Diagnostic significance of secondary bacteremia in patients with COVID-19.

OBJECTIVES: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. RESULTS: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. CONCLUSIONS: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.

Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study.

BACKGROUND: Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. METHODS: We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. RESULTS: Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil-lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. CONCLUSIONS: Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.

Clinical Characteristics and Outcomes of Heart Failure Patients With Long-Term Care Insurance　- Insights From the Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

BACKGROUND: In Japan, the long-term care insurance (LTCI) system has an important role in helping elderly people, but there have been no clinical studies that have examined the relationship between the LTCI and prognosis for patients with acute heart failure (HF).Methods and Results:This registry was a prospective multicenter cohort, 1,253 patients were enrolled and 965 patients with acute HF aged ≥65 years were comprised the study group. The composite endpoint included all-cause death and hospitalization for HF after discharge. We divided the patients into 4 groups: (i) patients without LTCI, (ii) patients requiring support level 1 or 2, (iii) patients with care level 1 or 2, and (iv) patients with care levels 3-5. The Kaplan-Meier analysis identified a lower rate of the composite endpoint in group (i) than in the other groups. After adjusting for potentially confounding effects using a Cox proportional regression model, the hazard ratio (HR) of the composite endpoint increased significantly in groups (iii) and (iv) (adjusted HR, 1.62; 95% confidence interval [CI], 1.22-1.98 and adjusted HR, 1.62; 95% CI, 1.23-2.14, respectively) when compared with group (i). However, there was no significant difference between groups (i) and (ii). CONCLUSIONS: The level of LTCI was associated with a higher risk of the composite endpoint after discharge in acute HF patients.

Increased amygdala reactivity following early life stress: a potential resilience enhancer role.

BACKGROUND: Amygdala hyper-reactivity is sometimes assumed to be a vulnerability factor that predates depression; however, in healthy people, who experience early life stress but do not become depressed, it may represent a resilience mechanism. We aimed to test these hypothesis examining whether increased amygdala activity in association with a history of early life stress (ELS) was negatively or positively associated with depressive symptoms and impact of negative life event stress in never-depressed adults. METHODS: Twenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS. RESULTS: Mood change and amygdala reactivity were increased in never-depressed participants who reported ELS compared to participants who reported no ELS. Yet, increased amygdala reactivity lowered effects of ELS on depressive symptoms and negative life events stress. Amygdala reactivity also had positive functional connectivity with the bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory recall. CONCLUSIONS: Increased amygdala activity in those with ELS was associated with decreased symptoms and increased neural features, consistent with emotion regulation, suggesting that preservation of robust amygdala reactions may reflect a stress buffering or resilience enhancing factor against depression and negative stressful events.

Clinical Characteristics and Social Frailty of Super-Elderly Patients With Heart Failure　- The Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

BACKGROUND: Social background is important in preventing admission/readmission of heart failure (HF) patients. However, few clinical studies have been conducted to assess the social background of these patients, especially elderly patients.Methods and Results:The Kitakawachi Clinical Background and Outcome of Heart Failure (KICKOFF) Registry is a prospective multicenter community-based cohort of HF patients, established in April 2015. We compared the clinical characteristics and social background of the super-elderly group (≥85 years old) and the non-super-elderly group (<85 years old). This study included 647 patients; 11.8% of the super-elderly patients were living alone, 15.6% were living with only a partner, and of these, only 66.7% had the support of other family members. The super-elderly group had less control over their diet and drug therapies than the non-super-elderly group. Most patients in the super-elderly group were registered for long-term care insurance (77.4%); 73.5% of the super-elderly patients could walk independently before admission, but only 55.5% could walk independently at discharge, whereas 94% of the non-super-elderly patients could walk independently before admission and 89.4% could walk independently at discharge. CONCLUSIONS: The KICKOFF Registry provides unique detailed social background information of Japanese patients with HF. Super-elderly patients are at serious risk of social frailty; they need the support of other people and their ability to perform activities of daily living decline when hospitalized.

[Detectability of High Intensity Areas in FLAIR and Multi Shot EPI-FLAIR: Phantom Study].

In magnetic resonance imaging (MRI) of brain, fast spin echo-fluid attenuated inversion recovery (FSE-FLAIR) is widely used to detect high intensity areas (HIAs). The way of getting FLAIR contrast at high speed includes echo planar imaging-FLAIR (EPI-FLAIR), and in EPI-FLAIR there are single shot EPI-FLAIR (SS-EPI-FLAIR) and multi shot EPI-FLAIR (MS-EPI-FLAIR). There were negative opinions for the reports of SS-EPI-FLAIR, and it is reported that SS-EPI-FLAIR is able to acquire image quality that is equal to FSE-FLAIR in a shorter time, recently. But there are few reports that utilized contrast of MS-EPI-FLAIR. Our object was to compare HIA detectability in FSE-FLAIR and MS-EPI-FLAIR in equal imaging time, and to evaluate a basic characteristic. We dissolved indigestive dextrin in the aqua destillata and created a 0-46 wt% phantom. The concentration that correspond to T1, T2 value of brain white matter was 42 wt%. We calculated contrast by using signal intensities of each phantom, and compared contrast by signal intensities of each phantom, and compared the contrast of MS-EPI-FLAIR and FSE-FLAIR. In the range of 18-46 wt%, the contrast of MS-EPI-FLAIR was positive value, and that of FSE-FLAIR was 26-42 wt%. By the statistical test, contrast of MS-EPI-FLAIR in 18-26% was significantly different for FSE-FLAIR. In conclusion, it was suggestive that MS-EPI-FLAIR is able to detect HIA equally or sharply.

Surgical repair of late aortic dissection after cardiac surgery.

Late aortic dissection is a rare but serious complication associated with cardiac surgery. We report two cases of late aortic dissection that occurred after cardiac surgery. The management and review of the preoperative factors, which may predispose to this complication, are the subject of this case report.

[Management of secondary normal pressure hydrocephalus and assessment of cortical reorganization using fMRI].

We assessed the motor recovery and cortical reorganization associated with intracranial pressure (ICP) control in a secondary normal pressure hydrocephalus (sNPH) patient. A 32-year-old man with sNPH resulting from a head injury presented with left hemiplegia. A ventricular-peritoneum shunt (VP shunt) was surgically inserted for the sNPH using a Codman Hakim Programmable Valve, and his ICP was controlled according to the ventricular size by CT scanning. The motor function of the patient was evaluated by functional MRI (fMRI) during ICP control in our hospital. The fMRI was performed at 3.0 T with timed dorsal flexion-extension movement of the foot. After 3 months of shunt valve pressure control, the primary sensorimotor cortex (SM1) was activated during the affected (left) foot movement, an area that had not been able to be activated just after admission. His walking ability also recovered markedly to the point of free independent walking. The motor function of the affected lower extremity appeared to recover to almost the some degree the original motor area after control of the ICP. This finding may reflect functional reorganization of the motor pathway following ICP normalization.

[Surgical treatment for ischemic mitral regurgitation].

BACKGROUND: Ischemic mitral regurgitation (IMR) is characterized by annular dilation and restricted leaflet closure with increased leaflet tethering caused by displaced attachment of the papillary muscles. Our surgical strategy for IMR consists of mitral annuloplasty (MAP) and additional left ventricular restoration procedures as needed. When the left ventricular dilation and mitral tethering are mild, we perform MAP alone. On the other hand, we add papillary muscle approximation (PMA) through left ventriculotomy with or without infero-posteiror wall exclusion (the Batista procedure) when left ventricular dilatation and leaflet tethering are severe. METHODS: From November 2007 to April 2011, we surgically treated 19 patients with IMR at our institution. Of those, 13 patients underwent MAP alone (group M) and 6 patients underwent MAP and PMA (group P). RESULTS: There were no hospital deaths. Postoperatively, echocardiography showed no or mild mitral regurgitation (MR) in all patients except 1 patient in group M. There was significant improvement in left ventricular ejection fraction (LVEF) in both groups. Moreover, left ventricular size decreased significantly in both groups. In group P, the tethering height, area and papillary muscle distance also decreased significantly. There were no patients who developed recurrent MR postoperatively. However, in group P, there were 2 late deaths caused by congestive heart failure and sepsis, and remaining 3 patients suffered from congestive heart failure. In group M, there were no late deaths and all patients were in New York Heart Association (NYHA) class I or II. CONCLUSION: Our surgical strategy for IMR yields excellent reduction of MR. Especially the PMA provides promising effect on tethering reduction. However, the absence of recurrent MR was not associated with an improvement in symptoms and survival in patients who presented with severe left ventricular dilatation and leaflet tethering.

[Solid malignancy in patients who received cyclosporine for fibrosing interstitial pneumonia].

OBJECTIVE: Since more solid malignancies are observed in transplant recipients treated with cyclosporine (CsA) than in healthy persons. We sought to describe the incidence of malignancy in patients treated with CsA for fibrosing interstitial pneumonia. METHODS: We prospectively reviewed 43 patients who received CsA and prednisolone for fibrosing interstitial pneumonia over 180 days at our hospital between April 2004 and October 2008. The duration of CsA treatment was 632 +/- 364 days. RESULTS: Malignancy developed in 6 (14.0%) patients. Time to diagnosis after medical intervention ranged from 394 days to 1325 days (mean, 783 days). Non-small cell lung cancer was diagnosed in 4 cases. These were discovered by routine computed tomography in all cases. Hepatocellular carcinoma and gastric cancer were each diagnosed in 1 case, respectively. Incidence of malignancy tended to be higher in patients who had been treated with CsA for 567 days or more than in those who had been treated for less than 567 days, but this was not statistically significant. CONCLUSION: Our results highlight the need for close follow-up for patients who receive CsA for over 2 years. This could lead to cancer detection at an early stage.

Evaluation of RF heating on hip joint implant in phantom during MRI examinations.

PURPOSE: We evaluate radiofrequency (RF) heating of two kinds of hip joint implants of different sizes, shapes and materials. Temperature rises at various positions of each implant are measured and compared with a computer simulation based on electromagnetic-field analysis. METHODS: Two kinds of implants made of cobalt-chromium alloy and titanium alloy were embedded at a 2-cm depth of tissue-equivalent gel-phantom. The phantom was placed parallel to the static magnetic field of a 1.5 T MRI device. Scans were conducted at the specific absorption rate of 2.5 W/kg for 15 min, and temperatures were recorded with RF-transparent fiberoptic sensors. Temperatures of the implant surface were measured at 6 positions, from the tip to the head. Measured temperature rises were compared with the results of electromagnetic-field analysis. RESULTS: The maximum temperature rise was observed at the tip of each implant, and it was 9.0 degrees C for the cobalt- chromium implant and 5.3 degrees C for the titanium implant. The simulated heating positions with electromagnetic-field analysis accorded with experimental results. However, a difference in temperature rise was seen with the titanium implant. CONCLUSION: RF heating was confirmed to take place at both ends of the implants in spite of their different shapes. The maximum temperature rise was observed at the tip where there is large curvature. The value was found to depend on physical properties of the implant materials. The discrepancy between experimental and simulated temperature rises was presumed to be the result of an incomplete model for the titanium implant.

Functional interactions between the cerebellum and the premotor cortex for error correction during the slow rate force production task: an fMRI study.

Although neuroimaging studies indicate that functional magnetic resonance imaging (fMRI) signal changes in the cerebellum (CB) during the performance of a target movement reflect functions of error detection and correction, it is not well known how the CB intervenes in task-demanded movement attributes during automated on-line movement, i.e., how the CB simultaneously coordinates movement rate and error correction. The present study was undertaken to address this issue by recording fMRI signals during the performance of a task at two different movement rates (0.4 and 0.8 Hz). The results showed that movement errors increased with increasing movement rates. We also demonstrated that activation of the left CB increased with decreasing movement rates, whereas activation of the ipsilateral (right) premotor cortex (PMC) increased with increasing movement rates. Furthermore, there were significant relationships between individual movement errors and left CB activation at both movement rates, but these relationships were not observed in the ipsilateral PMC. Taken together, it is suggested that during the performance of automated and well-controlled slow force production tasks, the interactions between cortical (right PMC) and subcortical (left CB) motor circuits, i.e., a functional dissociation between PMC and CB, is exclusively dedicated to controlling movement rate and error correction. In particular, the present results showing significant relationships between individual force-control errors and CB activation might reflect functional differences of an individual's internal model.

Brain activations in errorless and errorful learning in patients with diffuse axonal injury: a functional MRI study.

PRIMARY OBJECTIVE: Errorless learning has been reported to be effective in the rehabilitation of patients with impaired cognitive functions following brain injury. This study compared brain activations in errorless learning (EL) and errorful learning (EF) in patients with diffuse axonal injury (DAI) using a functional magnetic resonance imaging (fMRI). METHODS AND PROCEDURES: The participants were 13 patients with DAI. Thirteen healthy individuals were evaluated as a control group. The participants learned words under the EL and EF conditions in advance and performed the recognition task during fMRI scanning. MAIN OUTCOMES AND RESULTS: EL in the control group was significantly faster than EF (p = 0.005), but not in the DAI group. EL in the DAI group scored significantly higher than EF (p = 0.026). An fMRI showed significant activations in the posterior cingulate gyrus (BA 31) and precuneus (BA 7) in the control group when EF > EL, but in the precuneus (BA 7, 31) and bilateral inferior parietal lobules (BA 39, 40) in the DAI group. CONCLUSIONS: These results indicate the disadvantage of EF and advantage of EL to DAI patients. The findings also reflect brain plasticity in patients with DAI in the chronic phase.

A decline in activities of daily living due to acute heart failure is an independent risk factor of hospitalization for heart failure and mortality.

BACKGROUND: Although activities of daily living (ADL) are recognized as being pertinent in averting relevant readmission of heart failure (HF) and mortality, little research has been conducted to assess a correlation between a decline in ADL and outcomes in HF patients. METHODS: The Kitakawachi Clinical Background and Outcome of Heart Failure Registry is a prospective, multicenter, community-based cohort of HF patients. We categorized the patients into four types of ADL: independent outdoor walking, independent indoor walking, indoor walking with assistance, and abasia. We defined a decline in ADL (decline ADL) as downgrade of ADL and others (non-decline ADL) as preservation of ADL before discharge compared with admission. RESULTS: Among 1253 registered patients, 923 were eligible, comprising 98 (10.6%) with decline ADL and 825 (89.4%) with non-decline ADL. Decline ADL exhibited a higher risk of hospitalization for HF and mortality compared with non-decline ADL. A multivariate analysis revealed that decline ADL emerged as an independent risk factor of hospitalization for HF [hazard ratio (HR), 1.42; 95% confidence interval (CI): 1.01-1.96; p=0.046] and mortality (HR, 1.95; 95% CI: 1.23-2.99; p<0.01). Although 66.3% of patients with decline ADL were registered for long-term care insurance, few received daycare services (32.7%) or home-visit medical services (8.2%). CONCLUSIONS: Decline in ADL is a predictor of hospitalization for HF and mortality in HF patients.

Dependence of RF heating on SAR and implant position in a 1.5T MR system.

PURPOSE: We evaluated radiofrequency (RF) heating of a humerus implant embedded in a gel phantom during magnetic resonance (MR) imaging for the specific absorption rate (SAR), angle between the implant and static magnetic field (B(0)), and position of the implant in the irradiation coil. METHODS: We embedded a stainless steel humerus implant 2 cm deep in tissue-equivalent loop and mass phantoms, placed it parallel to the static magnetic field of a 1.5T MR scanner, and recorded the temperatures of the implant surface with RF-transparent fiberoptic sensors. We measured rises in temperature at the tips of the implant by varying the SAR from 0.2 to 4.0 W/kg and evaluated RF heating of the implant for its angle to B(0) and its displacement along B(0) from the center of the RF irradiation coil. RESULTS: RF heating was similar for the loop and mass phantoms because the eddy current flows through the periphery of both. As the SAR increased, the temperature at the implant tip increased, and there was a linear relationship between the SAR and temperature rise. The values were 6.4 degrees C at 2.0 W/kg and 12.7 degrees C at 4.0 W/kg. Rise in temperature decreased steeply as the angle between the implant and B(0) surpassed 45 degrees . In addition, as the implant was displaced from the center of the RF coil to both ends, the rise in temperature decreased. CONCLUSION: The rise in temperature in deep tissue was estimated to be higher than 1.0 degrees C for SAR above 0.4 W/kg. RF heating was greatest when the implant was set parallel to B(0). In MR imaging of patients with implants, there is a risk of RF heating when the loop of the eddy current is formed inside the body.

Evaluation of RF heating on humerus implant in phantoms during 1.5T MR imaging and comparisons with electromagnetic simulation.

PURPOSE: To evaluate the effect of radiofrequency (RF) heating on a metallic implant during magnetic resonance imaging (MRI), temperatures at several positions of an implant were measured, and results are compared with electromagnetic simulations using a finite element method. METHODS: A humerus nail implant made of stainless steel was embedded at various depths of tissue-equivalent gel-phantoms with loop (loop phantom) and partially cut loop (loop-cut phantom), and the phantoms were placed parallel to the static magnetic field of a 1.5T MRI device. Scans were conducted at maximum RF for 15 min, and temperatures were recorded with 2 RF-transparent fiberoptic sensors. Finally, electromagnetic-field analysis was performed. RESULTS: Temperatures increased at both ends of the implants at various depths, and temperature increase was suppressed with increasing depth. The maximum temperature rise was 12.3 degrees C at the tip of the implant and decreased for the loop-cut phantom. These tendencies resembled the results of electromagnetic simulations. CONCLUSION: RF heating was verified even in a nonmagnetizing metal implant in a case of excessive RF irradiation. Particularly, rapid temperature rise was observed at both ends of the implant having large curvatures. The difference in temperature increase by depth was found to reflect the skin-depth effect of RF intensity. Electromagnetic simulation was extremely useful for visualizing the eddy currents within the loop and loop-cut phantoms and for evaluating RF heating of a metallic implant for MRI safety.

[Clinical analysis of the acute exacerbation in patients with idiopathic pulmonary fibrosis].

The clinical course of idiopathic pulmonary fibrosis (IPF) is chronic, but some patients with IPF have phases of accelerated deterioration superimposed on the chronic course of their illness, which is referred to as acute exacerbation (Aex) of IPF. To evaluate the clinical feature of Aex of IPF, we analyzed clinical findings of the 112 patients with IPF admitted to our hospital from 1994 to 2004. Of the 112 patients 56 with IPF died during the observation period due to Aex (42.9%), lung cancer (21.4%), chronic respiratory failure (14.3%), and lower respiratory infections (8.9%). Aex of IPF was seen 28 of 112 patients with IPF (25.0%) and 24 patients (85.7%) died with Aex. The median survival time (MST) after the onset of Aex was 0.9 months. The 5-yr survival rate of all patients with IPF was 38.3% and the MST was 3.1 yrs after diagnosis. On the other hand, the 5-yr survival rate and MST was 10.7% and 0.6 yrs in patients with Aex of IPF. We treated the patients with Aex with methylprednisolone pulse therapy in combination with cyclophosphamide or cyclosporine A, which did not significantly improve the outcome of Aex. In conclusion, there is little evidence that currently accepted treatments are effective in Aex of IPF, and further studies are needed to clarify the pathogenesis and contribute to the prevention of Aex.

[Ischemic cardiomyopathy with mitral valve regurgitation and atrial fibrillation; report of a case].

A 45-year-old man suffering from severe heart failure due to mitral regurgitation and atrial fibrillation was admitted to our hospital. He underwent intracoronary thrombolysis for left anterior descending artery 10 years ago and stent insertion for right coronary artery 3 years ago. We performed mitral annuloplasty using a Carpentier-Edwards Physio ring 28mm and modified maze procedure. The modified maze procedure consists of right sided left atriotomy extended to the left margin of the left pulmonary vein orifices and cryoablation applied to the remnant of the left atrial wall between the left upper and lower pulmonary vein orifice and cryoablation applied to the right atrial isthmus. These procedures could be effective for endstage heart failure.

[Influence of implants on human body during MRI examinations: fundamental experiment using metal balls].

It is increasingly the case that patients who have implants feel pain during high-field MRI examinations. A probable reason for the pain is the generation by irradiation of RF pulses and changing of the magnetic field gradient. As a fundamental study on the effect of implants on the human body under MRI procedures, temperature measurements were obtained from metal balls incorporated into gel-filled phantoms by using two kinds of measuring instruments, a copper-constantan thermocouple and a fluorescence fiber thermometer. At first we pursued a correlation between a copper-constantan thermocouple (absolute measurement) and fluoroptic thermometer and confirmed the precision and stability of the fluoroptic thermometer under MRI procedures. When a stainless steel ball with or without a loop antenna was used, only in the former case did the temperature rise during RF pulse irradiation. There was no significant difference between the magnetic field gradient ON and OFF. Furthermore, differences in metal (steel, aluminum, brass, stainless steel, copper) and size (5, 10, 20 mmPhi) were affected according to the increase of temperature. In conclusion, both RF pulse irradiation and a loop antenna are necessary for heat generation on the surface of metals.

The immunomodulatory effect of cryopreservation in rat tracheal allotransplantation.

BACKGROUND: Cryopreservation is one solution to the problem of donor organ deficit. To investigate the effect of cryopreservation on tracheal allografts, we performed 2 experiments in rats. METHODS: In Experiment 1, we assessed second-set graft rejection. Two weeks after primary heterotopic transplantation (Group 1, fresh isografts; Group 2, fresh allografts from Lewis rats; and Group 3, cryopreserved allografts from Lewis rats; n = 5, respectively), each animal underwent secondary heterotopic grafting with isografts and allografts from Lewis and Wistar Furth rats (n = 5, respectively). Four weeks after the secondary transplantation, all grafts were retrieved for histologic analysis. In Experiment 2, we assessed the long-term results of allograft cryopreservation, without immunosuppression therapy. Six months after transplantation of fresh (Group 4) and cryopreserved (Group 5) allografts, the tracheal segments (each group, n = 5) were histologically evaluated. RESULTS: In Experiment 1, only the secondary allografts from Lewis rats in Group 2 did not maintain lumen structure and often showed dislocated or destroyed cartilage. Second-set graft rejection was specifically recognized in Group 2, but not in Group 1 or 3. In Experiment 2, the cryopreserved allografts appeared almost normal and lumen rigidity was preserved 6 months after transplantation. These allografts were superior to the fresh allografts in patency and in cartilage dislocation and mononuclear cell infiltration scores, but not in the viable chondrocyte ratio. CONCLUSIONS: We conclude that cryopreservation may produce successful long-term results because of its immunomodulatory effect on tracheal allografts.