Richard Kloos - Academia.edu (original) (raw)

Papers by Richard Kloos

Cancer treatment and research, 1997

I. Introduction: BEFORE 1974, the literature contained 178 clinical cases of nonhypersecretory ad... more I. Introduction: BEFORE 1974, the literature contained 178 clinical cases of nonhypersecretory adrenal cortical tumors (see Table 1 for nomenclature) (4). Since the early 1980s, incidentally discovered adrenal masses have become a common clinical problem as a result of the ...

Journal of the Endocrine Society, Apr 1, 2020

children admitted with DKA, those with pump failure were primarily older (60% above age 12), most... more children admitted with DKA, those with pump failure were primarily older (60% above age 12), mostly white (63%), female (57%), from urban areas (78%), and almost 2/3rds had private insurance (60%). Adjusted analyses revealed that compared to DKA admissions without pump failure, pump failure was associated with older age, white race, residing in a rural area, private insurance, and higher income. Pump failure admissions were more likely in western and southern hospitals, otherwise there were no significant differences with respect to hospital characteristics. Compared to DKA admissions without pump failure, DKA admissions associated with pump failure had a longer mean length of stay (2.6 vs 1.5 days) and were more likely to have a higher severity of illness category. Conclusion: In this national sample, DKA with pump failure was more often observed among white, privately insured and high income children; these patient characteristics likely reflect the population of youth with diabetes who are more likely prescribed pumps in the US. Admissions for DKA concurrent with insulin pump failure accounted for a minority of pediatric DKA admissions but these admissions were associated with longer lengths of stay and severity of illness. Pump failure has important implications for care and management of children with diabetes.

There are 3 main histologic types of thyroid carcinoma: differentiated (including papillary, foll... more There are 3 main histologic types of thyroid carcinoma: differentiated (including papillary, follicular, and Hürthle), medullary, and anaplastic (aggressive undifferentiated tumor). Of 53,856 patients treated for thyroid carcinoma between 1985 and 1995, 80% had papillary, 11% had follicular, 3% had Hürthle cell, 4% had medullary, and 2% had anaplastic thyroid carcinoma. 1 These NCCN guidelines focus on medullary thyroid carcinoma (MTC). Another NCCN guideline addresses papillary, follicular, Hürthle cell, and anaplastic thyroid carcinomas (see NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma [to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org]). MTC derives from the neuroendocrine parafol-The NCCN Medullary Carcinoma

Cancer Cytopathology, Apr 24, 2019

Medicine, Sep 1, 1995

Spontaneous periodic hypothermia is a rare syndrome of recurrent, centrally mediated hypothermia ... more Spontaneous periodic hypothermia is a rare syndrome of recurrent, centrally mediated hypothermia without an identifiable systemic cause or brain lesion. Most patients defend a temporarily lowered temperature "set point" during episodes of hypothermia, despite manifesting many well-known systemic consequences of core temperature hypothermia. No case of death directly attributable to an episode of spontaneous periodic hypothermia has been reported, although many of the serious systemic effects of hypothermia have been documented in these cases, so it is not unlikely that death may occur. The syndrome's cause, and that of Shapiro syndrome, remains unknown. Pharmacologic trials to date have been only modestly successful. Anticonvulsant agents, clonidine, and cyproheptadine appear the most likely to succeed, with cyproheptadine being a reasonable first choice. Given that the term "spontaneous periodic hypothermia" describes a syndrome, and not a pathophysiologic mechanism, it is likely to encompass a common eventuality, arrived at via several different pathways. One can postulate mechanisms such as structural abnormalities, trauma, infection, irritation, and degeneration involving strategic locations which create a focus for epileptic or other periodic dysfunction whose scope involves the centers for thermoregulation. The existence of 2 distinct, oppositional thermoregulatory centers would allow for speculation of similar mechanisms accounting for cases of both periodic hypo- and hyperthermia (61). Postmortem data regarding the hypothalamic and surrounding areas from future cases of Shapiro syndrome and spontaneous periodic hypothermia would be of great interest. Further, more sensitive in vivo testing methods are clearly needed. The role of PET or single photon emission computed tomography (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m HMPAO) performed acutely during an episode remains to be characterized (64, 103, 105). The term "diencephalic epilepsy" may in fact be accurate, given the periodic episodes of the case presented here and similar cases resulting from non-generalized seizure activity, with or without an underlying predisposing lesion. The label diencephalic epilepsy has been merely speculative so far, however, as definitive evidence of seizure activity has not been documented. Further, it is expected that the descriptive terms "spontaneous periodic hypothermia" and "episodic spontaneous hypothermia with hyperhidrosis" will outlive their usefulness as researchers gain greater understanding of this syndrome, and be replaced with a more pathophysiologically meaningful nomenclature.

Journal of The National Comprehensive Cancer Network, May 1, 2010

PubMed, Sep 1, 1997

The high sensitivity of metaiodobenzylguanidine (MIBG) scintigraphy for sympathomedullary tumors ... more The high sensitivity of metaiodobenzylguanidine (MIBG) scintigraphy for sympathomedullary tumors such as neuroblastoma and pheochromocytoma is well documented. The specificity of MIBG scintigraphy for these tumors is also high but has been incompletely characterized for other neural crest tumors and non-neural crest tumors of childhood. Methods: The medical records and MIBG scans of all children who had undergone MIBG scintigraphy for known or suspected neuroblastoma or pheochromocytoma were retrospectively reviewed at five major referral centers. Those patients found to have pathologies other than neuroblastoma or pheochromocytoma form the basis of this study. Results: One hundred children with a total of 110 lesions met the inclusion criteria. All had negative MIBG scans except 1 of 2 children with infantile myofibromatosis, 1 of 2 with neuroendocrine carcinomas, 1 of 2 with pancreaticoblastomas and 1 of 10 with primitive neuroectodermal tumors. Conclusion: MIBG scintigraphy is highly specific for neuroblastoma and pheochromocytoma. Only 4% (4/100) of nonsympathomedullary tumors (non-pheochromocytoma and non-neuroblastoma) in childhood showed MIBG uptake, of which only 2% (2/100) were of non-neural crest origin.

Journal of The National Comprehensive Cancer Network, Nov 1, 2010

Thyroid nodules are approximately 4 times more common in women than in men. Palpable nodules incr... more Thyroid nodules are approximately 4 times more common in women than in men. Palpable nodules increase in frequency throughout life, reaching a prevalence of approximately 5% in the United States population aged 50 years and older. 1-3 Nodules are even more prevalent when the thyroid gland is examined at autopsy or surgery, or when using ultrasonography, and 50% of these have nodules, which are almost always benign. 2,4 New nodules develop at a rate of approximately 0.1% per year beginning in early life, but at a much higher rate (~2% per year) after exposure to head and neck irradiation. 5,6 By contrast, thyroid carcinoma is uncommon. For the United States population, the lifetime risk of NCCN

JAMA otolaryngology-- head & neck surgery, Mar 1, 2020

To the Editor Valderrabano et al 1 question the sensitivity and specificity of the Afirma gene ex... more To the Editor Valderrabano et al 1 question the sensitivity and specificity of the Afirma gene expression classifier (GEC) from its pivotal clinical validation, and by extension, its negative predictive value (NPV). 2 I disagree with their methodology and conclusions. The authors report that among 1071 Afirma GEC benign results from 20 independent clinical experience publications, only 23 (2.1%) were reported as malignant on surgical pathologic examination (eTable 3). This supports Afirma's validated 94% or greater NPV, 2 which has allowed most Afirma benign nodules to undergo conservative clinical observation in lieu of costly and invasive diagnostic surgery. 3 The authors compare the relationship of benign call rate (BCR) and positive predictive value (PPV) in postmarketing studies with that predicted from validation to assess diagnostic performance generalizability. In validation, the BCR and PPV are appropriately measured in the same cohort of thyroid nodules that underwent surgical resection. 2 However, the authors, in extracting data from published studies, measured BCR in all tested thyroid nodules, yet measure PPV only among the 80% of Afirma GEC suspicious nodules that were resected (eTable3). This is a flaw in the analysis. Because resected Afirma suspicious nodules are more likely to have cancer than Afirma suspicious nodules that had not undergone resection, the observed PPV is overestimated and the observed PPV to BCR relationship predictably shifts to the right when compared with validation. The effect of uncoupling the BCR and PPV by measuring them in different thyroid nodule subsets is seen in Figure 3A-D, but wrongly attributed to Afirma GEC performance.

Endocrine Reviews, Aug 1, 1995

Frontiers in Endocrinology, Dec 22, 2022

Objectives: To evaluate the frequency and risk of malignancy of TSHRpI568T mutations discovered i... more Objectives: To evaluate the frequency and risk of malignancy of TSHRpI568T mutations discovered in indeterminate thyroid nodules (ITN) within the Veracyte CLIA laboratory undergoing Afirma ® Genomic Sequencing Classifier (GSC) testing, and to evaluate a broader cohort of TSHR variants and their categorization as Afirma GSC benign (GSC-B) or suspicious (GSC-S). Finally, we seek to assess the risk of malignancy (ROM) of this group of TSHR mutated ITN in the GSC-S category.

Frontiers in Endocrinology, Sep 11, 2019

Introduction: The Afirma ® Xpression Atlas (XA) detects gene variants and fusions in thyroid nodu... more Introduction: The Afirma ® Xpression Atlas (XA) detects gene variants and fusions in thyroid nodule FNA samples from a curated panel of 511 genes using whole-transcriptome RNA-sequencing. Its intended use is among cytologically indeterminate nodules that are Afirma GSC suspicious, Bethesda V/VI nodules, or known thyroid metastases. Here we report its analytical and clinical validation. Methods: DNA and RNA were purified from the same sample across 943 blinded FNAs and compared by multiple methodologies, including whole-transcriptome RNA-seq, targeted RNA-seq, and targeted DNA-seq. An additional 695 blinded FNAs were used to define performance for fusions between whole-transcriptome RNA-seq and targeted RNA-seq. We quantified the reproducibility of the whole-transcriptome RNA-seq assay across laboratories and reagent lots. Finally, variants and fusions were compared to histopathology results. Results: Of variants detected in DNA at 5 or 20% variant allele frequency, 74 and 88% were also detected by XA, respectively. XA variant detection was 89% when compared to an alternative RNA-based detection method. Low levels of expression of the DNA allele carrying the variant, compared with the wild-type allele, was found in some variants not detected by XA. 82% of gene fusions detected in a targeted RNA fusion assay were detected by XA. Conversely, nearly all variants or fusions detected by XA were confirmed by an alternative method. Analytical validation studies demonstrated high intra-plate reproducibility (89%-94%), inter-plate reproducibility (86-91%), and inter-lab accuracy (90%). Multiple variants and fusions previously described across the spectrum of thyroid cancers were identified by XA, including some with approved or investigational targeted therapies. Among 190 Bethesda III/IV nodules, the sensitivity of XA as a standalone test was 49%. Angell et al. Afirma Xpression Atlas Validation Conclusion: When the Afirma Genomic Sequencing Classifier (GSC) is used first among Bethesda III/IV nodules as a rule-out test, XA supplements genomic insight among those that are GSC suspicious. Our data clinically and analytically validate XA for use among GSC suspicious, or Bethesda V/VI nodules. Genomic information provided by XA may inform clinical decision-making with precision medicine insights across a broad range of FNA sample types encountered in the care of patients with thyroid nodules and thyroid cancer.

Radiologic Clinics of North America, Sep 1, 1996

Archives of Otolaryngology-head & Neck Surgery, Aug 1, 2006