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1.
Clin Exp Med ; 23(7): 3147-3157, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36976378

ABSTRACT

Iron metabolism plays a crucial role in the development and progression of hepatocellular carcinoma (HCC), the most common type of primary liver cancer. Iron is an essential micronutrient that is involved in many physiological processes, including oxygen transport, DNA synthesis, and cellular growth and differentiation. However, excessive iron accumulation in the liver has been linked to oxidative stress, inflammation, and DNA damage, which can increase the risk of HCC. Studies have shown that iron overload is common in patients with HCC and that it is associated with a poor prognosis and reduced survival rates. Various iron metabolism-related proteins and signaling pathways such as the JAK/STAT pathway are dysregulated in HCC. Moreover, reduced hepcidin expression was reported to promote HCC in a JAK/STAT pathway-dependent manner. Therefore, it is important to understand the crosstalk between iron metabolism and the JAK/STAT pathway to prevent or treat iron overload in HCC. Iron chelators can bind to iron and remove it from the body, but its effect on JAK/STAT pathway is unclear. Also, HCC can be targeted by using the JAK/STAT pathway inhibitors, but their effect on hepatic iron metabolism is not known. In this review, for the first time, we focus on the role of the JAK/STAT signaling pathway in regulating cellular iron metabolism and its association with the development of HCC. We also discuss novel pharmacological agents and their therapeutic potential in manipulating iron metabolism and JAK/STAT signaling in HCC.


Subject(s)
Carcinoma, Hepatocellular , Iron Overload , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Signal Transduction , Janus Kinases/genetics , Janus Kinases/metabolism , Liver Neoplasms/genetics , Iron/metabolism , STAT Transcription Factors , Iron Overload/complications , Iron Overload/drug therapy
2.
J Intensive Care Med ; 38(6): 511-518, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36775970

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoaV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. In randomized clinical trials, patients who were treated with the anti-spike monoclonal antibody bamlanivimab had fewer COVID-19-related hospitalizations or emergency department (ED) visits than the control group. Methods: A retrospective cohort was assembled across a multisite healthcare system between November 20, 2020 and March 31, 2021. Ambulatory COVID-19 patients treated with bamlanivimab (n = 209) were propensity score matched without replacement (1:1) to a pool of 1024 eligible control patients who received similar care without bamlanivimab. The primary endpoint was all-cause mortality or admission at 30 days. Secondary endpoints included hospitalization, critical care admission, oxygenation requirements, and infusion-related reactions. Propensity score matching (PSM) analysis was used to assess the effect of bamlanivimab infusion on the composite endpoint and secondary endpoints. Results: A total of n = 209 matched patients were included in each arm of the study. The absolute standardized difference (stddiff) was calculated and indicated a balance between the groups. Almost all variables had a stddiff of less than 0.10, except for respiratory rate (RR) (stddiff = -0.11). For the primary composite endpoint of the matched cohort, 10.1% (n = 21) of patients in the intervention group were hospitalized or deceased within 30-day postbamlanivimab infusion versus 27.8% (n = 58) in the control group (adjusted odds ratio [aOR]: 0.29, 95% confidence interval [CI]: 0.17 to 0.51, P < .001). Conclusion: Patients with ambulatory COVID-19 who received bamlanivimab in the outpatient setting had a statistically significant reduction on the odds of admission postinfusion. Despite bamlanivimab's lack of efficacy on newer SARS-CoV-2 variants, this study demonstrates that neutralizing monoclonal antibodies can be effective against specific variants. If variant identification becomes a more accessible tool in outpatient centers or EDs, more targeted therapeutic options may be considered.


Subject(s)
Antibodies, Monoclonal , COVID-19 , Humans , Antibodies, Monoclonal/therapeutic use , SARS-CoV-2 , Retrospective Studies
3.
Cell Signal ; 104: 110591, 2023 04.
Article in English | MEDLINE | ID: mdl-36627007

ABSTRACT

The cellular trafficking protein secretory-carrier-membrane-protein 3 (SCAMP3) has been previously shown to promote hepatocellular carcinoma, melanoma, glioma and pancreatic adenocarcinoma. Moreover, previous work has shown that SCAMP3 regulates the epidermal growth factor receptor (EGFR) in triple negative breast cancer (TNBC). However, the oncogenic role of SCAMP3 in different molecular subtypes of breast cancer (BRCA) remains largely unknown. In this study, the role of SCAMP3 in different molecular subtypes of BRCA was investigated using in silico, in vitro and in vivo approaches. In silico analysis of BRCA patient samples showed that SCAMP3 is highly overexpressed in different BRCA molecular subtypes, advanced disease grades and lymph node metastatic stages. Depletion of SCAMP3 inhibited BRCA cell growth, stemness, clonogenic potential and migration and promoted autophagy and cellular senescence. The expression of stemness markers CD44 and OCT4A was reduced in SCAMP3-silenced MDA-MB-231 cells. SCAMP3 overexpression promoted cell proliferation, clonogenicity, tumor spheroid formation and migration in vitro and tumor growth in vivo. SCAMP3 promoted epithelial-mesenchymal-transition (EMT) by regulating E-cadherin expression. SCAMP3 enhanced in vivo tumor growth in MDA-MB-231 tumor xenograft mouse model. Mechanistically, SCAMP3 depletion inhibited ß-Catenin, c-MYC and SQSTM1 expression, while its overexpression increased the expression of the same oncogenic proteins. Increased SCAMP3 expression associated with increased chemoresistance in BRCA cells while its depletion associated with increased sensitivity to chemotherapy. BRCA patients with high SCAMP3 expression showed poor prognosis, decreased overall survival and relapse free survival relative to counterparts with reduced SCAMP3 expression. These findings suggest that SCAMP3 exerts a wide range of oncogenic effects in different molecular subtypes of BRCA by modulating the c-MYC-ß-Catenin-SQSTM1 axis that targets tumor growth, metastasis, stemness and chemoresistance.


Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Triple Negative Breast Neoplasms , Animals , Humans , Mice , beta Catenin/metabolism , Carrier Proteins/pharmacology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Membrane Proteins/metabolism , Sequestosome-1 Protein/metabolism , Triple Negative Breast Neoplasms/metabolism , Proto-Oncogene Proteins c-myc/metabolism
5.
Am J Manag Care ; 28(4): e121-e125, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35420749

ABSTRACT

OBJECTIVES: To evaluate the impact of the chronic medication optimization pharmacist (CMOP) program on blood pressure (BP) control and time to goal compared with usual care in the ambulatory care setting. STUDY DESIGN: This was a retrospective cohort study that included patients from June 2018 to June 2020 who were seen in an ambulatory care clinic for hypertension management. METHODS: Patients aged 18 to 80 years were divided into 2 cohorts based on hypertension management by usual care or the CMOP program. Patients were enrolled in the CMOP program either by referral or identification via a data analytics tool. The primary outcome assessed the proportion of patients within BP goal (< 140/90 mm Hg) at 3 months. Secondary outcomes assessed the proportion of patients within goal at 6 months, time and number of visits to goal, and adherence (CMOP cohort only). RESULTS: The primary end point demonstrated a greater proportion of patients within goal in the CMOP cohort compared with usual care (69.4% vs 42.3%; P < .001). The CMOP cohort also displayed a greater proportion of patients achieving goal within 6 months (75.7% vs 60.4%; P = .014) and faster time to goal (42.99 vs 63.12 days; P = .002), but more visits (1.67 vs 1.18; P = .001). Lastly, adherence improved from 50.4% to 72.1% in the patients with a documented adherence assessment in the pharmacist group (P = .03). CONCLUSIONS: The pharmacist intervention improved BP control in a primarily African American patient population compared with usual care. Future studies should assess the sustainability of this intervention.


Subject(s)
Hypertension , Pharmacists , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Blood Pressure , Electronic Health Records , Humans , Hypertension/complications , Hypertension/drug therapy , Retrospective Studies
6.
Am J Health Syst Pharm ; 79(14): 1151-1157, 2022 07 08.
Article in English | MEDLINE | ID: mdl-35136945

ABSTRACT

PURPOSE: To describe insulin adjustments made following initiation of glucagon-like peptide 1 agonist (GLP1a) or sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy in patients within a primary care setting. METHODS: This was a multicenter, retrospective cohort study conducted at an academic health system. Adults with type 2 diabetes mellitus initiated on a GLP1a or SGLT2i while on insulin and managed by an ambulatory care pharmacist were included. The primary endpoint was the percent change in total daily insulin dose at specified time points (2 weeks, 4 weeks, 6 weeks, 3 months, and 6 months) after agent initiation. The secondary endpoints included a glycosylated hemoglobin (HbA1c) value of less than 8%, change from baseline HbA1c, and safety profiles of GLP1a therapy and SGLT2i therapy. RESULTS: Of the 150 patients included, 123 were initiated on a GLP1a and 27 on an SGLT2i. After 6 months, GLP1a initiation had resulted in a mean 23.5% decrease (P < 0.001) in insulin dosage and SGLT2i resulted in a mean 0.2% increase (P = 0.20). Insulin dosage reduction with GLP1a use was significantly different between baseline and each time point (P < 0.001). About 72% of patients initiated on a GLP1a and 59% of those initiated on an SGLT2i achieved an HbA1c value of less than 8%. The mean absolute change from baseline in HbA1c concentration was -1.7% with GLP1a use and -1.5% with SGLT2i use (P < 0.001 for both comparisons with baseline values). Hypoglycemia occurred in 21% of patients on a GLP1a and 11% of those on an SGLT2i. CONCLUSION: After GLP1a initiation, the mean total daily insulin dose decreased by 23.5%; after SGLT2i initiation, insulin requirements increased by a mean of 0.2%. These results will help guide insulin adjustments after initiation of these medications.


Subject(s)
Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Adult , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide 1 , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/adverse effects , Insulin/therapeutic use , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
7.
Virchows Arch ; 480(2): 293-302, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34580763

ABSTRACT

DICER1 gene encodes an RNaseIII endoribonuclease essential for the cleavage of pre-microRNA to mature microRNA. Germline DICER1 mutation results in DICER syndrome, a cancer predisposition syndrome which manifests in the thyroid gland as early-onset multinodular goiter and increased risk for differentiated thyroid carcinoma. Recently, somatic DICER1 mutations were described in various thyroid neoplasms, including follicular adenoma, papillary thyroid carcinoma, follicular carcinoma, and poorly differentiated thyroid carcinoma. In this study, we identified and described 14 cases (1.7%) with somatic DICER1 mutations from a cohort of 829 patients with thyroid follicular cell-derived thyroid carcinomas which were sequenced using MSK-IMPACT targeted next-generation sequencing platform. We expanded the histologic spectrum of thyroid carcinomas with somatic DICER1 mutations to include Hurthle cell carcinoma, high-grade differentiated thyroid carcinoma, and anaplastic thyroid carcinoma. All patients were adults with a median age of diagnosis of 59 years (range: 22-82). Although rare, a subset of thyroid cancers, including the aggressive subtypes, display somatic DICER1 mutations, some of which have oncogenic potential.


Subject(s)
Adenocarcinoma, Follicular , Carcinoma , MicroRNAs , Thyroid Neoplasms , Adenocarcinoma, Follicular/genetics , Adenocarcinoma, Follicular/pathology , Adult , Aged , Aged, 80 and over , Carcinoma/genetics , DEAD-box RNA Helicases/genetics , Germ-Line Mutation , High-Throughput Nucleotide Sequencing , Humans , Middle Aged , Mutation/genetics , Ribonuclease III/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Young Adult
8.
Hum Pathol (N Y) ; 242021 Jun.
Article in English | MEDLINE | ID: mdl-34660202

ABSTRACT

Biphenotypic sinonasal sarcoma (BSNS) is a rare recently described distinct spindle cell sarcoma which arises exclusively in the sinonasal region and is characterized by concomitant neural and myogenic differentiation. Before this neoplasm was characterized, most were classified as other entities including adult fibrosarcoma, monophasic synovial sarcoma and malignant peripheral nerve sheath tumor. By immunohistochemistry, these tumors characteristically express S100 and smooth muscle actin (SMA) and/or muscle specific actin (MSA). Most cases harbor rearrangements of PAX3 (paired box gene 3), and the most frequent translocation partner is MAML3 (mastermind like transcriptional coactivator 3). Herein, we described three cases of BSNS involving the nasal cavity with or without paranasal sinus involvement. We also did a literature review of the clinical features, histologic and immunophenotypic findings, cytogenetics, pathogenesis and behavior of this rare entity.

9.
Am J Surg Pathol ; 45(11): 1573-1578, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34231547

ABSTRACT

p16 is the most useful diagnostic marker for human papillomavirus (HPV)-associated anogenital lesions. In the cervix, the pattern of p16 immunoreactivity generally correlates with lesion severity. p16 expression in anal intraepithelial neoplasia (AIN) is far less studied. Whether such correlation holds true has to be determined. We correlated the degree and pattern of p16 immunohistochemistry (IHC) results with morphologic diagnoses of 1000 anal squamous and transitional zone biopsy specimens. Using the Lower Anogenital Squamous Terminology criteria, p16 IHC results were classified as block staining, partial staining, or negative. Among 150 samples without morphologic evidence of AIN, p16 was negative in 85% and partial staining in 15%. AIN 1 (n=400) revealed diverse results: 28% negative, 35% partial, and 37% block staining. Among AIN 2 (n=298), 89% were block, 9% partial staining, and 2% negative. AIN 3 (n=152) revealed block (95%) or partial staining (5%). For the detection of AIN 2/3, p16 block staining yielded 91% sensitivity, 73% specificity, 80% positive predictive value, 91% negative predictive value, and a Youden Index of 0.64. Combining block staining and partial staining slightly increased sensitivity (99%) and negative predictive value (98%), but significantly decreased specificity (43%), positive predictive value (59%) and Youden Index (0.42, P<0.001). As with the cervix, p16 immunoreactivity correlates with morphologic diagnoses of AIN. Block staining offers the optimal diagnostic value for AIN 2/3. Caution is required since AIN 1 frequently exhibits block staining; the prognostic value of p16 warrants further investigation.


Subject(s)
Anus Neoplasms/chemistry , Biomarkers, Tumor/analysis , Carcinoma in Situ/chemistry , Cyclin-Dependent Kinase Inhibitor p16/analysis , Immunohistochemistry , Papillomaviridae/isolation & purification , Papillomavirus Infections/virology , Precancerous Conditions/metabolism , Squamous Intraepithelial Lesions/metabolism , Anus Neoplasms/pathology , Anus Neoplasms/virology , Biopsy , Carcinoma in Situ/pathology , Carcinoma in Situ/virology , Databases, Factual , Humans , In Situ Hybridization , Male , Neoplasm Grading , Papillomaviridae/genetics , Precancerous Conditions/pathology , Precancerous Conditions/virology , Predictive Value of Tests , RNA, Viral/genetics , Squamous Intraepithelial Lesions/pathology , Squamous Intraepithelial Lesions/virology
10.
Case Rep Ophthalmol Med ; 2021: 6654347, 2021.
Article in English | MEDLINE | ID: mdl-33604091

ABSTRACT

PURPOSE: To characterize the clinical presentation and report lab findings of Chlamydia trachomatis follicular conjunctivitis in two patients with a positive history of active COVID-19 infection. Participants. Two patients with follicular conjunctivitis with a recent history of COVID-19 infection. DESIGN: Retrospective, noncomparative, case report. METHODS: Demographic data including age, gender, and place of residence were recorded. A full exam with an emphasis on inflammatory characteristics and systematic workup. Sample follicles were surgically excised in selected cases, and molecular and histopathological analyses were performed. RESULTS: Both patients were initially treated for viral conjunctivitis. After symptoms failed to resolve, biopsy results indicated that both patients were positive for chlamydia conjunctivitis and treated accordingly. CONCLUSIONS: These cases illustrate the role of biopsy as an investigative tool in chronic conjunctivitis and the importance of having a broad differential when treating patients with acute conjunctivitis.

11.
Ophthalmic Plast Reconstr Surg ; 37(4): e133-e134, 2021.
Article in English | MEDLINE | ID: mdl-33481538

ABSTRACT

The authors describe a case of Warthin tumor arising in the caruncle of a 76-year-old man. Clinical examination identified a left medial canthus swelling that was treated by complete local excision. Pathologic examination revealed a benign epithelial tumor with diagnostic features of Warthin tumor. Clinical and histologic features, along with review of the literature, are discussed.


Subject(s)
Adenolymphoma , Adenolymphoma/surgery , Aged , Humans , Male
13.
Diabetes Obes Metab ; 22(4): 480-491, 2020 04.
Article in English | MEDLINE | ID: mdl-31696603

ABSTRACT

AIMS: To assess the pharmacokinetic (PK) and pharmacodynamic characteristics of VI-0521, a fixed-dose combination of immediate-release phentermine (PHEN) and extended-release topiramate (TPM) in adolescents aged 12 to 17 years with obesity, and to report weight loss and adverse events using this drug combination. MATERIALS AND METHODS: This was a multicentre, randomized, double-blind, parallel-design, placebo-controlled study in adolescents with obesity. A total of 42 adolescents were randomly assigned in a 1:1:1 ratio to placebo, or to a mid-dose (PHEN/TPM 7.5 mg/46 mg), or a top-dose (PHEN/TPM 15 mg/92 mg) of VI-0521. A total of 26 adolescents were included in the PK analysis (14 from the mid-dose group and 12 from the top-dose group). RESULTS: On day 56, arithmetic means of terminal elimination half-life, apparent clearance (CL/F) and apparent central volume of distribution (Vc/F) were consistent across dose levels for both PHEN and TPM. Arithmetic means of CL/F and Vc/F for PHEN and TPM administered as a combination in adolescents with obesity were within 10% to 30% of those previously assessed in adults with obesity enrolled in phase II and III studies. A higher proportion of adolescents in both the mid- and top-dose groups (13.3% and 50.0%, respectively) compared with placebo (0.0%) reached ≥5% weight loss at day 56. The least squares (LS) mean change in systolic blood pressure from baseline to day 56 was -5.2 mmHg for the placebo group, -2.5 mmHg for the mid-dose group, and - 5.5 mmHg for the top-dose group. The LS mean change in diastolic blood pressure from baseline to day 56 was -2.4 mmHg for the placebo group, +3.8 mmHg for the mid-dose group, and + 2.0 mmHg for the top-dose group. Participants in the top-dose group had increases in heart rate from baseline of 4.1 bpm, while participants in the mid-dose group experienced a mean decrease in heart rate of 4.5 bpm at day 56. Both PHEN/TPM dose combinations were safe and well tolerated. CONCLUSIONS: Treatment of adolescents with obesity using a fixed-dose combination of PHEN/TPM for 8 weeks resulted in exposure to PHEN and TPM that was comparable to that observed in adults, statistically significant weight loss, and a tolerable safety profile. These data indicate that both mid- and top-dose levels are appropriate for longer-term safety and efficacy studies in adolescents.


Subject(s)
Anti-Obesity Agents , Adolescent , Anti-Obesity Agents/adverse effects , Child , Double-Blind Method , Fructose/adverse effects , Humans , Obesity/complications , Obesity/drug therapy , Phentermine/adverse effects , Topiramate
14.
Am J Manag Care ; 25(7): e219-e223, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31318513

ABSTRACT

OBJECTIVES: To evaluate the effect of an interdisciplinary transitions of care (TOC) service on readmission rates in a geriatric population. STUDY DESIGN: Single-center retrospective cohort study of adults 60 years or older discharged from an academic medical center. METHODS: From July 1, 2013, to February 21, 2016, a total of 4626 patients discharged from 1 hospital, including inpatient, emergency department, observation, and short-stay units, were included. Cases were scheduled for a TOC service with the interdisciplinary team. Controls received usual care at other sites. All-cause 14-, 30-, and 90-day readmission rates between propensity score-matched study groups were evaluated by intention-to-treat (ITT), per-protocol (PP), and as-treated methods. RESULTS: During the study period, 513 patients were scheduled for at least 1 component of the TOC intervention (ITT group). Of those patients, 215 completed all scheduled visits (PP group). Readmission rate after 30 days demonstrated no difference in the ITT group compared with the control group (12.8% vs 10.7%; P = .215), although it was significantly lower in the PP group in comparison with the control group (12.8% vs 7.9%; P = .042). CONCLUSIONS: An interdisciplinary team based in a patient-centered medical home improved readmission rates for all patients who completed the intervention (PP group).


Subject(s)
Delivery of Health Care/organization & administration , Health Services for the Aged/organization & administration , Patient Care Team/organization & administration , Patient Discharge/statistics & numerical data , Patient Readmission/statistics & numerical data , Patient Transfer/organization & administration , Academic Medical Centers/statistics & numerical data , Aged , Aged, 80 and over , Cohort Studies , Delivery of Health Care/statistics & numerical data , Female , Health Services for the Aged/statistics & numerical data , Humans , Male , Middle Aged , Patient Care Team/statistics & numerical data , Patient Transfer/statistics & numerical data , Retrospective Studies , United States
15.
J Am Pharm Assoc (2003) ; 59(5): 642-645, 2019.
Article in English | MEDLINE | ID: mdl-31307965

ABSTRACT

OBJECTIVES: To propose a metric evaluating the quality of comprehensive medication reviews (CMRs), and to discuss the optimal setting for CMR delivery. SUMMARY: First, we provide a current assessment of the quality of CMRs performed in community, payer, and health system/clinic settings, with recommended opportunities for improvement. Thereafter, a companion metric for CMR quality is discussed, because this is critical to ensuring that patients are not just receiving CMR services, but that CMRs reflect evidence-based recommendations supporting optimal patient outcomes. CONCLUSION: Based on the data currently available, accessibility to electronic medical records would enhance patient-specific recommendations to optimize CMR delivery and patient outcomes. Future studies may help to identify additional factors, such as pharmacist-physician collaboration in clinic and use of evidence-based recommendations, that can further enhance CMR quality.


Subject(s)
Community Pharmacy Services/organization & administration , Quality Assurance, Health Care/standards , Electronic Health Records , Humans , Medicare Part D/standards , Medication Therapy Management/organization & administration , Patient Outcome Assessment , United States
16.
Endocr Pathol ; 30(2): 90-95, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31001800

ABSTRACT

We describe a consistently present, previously unrecognized, population of monocytes in pheochromocytomas and paragangliomas. Although sustentacular cells are generally recognized as a common component of these tumors, differential immunohistochemical staining for CD163 and S100 shows that monocytes can in fact be more numerous. These cells frequently resemble sustentacular cells topographically and cytologically, possibly explaining why they have not been previously noticed. They contribute to the tumor proteome and may have implications for tumor biology. No correlations were identifiable between the presence of these cells and any clinical characteristics of the tumors in the present study. A possible association with genotype is suggested by immunoblot showing high expression of CD163 protein in tumors with succinate dehydrogenase mutations.


Subject(s)
Adrenal Gland Neoplasms/pathology , Monocytes/pathology , Paraganglioma/pathology , Pheochromocytoma/pathology , Adrenal Gland Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mutation/genetics , Paraganglioma/genetics , Pheochromocytoma/genetics , Receptors, Cell Surface/analysis , S100 Proteins/analysis , Succinate Dehydrogenase/genetics
17.
J Pharm Pract ; 31(5): 497-502, 2018 Oct.
Article in English | MEDLINE | ID: mdl-28891393

ABSTRACT

PURPOSE: The development of an outpatient psychiatry clinical practice learning experience for PGY2 ambulatory care pharmacy residents in preparation for the treatment of psychiatric disorders in the primary care setting is described. SUMMARY: With the increased prevalence of psychiatric disorders, significant mortality, and limited access to care, integration of mental health treatment into the primary care setting is necessary to improve patient outcomes. Given the majority of mental health treatment occurs in the primary care setting, pharmacists in patient-centered medical homes (PCMHs) are in a unique position with direct access to patients to effectively manage these illnesses. However, the increased need for pharmacist education and training in psychiatry has prompted a large, Midwestern academic health system to develop an outpatient psychiatry learning experience for PGY2 (Postgraduate Year 2) ambulatory care pharmacy residents in 2015. The goal of this learning experience is to introduce the PGY2 ambulatory care residents to the role and impact of psychiatric clinical pharmacists and to orient the residents to the basics of psychiatric pharmacotherapy to be applied to their future practice in the primary care setting. CONCLUSION: The development of an outpatient psychiatry learning experience for PGY2 ambulatory care pharmacy residents will allow for more integrated and comprehensive care for patients with psychiatric conditions, many of whom are treated and managed in the PCMH setting.


Subject(s)
Ambulatory Care/methods , Mental Disorders/drug therapy , Pharmacy Residencies/methods , Primary Health Care/methods , Ambulatory Care/trends , Humans , Mental Disorders/psychology , Pharmacy Residencies/trends , Primary Health Care/trends
18.
Endocrine ; 59(1): 143-150, 2018 01.
Article in English | MEDLINE | ID: mdl-29204912

ABSTRACT

OBJECTIVE: In 2016, non-invasive, well-circumscribed and encapsulated, follicular variant of papillary thyroid carcinoma (NI-EFV PTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in order to reduce overtreatment of this indolent tumor. However, the study cohort did not include subcentimeter tumors, i.e., papillary thyroid microcarcinoma (mPTC) with NI-EFV morphology, and such lesions are still regarded and staged by most pathologists as microcarcinomas. It is therefore crucial to evaluate the clinical outcome of subcentimeter NI-EFVs. METHODS: A total of 52 patients with unifocal mPTC, NI-EFV from five tertiary hospitals who had at least one year clinical follow-up (FU) without post-operative RAI administration were included in the study. A control group of 57 invasive mPTC follicular variant was also included. RESULTS: The median tumor size was 0.44 cm (range 0.1-0.9 cm). There were no distant or lymph node metastases at diagnosis in all patients. Twenty-three patients (44%) underwent lobectomy alone, while the remaining received total thyroidectomy. No recurrence was observed in the entire cohort (n = 52) including all 38 patients with at least 2 years of FU (median FU: 6.3 years). Among 25 patients with ≥5 years of FU, none recurred with a median FU of 9.6 years (range 5.2-18.1 years). In contrast, in the control group with invasive mPTC follicular variant, there were 5 (9%) patients with nodal metastasis at presentation and 1 (2%) who displayed nodal recurrence. CONCLUSION: Papillary thyroid microcarcinoma, NI-EFV, when stringently selected for, lacks metastasis at presentation and follows an extremely indolent clinical course, even when treated conservatively without RAI therapy. Provided stringent inclusion criteria are met, classification of subcentimeter mPTC, NI-EFV as NIFTP should be considered in order to avoid overtreatment of these biologically indolent lesions.


Subject(s)
Adenocarcinoma, Follicular/pathology , Carcinoma, Papillary/pathology , Cell Nucleus/pathology , Thyroid Neoplasms/classification , Thyroid Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Retrospective Studies , Thyroid Cancer, Papillary , Tumor Burden
19.
Am J Clin Pathol ; 148(3): 251-258, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28821194

ABSTRACT

OBJECTIVES: Signet ring cells (SRCs) can be seen in a variety of thyroid tumors and can pose a diagnostic pitfall on cytology. This study describes the cytologic, histomorphologic, and molecular aspects of a cohort of primary thyroid tumors with SRCs. METHODS: A search was performed of the Massachusetts General Hospital and Brigham and Women's Hospital (Boston, MA) pathology archives for the keywords thyroid, signet, and signet ring features between 2000 and 2014. Seven thyroidectomy specimens with corresponding thyroid fine-needle aspiration (FNA) were obtained. Cytology and histopathology slides were evaluated. Molecular analysis was performed using anchored multiplex polymerase chain reaction (AMP). RESULTS: The cohort consisted of four follicular adenomas (FAs), two noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), and one secretory carcinoma (SC). The FNA diagnoses were atypia of undetermined significance (n = 3), suspicious for follicular neoplasm (n = 3), and suspicious for malignancy (n = 1). Molecular analyses revealed PTEN and FGFR3 mutations in an FA and NIFTP, respectively, and an ETV6-NTRK3 fusion in a case of primary thyroid gland SC. CONCLUSIONS: Our study demonstrates the range of thyroid tumors with SRCs. While most thyroid tumors with SRCs are benign, primary thyroid SC should also be considered in the differential diagnosis.


Subject(s)
Adenocarcinoma, Follicular/pathology , Adenoma/pathology , Thyroid Neoplasms/pathology , Adenocarcinoma, Follicular/metabolism , Adenocarcinoma, Follicular/surgery , Adenoma/metabolism , Adenoma/surgery , Adolescent , Aged , Aged, 80 and over , Biopsy, Fine-Needle , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Mutation , PTEN Phosphohydrolase/metabolism , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/surgery , Thyroidectomy
20.
J Neuropathol Exp Neurol ; 76(3): 238-244, 2017 03 01.
Article in English | MEDLINE | ID: mdl-28395083

ABSTRACT

Clinical data suggest that optic neuropathy and retinal ganglion cell loss are the main cause of visual decline in patients with familial dysautonomia, but this has not previously been confirmed by pathological analyses. We studied retinas and optic nerves in 6 eyes from 3 affected patients obtained at autopsy. Analyses included routine neurohistology and immunohistochemistry for neurofilaments, cytochrome c oxidase (COX), and melanopsin-containing ganglion cells. We observed profound axon loss in the temporal portions of optic nerves with relative preservation in the nasal portions; this correlated with clinical and optical coherence tomography findings in 1 patient. Retinal ganglion cell layers were markedly reduced in the central retina, whereas melanopsin-containing ganglion cells were relatively spared. COX staining was reduced in the temporal portions of the optic nerve indicating reduced mitochondrial density. Axonal swelling with degenerating lysosomes and mitochondria were observed by electron microscopy. These findings support the concept that there is a specific optic neuropathy and retinopathy in patients with familial dysautonomia similar to that seen in other optic neuropathies with mitochondrial dysfunction. This raises the possibility that defective expression of the IkB kinase complex-associated protein (IKAP) resulting from mutations in IKBKAP affects mitochondrial function in the metabolism-dependent retinal parvocellular ganglion cells in this condition.


Subject(s)
Dysautonomia, Familial/complications , Dysautonomia, Familial/pathology , Optic Nerve Diseases/complications , Optic Nerve Diseases/pathology , Adolescent , Child , Female , Humans , Male , Middle Aged , Optic Nerve/pathology , Retinal Ganglion Cells/pathology
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