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1.
Asian Spine Journal ; : 539-544, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-897277

ABSTRACT

Study DesignThis study enrolled patients in from a single center who underwent primary spinal fusion procedure and divided them into two groups (group-control study).PurposeGood local infiltration can reduce postoperative analgesic requirements and enable expedited discharge. Administration of a combination of levobupivacaine (200 mg/100 mL, 0.9% normal saline), ketorolac (30 mg), and adrenaline (0.5 mg) as a wound infiltrate is recommended at an optimum combination.Overview of LiteratureThere is currently no consensus on the optimum intraoperative local infiltration of spinal surgery patients undergoing operative fusion.MethodsPatients who were enrolled in two spinal centers (over 24 months) undergoing primary spinal fusion procedures were allocated into two groups, comparing the type of local infiltration used at the time of the procedure. Group 1 received the combination of levobupivacaine (200 mg), ketorolac (30 mg), and adrenaline (0.5 mg), while group 2 received other types of local anesthetics. Primary outcome measures include patient-controlled analgesia (PCA) use, morphine consumption, and length of hospital stay. Secondary outcome measure are as follows: days of physiotherapy, pain score, side effects, and complications.ResultsThere are a total of 140 patients enrolled. Seventy-five patients enrolled were allocated to group 1, receiving the study combination, and 65 patients were assigned in group 2, receiving other local infiltrations. All primary outcome measures (consumption of morphine, use of PCA, and length of stay) were significantly higher in group 2 than the study combination (pppConclusionsOur data suggest that the studied wound infiltration is a safe and feasible option that could provide good postoperative pain control without significant side effects. It also allowed to reduce dependence of opioids and PCA, earlier postoperative mobilization, lower pain scores postoperatively, and reduced hospital stay.

2.
Asian Spine Journal ; : 539-544, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-889573

ABSTRACT

Study DesignThis study enrolled patients in from a single center who underwent primary spinal fusion procedure and divided them into two groups (group-control study).PurposeGood local infiltration can reduce postoperative analgesic requirements and enable expedited discharge. Administration of a combination of levobupivacaine (200 mg/100 mL, 0.9% normal saline), ketorolac (30 mg), and adrenaline (0.5 mg) as a wound infiltrate is recommended at an optimum combination.Overview of LiteratureThere is currently no consensus on the optimum intraoperative local infiltration of spinal surgery patients undergoing operative fusion.MethodsPatients who were enrolled in two spinal centers (over 24 months) undergoing primary spinal fusion procedures were allocated into two groups, comparing the type of local infiltration used at the time of the procedure. Group 1 received the combination of levobupivacaine (200 mg), ketorolac (30 mg), and adrenaline (0.5 mg), while group 2 received other types of local anesthetics. Primary outcome measures include patient-controlled analgesia (PCA) use, morphine consumption, and length of hospital stay. Secondary outcome measure are as follows: days of physiotherapy, pain score, side effects, and complications.ResultsThere are a total of 140 patients enrolled. Seventy-five patients enrolled were allocated to group 1, receiving the study combination, and 65 patients were assigned in group 2, receiving other local infiltrations. All primary outcome measures (consumption of morphine, use of PCA, and length of stay) were significantly higher in group 2 than the study combination (pppConclusionsOur data suggest that the studied wound infiltration is a safe and feasible option that could provide good postoperative pain control without significant side effects. It also allowed to reduce dependence of opioids and PCA, earlier postoperative mobilization, lower pain scores postoperatively, and reduced hospital stay.

3.
Head Neck ; 38(12): 1759-1764, 2016 12.
Article in English | MEDLINE | ID: mdl-27232378

ABSTRACT

BACKGROUND: Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC. METHODS: This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway. RESULTS: Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue. CONCLUSION: Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1759-1764, 2016.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Everolimus/therapeutic use , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Neoplasm Recurrence, Local/drug therapy , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Administration Schedule , Everolimus/adverse effects , Female , Head and Neck Neoplasms/mortality , Humans , Kaplan-Meier Estimate , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Risk Assessment , Survival Analysis , Treatment Outcome
4.
Nat Commun ; 6: 7768, 2015 Jul 16.
Article in English | MEDLINE | ID: mdl-26178471

ABSTRACT

Isocitrate dehydrogenases (IDH) convert isocitrate to alpha-ketoglutarate (α-KG). In cancer, mutant IDH1/2 reduces α-KG to D2-hydroxyglutarate (D2-HG) disrupting α-KG-dependent dioxygenases. However, the physiological relevance of controlling the interconversion of D2-HG into α-KG, mediated by D2-hydroxyglutarate dehydrogenase (D2HGDH), remains obscure. Here we show that wild-type D2HGDH elevates α-KG levels, influencing histone and DNA methylation, and HIF1α hydroxylation. Conversely, the D2HGDH mutants that we find in diffuse large B-cell lymphoma are enzymatically inert. D2-HG is a low-abundance metabolite, but we show that it can meaningfully elevate α-KG levels by positively modulating mitochondrial IDH activity and inducing IDH2 expression. Accordingly, genetic depletion of IDH2 abrogates D2HGDH effects, whereas ectopic IDH2 rescues D2HGDH-deficient cells. Our data link D2HGDH to cancer and describe an additional role for the enzyme: the regulation of IDH2 activity and α-KG-mediated epigenetic remodelling. These data further expose the intricacies of mitochondrial metabolism and inform on the pathogenesis of D2HGDH-deficient diseases.


Subject(s)
Alcohol Oxidoreductases/genetics , Dioxygenases/metabolism , Gene Expression Regulation, Neoplastic , Isocitrate Dehydrogenase/genetics , Ketoglutaric Acids/metabolism , Lymphoma, Large B-Cell, Diffuse/genetics , Blotting, Western , Cell Line, Tumor , DNA Methylation/genetics , Epigenesis, Genetic , HEK293 Cells , Histones/metabolism , Humans , Hydroxylation/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Isocitrate Dehydrogenase/metabolism , Methylation , Real-Time Polymerase Chain Reaction
5.
Support Care Cancer ; 20(11): 2969-75, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22418599

ABSTRACT

PURPOSE: There is no information regarding the toxicity associated with autologous hematopoietic progenitor cell transplantation (AHPCT) in patients with multiple myeloma (MM) who have bisphosphonate-induced osteonecrosis of the jaw (ONJ). There is also limited information regarding long-term outcome of these patients. METHODS: In this retrospective cohort study, we compared the toxicity after AHPCT in MM patients with and without ONJ. We also analyzed the response rate and overall survival of this population of patients. RESULTS: During the study period, 176 patients underwent AHPCT at our institution for MM. Ten patients with ONJ prior to AHPCT were matched to 40 control patients without ONJ. The incidence and severity of transplantation-associated toxicities were similar in both groups, including mucositis, 50 % in patients with ONJ vs. 68 % in controls (p = 0.889) and febrile days, median 1 vs. 3 days, respectively (p = 0.524). Myeloid engraftment and hospital length of stay were also similar between patients with ONJ and controls. There were significantly more complete remissions in patients with ONJ than in control patients (45 % vs. 15 %, p = 0.0336), but survival between the groups was not significantly different (log-rank p = 0.0818). CONCLUSIONS: We conclude that the incidence and severity of transplantation-associated toxicities are similar in MM patients with and without ONJ. Long-term survival was also similar between both groups.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/pathology , Bone Density Conservation Agents/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Multiple Myeloma/therapy , Adult , Aged , Bone Density Conservation Agents/administration & dosage , Case-Control Studies , Cohort Studies , Diphosphonates/administration & dosage , Diphosphonates/adverse effects , Follow-Up Studies , Hematopoietic Stem Cell Transplantation/methods , Humans , Length of Stay , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Survival Rate , Transplantation, Autologous , Treatment Outcome
6.
Biol Blood Marrow Transplant ; 15(5): 643-8, 2009 May.
Article in English | MEDLINE | ID: mdl-19361758

ABSTRACT

Early recognition of gastrointestinal graft-versus-host disease (GI GVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) is vital to initiation of therapy. However, the most common location, the small bowel (SB), is difficult to access with upper and lower endoscopy (UGE/LGE). Wireless capsule endoscopy (WCE) is a noninvasive technology allowing complete SB evaluation. The capsule location can also be tracked to identify motility derangements. From August 2006 to July 2007, 11 alloHSCT patients with GI symptoms underwent WCE, and visual grading was performed. UGE and LGE with biopsies were done when clinically indicated. All patients had evidence of probable acute GVHD (aGVHD) on WCE. WCE revealed lesions of greater severity than those seen by UGE or LGE in most patients. WCE demonstrated that 45% of patients had delayed gastric transit time. WCE is an excellent, noninvasive method for assessing GI GVHD, with the ability to more accurately assess the severity of GVHD, evaluate clinical symptoms, and follow response to treatment.


Subject(s)
Capsule Endoscopy/methods , Diagnostic Imaging/instrumentation , Gastrointestinal Diseases/diagnosis , Graft vs Host Disease/diagnosis , Intestine, Small , Adolescent , Adult , Aged , Capsule Endoscopy/standards , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Incidence , Male , Middle Aged , Severity of Illness Index , Transplantation, Homologous , Young Adult
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