Preventive interventions for throwing injuries in baseball players: a scoping review.

BACKGROUND: Shoulder and elbow pain are the common complaints associated with throwing injuries in baseball players. Prospective studies evaluating the effectiveness of stretching in increasing posterior shoulder flexibility or strengthening the external rotator muscles as preventive strategies for throwing injuries in baseball players have been published. However, there are limited reviews highlighting the role of preventive interventions for throwing injuries in baseball players. Therefore, this scoping review aimed to summarize the existing literature on preventive interventions for throwing injuries in baseball players. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Scopus databases on 3 March 2023. Two independent reviewers screened the studies based on the eligibility criteria. We extracted existing literature on preventive interventions and effectiveness for throwing injuries in baseball players, and participants' characteristics and results were extracted from the studies. This scoping review was performed in accordance with the Extended Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement for Scoping Reviews. RESULTS: The initial database search yielded 1170 articles, four of which met the eligibility criteria. Of the included studies, two were randomized controlled trials, and the remaining two were prospective cohort studies. Eligible studies targeted youth-to high school-level players and focused on preventive programs for throwing injuries that manifest in the upper extremities of baseball players. The outcome measure most commonly used to quantify the effectiveness of prevention programs was the incidence of shoulder and elbow injuries, although the definitions vary among studies. The prevention program included sleeper stretching, shoulder external rotation strengthening exercises, and comprehensive prevention programs (focusing on improving the elbow, shoulder, and hip range of motion; rotator cuff and periscapular muscle strength; posture; and lower extremity balance). Each prevention program was reported to have the potential to reduce the incidence of throwing injuries in baseball players, and two studies suggested that high compliance with the program led to a lower injury risk. CONCLUSION: This scoping review confirmed the presence of studies that examined preventive interventions for throwing injuries in baseball players. Preventive interventions that may reduce throwing injuries in baseball players include sleeper stretching, shoulder external rotation strengthening exercises, and comprehensive prevention programs. However, the characteristics of participants (eg, age, sports level, and position) and the definition of injury varied among previous studies. Injury profiles and prevention strategies may differ according to age, sport level, and position of players, and more studies are needed to prove this issue.

Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study.

Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65. PPI use for ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65.

Long-term efficacies of selective vasodilators in pulmonary arterial hypertension: a comprehensive comparison using a spontaneous reporting database.

There is no clinical evidence of differences in drugs associated with long-term survival in patients with pulmonary arterial hypertension (PAH) due to the small population and lack of information on death in Japanese medical database systems. This study evaluated whether patient data from a spontaneous reporting database could be used for comparing the effects of pulmonary vasodilators on long-term survival in PAH patients. PAH patient data reported in the Japanese Adverse Drug Event Report (JADER) database from April 2004 to July 2022 were extracted. Kaplan-Meier curves were used to compare survival times. Adjusted hazard ratios (aHRs) for all-cause mortality were determined using Cox proportional hazards models. Of 1969 PAH patients reported in the JADER database, 1208 were included in the survival analyses. The patient demographics were similar to those of the PAH population reported in the Japan Pulmonary Hypertension Registry. Among drugs targeting the prostacyclin pathway, epoprostenol was most associated with long-term survival (aHR, 0.38; 95% confidence interval (CI), 0.23-0.64). The PAH patients treated with endothelin receptor antagonists had improved survival, especially among the macitentan users (aHR, 0.30; 95% CI, 0.22-0.42). Sildenafil was associated with a poor prognosis in the PAH patients (aHR, 1.56; 95% CI, 1.19-2.04). Although our results must be interpreted with caution due to several limitations inherent to spontaneous reporting databases, our approach using the JADER database for survival analysis may provide useful information in limited situations such as the treatment of rare diseases including PAH.

[Exploration of Risk Factors of the Onset of Antibiotics-induced Acute Kidney Injury and Its Transfer to Chronic Kidney Disease Using the Medical Information Database].

Drug-induced acute kidney injury (AKI) is a serious adverse drug reaction, which results in a significant decline in renal function and is known to progress to chronic kidney disease (CKD). Therefore, appropriate drug therapy is important to avoid the risk of drug-induced AKI and CKD, which are serious concerns in clinical practice. In this study, using the medical information database of Hamamatsu University Hospital, we investigated the risk factors that accelerate the onset of drug-induced AKI or its progression to CKD in patients who received aminoglycoside antibiotics (AGs) or glycopeptide antibiotics (GPs), which are strongly associated with drug-induced AKI and CKD. We performed logistic regression analysis using patients' background, laboratory test results, and concomitant drug use, among other such factors as explanatory variables and drug-induced AKI or CKD onset as objective variables to explore the risk factors for drug-induced AKI and CKD. Our results showed that co-administration of amphotericin B, piperacillin-tazobactam and other AGs and GPs, increased serum creatinine (Scr) and chloride concentrations, serum lactate dehydrogenase activity, and decreased serum albumin concentration were risk factors for drug-induced AKI onset. Moreover, a reduced blood urea nitrogen : Scr ratio at drug-induced AKI onset served as a risk factor for CKD. These results suggest that careful monitoring of the aforementioned factors is important to ensure appropriate usage of these drugs in patients treated with AGs and GPs.

Impacts of genetic polymorphisms and cancer cachexia on naldemedine pharmacokinetics and bowel movements in patients receiving opioid analgesics.

BACKGROUND/OBJECTIVES: Clinical responses to naldemedine vary between individuals with advanced cancer. This is a prospective, single-center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses. METHODS: Forty-eight patients being treated with naldemedine for opioid-induced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed. RESULTS: Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous CYP3A5*3 had a higher plasma concentration of naldemedine than those with the *1 allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4ß-hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin-6 (IL-6) and acute-phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, CYP3A5*3/*3, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements. CONCLUSION: Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL-6 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements.

Does physiotherapy after rotator cuff repair require supervision by a physical therapist?: a meta-analysis.

BACKGROUND: A supervised physiotherapy program (SPP) is a standard regimen after surgical rotator cuff repair (RCR); however, the effect of a home-based exercise program (HEP), as an alternative, on postoperative functional recovery remains unclear. Therefore, the purpose of this meta-analysis was to compare the functional effects of SPP and HEP after RCR. METHODS: We searched electronic databases including Central, Medline, and Embase in April 2022. The primary outcomes included the Constant score, American Shoulder and Elbow Surgeons score, University of California Los Angeles shoulder score, and pain score. Secondary outcomes included range of motion, muscle strength, retear rate, and patient satisfaction rate. A meta-analysis using random-effects models was performed on the pooled results to determine the significance. RESULTS: The initial database search yielded 848 records, five of which met our criteria. Variables at 3 months after surgery were successfully analyzed, including the Constant score (mean difference, -8.51 points; 95% confidence interval [CI], -32.72 to 15.69; P=0.49) and pain score (mean difference, 0.02 cm; 95% CI, -2.29 to 2.33; P=0.99). There were no significant differences between the SPP and HEP. Other variables were not analyzed owing to the lack of data. CONCLUSIONS: Our data showed no significant differences between SSP and HEP with regard to the Constant and pain scores at 3 months after RCR. These results suggest that HEP may be an alternative regimen after RCR. Level of evidence: I.

Effects of elevation on shoulder joint motion: comparison of dynamic and static conditions.

BACKGROUND: Although visual examination and palpation are used to assess shoulder motion in clinical practice, there is no consensus on shoulder motion under dynamic and static conditions. This study aimed to compare shoulder joint motion under dynamic and static conditions. METHODS: The dominant arm of 14 healthy adult males was investigated. Electromagnetic sensors attached to the scapular, thorax, and humerus were used to measure three-dimensional shoulder joint motion under dynamic and static elevation conditions and compare scapular upward rotation and glenohumeral joint elevation in different elevation planes and angles. RESULTS: At 120° of elevation in the scapular and coronal planes, the scapular upward rotation angle was higher in the static condition and the glenohumeral joint elevation angle was higher in the dynamic condition (P<0.05). In scapular plane and coronal plane elevation 90°- 120°, the angular change in scapular upward rotation was higher in the static condition and the angular change in scapulohumeral joint elevation was higher in the dynamic condition (P<0.05). No differences were found in shoulder joint motion in the sagittal plane elevation between the dynamic and static conditions. No interaction effects were found between elevation condition and elevation angle in all elevation planes. CONCLUSIONS: Differences in shoulder joint motion should be noted when assessing shoulder joint motion in different dynamic and static conditions. Level of evidence: Level III, diagnostic cross-sectional study.

Associations of plasma aprepitant and its N-dealkylated metabolite with cachexia status and clinical responses in head and neck cancer patients.

PURPOSE: Oral aprepitant has a large interindividual variation in clinical responses in advanced cancer. This study aimed to characterize plasma aprepitant and its N-dealkylated metabolite (ND-AP) based on the cachexia status and clinical responses in head and neck cancer patients. METHODS: Fifty-three head and neck cancer patients receiving cisplatin-based chemotherapy with oral aprepitant were enrolled. Plasma concentrations of total and free aprepitant and ND-AP were determined at 24 h after a 3-day aprepitant treatment. The clinical responses to aprepitant and degrees of cachexia status were assessed using a questionnaire and Glasgow Prognostic Score (GPS). RESULTS: Serum albumin level was negatively correlated with the plasma concentrations of total and free aprepitant but not ND-AP. The serum albumin level had a negative correlation with the metabolic ratio of aprepitant. The patients with GPS 1 or 2 had higher plasma concentrations of total and free aprepitant than those with GPS 0. No difference was observed in the plasma concentration of ND-AP between the GPS classifications. The plasma interleukin-6 level was higher in patients with GPS 1 or 2 than 0. The absolute plasma concentration of free ND-AP was higher in patients without the delayed nausea, and its concentration to determine the occurrence was 18.9 ng/mL. The occurrence of delayed nausea had no relation with absolute plasma aprepitant. CONCLUSION: Cancer patients with a lower serum albumin and progressive cachectic condition had a higher plasma aprepitant level. In contrast, plasma free ND-AP but not aprepitant was related to the antiemetic efficacy of oral aprepitant.

Shoulder pain in wheelchair basketball athletes: A scoping review.

CONTEXT: Wheelchair basketball athletes have increased upper limb stress, which frequently leads to shoulder pain. OBJECTIVE: The purpose of this scoping review was to summarize the existing literature on shoulder pain in wheelchair basketball athletes. METHODS: We searched PubMed, Cochrane Library, Scopus, and PEDro databases for studies performed between January 1990 and February 2021. Two independent reviewers screened the studies according to the inclusion and exclusion criteria. Participants' characteristics and results were extracted from the study. RESULTS: The initial database search yielded 2455 articles, 11 of which met the inclusion criteria. This review included seven studies in its final analysis; among them, seven determined the prevalence and incidence of shoulder pain, five investigated the factors and mechanisms contributing to shoulder pain, and two reported the treatment and preventive measures. The prevalence of shoulder pain in wheelchair basketball players ranged from 38%-75%, and the incidence of shoulder pain was 14%. Factors/mechanisms included overuse, decreased trunk control, and driving posture. Treatment/preventive measures consisted of shoulder and scapular muscle strengthening and stretching exercises. However, the literature on treatment/prevention was scarce, and its effectiveness was unclear. CONCLUSION: This scoping review confirmed the high prevalence of shoulder pain in wheelchair basketball players; despite this, studies regarding treatment or preventive measures remain lacking. Further studies investigating the mechanism of onset of shoulder pain and the effectiveness of therapeutic and preventive measures are needed in the future.

Characterization of plasma daptomycin in patients with serum highly glycated albumin and obesity.

PURPOSE: Plasma daptomycin has not been fully characterized in diabetic and obese patients. This study aimed to evaluate the associations of plasma daptomycin with glycation of serum albumin and obesity. METHODS: Infectious patients (n = 70) receiving intravenous daptomycin were enrolled. The plasma concentration of total and free daptomycin were determined using liquid chromatograph-tandem mass spectrometer. The associations of the plasma concentrations of daptomycin with clinical factors including serum albumin fractionations and physical status (obese including overweight, body mass index ≥ 25.0) were investigated. Daptomycin doses were adjusted using total body-weight. RESULTS: The serum albumin level was positively and negatively correlated with the plasma concentration of total daptomycin and its free fraction proportion, respectively. The serum non-glycated albumin was negatively correlated with the free fraction proportion. The dose-normalized plasma concentration of total daptomycin was higher in the obese patients than in non-obese patients when the body-weight was corrected with total and adjusted values. For the dose adjustment with lean body-weight, no difference was observed in the dose-normalized plasma concentration of total daptomycin between the physical statuses. For each body-weight correction method, physical status did not affect the dose-normalized plasma concentration of free daptomycin. CONCLUSION: The glycation of serum albumin and obesity did not associate with dose-normalized plasma free daptomycin. In obese patients, daptomycin dosage adjustment with total body-weight and adjusted body-weight may lead to an apparent excessive exposure resulting in overdosage compared to lean body-weight.

Characterization of endogenous markers of hepatic function in patients receiving itraconazole treatment for prophylaxis of deep mycosis.

BACKGROUND: Long-term use of itraconazole (ITZ) is associated with a risk of inducing hepatotoxicity. This study aimed to evaluate the associations of plasma concentrations of ITZ and its hydroxylated metabolite (OH-ITZ) with endogenous markers of hepatic function. METHODS: Thirty six patients treated with oral ITZ solution for prophylaxis of deep mycosis were enrolled. Plasma concentrations of ITZ and OH-ITZ were determined on the 14th day or later after administration of ITZ. Their associations with endogenous marker levels of hepatic function including plasma coproporphyrin (CP)-I and OATP1B1 genotypes were assessed. RESULTS: The serum level of total bilirubin (T-Bil) was moderately correlated with the plasma concentration of total ITZ (tITZ) and OH-ITZ (tOH-ITZ). T-Bil elevation above 0.3 mg/dL was observed in 19% of patients, although statistically significant difference was not identified. The plasma concentration of tITZ had no correlation with other endogenous markers levels including AST, ALT, albumin, and plasma CP-I. The serum AST and plasma CP-I levels were correlated with the plasma concentration of free OH-ITZ (fOH-ITZ). T-Bil and plasma CP-I, a marker of OATP1B1 activity, were not correlated with each other, and neither was associated with the OATP1B1 genotypes. CONCLUSIONS: Plasma ITZ and OH-ITZ had a positive association with T-Bil. The patients with a higher fOH-ITZ level had lower OATP1B1 activity on the basis of plasma CP-I level. ITZ and OH-ITZ have the potential to slightly increase endogenous marker levels of hepatic function, although most likely by different mechanisms.

Investigation of the boxed warnings in package inserts of prescription medicines for medical professionals in Japan

Objective: In the Japanese Pharmacists Act, article 25-2, revised in 2013, it states that pharmacists shall provide the necessary information and guidance to the patient based on pharmaceutical knowledge and experience for ensuring the proper use of the medicine dispensed. The package insert is one of the documents to be referred to when providing the information and guidance. The boxed warnings in package inserts that include the precautions and responses are the most significant parts, however, the suitability of boxed warnings for pharmaceutical practice has not been evaluated. The aim of this study was to investigate the boxed warning descriptions in package inserts of prescription medicines for medical professionals in Japan. Methods: Package inserts of prescription medicines listed in the Japanese National Health Insurance drug price list on March 1st 2015 were collected one by one by hand from the website of the Japanese Pharmaceuticals and Medical Devices Agency (https://www.pmda.go.jp/english/). Package inserts with boxed warnings were classified according to the Standard Commodity Classification Number of Japan based on the pharmacological activity of each medicine. They were also compiled according to their formulations. The boxed warnings were divided into the precautions and responses parts, and their characteristics were compared among medicines. (AU)

Stereoselective interaction of tolvaptan with amiodarone under racemic metabolic impact by CYP3A5 genotypes in heart failure patients.

PURPOSE: The diuretic effect of tolvaptan is largely blood level-dependent although it does exhibit interindividual differences according to cytochrome P450 (CYP) 3A5 genotype. This study aimed to investigate the pharmacokinetic relationship between plasma tolvaptan and its monohydroxylate enantiomers and the factors affecting their metabolism in heart failure patients. METHODS: Japanese heart failure patients (n = 88) receiving oral tolvaptan (median dosage 7.5 mg/day) were enrolled. Blood samples were collected prior to the dosing on day 6 or later after first administration to determine the plasma concentrations of tolvaptan and its monohydroxylate enantiomers. Gene polymorphisms of CYP3A5, carbonyl reductase (CBR) 1/3, and ATP-binding cassette subfamily B member (ABCB) 1 were analyzed for their impact on tolvaptan pharmacokinetics. Serum laboratory test values and concomitant use of amiodarone were evaluated as factors related to tolvaptan metabolism. RESULTS: The median of the sum of the 5S- and 5R-tolvaptan plasma concentrations was 48.9 (range, 15.3-100) ng/mL. CYP3A5 genotypes significantly affected the concentration ratio of all enantiomeric metabolites to tolvaptan, while the other metabolic-related gene polymorphisms had no influence. A negative correlation was found between serum albumin and the enantiomeric ratio of tolvaptan and monohydroxylate DM-4111. Concomitant use of amiodarone increased the plasma levels of whole tolvaptan but significantly decreased the metabolic ratios of 5R-tolvaptan. 5S-tolvaptan was selectively synthesized from ketone MOP-21826 by CBR1 with a substantially smaller reaction velocity compared to tolvaptan monohydroxylation by CYP3A4/5. CONCLUSION: This study clarified the racemic impact of CYP3A5 genotypes on tolvaptan metabolism. Amiodarone may stereoselectively interact with R-forms rather than S-forms of tolvaptan.

LC-MS/MS method for the quantitation of serum tocilizumab in rheumatoid arthritis patients using rapid tryptic digestion without IgG purification.

The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry (LC-MS/MS) method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments. The present study aimed to develop a validated LC-MS/MS method for detecting serum tocilizumab by utilizing immobilized trypsin without an immunoglobulin G purification step and evaluate its applicability in the treatment of rheumatoid arthritis (RA) patients administered intravenously or subcutaneously with tocilizumab. The tocilizumab-derived signature peptide was deciphered using a nano-LC system coupled to a hybrid quadrupole-orbitrap mass spectrometer. The serum tocilizumab was rapidly digested by immobilized trypsin for 30 min. The chromatographic peak of the signature peptide and that of the internal standard were separated from the serum digests for a total run time of 15 min. The calibration curve of serum tocilizumab concentration was linear with a range of 2-200 µg/mL. The intra- and inter-day accuracy and relative standard deviation (RSD) were 90.7%-109.4% and <10%, respectively. The serum tocilizumab concentrations in the RA patients receiving intravenous and subcutaneous injections were 5.8-28.9 and 2.4-63.5 µg/mL, respectively. The serum tocilizumab concentrations using the current method positively correlated with those using the enzyme-linked immunosorbent assay, although a systematic error was observed between these methods. In conclusion, a validated LC-MS/MS method with minimal sample pretreatments for monitoring serum tocilizumab concentrations in RA patients was developed.

Investigation of the boxed warnings in package inserts of prescription medicines for medical professionals in Japan.

Objective: In the Japanese Pharmacists Act, article 25-2, revised in 2013, it states that pharmacists shall provide the necessary information and guidance to the patient based on pharmaceutical knowledge and experience for ensuring the proper use of the medicine dispensed. The package insert is one of the documents to be referred to when providing the information and guidance. The boxed warnings in package inserts that include the precautions and responses are the most significant parts, however, the suitability of boxed warnings for pharmaceutical practice has not been evaluated. The aim of this study was to investigate the boxed warning descriptions in package inserts of prescription medicines for medical professionals in Japan. Methods: Package inserts of prescription medicines listed in the Japanese National Health Insurance drug price list on March 1st 2015 were collected one by one by hand from the website of the Japanese Pharmaceuticals and Medical Devices Agency (https://www.pmda.go.jp/english/). Package inserts with boxed warnings were classified according to the Standard Commodity Classification Number of Japan based on the pharmacological activity of each medicine. They were also compiled according to their formulations. The boxed warnings were divided into the precautions and responses parts, and their characteristics were compared among medicines. Results: The number of package inserts found on the website of the Pharmaceuticals and Medical Devices Agency was 15,828. Boxed warnings were present in 8.1% of the package inserts. A description of adverse drug reactions accounted for 74% of all precautions. Most of the precautions were observed in the warning boxes of antineoplastic agents. Blood and lymphatic system disorders were the most common precaution. Responses in the boxed warnings directed toward medical doctors, pharmacists, and other healthcare professionals accounted for 100, 77, and 8% of all package inserts with a boxed warning, respectively. Explanations for patients were the second most frequent response. Conclusions: The majority of boxed warnings request therapeutic contribution by pharmacists, and the descriptions of these explanations and guidance by pharmacists to patients were found to be consistent with the Pharmacists Act.

Impacts of cachexia progression in addition to serum IgG and blood lymphocytes on serum nivolumab in advanced cancer patients.

PURPOSE: Serum nivolumab concentrations exhibit a large variation in cancer patients. Cancer cachexia inducing systemic inflammation promotes the elimination of endogenous proteins, while its association with serum nivolumab remains unclear. The present study aimed to evaluate the impacts of cachexia progression in addition to blood components on serum nivolumab in cancer patients. METHODS: Thirty-eight non-small-cell lung cancer or renal cell cancer patients receiving biweekly intravenous nivolumab were enrolled. Blood samples were collected just before dosing at the 7th administration of nivolumab or later. Serum nivolumab together with serum proteins, inflammatory markers, and peripheral blood leukocytes were determined. Cancer cachexia was classified using the Glasgow Prognostic Score (GPS). Immune-related adverse events (irAEs) were monitored during the study period. RESULTS: Cancer patients had a large variation in serum nivolumab concentrations (interquartile range, 12-21 µg/mL per mg/kg). The serum nivolumab concentration was positively correlated with serum albumin, while negatively associated with serum globulin and immunoglobulin G (IgG). A negative correlation was observed between serum nivolumab and blood lymphocytes. Regarding cachexia progression, the patients with GPS 2 had a higher serum interleukin-6 concentration and a lower serum nivolumab concentration than those with GPS 0 or 1. The GPS, serum IgG, and blood lymphocytes were identified as independent variables for serum nivolumab. The incidence of irAEs was not associated with the nivolumab dose or serum nivolumab. CONCLUSION: Cachexia progression had a negative impact on serum nivolumab in cancer patients. The interindividual variation in serum nivolumab was characterized by cachexia progression in addition to blood components.

Clinical outcomes in patients with retear after arthroscopic rotator cuff repair: A meta-analysis.

BACKGROUND: Rotator cuff retear is a major concern after arthroscopic rotator cuff repair (ARCR); however, the effects of retear remain unclear. Therefore, the purpose of this study was to assess the clinical outcomes of postoperative retear and intact tendons after ARCR. METHODS: We searched PubMed, Cochrane Library, Scopus, and PEDro databases for studies performed from January 2000 to June 2020. Clinical outcomes included the Constant score, American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles shoulder (UCLA) score, pain score, range of motion, and muscle strength. Meta-analysis using random-effects models was performed on the pooled results to determine significance. RESULTS: The initial database search yielded 3141 records. After removal of duplicates, 26 of which met the inclusion criteria. Patients in the retear group had significantly lower Constant score [- 8.51 points (95% CI, - 10.29 to - 6.73); P < 0.001], ASES score [- 12.53 points (95% CI, - 16.27 to - 8.79); P < 0.001], UCLA score [- 3.77 points (95% CI, - 4.72 to - 2.82); P < 0.001], and significantly higher pain score [0.56 cm (95% CI, 0.10 to 1.01); P = 0.02] than the intact group. In addition, the retear group had significantly lower flexion [- 10.46° (95% CI, - 19.86 to - 1.07); P = 0.03], abduction [- 14.84° (95% CI, - 28.55 to - 1.14); P = 0.03], and external rotation [- 7.22° (95% CI, - 13.71 to - 0.74); P = 0.03] range of motion, and flexion [- 1.65 kg·f (95% CI, - 2.29 to - 1.01); P < 0.001], abduction [- 1.87 kg·f (95% CI, - 3.02 to - 0.72); P = 0.001], and external rotation [- 1.66 kg·f (95% CI, - 3.25 to - 0.07); P = 0.04] muscle strength. CONCLUSION: Our results suggest that retear after ARCR leads to poor clinical outcomes after surgery.

LC-MS/MS method for the quantitation of serum tocilizumab in rheumatoid arthritis patients using rapid tryptic digestion without IgG purification / 药物分析学报

The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments.The present study aimed to develop a validated LC-MS/MS method for detecting serum tocilizumab by utilizing immobilized trypsin without an immunoglobulin G purification step and evaluate its applicability in the treatment of rheumatoid arthritis(RA)patients administered intrave-nously or subcutaneously with tocilizumab.The tocilizumab-derived signature peptide was deciphered using a nano-LC system coupled to a hybrid quadrupole-orbitrap mass spectrometer.The serum tocili-zumab was rapidly digested by immobilized trypsin for 30 min.The chromatographic peak of the signature peptide and that of the internal standard were separated from the serum digests for a total run time of 15 min.The calibration curve of serum tocilizumab concentration was linear with a range of 2-200 μg/mL.The intra-and inter-day accuracy and relative standard deviation(RSD)were 90.7％-109.4％and＜10％,respectively.The serum tocilizumab concentrations in the RA patients receiving intravenous and subcutaneous injections were 5.8-28.9 and 2.4-63.5 pg/mL,respectively.The serum tocilizumab concentrations using the current method positively correlated with those using the enzyme-linked immunosorbent assay,although a systematic error was observed between these methods.In conclu-sion,a validated LC-MS/MS method with minimal sample pretreatments for monitoring serum tocili-zumab concentrations in RA patients was developed.

Prediction of the Area under the Curve Using Limited-Point Blood Sampling in a Cocktail Study to Assess Multiple CYP Activities.

A cocktail study is an in vivo evaluation method to assess multiple CYP activities via a single trial and single administration of a cocktail drug that is a combination of multiple CYP substrates. However, multiple blood samples are required to evaluate the pharmacokinetics of a CYP probe drug. A limited-point sampling method is generally beneficial in clinical studies because of the simplified protocol and reduced participant burden. The aim of this study was to evaluate whether a limited-point plasma concentration analysis of CYP substrates in a cocktail drug could predict their area under the curve (AUC). We created prediction models of five CYP substrates (caffeine, losartan, omeprazole, dextromethorphan, and midazolam) using multiple linear regressions from the data of two cocktail studies, and then performed predictability analysis of these models using data derived from data in the co-administration with inducer (rifampicin) and inhibitors (fluvoxamine and cimetidine). For the administration of inhibitors, the AUC prediction accuracy (mean absolute error (MAE)) were <39.5% in Model 1 and <26.2% in Model 2 which were created using 1- and 4-point sampling data. MAE shows larger values in the administration of inducer in compared with the administration of inhibitors. The accuracy of the prediction in Model 2 could be acceptable for screening of inhibitions. MAE for caffeine, dextromethorphan, and midazolam were acceptable in the model that used 4 sampling points from all data. The use of this method could reduce the burden on the subject and make it possible to evaluate each AUC in a minimally invasive manner.