On-Field and Pitch-Side (Sideline) Assessment of Sports Concussion in Collision Sports: An Expert Consensus Statement Using the Modified Delphi Technique.

PURPOSE: To perform a Delphi consensus for on-field and pitch-side assessment of sports-related concussion (SRC). METHODS: Open-ended questions in rounds 1 and 2 were answered. The results of the first 2 rounds were used to develop a Likert-style questionnaire for round 3. If agreement at round 3 was ≤80% for an item, if panel members were outside consensus, or there were >30% neither agree/disagree responses, the results were carried forward into round 4. The level of agreement and consensus was defined as 90%. RESULTS: Loss of consciousness (LOC) or suspected LOC, motor incoordination/ataxia, balance disturbance, confusion/disorientation, memory disturbance/amnesia, blurred vision/light sensitivity, irritability, slurred speech, slow reaction time, lying motionless, dizziness, headaches/pressure in the head, falling to the ground with no protective action, slow to get up after a hit, dazed look, and posturing/seizures were clinical signs of SRC and indicate removal from play. Video assessment is helpful but should not replace clinical judgment. LOC/unresponsiveness, signs of cervical spine injury, suspicion of other fractures (skull/maxillo-facial), seizures, Glasgow Coma Scale score <14 and abnormal neurologic examination findings are indications for hospitalization. Return to play should only be considered when no clinical signs of SRC are present. Every suspected concussion should be referred to an experienced physician. CONCLUSIONS: Consensus was achieved for 85% of the clinical signs indicating concussion. On-field and pitch-side assessment should include the observation of the mechanism, a clinical examination, and cervical spine assessment. Of the 19 signs and red flags requiring removal from play, consensus was reached for 74%. Normal clinical examination and HIA with no signs of concussion allow return to play. Video assessment should be mandatory for professional games but should not replace clinical decision-making. Sports Concussion Assessment Tool, Glasgow Coma Scale, vestibular/ocular motor screening, Head Injury Assessment Criteria 1, and Maddocks questions are useful tools. Guidelines are helpful for non-health professionals. LEVEL OF EVIDENCE: Level V, expert opinion.

Return to Sports Following Sports-Related Concussion in Collision Sports: An Expert Consensus Statement Using the Modified Delphi Technique.

PURPOSE: To perform a Delphi consensus for return to sports (RTS) following sports-related concussion (SRC). METHODS: Open-ended questions in rounds 1 and 2 were answered. The results of the first 2 rounds were used to develop a Likert-style questionnaire for round 3. If agreement at round 3 was ≤80% for an item, if panel members were outside consensus or there were >30% neither agree/disagree responses, the results were carried forward into round 4. The level of agreement and consensus was defined as 90%. RESULTS: Individualized graduated RTS protocols should be used. A normal clinical, ocular and balance examination with no more headaches, and asymptomatic exertional test allows RTS. Earlier RTS can be considered if athletes are symptom free. The Sports Concussion Assessment Tool 5 and vestibular and ocular motor screening are recognized as useful tools to assist in decision-making. Ultimately RTS is a clinical decision. Baseline assessments should be performed at both collegiate and professional level and a combination of neurocognitive and clinical tests should be used. A specific number of recurrent concussions for season-or career-ending decisions could not be determined but will affect decision making for RTS. CONCLUSIONS: Consensus was achieved for 10 of the 25 RTS criteria: early RTS can be considered earlier than 48 to 72 hours if athletes are completely symptom-free with no headaches, a normal clinical, ocular and balance examination. A graduated RTS should be used but should be individualized. Only 2 of the 9 assessment tools were considered to be useful: Sports Concussion Assessment Tool 5 and vestibular and ocular motor screening. RTS is mainly a clinical decision. Only 31% of the baseline assessment items achieved consensus: baseline assessments should be performed at collegiate and professional levels using a combination of neurocognitive and clinical tests. The panel disagreed on the number of recurrent concussions that should be season- or career-ending. LEVEL OF EVIDENCE: Level V, expert Opinion.

Differential expression of immunity-related genes in larval Manduca sexta tissues in response to gut and systemic infection.

Introduction: The midgut epithelium functions as tissue for nutrient uptake as well as physical barrier against pathogens. Additionally, it responds to pathogen contact by production and release of various factors including antimicrobial peptides, similar to the systemic innate immune response. However, if such a response is restricted to a local stimulus or if it appears in response to a systemic infection, too is a rather underexplored topic in insect immunity. We addressed the role of the midgut and the role of systemic immune tissues in the defense against gut-borne and systemic infections, respectively. Methods: Manduca sexta larvae were challenged with DAP-type peptidoglycan bacteria - Bacillus thuringiensis for local gut infection and Escherichia coli for systemic stimulation. We compared the immune response to both infection models by measuring mRNA levels of four selected immunity-related genes in midgut, fat body, hematopoietic organs (HOs), and hemocytes, and determined hemolymph antimicrobial activity. Hemocytes and HOs were tested for presence and distribution of lysozyme mRNA and protein. Results: The midgut and circulating hemocytes exhibited a significantly increased level of lysozyme mRNA in response to gut infection but did not significantly alter expression in response to a systemic infection. Conversely, fat body and HOs responded to both infection models by altered mRNA levels of at least one gene monitored. Most, but not all hemocytes and HO cells contain lysozyme mRNA and protein. Discussion: These data suggest that the gut recruits immune-related tissues in response to gut infection whereas systemic infections do not induce a response in the midgut. The experimental approach implies a skewed cross-talk: An intestinal infection triggers immune activity in systemic immune organs, while a systemic infection does not elicit any or only a restricted immune response in the midgut. The HOs, which form and release hemocytes in larval M. sexta, i) synthesize lysozyme, and ii) respond to immune challenges by increased immune gene expression. These findings strongly suggest that they not only provide phagocytes for the cellular immune response but also synthesize humoral immune components.

Uterine leiomyoma with RAD51B::NUDT3 fusion: a report of 2 cases.

Three main uterine leiomyoma molecular subtypes include tumors with MED12 mutation, molecular aberrations leading to HMGA2 overexpression, and biallelic loss of FH. These aberrations are mutually exclusive and can be found in approximately 80-90% of uterine leiomyoma, in which they seem to be a driver event. Approximately 10% of uterine leiomyoma, however, does not belong to any of these categories. Uterine leiomyoma with HMGA2 overexpression is the most common subtype in cellular and second most common category of usual leiomyoma. In some of these tumors, rearrangement of HMGA2 gene is present. The most common fusion partner of HMGA2 gene is RAD51B. Limited data suggests that RAD51B fusions with other genes may be present in uterine leiomyoma. In our study, we described two cases of uterine leiomyoma with RAD51B::NUDT3 fusion, which occur in one case of usual and one case of highly cellular leiomyoma. In both cases, no other driver molecular aberrations were found. The results of our study showed that RAD51::NUDT3 fusion can occur in both usual and cellular leiomyoma. RAD51B may be a fusion partner of multiple genes other than HMGA2 and HMGA1. In these cases, RAD51B fusion seems to be mutually exclusive with other driver aberrations defining molecular leiomyoma subtypes. RAD51B::NUDT3 fusion should be added to the spectrum of fusions which may occur in uterine leiomyoma, which can be of value especially in cellular leiomyoma in the context of differential diagnosis against endometrial stromal tumors.

A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations.

BACKGROUND: Molecular aberrations occurring in primary ovarian clear cell carcinoma (OCCC) can be of diagnostic, predictive, and prognostic significance. However, a complex molecular study including genomic and transcriptomic analysis of large number of OCCC has been lacking. METHODS: 113 pathologically confirmed primary OCCCs were analyzed using capture DNA NGS (100 cases; 727 solid cancer related genes) and RNA-Seq (105 cases; 147 genes) in order to describe spectra and frequency of genomic and transcriptomic alterations, as well as their prognostic and predictive significance. RESULTS: The most frequent mutations were detected in genes ARID1A, PIK3CA, TERTp, KRAS, TP53, ATM, PPP2R1A, NF1, PTEN, and POLE (51,47,27,18,13,10,7,6,6, and 4%, respectively). TMB-High cases were detected in 9% of cases. Cases with POLEmut and/or MSI-High had better relapse-free survival. RNA-Seq revealed gene fusions in 14/105 (13%) cases, and heterogeneous expression pattern. The majority of gene fusions affected tyrosine kinase receptors (6/14; four of those were MET fusions) or DNA repair genes (2/14). Based on the mRNA expression pattern, a cluster of 12 OCCCs characterized by overexpression of tyrosine kinase receptors (TKRs) AKT3, CTNNB1, DDR2, JAK2, KIT, or PDGFRA (p < 0.00001) was identified. CONCLUSIONS: The current work has elucidated the complex genomic and transcriptomic molecular hallmarks of primary OCCCs. Our results confirmed the favorable outcomes of POLEmut and MSI-High OCCC. Moreover, the molecular landscape of OCCC revealed several potential therapeutical targets. Molecular testing can provide the potential for targeted therapy in patients with recurrent or metastatic tumors.

Examining later-in-life health risks associated with sport-related concussion and repetitive head impacts: a systematic review of case-control and cohort studies.

OBJECTIVE: Concern exists about possible problems with later-in-life brain health, such as cognitive impairment, mental health problems and neurological diseases, in former athletes. We examined the future risk for adverse health effects associated with sport-related concussion, or exposure to repetitive head impacts, in former athletes. DESIGN: Systematic review. DATA SOURCES: Search of MEDLINE, Embase, Cochrane, CINAHL Plus and SPORTDiscus in October 2019 and updated in March 2022. ELIGIBILITY CRITERIA: Studies measuring future risk (cohort studies) or approximating that risk (case-control studies). RESULTS: Ten studies of former amateur athletes and 18 studies of former professional athletes were included. No postmortem neuropathology studies or neuroimaging studies met criteria for inclusion. Depression was examined in five studies in former amateur athletes, none identifying an increased risk. Nine studies examined suicidality or suicide as a manner of death, and none found an association with increased risk. Some studies comparing professional athletes with the general population reported associations between sports participation and dementia or amyotrophic lateral sclerosis (ALS) as a cause of death. Most did not control for potential confounding factors (eg, genetic, demographic, health-related or environmental), were ecological in design and had high risk of bias. CONCLUSION: Evidence does not support an increased risk of mental health or neurological diseases in former amateur athletes with exposure to repetitive head impacts. Some studies in former professional athletes suggest an increased risk of neurological disorders such as ALS and dementia; these findings need to be confirmed in higher quality studies with better control of confounding factors. PROSPERO REGISTRATION NUMBER: CRD42022159486.

Amsterdam 2022 process: A summary of the methodology for the Amsterdam International Consensus on Concussion in Sport.

The purpose of this paper is to summarise the consensus methodology that was used to inform the International Consensus Statement on Concussion in Sport (Amsterdam 2022). Building on a Delphi process to inform the questions and outcomes from the 5th International Conference on Concussion in Sport, the Scientific Committee identified key questions, the answers to which would help encapsulate the current science in sport-related concussion and help guide clinical practice. Over 3½ years, delayed by 2 years due to the pandemic, author groups conducted systematic reviews on each selected topic. The 6th International Conference on Concussion in Sport was held in Amsterdam (27-30 October 2022) and consisted of 2 days of systematic review presentations, panel discussions, question and answer engagement with the 600 attendees, and abstract presentations. This was followed by a closed third day of consensus deliberations by an expert panel of 29 with observers in attendance. The fourth day, also closed, was dedicated to a workshop to discuss and refine the sports concussion tools (Concussion Recognition Tool 6 (CRT6), Sport Concussion Assessment Tool 6 (SCAT6), Child SCAT6, Sport Concussion Office Assessment Tool 6 (SCOAT6) and Child SCOAT6). We include a summary of recommendations for methodological improvements for future research that grew out of the systematic reviews.

Consensus statement on concussion in sport: the 6th International Conference on Concussion in Sport-Amsterdam, October 2022.

For over two decades, the Concussion in Sport Group has held meetings and developed five international statements on concussion in sport. This 6th statement summarises the processes and outcomes of the 6th International Conference on Concussion in Sport held in Amsterdam on 27-30 October 2022 and should be read in conjunction with the (1) methodology paper that outlines the consensus process in detail and (2) 10 systematic reviews that informed the conference outcomes. Over 3½ years, author groups conducted systematic reviews of predetermined priority topics relevant to concussion in sport. The format of the conference, expert panel meetings and workshops to revise or develop new clinical assessment tools, as described in the methodology paper, evolved from previous consensus meetings with several new components. Apart from this consensus statement, the conference process yielded revised tools including the Concussion Recognition Tool-6 (CRT6) and Sport Concussion Assessment Tool-6 (SCAT6, Child SCAT6), as well as a new tool, the Sport Concussion Office Assessment Tool-6 (SCOAT6, Child SCOAT6). This consensus process also integrated new features including a focus on the para athlete, the athlete's perspective, concussion-specific medical ethics and matters related to both athlete retirement and the potential long-term effects of SRC, including neurodegenerative disease. This statement summarises evidence-informed principles of concussion prevention, assessment and management, and emphasises those areas requiring more research.

The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury.

OBJECTIVE: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. DESIGN: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus. PARTICIPANTS: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. RESULTS: The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that 'the diagnostic label 'concussion' may be used interchangeably with 'mild TBI' when neuroimaging is normal or not clinically indicated.' CONCLUSIONS: New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.

Cross-sectional study of characteristics and prevalence of musculoskeletal complaints in 1170 male golfers.

Objectives: The primary aim was to describe the characteristics and prevalence of musculoskeletal complaints of a large group of non-professional golfers. Secondary aims were to compare golfers different in (A) skill-level, (B) presence of low back pain (LBP) and (C) performance of prevention exercises. Methods: A sample of 1170 male golfers (mean age 54.98, SD=13.3) were surveyed online on personal and golf-specific characteristics, medical history and complaints in the preceding 7 days. Subgroups (A) with different golfing handicap (0 to 5, >5 to 10, >10), (B) with and without LBP and (C) who performed versus did not perform injury prevention exercises were compared using analysis of variance and χ2 test. Results: The prevalence and severity of musculoskeletal complaints was similar in everyday life and when playing golf. More than one-third of the golfers (n=436; 37.3%) reported LBP in the preceding 7 days, while other frequently affected body parts were the shoulder and knee. Golfers with different skill level differed in age and most golf-related characteristics but not in prevalence and severity of musculoskeletal complaints. Golfers with and without LBP were similar in almost all variables. Golfers who performed prevention exercises (n=371; 27.1%) were older and had a higher prevalence of complaints. Conclusion: The prevalence and severity of musculoskeletal complaints in golfers were similar to the wider population. It seems that injury prevention exercises were implemented after injury, rather than as primary prevention. Prospective studies looking at the epidemiology of injury, risk factors and interventions are required.

Affecting Microstructure and Properties of Additively Manufactured AISI 316L Steel by Rotary Swaging.

The presented work focused on the development of the microstructural and mechanical properties of a AISI 316L stainless steel workpiece prepared through additive manufacturing and subsequently processed by hot rotary swaging. In order to characterize the effects of swaging on the structural development, samples were taken for electron microscopy scanning and microhardness measurements were taken after each swaging reduction. The as-built and final swaged pieces were also subjected to tensile testing at room temperature and at 900 °C. The structural analyses showed that the hot swaging introduced a substructural formation; low angle grain boundaries prevailed over high angle ones after each pass. The swaging also imparted an almost complete elimination of the porosity and significant grain size; the average grain area decreased from the original value of 365.5 µm2 to 4.4 µm2 after the final swaging pass. The changes in the texture between the passes were negligible, however, the grain refinement went hand in hand with the microhardness increase (up to almost 300 HV1). The results of the tensile testing confirmed that the mechanical properties of the swaged pieces which improved dramatically and remained favorable up to high temperatures.

Effects of silver sulfide nanoparticles on the earthworm Eisenia andrei.

The massive production and use of silver nanoparticles (Ag NPs) have led to their increasing release into the environment. Even though the antimicrobial and cytotoxic effects of native nanoparticles have been well studied, the environmental impacts of transformation products such as silver sulfide nanoparticles (Ag2S NPs) have not been elucidated. In the present study, we assessed the toxicity of Ag2S NPs and silver nitrate (AgNO3), as a source of Ag, to the earthworm Eisenia andrei using a nominal concentration of 5 mg Ag kg-1 soil. We used the OECD guidelines to assess effects on weight loss and mortality for 14 days. After exposure, we also extracted the immune effector cells (coelomocytes) and conducted a battery of biomarker tests. To ensure the quality of the toxicological results, the structural changes of NPs during the experiment and the uptake of silver by the earthworms were monitored. During the experiment, mortality effects were not detected, but a weight loss was observed in the earthworms exposed to Ag2S NPs. Altough Ag2S NPs were engulfed by E. andrei cells, neither phenoloxidase activity nor lipid peroxidation differed from the untreated control group. Cells from earthworms treated with Ag2S NPs exerted very broad value range of nitric oxide (NO) generation, suggesting an imbalance in the NO metabolism. Overall, this study suggests minimal risks associated with Ag2S NPs exposure to earthworms. However, further studies are needed to assure no immunotoxicological or chronic effects on a wider range of terrestrial organisms.

Influence of Cryo-Processing and Post-SPD Annealing on Creep Behavior of CP Titanium.

The commercial purity of VT1-0 titanium was processed by the rolling process and executed at elevated, room, and cryo-temperatures. These processings led to the formation of an ultrafine-grained microstructure, with the mean grain size at a nanometer level. Some of these materials were statically annealed at a temperature of 823 K for 1 h, which led to significant subgrains and grain coarsening. The constant load creep tests in tension were carried out in argon on all states of materials, at temperatures of 648-723 K and different ranges of applied stresses. From the value of the steady-state creep rate, the control creep mechanisms were determined. The microstructure analyses were carried out via SEM and TEM. It was found that titanium prepared at elevated and room temperatures have a higher creep strength than titanium prepared at cryo-temperatures. Furthermore, the post-SPD -annealing led to a significant decrease in the creep properties. The influence of the preparation temperature on the difference of the creep behavior were discussed and explained using the microstructure analyses of the tests' samples.

Creep Resistance of S304H Austenitic Steel Processed by High-Pressure Sliding.

Sheets of coarse-grained S304H austenitic steel were processed by high-pressure sliding (HPS) at room temperature and a ultrafine-grained microstructure with a mean grain size of about 0.14 µm was prepared. The microstructure changes and creep behavior of coarse-grained and HPS-processed steel were investigated at 500-700 °C under the application of different loads. It was found that the processing of S304H steel led to a significant improvement in creep strength at 500 °C. However, a further increase in creep temperature to 600 °C and 700 °C led to the deterioration of creep behavior of HPS-processed steel. The microstructure results suggest that the creep behavior of HPS-processed steel is associated with the thermal stability of the SPD-processed microstructure. The recrystallization, grain growth, the coarsening of precipitates led to a reduction in creep strength of the HPS-processed state. It was also observed that in the HPS-processed microstructure the fast formation of σ-phase occurs. The σ-phase was already formed during slight grain coarsening at 600 °C and its formation was enhanced after recrystallization at 700 °C.

FIFA Sudden Death Registry (FIFA-SDR): a prospective, observational study of sudden death in worldwide football from 2014 to 2018.

OBJECTIVE: To investigate the underlying causes and regional patterns of sudden death in football (soccer) players worldwide to inform and improve existing screening and prevention measures. METHODS: From 2014 to 2018 cases of sudden cardiac death (SCD), survived sudden cardiac arrest (SCA) and traumatic sudden death were recorded by media monitoring (Meltwater), a confidential web-based data platform and data synchronisation with existing national Sudden Death Registries (n=16). Inclusion criteria were met when sudden death occurred during football-specific activity or up to 1 hour afterwards. Death during other activities was excluded. RESULTS: A total of 617 players (mean age 34±16 years, 96% men) with sudden death were reported from 67 countries; 142 players (23%) survived. A diagnosis by autopsy or definite medical reports was established in 211 cases (34%). The leading cause in players >35 years was coronary artery disease (76%) and in players ≤35 years was sudden unexplained death (SUD, 22%). In players ≤35 years the leading cause of SCD varied by region: cardiomyopathy in South America (42%), coronary artery anomaly in North America (33%) and SUD in Europe (26%). Traumatic sudden death including commotio cordis occurred infrequently (6%). Cardiopulmonary resuscitation (CPR) resulted in a survival rate of 85% with the use of an automated external defibrillator (AED) compared with 35% without. CONCLUSIONS: Regional variation in SCD aetiology should be verified by expansion of national registries and uniform autopsy protocols. Immediate access to an AED at training and competition sites, as well as CPR training for players, coaches and staff members, is needed to improve survival from SCA.

NMR- and MS-Based Untargeted Metabolomic Study of Stool and Serum Samples from Patients with Anorexia Nervosa.

Anorexia nervosa (AN), a pathological restriction of food intake, leads to metabolic dysregulation. We conducted a metabolomics study to reveal changes caused by AN and the effect of hospital realimentation on metabolism. Both stool and serum from patients with AN and healthy controls were analyzed by NMR and MS. Statistical analysis revealed several altered biochemical and anthropometric parameters and 50 changed metabolites, including phospholipids, acylcarnitines, amino acids, derivatives of nicotinic acid, nucleotides, and energy metabolism intermediates. Biochemical and anthropometric parameters were correlated with metabolomic data. Metabolic changes in patients with AN described in our study imply serious system disruption defects, such as the development of inflammation and oxidative stress, changed free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels, a deficit of vitamins, muscle mass breakdown, and a decrease in ketone bodies as an important source of energy for the brain and heart. Furthermore, our data indicate only a very slight improvement after treatment. However, correlations of metabolomic results with body weight, interleukin 6, tumor necrosis factor α, fT4, and TSH might entail better prognoses and treatment effectiveness in patients with better system parameter status. Data sets are deposited in MassIVE: MSV000087713, DOI: 10.25345/C57R7X.

Altered Serum Immunological and Biochemical Parameters and Microbiota Composition in Patients With AN During Realimentation.

Anorexia nervosa (AN) is a life-threatening psychiatric disorder with not well-described pathogenesis. Besides the genetic and sociological factors, autoimmunity is also considered to take part in AN pathogenesis. We evaluated general serological factors showing the physiological state of 59 patients with AN at hospital admission and their discharge. We detected the altered levels of some general biochemical and immunological parameters. We also detected decreased levels of appetite-regulating alpha-melanocyte stimulating hormone (α-MSH) in patients at hospital admission. Moreover, elevated anti-α-MSH IgM levels and decreased anti-α-MSH IgA levels were observed in patients with AN. Therefore, we analyzed the gut microbiota composition with special focus on α-MSH antigen-mimetic containing microbes from the Enterobacteriaceae family. We correlated gut bacterial composition with anti-α-MSH Ig levels and detected decreasing IgG levels with increasing alpha diversity. The upregulation of pro-inflammatory cytokines IL-6, IL-17, and TNF-α were detected in patients with AN both prior and after hospitalization. We also evaluated the treatment outcome and improvement was observed in the majority of patients with AN. We provide new data about various serum biochemical parameters and their changes during the patients' hospitalization, with emphasis on the immune system, and its possible participation in AN pathogenesis.

Structural Factors Inducing Cracking of Brass Fittings.

Cu-Zn-Pb brasses are popular materials, from which numerous industrially and commercially used components are fabricated. These alloys are typically subjected to multiple-step processing-involving casting, extrusion, hot forming, and machining-which can introduce various defects to the final product. The present study focuses on the detailed characterization of the structure of a brass fitting-i.e., a pre-shaped medical gas valve, produced by hot die forging-and attempts to assess the factors beyond local cracking occurring during processing. The analyses involved characterization of plastic flow via optical microscopy, and investigations of the phenomena in the vicinity of the crack, for which we used scanning and transmission electron microscopy. Numerical simulation was implemented not only to characterize the plastic flow more in detail, but primarily to investigate the probability of the occurrence of cracking based on the presence of stress. Last, but not least, microhardness in specific locations of the fitting were examined. The results reveal that the cracking occurring in the location with the highest probability of the occurrence of defects was most likely induced by differences in the chemical composition; the location the crack in which developed exhibited local changes not only in chemical composition-which manifested as the presence of brittle precipitates-but also in beta phase depletion. Moreover, as a result of the presence of oxidic precipitates and the hard and brittle alpha phase, the vicinity of the crack exhibited an increase in microhardness, which contributed to local brittleness.