Publications by authors named "Lisa Kohler"

14 Publications

  • Page 1 of 1

The Impact of Anticoagulation on COVID-19 (SARS CoV-2) Patient Outcomes: A Systematic Review.

J Pharm Pract 2021 May 7:8971900211015055. Epub 2021 May 7.

Florida A&M University College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Davie, FL, USA.

Background: Emerging data suggest that coagulopathy, cytokine storm, and acute respiratory distress syndrome are associated with the 2019 coronavirus disease (COVID-19). The prevalence of hypercoagulable state in these patients is unknown, but appears to be higher compared to those with other critically ill patients. Elevated D-dimer, large blood vessels clots, deep vein thrombosis, pulmonary embolism and disseminated intravascular coagulation have been reported in patients diagnosed with COVID-19 either on admission or during hospitalization and may be predictors of poor outcomes.

Methods: We performed a comprehensive literature review using the search terms of COVID-19; severe acute respiratory syndrome coronavirus-2, coagulopathy, thrombosis and anticoagulation in PubMed, Ovid, google scholar, Medline and EMBASE databases from December 2019 to May 30, 2020.

Results: A total of 64 relevant studies were reviewed; of which, 4 studies met the inclusion criteria and were included for analysis. The majority of the studies were retrospective involving 525 critically ill COVID-19 patients. The most commonly studied anticoagulant administered was low molecular weight heparins. Anticoagulation dosing varied throughout the studies and may be classified as standard venous thromboembolism prophylaxis, intermediate dosing, or full dose anticoagulation. The most studied objective was improvement in coagulopathy. Significant reduction in D-dimer, improvement in coagulopathy markers such as Interlukin-6, fibrinogen degradation product level, as well as lymphocyte count were reported.

Conclusion: Despite the limited quality of studies analyzed, prophylaxis and higher intensity dosed anticoagulation is associated with improved pulmonary oxygenation, decreased coagulopathy markers and decreased mortality in COVID-19 patients.
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http://dx.doi.org/10.1177/08971900211015055DOI Listing
May 2021

Hydrogen Bond between a Tyrosine Residue and the -Ring Propionate Has a Direct Influence on Conformation and Absorption of the Bilin Cofactor in Red/Green Cyanobacteriochromes.

J Phys Chem B 2021 02 1;125(5):1331-1342. Epub 2021 Feb 1.

Institut für Analytische Chemie, Universität Leipzig, Linnéstraße 3, 04103 Leipzig, Germany.

Cyanobacteriochromes (CBCRs) are photoreceptors of the phytochrome superfamily showing remarkable variability in the wavelengths of the first electronic transition-sometimes denoted as Q band-compared to canonical phytochromes. Both classes carry the same cofactor, a bilin, but the molecular basis for the wide variation of their absorption properties is still a matter of debate. The interaction between the cofactor and the surrounding protein moiety has been proposed as a possible tuning factor. Here, we address the impact of hydrogen-bonding interaction between the covalently bound tetrapyrrole cofactor (phycocyanobilin, PCB) and a conserved tyrosine residue (Y302) in the second GAF (cMP-specific phosphodiesterase, denylyl cyclases, and hlA) domain of the red-/green-switching CBCR AnPixJ (AnPixJg2). In the wild type, AnPixJg2 shows absorption maxima of 648 and 543 nm for the dark-adapted (Pr) and photoproduct (Pg) states, respectively. The Y302F mutation leads to the occurrence of an additional absorption band at 687 nm, which is assigned to a new spectroscopically identified sub-state called P. Similar spectral changes result upon mutating the Y302F-homologue in another representative red-/green-switching CBCR, Slr1393g3. Molecular dynamics simulations on the dark-adapted state suggest that the removal of the hydrogen bond leads to an additional PCB sub-state differing in its - and -ring geometries. The origin of the Q band satellite in the dark-adapted state is discussed.
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http://dx.doi.org/10.1021/acs.jpcb.0c08518DOI Listing
February 2021

Volumetric measurements of paranasal sinuses and examination of sinonasal communication in healthy Shetland ponies: anatomical and morphometric characteristics using computed tomography.

BMC Vet Res 2021 Jan 21;17(1):41. Epub 2021 Jan 21.

Department for Horses, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 21, D-04103, Leipzig, Germany.

Background: Despite clinical importance and frequent occurrence of sinus disease, little is known about the size of paranasal sinuses and their communication in ponies and small horses. To examine the shape and volume of the paranasal sinuses and evaluate the sinonasal communication, three-dimensional (3D) reconstructions of computed tomography (CT) datasets of 12 healthy adult Shetland ponies were performed and analysed. Linear measurements of head length and width were taken. Using semi-automatic segmentation, 3D-models of all sinus compartments were created. Volumetric measurement of the seven sinus compartments were conducted and statistical analysis was performed. Sinus volumes were compared between the left and right sinuses and the relation to age and head size was evaluated.

Results: Structure and shape of the paranasal sinus system in Shetland ponies was similar to that of large horses. All seven sinus compartments on each side of the head were identified (rostral maxillary sinus, ventral conchal sinus, caudal maxillary sinus, dorsal conchal sinus, middle conchal sinus, frontal sinus, sphenopalatine sinus). The existence of a bilateral cranial and a caudal system formed by a maxillary septum was visible in all 12 individuals. The volumetric sizes of the left and right sinuses did not differ significantly (p > 0.05). A positive correlation between the size of the paranasal sinuses and the head length was shown. A relation between sinus volumes and age could not be proved in adult ponies aged > six years. Communication between single sinus compartments was identified. Furthermore, communication with the nasal cavity over the nasomaxillary aperture (Apertura nasomaxillaris) and a common sinonasal channel (Canalis sinunasalis communis) as well as its splitting up into a rostral and a caudolateral channel could be seen. Examination of the sinonasal communication was challenging and only a descriptive evaluation was possible.

Conclusions: Our findings concerning the size, shape and volumetric dimensions of Shetland pony CT images could help improve CT interpretation of abnormal clinical cases as well as aiding clinicians to develop and select appropriate instruments for medical inspection and treatments.
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http://dx.doi.org/10.1186/s12917-021-02748-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818571PMC
January 2021

Integral Use of Thromboelastography With Platelet Mapping to Guide Appropriate Treatment, Avoid Complications, and Improve Survival of Patients With Coronavirus Disease 2019-Related Coagulopathy.

Crit Care Explor 2020 Dec 21;2(12):e0287. Epub 2020 Dec 21.

Metropolitan Emergency Medical Services Medical Directors Alliance, Dallas, TX.

Objectives: Coagulopathy of coronavirus disease 2019 is largely described as hypercoagulability, yet both thrombotic and hemorrhagic complications occur. Although therapeutic and prophylactic anticoagulant interventions have been recommended, empiric use of antifactor medications (heparin/enoxaparin) may result in hemorrhagic complications, including death. Furthermore, traditional (antifactor) anticoagulation does not address the impact of overactive platelets in coronavirus disease 2019. The primary aim was to evaluate if algorithm-guided thromboelastography with platelet mapping could better characterize an individual's coronavirus disease 2019-relatedcoagulopathic state and, secondarily, improve outcomes.

Design Setting And Patients: Coronavirus disease 2019 patients ( = 100), receiving thromboelastography with platelet mapping assay upon admission to an 800-bed tertiary-care hospital, were followed prospectively by a hospital-based thromboelastography team. Treating clinicians were provided with the option of using a pre-established algorithm for anticoagulation, including follow-up thromboelastography with platelet mapping assays. Two groups evolved: 1) patients managed by thromboelastography with platelet mapping algorithm (algorithm-guided-thromboelastography); 2) those treated without thromboelastography with platelet mapping protocols (non-algorithm-guided). Outcomes included thrombotic/hemorrhagic complications, pulmonary failure, need for mechanical ventilation, acute kidney injury, dialysis requirement, and nonsurvival.

Interventions: Standard-of-care therapy with or without algorithm-guided-thromboelastography support.

Measurements And Main Results: Although d-dimer, C-reactive protein, and ferritin were elevated significantly in critically ill (nonsurvivors, acute kidney injury, pulmonary failure), they did not distinguish between coagulopathic and noncoagulopathic patients. Platelet hyperactivity (maximum amplitude-arachidonic acid/adenosine diphosphate > 50 min), with or without thrombocytosis, was associated with thrombotic/ischemic complications, whereas severe thrombocytopenia (platelet count < 100,000/μL) was uniformly fatal. Hemorrhagic complications were observed with decreased factor activity (reaction time > 8 min). Non-algorithm-guided patients had increased risk for subsequent mechanical ventilation (relative risk = 10.9; < 0.0001), acute kidney injury (relative risk = 2.3; = 0.0017), dialysis (relative risk = 7.8; < 0.0001), and death (relative risk = 7.7; < 0.0001), with 17 of 28 non-algorithm-guided patients (60.7%) dying versus four algorithm-guided-thromboelastography patients (5.6%) ( < 0.0001). Thromboelastography with platelet mapping-guided antiplatelet treatment decreased mortality 82% ( = 0.0002), whereas non-algorithm-guided (compared with algorithm-guided-thromboelastography) use of antifactor therapy (heparin/enoxaparin) resulted in 10.3-fold increased mortality risk ( = 0.0001).

Conclusions: Thromboelastography with platelet mapping better characterizes the spectrum of coronavirus disease 2019 coagulation-related abnormalities and may guide more tailored, patient-specific therapies in those infected with coronavirus disease 2019.
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http://dx.doi.org/10.1097/CCE.0000000000000287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769351PMC
December 2020

An anatomical study of the dorsal and ventral nasal conchal bullae and middle nasal conchae in normal Shetland ponies: Computed tomographic anatomical and morphometric findings.

Anat Histol Embryol 2021 May 16;50(3):431-438. Epub 2020 Dec 16.

Max Planck Institute for Evolutionary Anthropology, Max Planck Weizmann Center for Integrative Archaeology and Anthropology (MPWC), Leipzig, Germany.

Equine paranasal sinuses are susceptible to inflammation. Insufficient drainage through the nasal passages and meatus may lead to the accumulation of inspissated purulent discharge. Particularly in ponies, these anatomical structures are suspected to be relatively small. To date, there are no reports considering the morphology of nasal conchal bullae in small horse breeds such as Shetland ponies. The aim of the present study was to evaluate the size of the conchal bullae and the medial nasal conchae of Shetland ponies and their relation to the skull dimension using computed tomography. Reconstructed images of healthy adult heads of Shetland ponies were used. Linear skull measurements as well as two cranial indices of the head dimensions were taken. Length, width and height of the dorsal and ventral conchal bullae and the medial nasal conchae were measured in relation to the skull and compared with the data of skulls of large breed horses. The anatomical proportions of pony heads were characterized by a smaller cranial index and a greater nasal index than those of large breed horses. Shetland ponies showed a longer cranial length compared with the nasal length. Heads are consistently smaller, and the relationship of the bullae to the head length was also smaller than those measured in large breed horses. A negative correlation between the head and bullae size was found. In conclusion, this study suggests that Shetland ponies have distinguishing proportions of the head. These findings are relevant for clinical examination and surgical treatment of equine sinus disease in those breeds.
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http://dx.doi.org/10.1111/ahe.12646DOI Listing
May 2021

Scoping review of biological treatment of deficiency of interleukin-36 receptor antagonist (DITRA) in children and adolescents.

Pediatr Rheumatol Online J 2019 Jul 8;17(1):37. Epub 2019 Jul 8.

Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU, Munich, Germany.

Background: Deficiency of interleukin-36 receptor antagonist (DITRA) is a life threatening monogenic autoinflammatory disease caused by loss of function mutations in the IL36RN gene. Affected patients develop recurrent episodes of generalized pustular psoriasis (GPP) with systemic inflammation and fever. We here review and analyze the literature on pediatric DITRA patients who have been treated by biologicals targeting inflammatory cytokines.

Method: A database research was performed to identify all relevant articles on pediatric DITRA patients treated with biologicals. According to defined response criteria therapeutic efficacy was analyzed.

Results: Our literature research revealed 12 pediatric patients with DITRA who have received treatment with biologicals and we add a further not yet reported patient. Out of these 13 patients 10 were homozygous including 6 with the p.Leu27Pro, 3 with the p.Arg10 Argfs* and 1 with the p.Thr123Met mutation. 3 patients were compound heterozygous. In total 28 flares were treated with biological agents- targeting IL-1, IL-17, IL-12/23 and TNF-α. Complete response was achieved in 16 flares (57%), a partial reponse was seen in 2 flares (7%), and no response was observed in 10 flares (36%). Response rates were heterogeneous among the different agents. While complete/partial/no response with inhibition of TNF-alpha could be achieved in 7 (58%)/1 (8%)/4 (33%), the inhibition of IL-17 and of IL-12/23 led in each 4 flares to a 100% complete response. IL-1 inhibition led to complete/partial response in each 1 (13%) and was not effective in 6 (76%) flares. Of note, the novel patient was successfully treated with weekly dosed adalimumab.

Conclusions: DITRA is a rare disease that has to be considered in GPP with systemic inflammation and fever. It can be effectively treated with specific biological inhibition of TNF-alpha, IL-12/23 and IL- 17, while anti-IL-1 treatment seems less effective. Weekly dosed adalimumab appears to be a treatment option for pediatric patients. Further reports and studies of biological treated pediatric DITRA patients are warranted for evaluation of optimal treatment.
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http://dx.doi.org/10.1186/s12969-019-0338-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615208PMC
July 2019

Carfentanil and Current Opioid Trends in Summit County, Ohio.

Acad Forensic Pathol 2017 Dec 1;7(4):632-639. Epub 2017 Dec 1.

Summit County Medical Examiners Office.

Introduction: The Summit County Medical Examiner's Office (SCMEO) observed 52 unexplained deaths during the month of July 2016 in which drug overdose was suspected. A fentanyl screening immunoassay performed on autopsy specimens was positive, but gas chromatograph/mass spectrometry (GC/MS) failed to confirm its presence. Carfentanil, a large wildlife tranquilizer, was later identified through reference lab testing as the cause of the sudden increase in overdoses.

Methods: Due to the large volume of cases which followed, a method for identifying carfentanil was developed utilizing in-house instrumentation. In addition, a retrospective analysis for all drug overdose cases was conducted through the SCMEO database from January 2009 through December 2016.

Results: Assessment of the data revealed a 277% increase in yearly overdose-related fatalities when comparing 2009 to 2016. Carfentanil was not identified in any other fatal drug overdoses in the area before the first appearance in Akron in July of 2016. There was an initial spike of 35 deaths in both July and August, which then decreased to 12 deaths in December. There was an almost equal distribution of carfentanil as a single agent and carfentanil mixed with multiple other illicit drugs.

Discussion: Current observations suggest carfentanil concentrations in overdose cases are decreasing; however, it may be present in combination with other drugs, especially other fentanyl analogs. The lower concentrations of carfentanil are much more difficult to detect in urine and peripheral blood, therefore making the testing of scene paraphernalia, central blood, and organ tissue more of a necessity.
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http://dx.doi.org/10.23907/2017.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474443PMC
December 2017

The Doktabörse - an innovative online platform for research projects at the medical faculty of the LMU Munich.

GMS J Med Educ 2017 15;34(3):Doc30. Epub 2017 Aug 15.

Klinikum der LMU München, Institut für Didaktik und Ausbildungsforschung in der Medizin, München, Germany.

One of the most important extracurricular aspects of medical studies in Germany is a research thesis completed by most students. This research project often times conveys relevant competencies for the physician's role as scientist. Nevertheless, the choice of the right project remains a challenge. Reasons for this are among others, missing structures for a comprehensive overview of research groups and their respective projects. We developed the online platform as an online marketplace for doctoral research projects. The platform enables authorized researchers to create working groups and upload, deactivate and change research projects within their institute. For interested students, a front end with integrated search function displays these projects in a structured and well-arranged way. In parallel, the provides for a comprehensive overview of research at the medical faculty. We evaluated Researchers' and students' use of the platform. 96,6% of students participating in the evaluation (n=400) were in favor of a centralized research platform at the medical faculty. The platform grew at a steady pace and included 120 research groups in June 2016. The students appreciated the structure and design of the Two thirds of all uploaded projects matched successfully with doctoral students via the platform and over 94% of researchers stated that they did not need technical assistance with uploading projects and handling the platform. : The represents an innovative and well accepted platform for doctoral research projects. The platform is perceived positively by researchers and students alike. However, students criticized limited extent and timeliness of offered projects. In addition, the platform serves as databank of research at the medical faculty of the LMU Munich. The future potential of this platform is to provide for an integrated management solution of doctoral thesis projects, possibly beyond the medical field and faculty.
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http://dx.doi.org/10.3205/zma001107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569987PMC
October 2018

Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap Cornelia de Lange syndrome.

Am J Med Genet A 2014 Jan 29;164A(1):251-8. Epub 2013 Oct 29.

Department of Genetics, Akron Children's Hospital, Akron, Ohio.

Rubinstein-Taybi syndrome (RTS) and Cornelia de Lange syndrome (CdLS) are genetically heterogeneous multiple anomalies syndromes, each having a distinctive facial gestalt. Two genes (CREBBP and EP300) are known to cause RTS, and five (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) have been associated with CdLS. A diagnosis of RTS or CdLS is molecularly confirmed in only 65% of clinically identified cases, suggesting that additional causative genes exist for both conditions. In addition, although EP300 and CREBBP encode homologous proteins and perform similar functions, only eight EP300 positive RTS patients have been reported, suggesting that patients with EP300 mutations might be escaping clinical recognition. We report on a child with multiple congenital abnormalities and intellectual disability whose facial features and complex phenotype resemble CdLS. However, no mutations in CdLS-related genes were identified. Rather, a novel EP300 mutation was found on whole exome sequencing. Possible links between EP300 and genes causing CdLS are evident in the literature. Both EP300 and HDAC8 are involved in the regulation of TP53 transcriptional activity. In addition, p300 and other chromatin associated proteins, including NIPBL, SMCA1, and SMC3, have been found at enhancer regions in different cell types. It is therefore possible that EP300 and CdLS-related genes are involved in additional shared pathways, producing overlapping phenotypes. As whole exome sequencing becomes more widely utilized, the diverse phenotypes associated with EP300 mutations should be better understood. In the meantime, testing for EP300 mutations in those with features of CdLS may be warranted.
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http://dx.doi.org/10.1002/ajmg.a.36237DOI Listing
January 2014

Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap Cornelia de Lange syndrome.

Am J Med Genet A 2014 Jan 29;164A(1):251-8. Epub 2013 Oct 29.

Department of Genetics, Akron Children's Hospital, Akron, Ohio.

Rubinstein-Taybi syndrome (RTS) and Cornelia de Lange syndrome (CdLS) are genetically heterogeneous multiple anomalies syndromes, each having a distinctive facial gestalt. Two genes (CREBBP and EP300) are known to cause RTS, and five (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) have been associated with CdLS. A diagnosis of RTS or CdLS is molecularly confirmed in only 65% of clinically identified cases, suggesting that additional causative genes exist for both conditions. In addition, although EP300 and CREBBP encode homologous proteins and perform similar functions, only eight EP300 positive RTS patients have been reported, suggesting that patients with EP300 mutations might be escaping clinical recognition. We report on a child with multiple congenital abnormalities and intellectual disability whose facial features and complex phenotype resemble CdLS. However, no mutations in CdLS-related genes were identified. Rather, a novel EP300 mutation was found on whole exome sequencing. Possible links between EP300 and genes causing CdLS are evident in the literature. Both EP300 and HDAC8 are involved in the regulation of TP53 transcriptional activity. In addition, p300 and other chromatin associated proteins, including NIPBL, SMCA1, and SMC3, have been found at enhancer regions in different cell types. It is therefore possible that EP300 and CdLS-related genes are involved in additional shared pathways, producing overlapping phenotypes. As whole exome sequencing becomes more widely utilized, the diverse phenotypes associated with EP300 mutations should be better understood. In the meantime, testing for EP300 mutations in those with features of CdLS may be warranted.
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http://dx.doi.org/10.1002/ajmg.a.36237DOI Listing
January 2014

A clinical pharmacist's role in screening for metabolic syndrome in a rural pediatric ambulatory clinic.

J Rural Health 2011 17;27(2):184-9. Epub 2010 Sep 17.

Department of Pharmacy Practice, Nova Southeastern University, Fort Lauderdale, Florida 33228, USA.

Purpose: The prevalence of metabolic syndrome in the pediatric population is increasing. Barriers, including the lack of consensus of a definition for metabolic syndrome and time constraints for the pediatrician, may limit the identification and diagnosis of metabolic syndrome in children. The objective of this pilot study was to evaluate the role of a clinical pharmacist (CP) in screening children and adolescents for metabolic syndrome.

Methods: A 3-month, prospective, cross-sectional study aimed at utilizing a CP to identify metabolic syndrome in high-risk children, ages 10-18 years, in a pediatric ambulatory clinic located in a rural community health center was conducted. Upon enrollment a personal and family medical history was obtained, physical examination was reviewed, and a fasting laboratory analysis was performed. The CP evaluated each component of metabolic syndrome to determine if the participant met criteria for diagnosis. The CP provided a summary of the risk factors and treatment recommendations to the pediatrician.

Findings: Twenty-five Mexican American participants (ages 13.7 ± 2.3 years) enrolled and completed the study. One child (4%) met 3 or more criteria required for diagnosis of metabolic syndrome. Of the remaining participants, 7 (28%) met 2 criteria, 9 (36%) met 1 criterion, and 8 (32%) met no criteria for metabolic syndrome. The CP provided treatment recommendations for 68% of the participants.

Conclusion: CPs can have an active role in early identification of specific components of metabolic syndrome in a rural community health center.
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http://dx.doi.org/10.1111/j.1748-0361.2010.00329.xDOI Listing
August 2011

Erdheim-chester disease associated with marginal zone lymphoma and monoclonal proteinemia.

Case Rep Hematol 2011 20;2011:941637. Epub 2011 Oct 20.

Department of Pathology, University Hospitals Case Medical Center and Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5056, USA.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. We report a fatal case of ECD with extensive cardiac involvement associated with a marginal zone lymphoma and monoclonal proteinemia in a young man. This is the first reported association of ECD with a monoclonal gammopathy or a lymphoma.
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http://dx.doi.org/10.1155/2011/941637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420507PMC
August 2012

Deaths associated with liposuction: case reports and review of the literature.

J Forensic Sci 2002 Jan;47(1):205-7

Summit County Medical Examiner's Office, Akron, OH 44308, USA.

Tumescent liposuction is a common cosmetic procedure that is performed as an outpatient service in physician's offices and is largely believed to be safe. The protuberant areas of the body containing the undesirable fat deposits are injected with normal saline containing lidocaine and epinephrine for pain control and hemostasis, and the waterlogged cells are suctioned out via cannula through a small incision. We recently encountered three cases in which deaths were attributed to this procedure. Two showed fat embolization in the lung and one died from fluid overload. The osmium tetroxide post-fixed lung sections showed fat emboli in the interstitial capillaries and arterioles. We reviewed the recent literature and found that pulmonary thromboemboli, fat embolization, fluid overload, and lidocaine and epinephrine intoxication are found at autopsy in many cases. Forensic pathologists responsible for determining the cause and manner of death should become familiar with the postmortem findings and risks of liposuction therapy and communicate them to their clinical colleagues and communities.
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January 2002