1.Next step of molecular pathology: next-generation sequencing in cytology
Ricella Souza da SILVA ; Fernando SCHMITT
Journal of Pathology and Translational Medicine 2024;58(6):291-298
		                        		
		                        			
		                        			 The evolving landscape of precision oncology underscores the pivotal shift from morphological diagnosis to treatment decisions driven by molecular profiling. Recent guidelines from the European Society for Medical Oncology recomend the use of next-generation sequencing (NGS) across a broader range of cancers, reflecting its superior efficiency and clinical value. NGS not only updates oncology testing by offering quicker, sample-friendly, and sensitive analysis but also reduces the need for multiple individual tests. Cytology samples, often obtained through less invasive methods, can yield high-quality genetic material suitable for molecular analysis. This article focuses on optimizing the use of cytology samples in NGS, and outlines their potential benefits in identifying actionable molecular alterations for targeted therapies across various solid tumors. It also addresses the need for validation studies and the strategies to incorporate or combine different types of samples into routine clinical practice. Integrating cytological and liquid biopsies into routine clinical practice, alongside conventional tissue biopsies, offers a comprehensive approach to tumor genotyping, early disease detection, and monitoring of therapeutic responses across various solid tumor types. For comprehensive biomarker characterization, all patient specimens, although limited, is always valuable. 
		                        		
		                        		
		                        		
		                        	
2.Next step of molecular pathology: next-generation sequencing in cytology
Ricella Souza da SILVA ; Fernando SCHMITT
Journal of Pathology and Translational Medicine 2024;58(6):291-298
		                        		
		                        			
		                        			 The evolving landscape of precision oncology underscores the pivotal shift from morphological diagnosis to treatment decisions driven by molecular profiling. Recent guidelines from the European Society for Medical Oncology recomend the use of next-generation sequencing (NGS) across a broader range of cancers, reflecting its superior efficiency and clinical value. NGS not only updates oncology testing by offering quicker, sample-friendly, and sensitive analysis but also reduces the need for multiple individual tests. Cytology samples, often obtained through less invasive methods, can yield high-quality genetic material suitable for molecular analysis. This article focuses on optimizing the use of cytology samples in NGS, and outlines their potential benefits in identifying actionable molecular alterations for targeted therapies across various solid tumors. It also addresses the need for validation studies and the strategies to incorporate or combine different types of samples into routine clinical practice. Integrating cytological and liquid biopsies into routine clinical practice, alongside conventional tissue biopsies, offers a comprehensive approach to tumor genotyping, early disease detection, and monitoring of therapeutic responses across various solid tumor types. For comprehensive biomarker characterization, all patient specimens, although limited, is always valuable. 
		                        		
		                        		
		                        		
		                        	
3.Next step of molecular pathology: next-generation sequencing in cytology
Ricella Souza da SILVA ; Fernando SCHMITT
Journal of Pathology and Translational Medicine 2024;58(6):291-298
		                        		
		                        			
		                        			 The evolving landscape of precision oncology underscores the pivotal shift from morphological diagnosis to treatment decisions driven by molecular profiling. Recent guidelines from the European Society for Medical Oncology recomend the use of next-generation sequencing (NGS) across a broader range of cancers, reflecting its superior efficiency and clinical value. NGS not only updates oncology testing by offering quicker, sample-friendly, and sensitive analysis but also reduces the need for multiple individual tests. Cytology samples, often obtained through less invasive methods, can yield high-quality genetic material suitable for molecular analysis. This article focuses on optimizing the use of cytology samples in NGS, and outlines their potential benefits in identifying actionable molecular alterations for targeted therapies across various solid tumors. It also addresses the need for validation studies and the strategies to incorporate or combine different types of samples into routine clinical practice. Integrating cytological and liquid biopsies into routine clinical practice, alongside conventional tissue biopsies, offers a comprehensive approach to tumor genotyping, early disease detection, and monitoring of therapeutic responses across various solid tumor types. For comprehensive biomarker characterization, all patient specimens, although limited, is always valuable. 
		                        		
		                        		
		                        		
		                        	
4.Transcranial Doppler emboli monitoring for stroke prevention after flow diverting stents
Matias COSTA ; Paul SCHMITT ; Jaleel N ; Matias BALDONCINI ; Juan VIVANCO-SUAREZ ; Bipin CHAURASIA ; Colleen DOUVILLE ; Loh YINCE ; Akshal PATEL ; Stephen MONTEITH
Journal of Cerebrovascular and Endovascular Neurosurgery 2024;26(1):23-29
		                        		
		                        			 Objective:
		                        			Flow diverting stents (FDS) are increasingly used for the treatment of intracranial aneurysms. While FDS can provide flow diversion of parent vessels, their high metal surface coverage can cause thromboembolism. Transcranial Doppler (TCD) emboli monitoring can be used to identify subclinical embolic phenomena after neurovascular procedures. Limited data exists regarding the use of TCDs for emboli monitoring in the periprocedural period after FDS placement. We evaluated the rate of positive TCDs microembolic signals and stroke after FDS deployment at our institution. 
		                        		
		                        			Methods:
		                        			We retrospectively evaluated 105 patients who underwent FDS treatment between 2012 and 2016 using the Pipeline stent (Medtronic, Minneapolis, MN, USA). Patients were pretreated with aspirin and clopidogrel. All patients were therapeutic on clopidogrel pre-operatively. TCD emboli monitoring was performed immediately after the procedure. Microembolic signals (mES) were classified as “positive” (<15 mES/hour) and “strongly positive” (>15 mES/hour). Clinical stroke rates were determined at 2-week and 6-month post-operatively. 
		                        		
		                        			Results:
		                        			A total of 132 intracranial aneurysms were treated in 105 patients. TCD emboli monitoring was “positive” in 11.4% (n=12) post-operatively and “strongly positive” in 4.8% (n=5). These positive cases were treated with heparin drips or modification of the antiplatelet regimen, and TCDs were repeated. Following medical management modifications, normalization of mES was achieved in 92% of cases. The overall stroke rates at 2-week and 6-months were 3.8% and 4.8%, respectively. 
		                        		
		                        			Conclusions
		                        			TCD emboli monitoring may help early in the identification of thromboembolic events after flow diversion stenting. This allows for modification of medical therapy and, potentially, preventionf of escalation into post-operative strokes. 
		                        		
		                        		
		                        		
		                        	
5.Age-related outcomes in patients with cardiogenic shock stratified by etiology.
Alexander SCHMITT ; Kathrin WEIDNER ; Jonas RUSNAK ; Marinela RUKA ; Sascha EGNER-WALTER ; Kambis MASHAYEKHI ; Péter TAJTI ; Mohamed AYOUB ; Ibrahim AKIN ; Michael BEHNES ; Tobias SCHUPP
Journal of Geriatric Cardiology 2023;20(8):555-566
		                        		
		                        			BACKGROUND:
		                        			As a result of improved and novel treatment strategies, the spectrum of patients with cardiovascular disease is consistently changing. Overall, those patients are typically older and characterized by increased burden with comorbidities. Limited data on the prognostic impact of age in cardiogenic shock (CS) is available. Therefore, this study investigates the prognostic impact of age in patients with CS.
		                        		
		                        			METHODS:
		                        			From 2019 to 2021, consecutive patients with CS of any cause were included. The prognostic value of age (i.e., 60-80 years and > 80 years) was investigated for 30-day all-cause mortality. Spearman's correlations, Kaplan-Meier analyses, as well as multivariable Cox proportional regression analyses were performed for statistics. Subsequent risk assessment was performed based on the presence or absence of CS related to acute myocardial infarction (AMI).
		                        		
		                        			RESULTS:
		                        			223 CS patients were included with a median age of 77 years (interquartile range: 69-82 years). No significant difference in 30-day all-cause mortality was observed for both age-groups (54.6% vs. 63.4%, log-rank P = 0.169; HR = 1.273, 95% CI: 0.886-1.831, P = 0.192). In contrast, when analyzing subgroups stratified by CS-etiology, AMI-related CS patients of the group > 80 years showed an increased risk of 30-day all-cause mortality (78.1% vs. 60.0%, log-rank P = 0.032; HR = 1.635, 95% CI: 1.000-2.673, P = 0.050), which was still evident after multivariable adjustment (HR = 2.072, 95% CI: 1.174-3.656, P = 0.012).
		                        		
		                        			CONCLUSIONS
		                        			Age was not associated with 30-day all-cause mortality in patients with CS of mixed etiology. However, increasing age was shown to be a significant predictor of increased mortality-risk in the subgroup of patients presenting with AMI-CS.
		                        		
		                        		
		                        		
		                        	
6.Evaluation of the Cost Effectiveness of Routine Histopathologic Femoral Head Analysis in Hip Arthroplasty
Zoe BROWN ; Michael PERRY ; Cameron KILLEN ; Daniel SCHMITT ; Michael WESOLOWSKI ; Nicholas M. BROWN
Hip & Pelvis 2022;34(1):56-61
		                        		
		                        			 Purpose:
		                        			Histopathologic analysis of femoral head specimens following total hip arthroplasty (THA) is a routine practice that represents a significant use of health care resources. However, it occasionally results in discovery of undiagnosed hematopoietic malignancy and other discrepant diagnoses such as avascular necrosis. The purpose of this study was to determine the rate of discordant and discrepant diagnoses discovered from routine histopathological evaluation of femoral heads following THA and perform a cost analysis of this practice. 
		                        		
		                        			Materials and Methods:
		                        			A review of patients undergoing primary THA between 2004-2017 was conducted. A comparison of the surgeon’s preoperative and postoperative diagnosis, and the histopathologic diagnosis was performed. In cases where the clinical and histopathology differed, a review determined whether this resulted in a change in clinical management. Medicare reimbursement and previously published cost data corrected for inflation were utilized for cost calculations. 
		                        		
		                        			Results:
		                        			A review of 2,134 procedures was performed. The pathologic diagnosis matched the postoperative diagnosis in 96.0% of cases. Eighty-three cases (4.0%) had a discrepant diagnosis where treatment was not substantially altered. There was one case of discordant diagnosis where lymphoma was diagnosed and subsequently treated. The cost per discrepant diagnosis was $141,880 and per discordant diagnosis was $1,669 when using 100% Medicare reimbursement and Current Procedural Terminology (CPT) code combination 88304+88311. 
		                        		
		                        			Conclusion
		                        			Histopathologic analysis of femoral head specimens in THAs showed an association with high costs given the rarity of discordant diagnoses. Routine use of the practice should be at the discretion of individual hospitals with consideration for cost and utility thresholds. 
		                        		
		                        		
		                        		
		                        	
7.DNA microarray-based characterization and antimicrobial resistance phenotypes of clinical MRSA strains from animal hosts
Sarah SCHMITT ; Roger STEPHAN ; Ella HUEBSCHKE ; Daniel SCHAEFLE ; Axel MERZ ; Sophia JOHLER
Journal of Veterinary Science 2020;21(4):e54-
		                        		
		                        			 Background:
		                        			Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of severe infections in humans and animals worldwide. Studies elucidating the population structure, staphylococcal cassette chromosome mec types, resistance phenotypes, and virulence gene profiles of animal-associated MRSA are needed to understand spread and transmission. 
		                        		
		                        			Objectives:
		                        			The objective of this study was to determine 1) clonal complexes and spa types, 2) resistance phenotypes, and 3) virulence/resistance gene profiles of MRSA isolated from animals in Switzerland. 
		                        		
		                        			Methods:
		                        			We analyzed 31 presumptive MRSA isolates collected from clinical infections in horses, dogs, cattle, sheep, and pigs, which had tested positive in the Staphaurex Latex Agglutination Test. The isolates were characterized by spa typing and DNA microarray profiling. In addition, we performed antimicrobial susceptibility testing using the VITEK 2 Compact system. 
		                        		
		                        			Results:
		                        			Characterization of the 31 presumptive MRSA isolates revealed 3 methicillin-resistant Staphylococcus pseudintermedius isolates, which were able to grow on MRSA2 Brilliance agar. Of the 28 MRSA isolates, the majority was assigned to CC398 (86%), but CC8 (11%) and CC1 (4%) were also detected. The predominant spa type was t011 (n = 23), followed by t009 (n = 2), t034 (n = 1), t008 (n = 1), and t127 (n = 1). 
		                        		
		                        			Conclusions
		                        			The results of this study extend the current body of knowledge on the population structure, resistance phenotypes, and virulence and resistance gene profiles of MRSA from livestock and companion animals. 
		                        		
		                        		
		                        		
		                        	
8.Unicompartmental knee arthroplasty and revision total knee arthroplasty have a lower risk of venous thromboembolism disease at 30 days than primary total knee arthroplasty
Andrew M. SCHNEIDER ; Daniel R. SCHMITT ; Nicholas M. BROWN
The Journal of Korean Knee Society 2020;32(4):e59-
		                        		
		                        			Background:
		                        			While multiple studies have demonstrated a lower venous thromboembolism disease (VTED) risk for unicompartmental knee arthroplasty (UKA) compared to primary total knee arthroplasty (TKA), recent reports have shown that revision TKA also had a lower VTED risk compared to primary TKA, an unexpected finding because of its theoretical increased risk. Given the paucity of up-to-date comparative studies, our goal was to perform a highpowered VTED risk comparison study of UKA and revision TKA to primary TKA using recent data. 
		                        		
		                        			Methods:
		                        			The National Surgical Quality Improvement Program (NSQIP) database was queried between 2011 and 2018, and we identified 213,234 patients for inclusion: 191,810 primary TKA, 9294 UKA, and 12,130 revision TKA.Demographics, medical comorbidities, and possible VTE risk factors were collected. Thirty-day outcomes, including deep vein thrombosis (DVT), pulmonary embolism (PE), and all-cause VTED were compared between knee arthroplasty types. 
		                        		
		                        			Results:
		                        			On multivariate analysis, UKA was significantly associated with lower rates of DVT [OR 0.44 (0.31–0.61); P < 0.001], PE [OR 0.42 (0.28–0.65); P < 0.001], and all-cause VTED [OR 0.42 (0.32–0.55); P < 0.001] when compared to primary TKA. Revision TKA was significantly associated with lower rates of PE [OR 0.62 (0.47–0.83); P = 0.002], and allcause VTED [OR 0.82 (0.70–0.98); P = 0.029] when compared to primary TKA. 
		                        		
		                        			Conclusions
		                        			Utilizing recent data from a nationwide patient cohort and controlling for confounding variables, our results showed that both revision TKA and UKA had a lower risk of VTED compared to primary TKA, corroborating the results of recent investigations. Additional prospective investigations are needed to explain this unexpected result.
		                        		
		                        		
		                        		
		                        	
9.Unicompartmental knee arthroplasty and revision total knee arthroplasty have a lower risk of venous thromboembolism disease at 30 days than primary total knee arthroplasty
Andrew M. SCHNEIDER ; Daniel R. SCHMITT ; Nicholas M. BROWN
The Journal of Korean Knee Society 2020;32(4):e59-
		                        		
		                        			Background:
		                        			While multiple studies have demonstrated a lower venous thromboembolism disease (VTED) risk for unicompartmental knee arthroplasty (UKA) compared to primary total knee arthroplasty (TKA), recent reports have shown that revision TKA also had a lower VTED risk compared to primary TKA, an unexpected finding because of its theoretical increased risk. Given the paucity of up-to-date comparative studies, our goal was to perform a highpowered VTED risk comparison study of UKA and revision TKA to primary TKA using recent data. 
		                        		
		                        			Methods:
		                        			The National Surgical Quality Improvement Program (NSQIP) database was queried between 2011 and 2018, and we identified 213,234 patients for inclusion: 191,810 primary TKA, 9294 UKA, and 12,130 revision TKA.Demographics, medical comorbidities, and possible VTE risk factors were collected. Thirty-day outcomes, including deep vein thrombosis (DVT), pulmonary embolism (PE), and all-cause VTED were compared between knee arthroplasty types. 
		                        		
		                        			Results:
		                        			On multivariate analysis, UKA was significantly associated with lower rates of DVT [OR 0.44 (0.31–0.61); P < 0.001], PE [OR 0.42 (0.28–0.65); P < 0.001], and all-cause VTED [OR 0.42 (0.32–0.55); P < 0.001] when compared to primary TKA. Revision TKA was significantly associated with lower rates of PE [OR 0.62 (0.47–0.83); P = 0.002], and allcause VTED [OR 0.82 (0.70–0.98); P = 0.029] when compared to primary TKA. 
		                        		
		                        			Conclusions
		                        			Utilizing recent data from a nationwide patient cohort and controlling for confounding variables, our results showed that both revision TKA and UKA had a lower risk of VTED compared to primary TKA, corroborating the results of recent investigations. Additional prospective investigations are needed to explain this unexpected result.
		                        		
		                        		
		                        		
		                        	
10.The Impact of Antibiotic-Loaded Bone Cement on Antibiotic Resistance in Periprosthetic Knee Infections
Daniel R. SCHMITT ; Cameron KILLEN ; Michael MURPHY ; Michael PERRY ; Joseph ROMANO ; Nicholas BROWN
Clinics in Orthopedic Surgery 2020;12(3):318-323
		                        		
		                        			 Background:
		                        			Antibiotic-loaded bone cement (ALBC) is commonly used in total knee arthroplasty (TKA), especially among high-risk patients. While previous studies have reported on the efficacy of ALBC in reducing the rate of periprosthetic joint infection (PJI), its impact on antibiotic resistance has not been determined. The purpose of this study was to investigate antibiotic resistance among organisms causing PJIs after TKA in which ALBC was utilized. 
		                        		
		                        			Methods:
		                        			A retrospective review from December 1998 through December 2017 identified 36 PJIs that met inclusion criteria. Patients with culture-negative infection and unknown cement type were excluded. Patient characteristics, infecting organism, and antibiotic susceptibilities were recorded. ABLC included an aminoglycoside in all cases. 
		                        		
		                        			Results:
		                        			There was no difference in the type of PJI between the 2 groups. Staphylococcus species was the most commonly isolated, with 9 of 16 cases (56.3%) using non-ALBC and 14 of 20 (65.0%) cases using ALBC. Of those infected with Staphylococcus, there was no significant difference in antibiotic susceptibilities between groups. Overall, there were only 3 cases where the infecting organism was aminoglycoside resistant (standard cement, 1; ALBC, 2). 
		                        		
		                        			Conclusions
		                        			These results suggest that the use of ALBC does not increase the risk of antibiotic resistance or affect the pattern of infection, even as the use of ALBC continues to increase, particularly among high-risk patients. 
		                        		
		                        		
		                        		
		                        	
            
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