ABSTRACT
BACKGROUND: Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown. METHODS: Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2-4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. RESULTS: Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3-5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations. CONCLUSION: Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Acrylamides , Aniline Compounds , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/adverse effectsABSTRACT
BACKGROUND: A subset analysis of the CA031 trial showed significant improvement in the overall response rate after administration of carboplatin plus weekly albumin-bound paclitaxel compared to carboplatin plus paclitaxel for squamous cell carcinoma of the lung (SQ). We conducted this phase II study to compare carboplatin plus weekly albumin-bound paclitaxel (CnP) to cisplatin plus gemcitabine (CG), a standard regimen for SQ. METHODS: Chemotherapy-naïve patients with SQ were randomly assigned to receive cisplatin (80 mg/m2) on day 1 plus gemcitabine (1000 mg/m2) on days 1 and 8 every 3 weeks or carboplatin (area under the curve: 6 mg/mL/min) on day 1 plus nab-paclitaxel (75 mg/m2) on days 1, 8, and 15 every 3 weeks. The primary endpoint was overall response rate. The secondary endpoints were progression-free survival, overall survival, disease control rate, and toxicity. RESULTS: Between June 2013 and October 2018, 71 patients were enrolled and assigned to either the CG arm (n = 35) or the CnP arm (n = 36) of the study. The overall response rate was 43% [95% confidence interval (CI) 27.3-58.5] in the CG arm and 47% (95% CI 31.7-62.7) in the CnP arm. Although drug combination efficacies did not differ, there were differences in toxicity: hematologic toxicities (leukopenia, neutropenia, and thrombocytopenia) were found mostly in the CG arm, whereas anemia and sensory neuropathy were more common in the CnP arm. CONCLUSIONS: CnP had similar response as CG despite being a carboplatin-based regimen and toxicities differed between arms. Regarding ORR, CnP was comparable to CG for SQ.
Subject(s)
Carcinoma, Squamous Cell , Lung Neoplasms , Albumins , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Carcinoma, Squamous Cell/drug therapy , Cisplatin/adverse effects , Deoxycytidine/analogs & derivatives , Humans , Japan , Lung Neoplasms/drug therapy , Paclitaxel/adverse effects , Treatment Outcome , GemcitabineABSTRACT
LESSONS LEARNED: Low-dose afatinib maintenance treatment among patients with EGFR-mutated NSCLC achieved long-time to treatment failure with fewer treatment-related AEs without detracting from the therapeutic efficacy. This modified regimen represents a practical usage that balances effectiveness and safety. BACKGROUND: Although afatinib is an effective therapy for patients with EGFR-mutated non-small cell lung cancer (NSCLC), drug-related adverse events (AEs) have often necessitated dose reductions. In a post hoc analysis of the LUX-Lung 3 and 6 trials, there was no difference in median progression-free survival (PFS) between patients who had the dose of afatinib reduced and those who did not. We thus evaluated the efficacy and tolerability of low-dose afatinib maintenance treatment among patients with NSCLC harboring EGFR mutations who had not been previously treated. METHODS: Eligible patients received afatinib 40 mg orally once daily. When prescribed grade ≥ 2 AEs, rash of grade ≥ 3, or unacceptable toxicity occurred, the afatinib dose was reduced from 40 to 30 mg and if needed from 30 to 20 mg. The primary endpoint was the 1-year PFS rate. Secondary endpoints were PFS, overall response rate (ORR), and toxicity. RESULTS: Among 30 patients, 93% had adenocarcinoma, 53% had exon 19 deletion, 37% had L858R, and 10% had minor mutations. The 1-year PFS rate was 50% (95% confidence interval [CI], 31.3-66.1) and the median PFS was 11.8 months (95% CI, 7.1-21.4). The incidence rate of grade ≥ 3 toxicities was 57%, including elevated aspartate aminotransferase/alanine aminotransferase level (13%), diarrhea (10%), and paronychia (10%). CONCLUSION: Low-dose afatinib maintenance treatment reduced treatment-related AEs without detracting from the therapeutic efficacy.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Afatinib/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Humans , Japan , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors , Quinazolines/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. MATERIAL AND METHODS: We performed a multi-institutional, retrospective study named NEJ023 for patients with advanced thymic carcinoma. Patients without indications for curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions in the North East Japan Study Group. Demographic and clinicopathologic characteristics, data on treatment methods, and outcomes of second-line chemotherapy were obtained from medical records. RESULTS: In total, 191 patients were enrolled in this study. Second-line chemotherapy included platinum-based doublets in 57.6% of patients, other multidrug chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide) in 13.6%, and monotherapy in 28.8%. The median follow-up time was 50.5 months, and the median overall survival (OS) from the start of second-line chemotherapy was 22.4 (95% confidence interval, 17.5-26.7) months. The average response rate (RR) was 20.0% overall; it was 21.6% for patients treated with platinum-based doublet chemotherapy, 13.6% for those treated with other multidrug chemotherapy, and 19.6% for those treated with single agent chemotherapy. There was no significant difference in OS between platinum-based doublet chemotherapy, other multidrug chemotherapy, and monotherapy (the median OS was 22.4, 25.7, and 21.4 months, respectively). CONCLUSION: The median OS was 22.4 months in patients with advanced thymic carcinoma treated with second-line chemotherapy. There were no significant differences in RR and OS between monotherapy and multidrug chemotherapy in this study. IMPLICATIONS FOR PRACTICE: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. This is the largest data for those patients treated with second-line chemotherapy. This study suggests there is no significant difference in efficacy between monotherapy and multidrug chemotherapy for previously treated advanced thymic carcinoma. This result can support the adequacy to select monotherapy as treatment of those patients.
Subject(s)
Thymoma , Thymus Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/therapeutic use , Humans , Japan , Retrospective Studies , Thymoma/drug therapy , Thymus Neoplasms/drug therapy , Treatment OutcomeABSTRACT
Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15â¯years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6â¯months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3⯱â¯22.0â¯mg/dl, 1â¯month: 63.8⯱â¯21.6â¯mg/dl, 6â¯months: 92.3⯱â¯63.6â¯mg/dl, pâ¯=â¯0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15⯱â¯0.06â¯ng/dl, 1â¯month: 1.00⯱â¯0.16â¯ng/dl, 6â¯months: 0.98⯱â¯0.14â¯ng/dl, pâ¯=â¯0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction.
Subject(s)
Anticonvulsants/adverse effects , Carbamazepine/adverse effects , Epilepsy/blood , Epilepsy/drug therapy , Levetiracetam/adverse effects , Thyroid Diseases/chemically induced , Thyrotropin/blood , Thyroxine/blood , Triglycerides/blood , Adolescent , Anticonvulsants/administration & dosage , Carbamazepine/administration & dosage , Child , Child, Preschool , Cholesterol, HDL/blood , Cholesterol, HDL/drug effects , Cholesterol, LDL/blood , Cholesterol, LDL/drug effects , Female , Humans , Levetiracetam/administration & dosage , Male , Prospective Studies , Thyrotropin/drug effects , Thyroxine/drug effectsABSTRACT
BACKGROUND: The optimal duration of antimicrobial therapy for Mycobacterium avium complex lung disease (MAC-LD) is unknown, and recurrence rates are high after treatment discontinuation. Intermittent therapy is recommended for the initial treatment of non-cavitary nodular/bronchiectatic MAC-LD. We hypothesized that intermittent maintenance therapy (IMT) could effectively prevent recurrence after successful treatment of MAC-LD. METHODS: Adult patients diagnosed with MAC-LD who received IMT after successful daily therapy (DT) between January 1, 2006 and December 31, 2016 were identified from clinical databases at three institutions in Japan. Treatment outcomes were evaluated for all patients. RESULTS: Of 38 patients (median age, 66 years; 29 women; nodular/bronchiectatic form, 29 patients) who received IMT after successful treatment, one was excluded due to death from an unknown cause, 1 month after IMT initiation. Finally, treatment outcomes were evaluated for 37 patients. Twenty-eight (76%) patients had sustained negative culture results over a median follow-up duration of 2.7 (interquartile range [IQR], 1.9-6.0) years, while six (16%) required switching to DT because of clinical deterioration over a median follow-up duration of 2.7 (IQR, 1.6-4.1) years. Favorable clinical outcomes were achieved for all patients who exhibited clinical deterioration. All patients tolerated the antimicrobials without discontinuation, and follow-up drug susceptibility testing showed negative results for clarithromycin-resistant MAC in the patients who experienced clinical deterioration. CONCLUSIONS: IMT after successful treatment may be a feasible option for patients with MAC-LD. Further studies should determine the population that would benefit from this strategy.
Subject(s)
Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Lung Diseases/drug therapy , Mycobacterium avium Complex , Mycobacterium avium-intracellulare Infection/drug therapy , Aged , Anti-Bacterial Agents/administration & dosage , Female , Humans , Lung Diseases/microbiology , Male , Middle Aged , Mycobacterium avium-intracellulare Infection/microbiology , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: Surgery remains the best curative treatment option for non-small cell lung cancer (NSCLC), but is of benefit only to patients with localized disease. A meta-analysis showed a significant beneficial effect of induction chemotherapy on survival, but there is still no clear evidence. This phase II study was conducted to establish whether induction chemotherapy with carboplatin (CBDCA) and paclitaxel (PTX) plus bevacizumab prior to surgery reduces the risk of progression. METHODS: The subjects of this study were 29 patients with treatment-naive nonsquamous NSCLC (clinical stages IIIA to IV). Patients received PTX (200 mg/m2), CBDCA (area under the curve, 5), and bevacizumab (15 mg/kg) followed by surgery. Chemotherapy was repeated every 3 weeks for up to six cycles. RESULTS: The overall response rate was 72.4%. Of the 29 patients, ten underwent surgery after the induction chemotherapy and complete resection was achieved in 7 (70%). The median progression-free-survival (PFS) time and the 3-year PFS rate were 0.92 years and 16.2%, respectively. The median overall survival (OS) time and the 3-year OS rate were 1.96 years and 44.9%, respectively. CONCLUSION: Combined modality therapy with surgery after induction chemotherapy with CBDCA and PTX plus bevacizumab is clinically feasible and tolerable for patients with unknown or negative molecular profiles.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Induction Chemotherapy , Lung Neoplasms/therapy , Aged , Bevacizumab/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Combined Modality Therapy , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Survival Rate , Treatment OutcomeABSTRACT
Mycobacterium avium subsp. hominissuis mainly causes disseminated infection in immunocompromised hosts, such as individuals with human immunodeficiency virus (HIV) infection, and pulmonary infection in immunocompetent hosts. However, many aspects of the different types of M. avium subsp. hominissuis infection remain unclear. We examined the antibiotic susceptibilities and genotypes of M. avium subsp. hominissuis isolates from different hosts by performing drug susceptibility testing using eight antibiotics (clarithromycin, rifampin, ethambutol, streptomycin, kanamycin, amikacin, ethionamide, and levofloxacin) and variable-number tandem-repeat (VNTR) typing analysis for 46 isolates from the sputa of HIV-negative patients with pulmonary M. avium subsp. hominissuis disease without previous antibiotic treatment and 30 isolates from the blood of HIV-positive patients with disseminated M. avium subsp. hominissuis disease. Interestingly, isolates from pulmonary M. avium subsp. hominissuis disease patients were more resistant to seven of the eight drugs, with the exception being rifampin, than isolates from HIV-positive patients. Moreover, VNTR typing analysis showed that the strains examined in this study were roughly classified into three clusters, and the genetic distance from reference strain 104 for isolates from pulmonary M. avium subsp. hominissuis disease patients was statistically significantly different from that for isolates from HIV-positive patients (P = 0.0018), suggesting that M. avium subsp. hominissuis strains that cause pulmonary and disseminated disease have genetically distinct features. Significant differences in susceptibility to seven of the eight drugs, with the exception being ethambutol, were noted among the three clusters. Collectively, these results suggest that an association between the type of M. avium subsp. hominissuis infection, drug susceptibility, and the VNTR genotype and the properties of M. avium subsp. hominissuis strains associated with the development of pulmonary disease are involved in higher levels of antibiotic resistance.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Genotype , Lung Diseases/drug therapy , Lung Diseases/microbiology , Mycobacterium avium/drug effects , Mycobacterium avium/genetics , Humans , Microbial Sensitivity Tests , Mycobacterium avium/pathogenicity , Tandem Repeat Sequences/geneticsABSTRACT
We herein reported a 4-month-old boy with transplantation-associated atypical hemolytic uremic syndrome (TA-aHUS) who was successfully treated with eculizumab. The patient diagnosed with type 3 of familial hemophagocytic lymphohistiocytosis underwent cord blood transplantation. After transplantation, he developed TA-aHUS, but plasma exchanges were unsuccessful. We identified deletions in CFH-related gene 1 (del-CFHR1) by the multiplex ligation-dependent probe amplification testing procedure and CFH autoantibodies. Eculizumab has been administered to the patient, with a marked improvement being achieved in thrombocytopenia. He has been well except for the persistent microhematuria for a year after transplantation. Uncontrolled complement activation might be involved in the pathophysiology of TA-aHUS.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Atypical Hemolytic Uremic Syndrome/drug therapy , Cord Blood Stem Cell Transplantation/adverse effects , Atypical Hemolytic Uremic Syndrome/etiology , Autoantibodies/immunology , Complement Factor H/deficiency , Complement Factor H/immunology , Hereditary Complement Deficiency Diseases , Humans , Infant , Kidney Diseases , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/therapy , Male , Plasma Exchange , Treatment OutcomeABSTRACT
BACKGROUND: The severity of anaphylaxis often varies with time. Because prehospital intervention and initial treatment at hospital are affected by changing symptoms, the aim of this study was to determine the clinical factors associated with prehospital remission and exacerbation in the course of anaphylaxis in children. METHODS: Data from medical records on anaphylactic children who were treated for 3 years at Kobe Children's Primary Emergency Medical Center were retrospectively analyzed. Severity of symptoms was evaluated using Sampson's grade (S-G). Patients with increased S-G at the hospital visit from disease onset (worsened group) were compared with those with decreased S-G at the visit (improved group). Uni- and multivariate analyses were performed to identify clinical differences between the groups, with P<0.05 considered statistically significant. RESULTS: Among 115 anaphylactic children who showed S-G changes from onset to hospital visit, 43 were assigned to the worsened group and 72 to the improved group. Univariate analysis showed no significant differences in age, sex, history of asthma, prehospital treatment, type of antigen, or period from symptom onset to hospital visit between the groups. However, the time from antigen exposure to symptom onset was significantly longer, and S-G at onset was significantly lower in the worsened group than in the improved group. Multivariate analysis identified time from antigen exposure to symptom onset (odds ratio: 3.89, P<0.01) and S-G at onset (odds ratio: 0.06, P<0.001) as independent predictors of exacerbation. CONCLUSIONS: Anaphylactic children with slower and milder symptoms at onset are more likely to show deterioration.
Subject(s)
Anaphylaxis/physiopathology , Antigens/immunology , Emergency Treatment/methods , Adolescent , Anaphylaxis/immunology , Anaphylaxis/therapy , Child , Child, Preschool , Emergency Service, Hospital , Female , Humans , Infant , Male , Multivariate Analysis , Remission Induction/methods , Retrospective Studies , Severity of Illness Index , Time FactorsABSTRACT
LESSONS LEARNED: Weekly nanoparticle albumin-bound-paclitaxel (75 mg/m2) in combination with carboplatin (area under the curve 6 mg/mL/min) in elderly patients with previously untreated, advanced non-small cell lung cancer showed favorable efficacy, was well tolerated, and showed less neuropathic toxicity.This modified regimen offers potential for the treatment of elderly patients. BACKGROUND: The CA031 trial suggested weekly nanoparticle albumin-bound-paclitaxel (nab-PTX) was superior in efficacy to paclitaxel (PTX) once every 3 weeks when combined with carboplatin (CBDCA) for advanced non-small cell lung cancer (NSCLC) patients; a subgroup analysis of elderly patients looked promising. In a multicenter phase II trial, we prospectively evaluated the efficacy and tolerability of modified CBDCA plus weekly nab-PTX for elderly patients with untreated advanced NSCLC. METHODS: Eligible patients received CBDCA (area under the curve [AUC] 6 mg/mL/min) on day 1 and nab-PTX (75 mg/m2) on days 1, 8, and 15 every 4 weeks. The primary endpoint was an overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Of 32 patients (median age of 78 years), 84% were male, 56% had stage IV NSCLC, and 56% had squamous cell carcinoma. ORR and disease control rates were 50% (95% confidence interval (CI): 33-67) and 94% (95% CI: 85-100), respectively. Median PFS and OS were 6.4 months (95% CI: 4.8-8.0) and 17.5 months (95% CI: 11.9-23.1), respectively. Grade ≥3 toxicities were neutropenia (47%), leukopenia (38%), anemia (34%), thrombocytopenia (25%), and anorexia (9%). Febrile neutropenia and treatment-related deaths were not observed. CONCLUSION: Modified CBDCA plus weekly nab-PTX demonstrated significant efficacy and acceptable toxicities in elderly patients with advanced NSCLC.
Subject(s)
Albumins/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug-Related Side Effects and Adverse Reactions/pathology , Paclitaxel/administration & dosage , Aged , Aged, 80 and over , Albumins/adverse effects , Antineoplastic Combined Chemotherapy Protocols , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/classification , Female , Humans , Japan , Male , Paclitaxel/adverse effects , Treatment OutcomeABSTRACT
Background The efficacy and safety of bevacizumab in elderly patients with non-small cell lung cancer remain controversial. This study focused on both selecting fit elderly patients and overcoming interpatient variability with respect to pharmacodynamics. Methods Elderly (age: ≥70 years) patients with advanced non-squamous non-small cell lung cancer were enrolled. Patients with uncontrolled congestive heart failure and uncontrolled diabetes were excluded. The treatment regimen comprised carboplatin at an area under the curve of 5 mg/ml/min on day 1, paclitaxel at 90 mg/m2 on days 1 and 8, and bevacizumab at 15 mg/kg on day 1 every 21 days for up to 4 cycles, followed by maintenance bevacizumab. Dose reduction due to side effects was performed, with a wide range of doses of paclitaxel from 23 mg/m2/week to 60 mg/m2/week. Results Of the 36 patients entered, 38.9% required a dose reduction or cancellation of paclitaxel administration on day 8, and 75% patients were able to complete 4 cycles of triplet therapy. The response rate, primary endpoint, was 69.4% (95% confidence interval [CI]: 51.9-83.7). The median progression free survival and overall survival were 8.4 months and 29.2 months, respectively. The most common adverse events included neutropenia, hypertension, anemia, and infection. Although Grade ≥ 3 adverse events were observed in 24 patients (66.7%), there were no deaths due to toxicity. Conclusion Carboplatin plus weekly paclitaxel with bevacizumab is a feasible, effective first-line regimen for elderly non-small cell lung cancer patients. (UMIN00006622).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Paclitaxel/therapeutic use , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Female , Humans , Kaplan-Meier Estimate , Male , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Treatment OutcomeABSTRACT
BACKGROUNDS: Remifentanil has been reported to cause post-anesthetic shivering (PAS). Higher doses of remifentanil reportedly induce more intense PAS. Tramadol, a synthetic opioid that acts at multiple sites, is considered to be an effective treatment for PAS, but the evidence for its therapeutic benefit after remifentanil anesthesia is limited. We investigated the effect of tramadol on the incidence of PAS after remifentanil anesthesia. METHODS: Sixty-three patients who had undergone upper abdominal surgery under general anesthesia were studied retrospectively. Tramadol was administered at induction of anesthesia. The patients were divided into four groups: HT(+), high dose remifentanil (1-1.5 µg/kg/min) with tramadol; HT(-), high dose remifentanil without tramadol; LT(+), low dose remifentanil (0.15-0.25 µg/kg/min) with tramadol; and LT(-), low dose remifentanil without tramadol. We recorded perioperative changes in nasopharyngeal temperature and episodes of PAS on emergence from anesthesia. RESULTS: The incidences of PAS in both tramadol treatment groups were significantly lower than the groups that did not receive tramadol. Nasopharyngeal temperature after surgery fell significantly more from baseline in the tramadol treatment groups compared with the non-treatment groups. CONCLUSION: Tramadol administered at induction of anesthesia appears to suppress PAS following remifentanil anesthesia.
Subject(s)
Piperidines/adverse effects , Piperidines/antagonists & inhibitors , Shivering/drug effects , Tramadol/therapeutic use , Administration, Intravenous , Adult , Aged , Aged, 80 and over , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Anesthesia Recovery Period , Body Temperature/drug effects , Dose-Response Relationship, Drug , Female , Humans , Male , Methyl Ethers/administration & dosage , Middle Aged , Remifentanil , Retrospective Studies , Sevoflurane , Tramadol/administration & dosageABSTRACT
Glycosylphosphatidylinositol (GPI) anchors tether proteins to the extracellular face of eukaryotic plasma membranes. Defects in the human GPI anchor biosynthetic pathway cause inherited GPI deficiencies (IGDs) characterized by multiple congenital anomalies: dysmorphic faces, developmental delay, hypotonia, and epilepsy. We report the case of a 6-year-old boy with severe psychomotor developmental delay, epilepsy, and decreased granulocyte surface expression of GPI-anchored protein that suggested autosomal recessive GPI deficiency. The case underwent target exome sequencing to screen for IGDs. Target exome sequencing of the proband identified an apparently homozygous c.808T > C (p.Ser270Pro) mutation in PIGN, a gene involved in the GPI anchor biosynthetic pathway. As his parents were expecting another child, genetic carrier screening was conducted for the parents. Direct sequencing of the parents identified a heterozygous c.808T > C PIGN mutation in the father but none in the mother. To identify the mother's mutation, we performed semi-quantitative real-time PCR of the PIGN exons and long PCR, identifying a microdeletion in PIGN (del exons 2-14). The proband had inherited this microdeletion from his mother. Prenatal diagnosis of the fetus revealed that it was a heterozygous carrier of the mother's pathogenic allele. Here, we report a sporadic case of inherited GPI deficiency with a PIGN mutation and the first case of prenatal diagnosis for GPI deficiency.
Subject(s)
Base Sequence/genetics , Glycosylphosphatidylinositols/deficiency , Phosphotransferases/genetics , Prenatal Diagnosis/methods , Sequence Deletion/genetics , Abnormalities, Multiple/genetics , Child , Developmental Disabilities/genetics , Epilepsy/genetics , Exome/genetics , Facies , Female , Glycosylphosphatidylinositols/genetics , Glycosylphosphatidylinositols/metabolism , Granulocytes/metabolism , Humans , Intellectual Disability/genetics , Male , Muscle Hypotonia/genetics , Pregnancy , Real-Time Polymerase Chain Reaction , Seizures , Sequence Analysis, DNAABSTRACT
BACKGROUND: Some cases of childhood steroid-resistant nephrotic syndrome (SRNS) are intractable. We examined the cases of three patients with SRNS resistant to various treatment, but who achieved complete remission after being treated with rituximab (RTX) followed by methylprednisolone pulse (MP) therapy. METHODS: A retrospective chart review of all new-onset SRNS in the period from January 1997 to December 2013 was performed. Three of the 13 patients who received conventional treatment continued to have NS for >6 months, despite also being treated with immunosuppressants and receiving frequent albumin treatment. In addition, two of the patients received plasma exchange therapy, but it was ineffective. Therefore, RTX was used once a week for 4 weeks, followed by several courses of MP therapy. RESULTS: Two of the three intractable SRNS patients achieved complete remission after treatment with RTX followed by MP therapy, and the remaining patient achieved incomplete remission after the first round of this treatment. That patient subsequently achieved complete remission after the second round of the treatment. RTX did not cause any serious side-effects, and all three patients had normal renal function at the final observation. CONCLUSIONS: Complete remission was achieved in all 13 SRNS patients. RTX followed by MP therapy might be effective against SRNS refractory to conventional treatments and requiring frequent albumin treatment. Prospective clinical study examining the effectiveness and safety of this approach is required.
Subject(s)
Rituximab/therapeutic use , Steroids/pharmacology , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Immunologic Factors/therapeutic use , Infant , Infant, Newborn , Male , Nephrotic Syndrome/drug therapy , Remission Induction , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Pulmonary disease caused by nontuberculous mycobacteria has a variable clinical course. Although this is possibly the result of not only host factors, but also bacterial factors, many questions remain to be answered regarding these manifestations. METHODS: To assess the relationship between the progression of pulmonary Mycobacterium avium disease and bacterial factors we performed variable number tandem repeats (VNTR) typing analysis of M. avium tandem repeats (MATR) in M. avium isolates from 46 patients with different clinical courses, and furthermore, examined the association between disease progression and a pMAH135 plasmid derived from M. avium. RESULTS: In patients whose treatment was initiated because of worsenedchest radiograph findings and/or clinical symptoms within 18 months after being diagnosed with pulmonary M. avium disease, the detection rate of 6 genes located in pMAH135 was 35.3-47.1% for 17 isolates. However, in untreated patients with a stable condition, these rates were 10.3-13.8% in 29 isolates. MATR-VNTR typing analysis showed that isolates from patients with worsened disease and those with stable disease are clustered differently. In cluster III, the number of isolates from patients with worsened disease was higher than that from patients with stable disease (p = 0.019), and furthermore, the number of isolates carrying pMAH135 genes was higher than that not carrying pMAH135 genes (p ≤ 0.001). CONCLUSION: These results indicate an association between the progression of pulmonary M. avium disease and pMAH135. The presence of pMAH135 genes might be a useful prognostic indicator for pulmonary M. avium disease and may serve as one criterion for treatment initiation.
Subject(s)
Mycobacterium avium/genetics , Tuberculosis/microbiology , Adult , Aged , Aged, 80 and over , Female , Genotype , Humans , Male , Middle Aged , Minisatellite Repeats , Phylogeny , Plasmids/geneticsABSTRACT
BACKGROUND: Patients receiving surgical treatment for Mycobacterium avium complex (MAC), lung disease should be followed up with careful attention paid to relapse/recurrence, but there is some debate regarding the findings based on which relapse/recurrence should be diagnosed. PURPOSE AND METHODS: We hypothesized that we might be able to use anti-GPL core IgA antibodies (MAC antibodies), which have been attracting attention as a factor that may support diagnosis of MAC lung disease, to diagnose postoperative relapse/recurrence. Therefore, we compared the levels of these antibodies before and at the time of relapse/recurrence, and also compared antibody titers before and after surgery. RESULT: MAC antibody titers were elevated by an average of about 50% at the time of relapse/recurrence compared to those before relapse/recurrence for 6 patients. In contrast, MAC antibody titers were about 30% lower after surgery compared to those before surgery for 37 patients. CONCLUSION: It may be possible to use MAC antibodies as an indicator of postoperative relapse/recurrence for MAC lung disease.
Subject(s)
Antibodies, Bacterial/blood , Immunoglobulin A/blood , Mycobacterium avium Complex/immunology , Mycobacterium avium-intracellulare Infection/diagnosis , Mycobacterium avium-intracellulare Infection/surgery , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/surgery , Aged , Biomarkers/blood , Female , Glycolipids/immunology , Glycopeptides/immunology , Humans , Male , Middle Aged , Postoperative Period , RecurrenceABSTRACT
Beta-propeller protein-associated neurodegeneration (BPAN) is one of the neurodegenerative disorders characterized by iron deposition in the brain and is the only known disease in humans to be caused by an aberration in autophagocytosis. Here, we present the case of a 42-year-old woman with BPAN identified by the WDR45 mutation. From early childhood, she was recognized as having global developmental delay, and she frequently sucked her hand, which was considered to be a stereotypical movement. She had a febrile convulsion at 6 months of age but there was no history of epilepsy. The delay in language development was more severe than the delay in motor development; she was able to dress herself, walk unaided, and follow simple instructions until adolescence. After the age of 20, her movement ability rapidly declined. By the time she was 42 years old, she was bedridden and unable to communicate. Brain magnetic resonance imaging (MRI) at 21 years revealed no abnormality except non-specific cerebral atrophy. However, MRI at 39 years revealed abnormalities in the globus pallidus and substantia nigra, with neurodegeneration and iron accumulation in the brain. Genetic analysis for WDR45 revealed that she had a splice site mutation (NM_007075.3: c.830 + 2 T > C) which was previously reported, and a diagnosis of BPAN was confirmed. For specific therapies to be developed for BPAN in the future, it is necessary to establish early diagnosis, including genetic analysis.
Subject(s)
Carrier Proteins/genetics , Iron Metabolism Disorders/diagnosis , Iron Metabolism Disorders/genetics , Mutation , Neuroaxonal Dystrophies/diagnosis , Neuroaxonal Dystrophies/genetics , Rett Syndrome , Adolescent , Adult , Autophagy/genetics , Child , Child, Preschool , Delayed Diagnosis , Diagnosis, Differential , Female , Genetic Testing , Humans , Infant , Iron Metabolism Disorders/physiopathology , Neuroaxonal Dystrophies/physiopathology , Young AdultABSTRACT
BACKGROUND: In the intensive care unit, the use of continuous electroencephalography (cEEG) in children with altered mental status often results in the detection of non-convulsive seizures (NCS). Children with influenza can occasionally display altered mental status, but the prevalence of NCS in children with influenza with altered mental status is yet to be determined. This study determined the prevalence of NCS in pediatric patients with altered mental status associated with influenza A(H1N1)pdm09 infection. METHODS: We retrospectively reviewed admissions to the pediatric intensive care unit between September 2009 and February 2010 and confirmed the presence of NCS on cEEG in children with influenza A(H1N1)pdm09 and with altered mental status. RESULTS: Of the 15 patients (aged 41-159 months old), NCS was identified on cEEG in five children (33%). CONCLUSIONS: Approximately one-third of the children infected with influenza A(H1N1)pdm09 with altered mental status had NCS. Further research is needed to determine if the detection and management of NCS improve outcome in these children.