Prediction Model for Severe Thrombocytopenia Induced by Gemcitabine Plus Cisplatin Combination Therapy in Patients with Urothelial Cancer.

BACKGROUND: Chemotherapy-induced thrombocytopenia is often a use-limiting adverse reaction to gemcitabine and cisplatin (GC) combination chemotherapy, reducing therapeutic intensity, and, in some cases, requiring platelet transfusion. OBJECTIVE: A retrospective cohort study was conducted on patients with urothelial cancer at the initiation of GC combination therapy and the objective was to develop a prediction model for the incidence of severe thrombocytopenia using machine learning. METHODS: We performed receiver operating characteristic analysis to determine the cut-off values of the associated factors. Multivariate analyses were conducted to identify risk factors associated with the occurrence of severe thrombocytopenia. The prediction model was constructed from an ensemble model and gradient-boosted decision trees to estimate the risk of an outcome using the risk factors associated with the occurrence of severe thrombocytopenia. RESULTS: Of 186 patients included in this study, 46 (25%) experienced severe thrombocytopenia induced by GC therapy. Multivariate analyses revealed that platelet count ≤ 21.4 (×104/µL) [odds ratio 7.19, p < 0.01], hemoglobin ≤ 12.1 (g/dL) [odds ratio 2.41, p = 0.03], lymphocyte count ≤ 1.458 (×103/µL) [odds ratio 2.47, p = 0.02], and dose of gemcitabine ≥ 775.245 (mg/m2) [odds ratio 4.00, p < 0.01] were risk factors of severe thrombocytopenia. The performance of the prediction model using these associated factors was high (area under the curve 0.76, accuracy 0.82, precision 0.68, recall 0.50, and F-measure 0.58). CONCLUSIONS: Platelet count, hemoglobin level, lymphocyte count, and gemcitabine dose contributed to the development of a novel prediction model to identify the incidence of GC-induced severe thrombocytopenia.

Risk Factors for Thrombocytopenia Induced by Capecitabine Plus Oxaliplatin Therapy in Patients With Colorectal Cancer.

BACKGROUND/AIM: Capecitabine plus oxaliplatin (CapeOX) therapy is used as an adjuvant chemotherapy regimen for patients with colorectal cancer (CRC). Although oxaliplatin induces thrombocytopenia, the risk factors for thrombocytopenia in oxaliplatin-treated patients with CRC are not well established. We aimed to investigate the risk factors for thrombocytopenia in CapeOX-treated patients with CRC. In addition, we evaluated platelet counts and non-invasive liver fibrosis indices, specifically the aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis-4 index (FIB-4), during CapeOX therapy in these patients. PATIENTS AND METHODS: Between July 2017 and June 2020, we enrolled CapeOX-treated patients with high-risk stage II or stage III CRC at seven hospitals collaborating with the Division of Oncology, Aichi Prefectural Society of Hospital Pharmacists (Aichi prefecture, Japan). In this retrospective study, we investigated patients' backgrounds, laboratory data, concomitant medications, number of cycles of CapeOX and oxaliplatin, cumulative dose of oxaliplatin, and administration period. The cut-off values were calculated using receiver operating characteristic analysis of platelet counts and APRI and FIB-4 scores. RESULTS: Fifty-five patients without thrombocytopenia and 44 patients with thrombocytopenia were enrolled. During CapeOX therapy, the thrombocytopenia group showed a significant decrease in platelet count and a significant increase in APRI and FIB-4 scores compared to the non-thrombocytopenia group. Baseline albumin level ≤3.5 g/dl and platelet count ≤238×103/µl were independently associated with ≥grade 2 thrombocytopenia in CapeOX-treated patients. CONCLUSION: Baseline albumin level and platelet count may be useful for predicting thrombocytopenia in CapeOX-treated patients with high-risk stage II or stage III CRC.

Development of panorama vision ring for thoracoscopy.

PURPOSE: Minimally invasive surgery (MIS) using a thoraco- or laparoscope is becoming a more common surgical technique. In MIS, a magnified view from a thoracoscope helps surgeons conduct precise operations. However, there is a risk of the visible area becoming narrow. To confirm that the operation field is safe, the surgeon will draw the thoracoscope back to check the marginal area of the target and insert it again many times during MIS. To reduce the surgeon's load, we aim to visualize the entire thoracic cavity using a newly developed device called "panorama vision ring" (PVR). METHOD: The PVR is used instead of a wound retractor or a trocar. It is a ring-type socket with one big hole for the thoracoscope and four small holes for tiny cameras placed around the big hole. The views from the tiny cameras are fused into one wider view that visualizes the entire thoracic cavity. A surgeon can proceed with an operation by checking what exists outside of the thoracoscopic view. Also, she/he can check whether or not bleeding has occurred from the image of the entire cavity. RESULTS: We evaluated the view-expansion ability of the PVR by using a three-dimensional full-scale thoracic model. The experimental results showed that the entire thoracic cavity could be visible in a panoramic view generated by the PVR. We also demonstrated pulmonary lobectomy in virtual MIS using the PVR. Surgeons could perform a pulmonary lobectomy while checking the entire cavity. CONCLUSION: We developed the PVR, which uses tiny auxiliary cameras to create a panoramic view of the entire thoracic cavity during MIS. We aim to make MIS safer for patients and more comfortable for surgeons through the development of the PVR.

Establishing a Universal RT-PCR Testing System Is Essential for the Safe Performance of Scheduled Surgeries During the COVID-19 Pandemic in Japan: A Retrospective Study.

Background Elective orthopedic surgery, as well as the procedures of many surgical departments, have been severely curtailed by coronavirus disease 2019. Here, we aimed to analyze how all surgeons could safely perform essential procedures during the coronavirus disease 2019 pandemic. Methods A retrospective review of elective surgeries performed between May 15, 2020, and February 28, 2022, was conducted. A screening questionnaire was used, and reverse transcription-polymerase chain reaction testing was assessed in all admitted surgical department patients. Their positivity rate and the positivity rate in our fever outpatient clinic were analyzed. Results Of 6099 patients who tested for severe acute respiratory syndrome coronavirus-2 during the study period, eight (0.13%) tested positive. The positive results were seen in four patients undergoing orthopedic surgery, two undergoing respiratory surgery, one undergoing breast surgery, and one undergoing plastic surgery. The number of patients who visited the outpatient clinic for fever was 15,639, including 1640 positive cases (positive rate of 10.5%). The positive rate of preoperative reverse transcription-polymerase chain reaction testing for scheduled surgery was consistently low and did not coincide with the peak of the wave of infection, while the positivity rate of outpatients with fever demonstrated a wave consistent with the national infection situation. All 6091 patients, excluding the eight positive patients, underwent surgery; all patients who underwent surgery were discharged from the hospital without developing coronavirus disease 2019 symptoms. Conclusions Our findings suggest that the establishment of a universal reverse transcription-polymerase chain reaction testing system is essential for the safe performance of scheduled surgeries during the coronavirus disease 2019 pandemic.

Treatment strategy for surgical site infection post posterior lumbar interbody fusion: A retrospective study.

Introduction: Posterior lumbar interbody fusion (PLIF) has been widely used to treat various degenerative spinal diseases. However, surgical site infection (SSI) post-PLIF is often difficult to cure. This study aimed to clarify the difference in clinical course due to the causative organism and develop a treatment strategy for SSI post-PLIF. Methods: Between January 2011 and March 2019, 581 PLIF surgeries were performed at our hospital. Deep SSI occurred in 14 patients who were followed up for more than 2 years. Causative bacterial species were diagnosed by preoperative puncture and/or intraoperative drainage or by tissue culture in 13 patients and by intradiscal puncture in one patient who underwent conservative treatment. Of the 13 patients who underwent surgeries for infection, 10 had Propionibacterium acnes (Group A; n = 4) or coagulase-negative Staphylococcus (CNS) (Group B; n = 6) as the causative bacterial species. Groups A and B were retrospectively compared in terms of age, sex, number of segments, presence of diabetes mellitus, operation time, blood loss, C-reactive protein on hematological examination, the elapsed time to diagnosis (ETD), the presence of clinical findings such as heat, redness, swelling, and discharge from the wound and healing time. Results: All infections were eradicated with surgery except in one patient whose causative bacteria was CNS; cages were finally removed in 11 patients. There was a significant difference (P = 0.0105) in the ETD and clinical findings (P = 0.0476) between Groups A and B. Posterior one-stage simultaneous revision (POSSR) was performed in nine patients, of whom eight were cured and one required additional surgery. Conclusions: The ETD and clinical findings were significantly different in SSI cases caused by different bacteria, which will be useful in predicting the causative bacteria in future cases. For the treatment of deep SSI post-PLIF, POSSR was effective.

Challenges and responses of elective orthopaedic surgery during the second wave of COVID-19.

BACKGROUND: Elective orthopaedic surgery has been severely curtailed because of coronavirus disease, 2019. There is scant scientific evidence to guide surgeons in assessing the protocols that must be implemented before resuming elective orthopaedic surgery safely after the second wave of the coronavirus disease, 2019. METHODS: A retrospective review of elective orthopaedic surgeries performed between May 15, 2020, and November 20, 2020, was conducted. A screening questionnaire was used, and reverse transcription-polymerase chain reaction and severe acute respiratory syndrome coronavirus-2 immunoglobulin G and IgM antibodies testing were assessed in all admitted patients. Screening and testing data for coronavirus disease was reviewed for all patients. RESULTS: Of 592 patients tested for severe acute respiratory syndrome coronavirus-2 during the study period, 21 (3.5%) tested positive. There were 2 patients (0.3%) with positive reverse transcription-polymerase chain reaction tests, 3 (0.5%) with positive IgG and IgM antibodies, 13 (2.2%) with positive IgG antibodies, and 10 (1.7%) with positive IgM antibodies. Among these 21 patients, 20 (95.2%) were asymptomatic. CONCLUSIONS: Our findings suggest that most elective orthopaedic surgery patients with severe acute respiratory syndrome coronavirus-2 are asymptomatic. In the second wave of coronavirus disease, 2019, universal testing of all patients should be strongly considered as an important measure to prevent clusters of in-hospital transmission of the disease.

Improvement of Learning and Memory in Senescence-Accelerated Mice by S-Allylcysteine in Mature Garlic Extract.

S-allylcysteine (SAC), a major thioallyl compound contained in mature garlic extract (MGE), is known to be a neuroactive compound. This study was designed to investigate the effects of SAC on primary cultured hippocampal neurons and cognitively impaired senescence-accelerated mice prone 10 (SAMP10). Treatment of these neurons with MGE or SAC significantly increased the total neurite length and number of dendrites. SAMP10 mice fed MGE or SAC showed a significant improvement in memory dysfunction in pharmacological behavioral analyses. The decrease of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, N-methyl-d-aspartate (NMDA) receptor, and phosphorylated α-calcium/calmodulin-dependent protein kinase II (CaMKII) in the hippocampal tissue of SAMP10 mice fed MGE or SAC was significantly suppressed, especially in the MGE-fed group. These findings suggest that SAC positively contributes to learning and memory formation, having a beneficial effect on brain function. In addition, multiple components (aside from SAC) contained in MGE could be useful for improving cognitive function by acting as neurotrophic factors.

Girdin phosphorylation is crucial for synaptic plasticity and memory: a potential role in the interaction of BDNF/TrkB/Akt signaling with NMDA receptor.

Synaptic plasticity in hippocampal neurons has been thought to represent a variety of memories. Although accumulating evidence indicates a crucial role of BDNF/TrkB/Akt signaling in the synaptic plasticity of the hippocampus, the mechanism by which Akt, a serine/threonine kinase, controls activity-dependent neuronal plasticity remains unclear. Girdin (also known as APE, GIV, and HkRP1), an actin-binding protein involved both in the remodeling of the actin cytoskeleton and in cell migration, has been identified as a substrate of Akt. Previous studies have demonstrated that deficit of neuronal migration in the hippocampus of Girdin-deficient (Girdin(-/-)) mice is independent on serine phosphorylation of Girdin at S1416 (Girdin S1416) by Akt. In the present study, we focused on the role of Girdin S1416 phosphorylation in BDNF/TrkB/Akt signaling associated with synaptic plasticity. We found that Girdin in the hippocampus was phosphorylated at S1416 in an activity-dependent manner. Phosphorylation-deficient knock-in mice (Girdin(SA/SA) mice), in which S1416 is replaced with alanine, exhibited shrinkage of spines, deficit of hippocampal long-term potentiation, and memory impairment. These phenotypes of Girdin(SA/SA) mice resembled those of Girdin(+/-) mice, which have 50% loss of Girdin expression. Furthermore, Girdin interacted with Src kinase and NR2B subunit of NMDA receptor, leading to phosphorylation of the NR2B subunit and NMDA receptor activation. Our findings suggest that Girdin has two different functions in the hippocampus: Akt-independent neuronal migration and Akt-dependent NR2B phosphorylation through the interaction with Src, which is associated with synaptic plasticity in the hippocampus underlying memory formation.

Early complications of primary total hip arthroplasty in the supine position with a modified Watson-Jones anterolateral approach.

BACKGROUND: For total hip arthroplasty (THA), minimally invasive surgery (MIS) has been developed to reduce incision length, muscle damage, and a shorter hospital stay. However, reduced exposure of anatomical landmarks may result in technical errors and inferior implant survivorships. The aim of this study was to report the short-term results and clinical complications of primary MIS THA in the supine position. METHODS: A consecutive series of 103 patients who underwent MIS cementless THA with a modified Watson-Jones anterolateral approach (AL) were enrolled. Outcomes data were reviewed at a minimum of 12 months following the procedure. Clinical evaluations were made using the Merle d'Aubigne and Postel hip score. The results of these procedures were retrospectively compared with those of a historical series of 98 total hip arthroplasties that had been performed by the same surgeon with use of a posterolateral approach (PL). RESULTS: In the MIS AL THA group, intraoperative fracture was observed in 6 hips; 3 in greater trochanter and 3 in calcar femoral. One hip was subjected to irrigation because of postoperative infection was suspected. In the PL group, intraoperative fracture was demonstrated in 4 hips in calcar femoral. No postoperative dislocation and no pulmonary embolism or nerve paralysis was observed in both groups. CONCLUSIONS: The MIS AL THA did not show a clinically relevant superior outcome compared with the PL THA. When performing MIS AL THA, special attention should pay for prevention of greater trochanter fracture.

Nobiletin, a citrus flavonoid, ameliorates cognitive impairment, oxidative burden, and hyperphosphorylation of tau in senescence-accelerated mouse.

Senescence-accelerated mouse prone 8 (SAMP8) is a model of aging characterized by the early onset of learning and memory impairment and various pathological features of Alzheimer's disease (AD). Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, ameliorates learning and memory impairment in olfactory-bulbectomized mice, amyloid precursor protein transgenic mice, and NMDA receptor antagonist-treated mice. Here, we present evidence that this natural compound improves age-related cognitive impairment and reduces oxidative stress and tau phosphorylation in SAMP8 mice. Treatment with nobiletin (10 or 50mg/kg) reversed the impairment of recognition memory and context-dependent fear memory in SAMP8 mice. Treatment with nobiletin also restored the decrease in the GSH/GSSG ratio in the brain of SAMP8 mice. In addition, increases in glutathione peroxidase and manganese-superoxide dismutase activities, as well as a decrease in protein carbonyl level, were observed in the brain of nobiletin-treated SAMP8 mice. Furthermore, nobiletin reduced tau phosphorylation in the hippocampus of SAMP8 mice. Together, the markedly beneficial effects of nobiletin represent a potentially useful treatment for ameliorating the learning and memory deficits, oxidative stress, and hyperphosphorylation of tau in aging as well as age-related neurodegenerative diseases such as AD.

A study of the usefulness of a periarticular multimodal drug cocktail injection for pain management after total hip arthroplasty.

BACKGROUND: Measures for pain management after total hip arthroplasty (THA) are important for early improvement in the quality of life after operation and early postoperative rehabilitation. We investigated the analgesic effect of locally injected drugs around the total hip prosthesis. METHODS: 54 patients undergoing THA were randomized either to receive a periarticular intraoperative injection of a 30-ml mixture containing morphine hydrochloride 10 mg, 0.5% bupivacaine 20 ml, epinephrine 0.3 mg, and saline 8.7 ml or to receive no injection. The perioperative analgesic regimen was standardized. The evaluation items included assessment of pain using a 100-point visual analog scale (VAS) after the patients awoke on the day of the operation and on postoperative day 1, the dose of diclofenac sodium suppository, the number of days for acquiring assisted ambulation with a walking cane, and side effects. RESULTS: The VAS score on the day of the operation was significantly low in the injection group. No cardiac or central nervous system toxicity was observed. CONCLUSIONS: Intraoperative periarticular injection with multimodal drugs can significantly reduce pain on the day of the operation, with no apparent risks, following THA.

Controlling pain after total knee arthroplasty using a multimodal protocol with local periarticular injections.

BACKGROUND: Measures for pain management after total knee arthroplasty (TKA) are important for early improvement in the quality of life after operation and early postoperative rehabilitation. We investigated the benefits and safety analgesic effect of locally injected drugs around the total knee prosthesis. METHODS: 60 patients undergoing TKA for osteoarthritis were divided randomly into three groups.Group A (20 knees; control group), this group did not receive multimodal drug cocktailtherapy; group B (21 knees), received intra-articular injection of a multimodal drug cocktail; and group C (19 knees), received localperiarticular injection of a multimodal drug cocktail. All analgesics administered in the first 24 h after surgery were recorded. The evaluation items included assessment of pain using a 100-point visual analogue scale (VAS) after the patients awoke on the day of the operation and on postoperative day 1, the dose of diclofenac sodium suppository, the number of days for acquiring assisted ambulation with a walking cane, and side effects. Assessment of flexion angles was conducted at postoperativeweek 1 and at theconclusion of the study. RESULTS: The VAS scores on the day of surgery and the amounts of diclofenac sodium used indicated good pain relief in groups B and C; the level of pain control was higher in group C than in group B. No cardiac or central nervous system toxicity was observed. CONCLUSIONS: Periarticular injection with multimodal drugs can significantly reduce the requirements for analgesia, with no apparent risks, following TKA.

Modulation of oxidative DNA damage and DNA-crosslink formation induced by cis-diammine-tetrachloro-platinum(IV) in the presence of endogenous reductants.

Platinum(IV) [Pt(IV)] complex, satraplatin, is currently in clinical trials for the treatment of various cancers. As a key step of the anti-cancer effect exertion, satraplatin is supposed to be reduced by endogenous reductants to platinum(II) [Pt(II)] complex. In this study, we investigated the interaction of DNA, Pt(IV), and the endogenous reductants such as ascorbic acid (AsA) and glutathione (GSH). As a model Pt(IV) compound, cis-diammine-tetrachloro-Pt(IV) [cis-Pt(IV)], which is a prodrug of cisplatin [cis-diammine-dichloro-Pt(II), cis-Pt(II)], was incubated with calf thymus DNA in the presence of AsA or GSH. In the presence of AsA, cis-Pt(IV) induced oxidative DNA damage. Hydroxyl radical scavengers suppressed the AsA-associated oxidative damage, thereby suggesting that hydroxyl radicals are involved in the DNA oxidation. cis-Pt(II)-like CD spectral change and crosslink formation in calf thymus DNA were also observed during this DNA oxidation, suggesting cis-Pt(IV) reduction by AsA and DNA conformational change induced by the newly formed cis-Pt(II) binding to DNA. GSH did not induce oxidative DNA damage likely due to its own hydroxyl radical scavenging ability. Further, GSH suppressed the Pt(II)-mediated DNA conformational change and crosslink formation, suggesting that GSH sequesters the cis-Pt(II) away from DNA by GSH-cis-Pt(II) complex formation.

Caudal epidural anesthesia administered intraoperatively provides for effective postoperative analgesia after total hip arthroplasty.

STUDY OBJECTIVE: To investigate the use of caudal epidural anesthesia for postoperative pain after total hip arthroplasty. DESIGN: Prospective study. SETTING: University-affiliated hospital. PATIENTS: 32 (4 men and 28 women) patients, aged 49 to 89 years, scheduled for total hip arthroplasty for osteoarthritis of the hip. INTERVENTIONS AND MEASUREMENTS: Patients were allocated to three groups: lumbar epidural anesthesia (EA group; n = 16) or caudal epidural anesthesia (CA group; n = 16) groups, which were case-matched according to patient demographics. Nine patients received general anesthesia only (GA group). We evaluated the level of postoperative pain using a 100-mm Visual Analog Scale (VAS) recorded at 3, 6, 9, 12, and 24 hours after surgery. MAIN RESULTS: Total requirement of diclofenac sodium suppositories was significantly larger in the GA group than in the EA or CA groups (444 +/- 302 vs 188 +/- 124 and 145 +/- 130 mg). The number of days requiring analgesics was significantly prolonged in the GA group compared with the EA or CA groups (14 +/- 9 vs 4 +/- 3 and 4 +/- 4 days). These items were similar between the EA group and the CA group. All VAS values for pain, rest, and movement in the postsurgical period over 24 hours were significantly higher in the GA group than in either the EA or CA groups. CONCLUSIONS: Caudal epidural anesthesia provides effective postoperative analgesia similar to lumbar epidural anesthesia.

Painful nonunion of fracture of the entire posterior process of the talus: a case report.

We report a 14-year-old boy in whom isolated nonunion fracture of the posterior process of the talus. He underwent surgical repair with Herbert Whipple screw fixation and plaster immobilization. Osseous union was achieved 3 months after surgery, resulting in the resolution of symptoms and complete functional recovery. To our knowledge, the present report is the first to describe a successful outcome for surgical treatment of painful nonunion of fracture of the entire posterior process of the talus.

Predictive value of a preoperative biochemical bone marker in relation to bone remodeling after cementless total hip arthroplasty.

To identify the factors predicting proximal bone resorption of the femur after cementless total hip arthroplasty (THA), we studied 24 postmenopausal women with osteoarthritis. Periprosthetic bone mineral density (BMD) measurements of the seven Gruen zones were determined with dual-energy X-ray absorptiometry at 3 wk, 6, 12, and 18 mo after operation. The greatest decrease in BMD (13.2%) was found in zone 7 at 18 mo. At 18 mo, preoperative serum bone alkaline phosphatase was associated univariately with BMD loss in zones 1 (r = 0.407, p = 0.048) and 7 (r = 0.543, p = 0.006) and urinary N-telopeptide cross-linked collagen type I (NTX) was associated univariately with that in zone 7 (r = 0.520, p = 0.009). Patient age correlated with BMD loss in zone 7 (r = 0.425, p = 0.039). Multiple regression analysis identified a significant relationship between the BMD loss and patient age and NTX in zone 7 at 18 mo (r2 = 0.422, p = 0.001). We conclude that preoperative bone markers are significant predictors of bone remodeling after THA with the particular implants used in our study.

Significant increases in serum and plasma concentrations of matrix metalloproteinases 3 and 9 in patients with rapidly destructive osteoarthritis of the hip.

OBJECTIVE: Rapidly destructive osteoarthritis (OA) of the hip is an uncommon subset of OA that affects mainly elderly women. Previous studies indicate that elevated levels of matrix metalloproteinases (MMPs) are produced within the tissue of patients with the condition. In the present study, we sought to determine whether serum and plasma levels of MMPs and tissue inhibitors of metalloproteinases (TIMPs) are also elevated. METHODS: Blood samples were obtained from 16 patients with rapidly destructive hip OA and from 20 patients with OA before total hip arthroplasty was performed. Synovial specimens were obtained during surgery. Synovial fibroblasts that had migrated sufficiently from explants were subcultured in vitro for 72 hours after confluency, and harvested supernatants were collected. Blood, tissue samples, and fibroblasts were assayed for MMPs 1, 2, 3, and 9, and TIMPs 1 and 2 by sandwich enzyme immunoassay. RESULTS: In blood samples, the levels of MMP-3 and MMP-9 in the group with rapidly destructive hip OA were significantly higher than the normal range and were also significantly higher than those in the OA group. In tissue samples, the levels of MMP-1, MMP-3, MMP-9, and TIMP-1 in the group with rapidly destructive hip OA were significantly higher than those in the OA group. CONCLUSION: The results of this study show that serum and plasma levels of MMP-3 and MMP-9 are significantly increased in patients with rapidly destructive hip OA. Significantly large amounts of these MMPs produced in synovial tissues within the hip joint could contribute in part to elevation of blood levels. Detection of increased levels of MMP-3 and MMP-9 in patients with painful, disabling hip OA may be of diagnostic value for rapidly destructive hip OA.