effectiveness assessment.
OBJECTIVE
To assess whether there are changes in patient-reported quality of life associated with breast MRI among women diagnosed with DCIS.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was a substudy of a nonrandomized clinical trial conducted at 75 participating US institutions from March 2015 to April 2016. Women recently diagnosed with unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. A total of 355 women met the eligibility criteria and underwent the study MRI. Data analysis was performed from June 3, 2020, to July 1, 2021.
EXPOSURES
Participants underwent bilateral breast MRI within 30 days of study registration and before surgery. Information on patient-reported testing burden for breast MRI was collected after MRI and before surgery.
MAIN OUTCOMES AND MEASURES
The primary outcome of this substudy was the patient-reported testing burden of breast MRI, measured by the Testing Morbidities Index (TMI) summated scale score. The TMI is a 7-item instrument that evaluates the temporary changes in quality of life associated with imaging before, during, and after the test (0 represents the worst possible, 100 the hypothetical ideal test experience).
RESULTS
Of the 355 women who met the eligibility criteria, 244 (69%) completed both questionnaires and were included in this analysis. The median age was 59 years (range, 34-85 years). The mean MRI TMI summated scale score was 85.9 (95% CI, 84.6-87.3). Of the 244 women, 142 (58%) experienced at least some fear and anxiety before the examination, and 120 women (49%) experienced fear and anxiety during the examination. A total of 156 women (64%) experienced pain or discomfort during the examination. In multivariable analyses, greater test-related burden was associated with higher levels of cancer worry (regression coefficient, -2.75; SE, 0.94; P = .004).
CONCLUSIONS AND RELEVANCE
In this cohort study, a clinically meaningful breast MRI testing burden among women with DCIS was revealed that was significantly associated with cancer worry. Understanding the potential quality-of-life reduction associated with MRI, especially when used in combination with mammography, may allow development of targeted interventions to improve the patient experience.
Topics: Adult; Aged; Aged, 80 and over; Anxiety; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Clinical Trials as Topic; Fear; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Quality of Life
PubMed: 34726748
DOI: 10.1001/jamanetworkopen.2021.29697