Tumor lysis syndrome followed by tumor regression after COVID-19 in a patient with chronic lymphocytic leukemia.

Coronavirus disease 2019 (COVID-19) can become lethal in patients with hematological malignancies; however, several cases of tumor regression after COVID-19 have been described, and the precise mechanism behind this paradoxical effect is unknown. Herein, we describe a case of Tumor lysis syndrome (TLS) followed by tumor regression after COVID-19. A 72-year-old woman with untreated chronic lymphocytic leukemia was admitted to our hospital with SARS-CoV-2 antigen-positive pneumonia. On admission, her anti-SARS-CoV-2 spike antibody was negative despite receiving two prior vaccinations. Immediately after admission, she developed confusion and ventricular tachycardia. Laboratory data showed acidosis, hyperkalemia, and a rapid decrease of tumor cells in peripheral blood, and she was diagnosed with clinical TLS. She was transferred to the intensive care unit and received continuous hemodialysis therapy. Although hyperferritinemia and bicytopenia, which suggest a cytokine storm followed, she recovered without steroids and additional COVID-19 treatment in 8 days. 2 months later, CT revealed a marked shrinking of lymphadenopathy, which was compatible with tumor regression after COVID-19. Considering the impaired humoral immunity and abrupt response, direct oncolysis caused by SARS-CoV-2 and cytokine storm-induced cell-mediated immune reaction may have been responsible for this paradoxical effect.

RTP4 silencing provokes tumor-intrinsic resistance to immune checkpoint blockade in colorectal cancer.

BACKGROUND: Recent advances in immune checkpoint blockade (ICB) have improved patient prognosis in mismatch repair-deficient and microsatellite instability-high colorectal cancer (dMMR/MSI-H CRC); however, PD-1 blockade has faced a challenge in early progressive disease. We aimed to understand the early event in ICB resistance using an in vivo model. METHODS: We subcutaneously transplanted the MC38 colon cancer cells into C57BL/6 mice, intraperitoneally injected anti-PD-1 antibody and then isolated ICB-resistant subclones from the recurrent tumors. RESULTS: Comparative gene expression analysis discovered seven genes significantly downregulated in the ICB-resistant cells. Tumorigenicity assay of the MC38 cells knocked out each of the seven candidate genes into C57BL/6 mice treated with anti-PD-1 antibody and bioinformatics analysis of the relationship between the expression of the seven candidate genes and the outcome of cancer patients receiving immunotherapy identified Rtp4, an interferon-stimulated gene and a chaperon protein of G protein-coupled receptors, as a gene involved in ICB resistance. Immunohistochemical analysis of transplanted tumor tissues demonstrated that anti-PD-1 antibody failed to recruit T lymphocytes in the Rtp4-KO MC38 cells. Mouse and human RTP4 expression could be silenced via histone H3 lysine 9 (H3K9) trimethylation, and public transcriptome data indicated the high expression level of RTP4 in most but not all of dMMR/MSI-H CRC. CONCLUSIONS: We clarified that RTP4 could be silenced by histone H3K9 methylation as the early event of ICB resistance. RTP4 expression could be a promising biomarker for predicting ICB response, and the combination of epigenetic drugs and immune checkpoint inhibitors might exhibit synergistic effects on dMMR/MSI-H CRC.

Evaluation of fibrinogen concentration by clot firmness using a dielectric blood coagulation test system.

PURPOSE: To determine if fibrinogen concentration can be evaluated by dielectric permittivity changes in dielectric blood coagulation testing (DBCM) during cardiovascular surgery with cardiopulmonary bypass (CPB). METHODS: We performed a single-center prospective observational study at a university hospital. One hundred patients undergoing cardiovascular surgery with CPB were enrolled. Whole-blood samples were obtained after weaning from CPB, and dielectric clot strength (DCS) was measured by intrinsic pathway testing with or without heparinase in DBCM. The FIBTEM test was performed during rotational thromboelastometry using the same samples, and maximum clot firmness (MCF) was evaluated. Spearman's correlation analysis was performed, and receiver operating characteristics (ROC) curve analyses were used to evaluate the performance of hypofibrinogenemia detection. RESULTS: DCS showed a strong positive correlation with plasma fibrinogen concentration (Rs = 0.76, P < 0.0001). The area under the ROC curve for evaluating plasma fibrinogen concentration < 200 mg/dL was 0.91 (95% confidence interval (CI) 0.85-0.97) for DCS, compared with 0.88 (95% CI 0.81-0.94) for FIBTEM MCF. The optimal cutoff value of DCS was 17.0 (sensitivity 94%, specificity 80%). CONCLUSIONS: DCS variables showed a significantly strong correlation with plasma fibrinogen concentration, and the diagnostic performance for hypofibrinogenemia was comparable to that for FIBTEM MCF. This novel methodology has the potential to provide a point-of-care test with sufficient accuracy for the detection of perioperative hypofibrinogenemia during cardiovascular surgery with CPB.

Newly-established in vitro inner BRB spheroids to elucidate retinal Ang2-linked substance transfer.

Conjugation of angiopep-2 (Ang2) with drugs/compounds is known to increase plasma membrane permeability across endothelial barriers. The inner blood-retinal barrier (BRB) regulates retinal drug distribution and is formed by retinal capillary endothelial cells, supported by Müller cells and retinal pericytes. To elucidate the potential of Ang2 conjugation in promoting retinal drug distribution after peripheral administration across the inner BRB, an in vivo administration study and in vitro transport experiments using newly developed multicellular inner BRB spheroids were performed. After intravenous administration of Ang2-linked green fluorescence protein (GFP-Ang2) in mice, GFP-derived signals were observed in the neural retina. In contrast, GFP-derived signals were not observed after intravenous GFP administration, suggesting the promotion of the retinal distribution of substances by Ang2 conjugation. To overcome the limitations of in vitro studies using cells cultured on dishes, inner BRB spheroids were established using conditionally immortalized rat retinal capillary endothelial cells, Müller cells, and retinal pericytes. Immunocytochemistry of marker molecules suggests that the central part of the spheroids is occupied by Müller cells, and encapsulated by retinal pericytes and capillary endothelial cells. Studies on the expression and functions of tight junctions suggest that tight junctions are formed on the surface of the inner BRB spheroids by retinal capillary endothelial cells. The functional expression of drug transporters, such as P-glycoprotein, was observed in the spheroids, implying that the inner side of the spheroids reflects the retinal side of the inner BRB. In the inner BRB spheroids, energy-dependent accumulation of GFP-Ang2 and Ang2-linked 5(6)-carboxyfluorescein (FAM-Ang2) was observed. Moreover, an endocytic inhibition study revealed that clathrin-dependent endocytosis/transcytosis was involved in the transcellular transport of Ang2-conjugated drugs/compounds across the inner BRB. Consequently, it is suggested that the Ang2 linkage is useful for promoting retinal drug distribution via clathrin-dependent transcytosis at the inner BRB.

TEG6s Platelet Mapping assay for the estimation of plasma fibrinogen concentration during cardiovascular surgery: a single-center prospective observational study.

PURPOSE: The Activator F (ActF) test on the TEG6s Platelet Mapping assay system is a means of quantifying blood viscoelasticity caused by fibrin network formation, triggered by reptilase and factor XIII, while platelets are inhibited. This unique methodology enables the measurement of blood viscoelasticity, even in highly heparinized blood. Here, we investigated whether fibrinogen concentration could be estimated using the ActF test in blood samples obtained during cardiopulmonary bypass (CPB) and after CPB in patients undergoing cardiovascular surgery. METHODS: We performed a single-center prospective observational study at a university hospital. Forty patients aged ≥ 18 years who underwent elective cardiovascular surgery with CPB were enrolled. Blood samples were drawn after the induction of anesthesia, after declamping of the aorta during CPB, and after the reversal of heparinization using protamine (after CPB). Coagulation profiles were evaluated using the Platelet Mapping assay and standard laboratory tests. RESULTS: There were strong correlations between the maximal amplitude of clot strength (MA) in the ActF test and fibrinogen concentration in samples drawn during CPB (R = 0.84, 95% confidence interval [CI] 0.72-0.91; P < 0.001) and after CPB (R = 0.83, 95% CI 0.70-0.91; P < 0.001). The areas under the receiver-operating characteristic curve for the ActF MA for fibrinogen concentrations < 150 mg/dL were 0.86 (95% CI 0.73-1.0) during CPB and 0.98 (95% CI 0.94-1.0) after CPB. CONCLUSION: TEG6s Platelet Mapping ActF MA values strongly correlated with plasma fibrinogen concentration in highly heparinized blood during CPB and yielded highly accurate measurements of low fibrinogen concentrations.

Epidemiological trends of imported infectious diseases in Japan: Analysis of imported 2-year infectious disease registry data.

INTRODUCTION: The epidemiology of infectious diseases in Japan remains undefined despite the increasing tourism. GeoSentinel, an epidemiological surveillance system for reporting imported infectious diseases, has only two participating facilities in Japan. Although the number of infectious diseases is reported by the National Institute of Infectious Diseases, there is no detailed clinical information about these cases. Therefore, we established J-RIDA (Japan Registry for Infectious Diseases from Abroad) to clarify the status of imported infectious diseases in Japan and provide detailed information. METHODS: J-RIDA was started as a registry of imported infectious diseases. Case registration began in October 2017. Between October 2017 and September 2019, 15 medical institutions participated in this clinical study. The registry collected information about the patient's age, sex, nationality, chief complaint, consultation date, date of onset, whether visit was made to a travel clinic before travel, blood test results (if samples were collected), travel history, and final diagnosis. RESULTS: Of the 3046 cases included in this study, 46.7% to Southeast Asia, 13.0% to Africa, 13.7% to East Asia, 11.5% to South Asia, 7.5% to Europe, 3.8% to Central and South America, 4.6% to North America, 3.9% to Oceania, and 2.8% to Central and west Asia. More than 85% of chief complaints were fever and general symptoms, gastrointestinal symptoms, respiratory symptoms, or dermatologic problems. The most common diseases were travelers' diarrhea, animal bite, upper respiratory infection, influenza, and dengue fever. CONCLUSIONS: We summarized two-year cases registered in Japan's imported infectious disease registry. These results will significantly contribute to the epidemiology in Japan.

[A Case of Pelvic Desmoid-Type Fibromatosis Treated by Radiation and Medication Therapies].

The treatment for desmoid-type fibromatosis involves surgical resection and medication therapy, but the standard treatment has not yet been established. In the West, the usefulness of radiation therapy has been reported. We encountered a patient with desmoid-type fibromatosis in the pelvis who was treated by radiation and medication therapies and achieved a good tumor reduction effect. The patient was a 70-year-old man. He had a 6-year history of pain in the right leg and had a palpable mass on the right side of the anus; he was admitted to our department. CT showed a 12×7×12 cm mass in the pelvis, and CT-guided needle biopsy revealed a desmoid-type fibromatosis. Because tumor exclusion resulted in obstruction of the rectum, radiation therapy(60 Gy in 30 Fr)was started after performing transverse colon colostomy; simultaneous medication therapy with a COX-2 inhibitor and the anti-allergic agent tranilast was administered. Cystic degeneration was observed 5 months after the end of radiation therapy, and after 12 months, the tumor volume had halved. Around 28 months after the end of radiation therapy, medication treatment has been continued with slow contraction.

Cytotoxicity of propofol in human induced pluripotent stem cell-derived cardiomyocytes.

PURPOSE: Propofol infusion syndrome (PRIS) is a lethal condition caused by propofol overdose. Previous studies suggest that pathophysiological mechanisms underlying PRIS involve mitochondrial dysfunction; however, these mechanisms have not been fully elucidated. This study aimed to establish an experimental model of propofol-induced cytotoxicity using cultured human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to determine the mechanisms behind propofol-induced mitochondrial dysfunction, and to evaluate the protective effects of coenzyme Q10 (CoQ10). METHODS: Human iPSC-derived cardiomyocytes were exposed to propofol (0, 2, 10, or 50 µg/ml) with or without 5 µM CoQ10. Mitochondrial function was assessed by measuring intracellular ATP, lactate concentrations in culture media, NAD+/NADH ratio, and the mitochondrial membrane potential. Propofol-induced cytotoxicity was evaluated by analysis of cell viability. Expression levels of genes associated with mitochondrial energy metabolism were determined by PCR. Intracellular morphological changes were analyzed by confocal microscopy. RESULTS: Treatment with 50 µg/ml propofol for 48 h reduced cell viability. High concentrations of propofol (≥ 10 µg/ml) induced mitochondrial dysfunction accompanied by downregulation of gene expression of PGC-1alpha and its downstream targets (NDUFS8 and SDHB, which are involved in the respiratory chain reaction; and CPT1B, which regulates beta-oxidation). Cardiomyocytes co-treated with 5 µM CoQ10 exhibited resistance to propofol-induced toxicity through recovery of gene expression. CONCLUSIONS: Propofol-induced cytotoxicity in human iPSC-derived cardiomyocytes may be associated with mitochondrial dysfunction via downregulation of PGC-1alpha-regulated genes associated with mitochondrial energy metabolism. Co-treatment with CoQ10 protected cardiomyocytes from propofol-induced cytotoxicity.

Cross-sectional and longitudinal investigation of human herpesvirus 8 seroprevalence in HIV-1-infected individuals in Osaka, Japan.

INTRODUCTION: High human herpesvirus 8 (HHV-8) seroprevalence has been reported in men who have sex with men (MSM) and are infected with HIV-1. However, it is unclear when they become infected with HHV-8. Thus, we conducted cross-sectional and longitudinal investigations of HHV-8 seroprevalence in HIV-1-infected individuals in Osaka, Japan. PATIENTS AND METHODS: Plasma was collected from 121 individuals infected with HIV-1 and the anti-HHV-8 antibody titer was measured using an enzyme-linked immunosorbent assay with whole virus lysate. Subjects were classified into those with and without a past medical history of HHV-8-associated disease; the latter group was then classified into 3 subgroups based on the assumed route of HIV-1 infection: blood products, homosexual contact, and other routes. HHV-8 seroprevalence was compared among the groups and measured again approximately 3 years after the baseline measurement. The relationship between HHV-8 seropositivity and possible associated factors was also investigated. RESULTS: All 15 subjects with HHV-8-associated disease were seropositive, and all 11 subjects in the blood product group were seronegative. In the MSM group, 25 (30%) of 79 subjects were HHV-8 seropositive and, in the non-MSM group, 1 (6%) of 16 subjects was (p < 0.0001). In the longitudinal investigation, seroconversion was observed in 10 (19%) of 52 subjects in the MSM group who were seronegative at baseline. A correlation was observed between seroconversion and symptomatic syphilis (p = 0.0432). CONCLUSIONS: HHV-8 seropositivity and seroconversion rates were high in HIV-1-infected MSM, suggesting that, currently, HHV-8 is an epidemic pathogen in this population.

Perioperative Elevation in Cell-Free DNA Levels in Patients Undergoing Cardiac Surgery: Possible Contribution of Neutrophil Extracellular Traps to Perioperative Renal Dysfunction.

Background. This study aimed to determine the perioperative change in serum double-strand DNA (dsDNA) as a marker potentially reflecting neutrophil extracellular trap concentration in samples from patients undergoing cardiac surgery and to analyze a relationship between serum dsDNA concentrations and perioperative renal dysfunction. Methods. Serum dsDNA concentrations in samples that were collected during a previously conducted, prospective, multicenter, observational study were measured. Eighty patients undergoing elective cardiac surgery were studied. Serum samples were collected at baseline, immediately after surgery, and the day after surgery (POD-1). Results. Serum dsDNA concentration was significantly increased from baseline (median, 398 ng/mL [interquartile range, 372-475 ng/mL]) to immediately after surgery (median, 540 ng/mL [437-682 ng/mL], p < 0.001), and they were reduced by POD-1 (median, 323 ng/mL [256-436 ng/mL]). The difference in serum creatinine concentration between baseline and POD-1 was correlated with dsDNA concentration on POD-1 (rs = 0.61, p < 0.001). Conclusions. In patients undergoing cardiac surgery, serum dsDNA concentration is elevated postoperatively. Prolonged elevation in dsDNA concentration is correlated with perioperative renal dysfunction. Further large-scale studies are needed to determine the relationship between serum concentration of circulating dsDNA and perioperative renal dysfunction.

[Three Cases of Long-Term Survival in Colon Cancer with Postoperative Peritoneal Recurrence].

Case 1 is a 57-year-old man with pelvic recurrence 1 year 8 months after surgery for ascending colon cancer.We performed a Hartmann's operation.He has been relapse-free for 11 years.Case 2 is a 67-year-old man with intraperitoneal small intestinal relapse 4 years after surgery for cecum cancer.We performed resection.He has brain metastases recurrence in 2 years 6 months after surgery, died after 2 years 9 months.Case 3 is a 53-year-old man with recurrence in the bladder rectal fossa 5 years after sigmoidectomy.We performed resection.He has been relapse-free survival at 1 year 2 months.

[Four Cases of Colorectal Cancer with Para-Aortic Lymph Node Metastases Successfully Resected Resulting in Long-Term Survival].

We encountered 4 cases of colorectal cancer with para-aortic lymph node(LN)metastases.Para -aortic LN dissection was performed after the diagnosis of solitary LN metastases.Case 1: A 69-year-old woman was diagnosed with ascending colon cancer.She underwent right hemicolectomy with D3 LN dissection.After 1 year and 3 months, tumor marker levels(CEA) were elevated, and para-aortic LN metastases were detected on CT.She was administered FOLFOX.After 1 year, para-aortic LN dissection was performed.She is doing well without any recurrence for 8 years and 9 months.Case 2: A 52-year-old man was diagnosed with rectal cancer.He underwent abdominoperineal resection with lateral pelvic LN dissection.After 5 months, his tumor marker levels(CEA)were elevated, and para-aortic LN metastases were detected on CT.He was administered various chemotherapies, but the LN were swollen.After 6 years and 2 months, para-aortic LN dissection was performed.He received systematic chemotherapy, and is alive with recurrent disease.Case 3: A 67-year-old man was diagnosed with obstructive sigmoid colon cancer.He underwent high-anterior resection with D3 LN and para-aortic LN dissection.He received systematic chemotherapy and is alive with recurrent disease.Case 4: A 61-year-old man was diagnosed with obstructive rectal cancer.He underwent low-anterior resection with D3 LN and para-aortic LN dissection.He is doing well without recurrences for 2 years and 1 month.Our results suggest that patients with localized para-aortic metastases of colorectal cancer may achieve good long-term survival after dissection of para-aortic LN.and surgical treatment is indicated in selected cases.

[A Case of Retroperitoneal Recurrence and Left Kidney Metastasis Occurring Four Years after Laparoscopy-Assisted Surgery for Sigmoid Colon Cancer].

A 67-year old woman underwent laparoscopy-assisted high anterior resection for sigmoid colon cancer. A histopathological examination revealed no lymph node metastasis, but extramural cancer deposits were present. Four years later, enhanced computed tomography revealed recurrence in the retroperitoneum and metastasis to the left kidney. A left nephrectomy and left hemicolectomy were performed. A year after the second operation, computed tomography revealed metastasis to the lung. Histopathological reexamination for extra-lymph nodal spread after the first operation revealed venous involvement. Generally, colon cancer with extra-lymph nodal spread has a higher risk of retroperitoneal recurrence, and venous involvement leads to a poor prognosis. We describe our case with the known report.

[A Case of Para-Aortic Lymph Node Metastases of Sigmoid Colon Cancer Treated with Complete Resection].

We present a case of sigmoid colon cancer with isolated para-aortic lymph node metastasis in a 67-year-old male patient. We treated this patient using simultaneous curative lymph node dissection with primary tumor resection. After inserting a transanal tube and decompressing the proximal colon for obstructive colitis, we performed high anterior resection with paraaortic lymph node dissection without neoadjuvant chemotherapy. The pathology results were as follows: tub2, SE, N3, H0, P0, M1(No. 216, 280), stage Ⅳ, curability B. Adjuvant chemotherapy with the XELOX regimen was administered, and the patient remains alive with no signs of recurrence 24 months after surgery. Although simultaneous dissection of para-aortic lymph node metastasis is controversial, curative dissection is advisable for localized cases.

[A Case of Long-Term Survival of a Patient with Gastric Cancer with Peritoneal Dissemination].

The patient was a 75-year-old man with a history of gastrectomy with combined resection of the transverse colon ligament for gastric cancer in July 2011. He was diagnosed with adenocarcinoma (tub2, tub1), L, Ant-Gre, type 2, pT4b (SI: transverse colon ligament) and pN3b, H0, M0, P0, CY0, Stage ⅢC. On abdominal computed tomography 7 months after surgery a peritoneal metastasis was seen near the transverse colon. The patient was treated with resection for peritoneal dissemination with part of the transverse colon. Three years after the last surgery, the patient is still alive without relapse.

[Colorectal Cancer with Macroscopic Invasion to Adjacent Organs--A Case Report].

We encountered a case of colorectal cancer with macroscopic invasion to the adjacent organs. A 61-year-old man with abdominal pain and nausea was diagnosed as having sigmoid colon cancer invading the ileum, ureter, internal iliac artery, and external iliac vein. A lower anterior resection and resection of the small bowel, ureter, external iliac vein, and internal iliac artery was performed and succeeded in an R0 resection. The patient was discharged from the hospital in 29 POD. Pathology results revealed an adenocarcinoma, pT4b, pSI, INF b, int, ly0, v, pPM0, pDM0, pN0, Type 2, Stage Ⅱ. Four courses of XELOX plus bevacizumab were administered. The patient underwent ileostomy closure, and is currently free of relapse 3 years 2 months after resection. The survival rate of patients with combined resection of the invaded organs is significantly higher than that of patients with a non-combined resection. The survival rate after curative resection is also significantly higher compared with non-curative resection. Aggressive resection of invaded organs seems to be important for a good outcome.

[A Case of Long-Term Survival after Resection of Liver and Adrenal Metastases from Rectal Cancer].

A 72-year-old man underwent Miles' operation for rectal cancer. Histological findings showed moderately differentiated adenocarcinoma, a, ly0, v1, n0, stage Ⅱ(ly0, v1). Five months later, left lateral segmentectomy and left adrenalectomy were performed owing to the metastasis of the rectal cancer to the liver and adrenal glands. Two years after these operations, left nephrectomy was performed for retroperitoneal recurrence around the left kidney. All resected specimens showed metastatic adenocarcinoma derived from the rectal cancer. No recurrence has been detected in the 4 years since the left nephrectomy. Aggressive resection of well-controlled metastatic lesions including those in the adrenal glands is recommended.

[Two cases showing the absence of motor evoked potentials without developing postoperative paraplegia following thoracoabdominal aortic repair--role of epidural cooling, spinal drainage and aorto-iliac side-arm conduit distal perfusion].

We describe two cases which developed loss of motor evoked potentials from bilateral lower limbs following thoracoabdominal aortic repair. Paraplegia was suspected in both cases; however, one case of Crawford type 2 aneurysm showed transient left leg monoplegia with a sensory deficit and the other case of aortic pseudoaneurysm showed no neurologic dysfunction postoperatively. We employed epidural cooling and spinal drainage for spinal protection and distal perfusion was provided through aorto-iliac side-arm conduit. Despite the prolonged spinal ischemia during thoracoabdominal aortic repair, spinal drainage and epidural cooling were very helpful for protecting the spinal cord from ischemia. The interpretation of MEPs seems very difficult especially when the potentials remain absent even after reconstruction or reperfusion of segmental arteries, because variety of intraoperative factors may affect them.

Retrospective analysis of spontaneous recovery from neuromuscular blockade produced by empirical use of rocuronium.

PURPOSE: A train-of-four ratio (TOF ratio) of >0.9 should be the clinical cut-off to avoid residual paralysis. However, it is not rare to extubate patients without measurement of the TOF ratio, although the safe interval from the last administration of rocuronium assuring a TOF ratio of >0.9 has not been established in the daily clinical setting. In this study, to estimate the safe interval to avoid residual paralysis, we retrospectively selected patients in whom the TOF ratio was measured during remifentanil administration before extubation, and we studied the characteristics of recovery from the neuromuscular blockade produced by the empirical use of rocuronium. METHODS: Patients undergoing surgery under general anesthesia with sevoflurane and remifentanil were studied (n = 134). Rocuronium was administered at 0.7-1.0 mg/kg for tracheal intubation, and repeated bolus administration (10 mg) or continuous infusion (15-25 mg/h) was performed by the anesthesiologists in charge of the patient to maintain intraoperative paralysis. At the end of the surgery, the TOF ratio was measured, during remifentanil infusion and the contribution of clinical parameters to spontaneous recovery from the rocuronium-induced paralysis was studied by multivariate logistic regression analyses. RESULTS: Spontaneous recovery from rocuronium-induced paralysis within 2 h after the last administration of rocuronium varied among the patients. Multivariate logistic regression analyses showed that age (P = 0.002) and time elapsed from the last administration of rocuronium (P < 0.0001) significantly contributed to TOF recovery, and elderly patients demonstrated significantly slower recovery. CONCLUSION: Because of the large variation in the recovery from rocuronium-induced paralysis, TOF-based evaluation of residual paralysis is essential to determine the appropriate indication for reversal, especially for elderly patients.