Effect of coronavirus (COVID-19) pandemic on orthopedic trauma patients presenting in the emergency department of a maximum care hospital and level 1 trauma center.

INTRODUCTION: While overcrowding of emergency departments was often reported in the recent years, during the early phase of the pandemic, a reduction in patient numbers was seen. The aim of the current study was to describe the orthopedic trauma patient cohort presenting to the emergency department (ED) during the early pandemic period as compared to the cohort from the analogue time period 2019. MATERIALS AND METHODS: A single-center case-control study was performed. All the consecutive orthopedic trauma patients > 12 years presenting to the ED were included. Patients in the same time period in 2019 served as the control group. RESULTS: Compared to 2019, in 2020, 33% less patients presented in the emergency department. Patients treated in 2020 were significantly older, significantly more often brought to ED by emergency medical services and significantly more often admitted. The number of fractures and diagnoses requiring surgical treatment decreased only slightly and the proportion of these patients among all the patients was significantly higher during the pandemic than in the control period. Furthermore, a higher percentage of polytrauma patients could be found in 2020 as well. Analysis of Manchester Triage System showed significantly less not urgent patients in 2020. CONCLUSION: The present study shows a significant decline in the number of patients treated in the ED during the pandemic period but at the same time almost identical numbers of patients with fractures or diagnoses requiring surgical treatment. In the context of an overall decline in patient numbers, a stronger concentration on level 1 trauma centers seems to be evident during the pandemic.

[Out-of-hospital cardiac arrest during lockdown]. / Prähospitaler Kreislaufstillstand im Lockdown: Auswirkungen der übergreifenden Infektionspräventionsmaßnahmen während der ersten SARS-CoV-2-Welle.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Consequences of infection prevention measures during such contagion events can cause disadvantages especially for patients in out-of-hospital cardiac arrest (OHCA). METHODS: Retrospective analysis of OHCAs in one county from January-May in 2018, 2019 and 2020, with the first appearance of the SARS-CoV­2 pandemic in 2020 and a high incidence of the influenza virus in 2018. RESULTS: A total of 497 OHCAs were investigated (2018 n = 173; 2019 n = 149; 2020 n = 175). In this study, a constant resuscitation incidence (85-99 resuscitations/100,000 population/year) and locally typical patients (mean 70 years, 66% male; median PES 3) were found. There were no statistically significant differences in the initial situation of the patients (number of observed OHCAs, frequency of lay resuscitations, suspected causes of OHCAs, initial ECG rhythm) and the treatment course (frequency of return of spontaneous circulation [ROSC]/hospital admission/survival to hospital discharge, neurological outcome). None of the OHCA patients in 2020 tested positive for SARS-CoV­2 and 3 patients in 2018 tested positive for the influenza virus. DISCUSSION: The lockdown during the first wave of SARS-CoV­2 pandemic does not seem to have affected the outcome of OHCA patients without coronavirus disease 2019 (COVID-19) in the end.

Early whole-body CT for treatment guidance in patients with return of spontaneous circulation after cardiac arrest.

PURPOSE: Non-traumatic cardiac arrest (CA) and return of spontaneous circulation (ROSC) after cardiopulmonary resuscitation (CPR) are often associated with multiple pathologies. Expecting a high prevalence of important findings, a whole-body CT (WBCT) could be of relevance for therapy. The aim of this study is to investigate the feasibility and diagnostic yield of an early WBCT in this setting. METHODS: This single-center retrospective study included 100 consecutive patients (27 female; 73 male; mean age 68.5± 12.57 years) with non-traumatic, in- and out-of-hospital CA and ROSC following CPR, who underwent a contrast-enhanced WBCT within 6 h after ROSC over 12 months. CT findings were determined corresponding to anatomical region. RESULTS: Early WBCT was successfully carried out in 100% of the patients with CA and ROSC after CPR. Acute pathologies were found not only in the chest but also in the head (15%) and the abdomen (6%). Early global brain edema (n = 12), acute stroke (n = 3), pulmonary embolism (n = 10), pneumothorax (26%), acute abdominal pathologies (n = 6), iatrogenic bleeding (4%), and CPR-related injuries (93%) were detected by CT right from the beginning of the post-cardiac arrest care. CONCLUSIONS: An early WBCT is feasible and provides added diagnostic value for patients with ROSC after non-traumatic CA.

Age-matched dendritic cell subpopulations reference values in childhood.

Dendritic cells (DCs) are the most potent antigen-presenting cells and are the key link between the innate and adaptive immune response. Only a few reports with study populations of up to 50 individuals have been published with age-based reference values for DC subpopulations in healthy children. Therefore, we aimed to establish reference ranges in a larger study population of 100 healthy children, which allowed age-matched subgroups. Most previous studies were performed using a dual-platform approach. In this study, a single-platform approach in a lyse no-wash procedure was used. DC subpopulations were defined as follows: CD45(+) CD85k(+) HLA-DR(+) CD14(-) CD16(-) CD33(+) cells as myeloid DCs (mDCs) and CD45(+) CD85k(+) HLA-DR(+) CD14(-) CD16(-) CD123(+) cells as plasmacytoid DCs (pDCs). Reference ranges were established using a semi-parametric regression of age-matched absolute and relative DC counts. We found a significant decline with increasing age in the medians of mDCs (P = 0.0003) and pDCs per µl peripheral blood (PB) (P = 0.004) and in the 50%, 90% and 95% reference ranges. We also identified significantly lower absolute cell counts of mDCs per µl PB in girls than in boys for all age groups (P = 0.0015). Due to the larger paediatric study population and single-platform approach, this study may give a more precise overview of the normal age-matched development of DC subpopulations and may provide a basis for analyzing abnormal DC counts in different illnesses or therapies such as post stem cell transplantation.

The quality of applied bone cement depends on the chemical composition of the application system.

UNLABELLED: The exothermal reaction of polymethylmethacrylate leads to an extensive interaction between bone cement and the synthetic material of the application system. This chemical reaction changes the structure of the cement and might generate air inclusions. METHODS AND MATERIALS: Two application systems for bone cement made of polycarbonate (PC) and polypropylene (PP) were evaluated. The application systems were mounted in a testing unit. The testing device injects a defined amount of bone cement with a certain pressure. After the injection procedure a microscopic examination was carried out. RESULTS: There were no differences in the size and the design of the used syringes. Forty procedures were carried out. The time frame for application of the cement was 5 min in the PC group and 9 min in the PP group. There was a remarkable interaction between the plastics and the cement with the appearance of numerous air inclusions in the PC group. Barely any interaction was found in the PP group. CONCLUSION: Application systems made of PP enable a prolonged application time and a reduced number of air inclusions. Further research, especially on a molecular level as well as material tests on the quality of the applied bone cement, should be carried out.

Point-of-care testing in out-of-hospital cardiac arrest: a retrospective analysis of relevance and consequences.

BACKGROUND: Metabolic and electrolyte imbalances are some of the reversible causes of cardiac arrest and can be diagnosed even in the pre-hospital setting with a mobile analyser for point-of-care testing (POCT). METHODS: We conducted a retrospective observational study, which included analysing all pre-hospital resuscitations in the study region between October 2015 and December 2016. A mobile POCT analyser (Alere epoc®) was available at the scene of each resuscitation. We analysed the frequency of use of POCT, the incidence of pathological findings, the specific interventions based on POCT as well as every patient's eventual outcome. RESULTS: N = 263 pre-hospital resuscitations were included and in n = 98 of them, the POCT analyser was used. Of these measurements, 64% were performed using venous blood and 36% using arterial blood. The results of POCT showed that 63% of tested patients had severe metabolic acidosis (pH < 7.2 + BE < - 5 mmol/l). Of these patients, 82% received buffering treatment with sodium bicarbonate. Potassium levels were markedly divergent normal (> 6.0 mmol/l/ < 2.5 mmol/l) in 17% of tested patients and 14% of them received a potassium infusion. On average, the pre-hospital treatment time between arrival of the first emergency medical responders and the beginning of transport was 54 (± 20) min without POCT and 60 (± 17) min with POCT (p = 0.07). Overall, 21% of patients survived to hospital discharge (POCT 30% vs no POCT 16%, p = 0.01, Φ = 0.16). CONCLUSIONS: Using a POCT analyser in pre-hospital resuscitation allows rapid detection of pathological acid-base imbalances and potassium concentrations and often leads to specific interventions on scene and could improve the probability of survival.

Isolation of a lipid A bound polypeptide responsible for "LPS-initiated" mitogenesis of C3H/HeJ spleen cells.

The experiments by Sultzer and Nilsson (1), and later by Watson and Riblet (2), established that spleen cells from the C3H/HeJ strain of mouse were refractory to the mitogenic effects of bacterial lipopolysaccharides (LPS). More recently, however, experiments from our laboratory (3) demonstrated that spleen cells from C3H/HeJ mice were in fact responsive to some preparations of LPS but not to others, and that the method of extraction played a critical role in determining activity. In particular, preparations of LPS prepared by extraction with aqueous butanol had potent mitogenic activity. Our data showed that the mitogenic activity of such positive preparations of LPS coisolated with the LPS during gel filtration chromatography and subsequent equilibrium banding on CsCl. In addition, lipid A isolated from positive preparations of LPS was also capable of stimulating C3H/HeJ spleen cells. Taken together, these experiments provided rather convincing data that it was the LPS (in particular the lipid A) itself, or some contaminant very tightly bound to the lipid A, which was responsible for its biological activity. We further demonstrated that treatment of positive preparations of LPS with hot phenol rendered such preparations nonmitogenic for C3H/HeJ spleens, yet activity for other strains was only moderately decreased. These experiments would suggest either that the phenol treatment chemically alters the lipid A region of the LPS molecule or that such treatment removes the putative tightly bound contaminant responsible for C3H/HeJ mitogenesis. In the experiments reported here, we have explored in greater detail the role of lipid A in the stimulation of C3H/HeJ spleen cells. For these experiments we have utilized our earlier observations that the antibiotic polymyxin B forms a highly stable molecular complex with the lipid A region of LPS (4), and that such polymyxin B-LPS complexes are unable to mitogenically stimulate B lymphocytes (5). In addition, we have attempted to distinguish between the two potential modes of action of phenol on LPS, namely, the chemical alteration of the lipid A or the removal of a tightly bound contaminant by phenol treatment. The results of the experiments we report here support the interpretation that mitogenic activity of positive preparations of LPS is associated with a low mol wt phenol soluble polypeptide of approximately 10,000 mol wt. After partial purification, this polypeptide intitiates a significant mitogenic response at concentrations as low as 10 mug/ml. We conclude that the C3H/HeJ strain of mouse is a true nonresponder to the stimulatory effects of the lipid A region of LPS.

Macrophage stimulation by bacterial lipopolysaccharides. II. Evidence for differentiation signals delivered by lipid A and by a protein rich fraction of lipopolysaccharides.

Stimulation of macrophages to lyse tumor cells is a property common to lipopolysaccharide (LPS) extracted from a variety of smooth and rough bacterial strains by several different preparative procedures. The relationship between macrophage stimulation and the structural characteristics of LPS is defined. In protein-free LPS, lipid A bears the stimulatory signal which results in the differentiation of elicited macrophages into killer cells. The polysaccharide moiety is neither stimulatory itself nor does it block the activity of complete LPS on macrophages. Extraction of LPS by the butanol or Boivin procedures produces preparations in which LPS is complexed through its lipid A moiety to a protein rich component, LAP. Isolated LAP delivers a macrophage differentiation signal which is independent of lipid A. The presence of these two structurally distinct constituents in the cell walls of gram-negative bacteria broadens the biological environments in which they can stimulate macrophages in vivo.

[Syncope in prehospital emergency medicine]. / Synkope in der präklinischen Notfallmedizin.

Loss of consciousness is a frequent cause for an emergency call to the emergency medical services (EMS). It can be associated with life-threatening conditions. A distinction must be made between transient loss of consciousness (TLOC) and syncope, which is of cardiovascular origin by definition. Initial assessment in prehospital emergency care should follow the ABCDE algorithm including a 12-lead ECG. The presence of important risk factors such as occurrence in supine position, physical stress, palpitations, history of heart diseases, and any abnormalities in the ECG warrants hospital admission. Initial treatment without admission to an emergency department may only be acceptable for healthy patients without any risk factors and injuries, when vital signs are normal and an orthostatic etiology seems most likely.

Time to change the times? Time of recurrence of ventricular fibrillation during OHCA.

AIM OF THE STUDY: For out-of-hospital-cardiac-arrest (OHCA) due to ventricular fibrillation (VF) guidelines recommend early defibrillation followed by chest compressions for two minutes before analyzing shock success. If rhythm analysis reveals VF again, it is obscure whether VF persisted or reoccurred within the two-minutes-cycle of chest compressions after successful defibrillation. We investigated the time of VF-recurrence in OHCA. METHODS: We examined all cases of OHCA presenting with initial VF rhythm at arrival of ALS-ambulance (Marburg-Biedenkopf-County, 246.648 inhabitants) from January 2014 to March 2018. Three independent investigators analyzed corpuls3® ECG-recordings. We included ECG-data from CPR-beginning until four minutes after the third shock. VF termination was defined as the absence of a VF-waveform within 5 s of shock delivery. VF recurrence was defined as the presence of a VF-waveform in the interval 5 s post shock delivery. RESULTS: We included 185 shocks in 82 patients. 74.1% (n = 137) of all shocks terminated VF, but VF recurred in 81% (n = 111). The median (IQR) time of VF-recurrences was 27 s (13.5 s/80.5 s) after shock. 51.4% (n = 57) of VF-recurrence occurred 5-30 s after shock, 13.5% (n = 15) VF-recurrence occurred 31-60 s after shock, 21.6% (n = 24) of VF-recurrence occurred 61-120 s after shock, 13.5% (n = 15) of VF-recurrence occurred 121-240 s after shock. CONCLUSIONS: Although VF was terminated by defibrillation in 74.1%, VF recurred in 81% subsequent to the chest compression interval. Thus, VF reappears frequently and early. It is unclear to which extend chest compressions influence VF-relapse. Further studies need to re-evaluate the algorithm, timing of antiarrhythmic therapy or novel defibrillation strategies to minimize refibrillation during shockable OHCA.

Comparison of different resuscitation methods with regard to injury patterns in cardiac arrest survivors based on computer tomography.

PURPOSE: To ensure that patients survive cardiac arrest, cardiopulmonary resuscitation (CPR) is needed. However, the procedure itself can lead to severe injuries. This study aims to examine both possibilities of resuscitation - mechanical or manual - with regard to their risk of injury. To this end, we compare the injuries patterns in both groups of patients after successful resuscitation based on computer tomography (CT). METHODS: This single-centre retrospective study included 32 patients (female: 21.87 %, male: 78.12 %, Mean age: 60.22 ± 13.93 years) with cardiac arrest followed by successful mechanical CPR, who underwent an early whole-body CT. A control group of 32 patients (female: 21.87 %, male: 78.12 %, mean age: 60.75 ± 13.34 years) that had been resuscitated successfully with manual CPR was matched according to gender and age for a better statistical comparison. Patients with cardiac arrest due to trauma were excluded from the study population. RESULTS: Mechanically resuscitated patients showed significantly more CPR-related injuries than those who were resuscitated manually (100 % vs. 84.37 %; p = 0.02). In particular, dislocated rib fractures (40.47 vs. 23.80 mean rank, p < 0.01), sternal fractures (74.19 % vs. 25 %; p < 0,01), bleeding complications (29.03 % vs. 3.12 %; p = 0.01), pneumothorax (38.71 % vs. 9.37 %; p = 0.01), mediastinal haematomas (58.01 % vs. 25 %, p = 0.01) and liver lacerations (29.03 % vs. 0 %, p = 0.04) were observed significantly more in patients after mechanical CPR compared to those with manual resuscitation. CONCLUSIONS: The guideline-based use of mechanical CPR results in a significant increase of internal and musculoskeletal injuries compared to manual CPR.

Protein design: a hierarchic approach.

The de novo design of peptides and proteins has recently emerged as an approach for investigating protein structure and function. Designed, helical peptides provide model systems for dissecting and quantifying the multiple interactions that stabilize secondary structure formation. De novo design is also useful for exploring the features that specify the stoichiometry and stability of alpha-helical coiled coils and for defining the requirements for folding into structures that resemble native, functional proteins. The design process often occurs in a series of discrete steps. Such steps reflect the hierarchy of forces required for stabilizing tertiary structures, beginning with hydrophobic forces and adding more specific interactions as required to achieve a unique, functional protein.

Native-like and structurally characterized designed alpha-helical bundles.

A number of coiled coils and alpha-helical bundles have recently been designed, and many have now been structurally characterized by X-ray crystallography. Others have not been as well characterized structurally but exhibit native-like properties in aqueous solution. Both areas of investigation have contributed greatly to our understanding of the nature of specificity in this class of molecules.

Hydrophobic core malleability of a de novo designed three-helix bundle protein.

De novo protein design provides a tool for testing the principles that stabilize the structures of proteins. Recently, we described the design and structure determination of alpha(3)D, a three-helix bundle protein with a well-packed hydrophobic core. Here, we test the malleability and adaptability of this protein's structure by mutating a small, Ala residue (A60) in its core to larger, hydrophobic side-chains, Leu and Ile. Such changes introduce strain into the structures of natural proteins, and therefore generally destabilize the native state. By contrast, these mutations were slightly stabilizing ( approximately 1.5 kcal mol(-1)) to the tertiary structure of alpha(3)D. The value of DeltaC(p) for unfolding of these mutants was not greatly affected relative to wild-type, indicating that the change in solvent accessibility for unfolding was similar. However, two-dimensional heteronuclear single quantum coherence spectra indicate that the protein adjusts to the introduction of steric bulk in different ways. A60L-alpha(3)D showed serious erosion in the dispersion of both the amide backbone as well as the side-chain methyl chemical shifts. By contrast, A60I-alpha(3)D showed excellent dispersion of the backbone resonances, and selective changes in dispersion of the aliphatic side-chains proximal to the site of mutation. Together, these data suggest that alpha(3)D, although folded into a unique three-dimensional structure, is nevertheless more malleable and flexible than most natural, native proteins.

Disulfide bonds and the stability of globular proteins.

An understanding of the forces that contribute to stability is pivotal in solving the protein-folding problem. Classical theory suggests that disulfide bonds stabilize proteins by reducing the entropy of the denatured state. More recent theories have attempted to expand this idea, suggesting that in addition to configurational entropic effects, enthalpic and native-state effects occur and cannot be neglected. Experimental thermodynamic evidence is examined from two sources: (1) the disruption of naturally occurring disulfides, and (2) the insertion of novel disulfides. The data confirm that enthalpic and native-state effects are often significant. The experimental changes in free energy are compared to those predicted by different theories. The differences between theory and experiment are large near 300 K and do not lend support to any of the current theories regarding the stabilization of proteins by disulfide bonds. This observation is a result of not only deficiencies in the theoretical models but also from difficulties in determining the effects of disulfide bonds on protein stability against the backdrop of numerous subtle stabilizing factors (in both the native and denatured states), which they may also affect.

Probing weakly polar interactions in cytochrome c.

Theoretical, statistical, and model studies suggest that proteins are stabilized by weakly polar attractions between sulfur atoms and properly oriented aromatic rings. The two sulfur-containing amino acids, methionine and cysteine, occur frequently among functional alleles in random mutant libraries of Saccharomyces cerevisiae iso-1-cytochrome c genes at positions that form a weakly polar aromatic-aromatic interaction, the wild-type protein. To determine if a weakly polar sulfur-aromatic interaction replaced the aromatic-aromatic interaction, the structure and stability of two variants were examined. Phenylalanine 10, which interacts with tyrosine 97, was replaced by methionine and cysteine. The cysteine was modified to form the methionine and cysteine analog, S-methyl cysteine (CysSMe). Proton NMR studies indicate that changing Phe 10 to Met or CysSMe affects only local structure and that the structures of sulfur-containing variants are nearly identical. Analysis of chemical shifts and nuclear Overhauser effect data indicates that both sulfur-containing side chains are in position to form a weakly polar interaction with Tyr 97. The F10M and F10CSMe variants are 2-3 kcal mol-1 less stable than iso-1-cytochrome c at 300 K. Comparison of the stabilities of the F10M and F10CSMe variants allows evaluation of the potential weakly polar interaction between the additional sulfur atom of F10CSMe and the aromatic moiety of Tyr 97. The F10CSMe;C102T variant is 0.7 +/- 0.3 kcal mol-1 more stable than the F10M;C102T protein. The increased stability is explained by the difference in hydrophobicity of the sulfur-containing side chains. We conclude that any weakly polar interaction between the additional sulfur and the aromatic ring is too weak to detect or is masked by destabilizing contributions to the free energy of denaturation.

Amide proton exchange rates of oxidized and reduced Saccharomyces cerevisiae iso-1-cytochrome c.

Proton NMR spectroscopy was used to determine the rate constant, kobs, for exchange of labile protons in both oxidized (Fe(III)) and reduced (Fe(II)) iso-1-cytochrome c. We find that slowly exchanging backbone amide protons tend to lack solvent-accessible surface area, possess backbone hydrogen bonds, and are present in regions of regular secondary structure as well as in omega-loops. Furthermore, there is no correlation between kobs and the distance from a backbone amide nitrogen to the nearest solvent-accessible atom. These observations are consistent with the local unfolding model. Comparisons of the free energy change for denaturation, delta Gd, at 298 K to the free energy change for local unfolding, delta Gop, at 298 K for the oxidized protein suggest that certain conformations possessing higher free energy than the denatured state are detected at equilibrium. Reduction of the protein results in a general increase in delta Gop. Comparisons of delta Gd to delta Gop for the reduced protein show that the most open states of the reduced protein possess more structure than its chemically denatured form. This persistent structure in high-energy conformations of the reduced form appears to involve the axially coordinated heme.

Eosinophil migration in atopic dermatitis. I: Increased migratory responses to N-formyl-methionyl-leucyl-phenylalanine, neutrophil-activating factor, platelet-activating factor, and platelet factor 4.

Eosinophil granular protein deposits have been demonstrated in lesional atopic dermatitis skin. This suggests active tissue infiltration of eosinophils. To find an explanation for the tissue influx of eosinophils, eosinophil migration was studied in vitro by means of a microchemotaxis assay. Eosinophils from the circulation of patients with atopic dermatitis showed an altered capacity to respond to chemotactic stimuli in vitro compared with eosinophils from healthy donors. Eosinophils from patients with atopic dermatitis had significantly increased migratory responses toward dose ranges of N-formyl-methionyl-leucyl-phenylalanine, neutrophil-activating factor, platelet-activating factor, and platelet factor 4. Eosinophils from normal individuals did not respond to N-formyl-methionyl-leucyl-phenylalanine and neutrophil-activating factor and responded only slightly to platelet factor 4. The migratory responses toward tumor necrosis factor-alpha and complement factor C5a were identical in both groups. Interleukin-5, an eosinophil-selective cytokine, is a strong modulator of the migratory responses to these chemotaxins in eosinophils from normal donors. A migratory response toward N-formyl-methionyl-leucyl-phenylalanine and neutrophil-activating factor was induced by interleukin-5, whereas the migratory response toward platelet-activating factor and platelet factor 4 was markedly potentiated. In contrast, the response to complement fragment C5a was only slightly influenced. Our findings indicate that the increased migratory responsiveness of eosinophils from patients with atopic dermatitis to various chemotaxins reflects in vivo "priming" of eosinophils, presumably by circulating cytokines such as interleukin-5. This in vivo "priming" is not optimal because it can be further potentiated by renewed contact with interleukin-5.

An improved immunomagnetic procedure for the isolation of highly purified human blood eosinophils.

A simple method is described for the isolation of human peripheral blood eosinophils by an immunomagnetic procedure. Superparamagnetic particles were coupled to a monoclonal antibody against CD16, a molecule present on neutrophils but not on eosinophils. A peripheral blood granulocyte preparation, containing neutrophils and eosinophils, was incubated with these anti-CD16 particles. In the magnetic field of a permanent magnet, magnetically labelled neutrophils were then retained on columns with a ferromagnetic matrix. By this negative selection procedure, eosinophils of 99.5% purity were obtained from normal individuals and 99.6% purity from patients with eczema. A comparison was made between the immunomagnetic method and eosinophil isolation after N-formyl-methionyl-leucyl-phenyl-alanine treatment. Even in the case of individuals with very low eosinophil counts, the immunomagnetic method permits the efficient isolation of highly purified and functionally active eosinophils.

Granulomatous inflammation in bladder wash specimens after intravesical bacillus Calmette-Guerin therapy for transitional cell carcinoma of the bladder.

The authors retrospectively reviewed a series of bladder wash cytologic specimens and concurrently available bladder biopsy samples to evaluate granulomatous inflammation in patients receiving intravesical bacillus Calmette-Guerin (BCG) immunotherapy for transitional cell carcinoma of the bladder. Comparisons were made during the 2-month period following six weekly BCG instillations in 25 patients and during the 1-year period following the last dose of BCG in 23 patients. At some point during the 2-month follow-up period, cytologic specimens contained free histiocytes in 64%, histiocyte aggregates (resembling fragments of granulomas) in 76%, and multinucleated histiocytic giant cells in 56% of patients. Similarly, concurrent biopsy samples contained granulomas in 78% and multinucleated giant cells in 56% of patients. During the 1-year period following the last dose of BCG, inflammatory changes peaked within the first 3 months and gradually resolved at 9-12 months. In none of these instances were the cytologic features of granulomatous inflammation misinterpreted as malignant. It was concluded that the cytologic findings after intravesical BCG are more specific than previously realized and closely parallel the histologic changes seen in corresponding bladder biopsy specimens.