Occurrence of somnolence and respiratory depression induced by pregabalin and mirogabalin use and the influence of opioid treatment using the Japanese adverse drug event report database.

Background: Gabapentinoid anticonvulsants are standard treatment for neuropathic pain and are often combined with opioids for treating cancer. It is assumed that this combination may heighten somnolence and respiratory depression due to the inhibitory effects of opioids on the central nervous system. Although pregabalin, a gabapentinoid, is known to increase somnolence frequency during opioid therapy, whether mirogabalin exerts similar effects on somnolence frequency under opioid therapy remains unknown. This study examined the signals of somnolence and respiratory depression in response to pregabalin and mirogabalin use by utilizing data from the Japanese Adverse Drug Event Report database and assessed their interaction with strong opioid analgesics. Methods: Information was obtained from the JADER database from April 2004 to August 2023 via the Pharmaceuticals and Medical Devices Agency website. The study focused on neuropathic pain medications, specifically "pregabalin" and "mirogabalin besilate." Adverse events were defined using preferred terms (PTs) from the Medical Dictionary for Regulatory Activities version 26.1. The PTs considered were "Somnolence (10041349)" and "Respiratory depression (10038678)." To investigate the effect of the combination of strong opioid analgesics with pregabalin and mirogabalin on the occurrence of somnolence, a multivariable logistic regression analysis was conducted. Results: Signals for somnolence were detected with the use of both drugs (pregabalin: information component (IC) [95% confidence intervals (CIs)]: 2.89 [2.70 to 3.08]; mirogabalin: IC [95% CIs] 2.50 [1.85 to 3.16]). When evaluating respiratory depression, a typical and serious adverse event of opioid analgesic use, a signal was detected with pregabalin use but not with mirogabalin use (pregabalin: (IC [95% CIs] 1.28 [0.83 to 1.73]; mirogabalin: IC [95% CIs] -0.15 [-2.20 to 1.89]). Multivariable analysis indicated that the use of strong opioid analgesics increased the occurrence of somnolence when combined with pregabalin but not when combined with mirogabalin (p = 0.004). Conclusion: While the safety of concomitant administation of mirogabalin with opioids remains controversial, caution should be exercised when using pregabalin, especially in combination with opioids for neuropathic pain, compared to that for mirogabalin.

A comparative study of the CT effective dose in whole-body 18F-FDG PET/CT for arm-raised position and arm-lowered position.

INTRODUCTION: This study aimed to investigate and compare the effective dose (ED) delivered by computed tomography (CT) in whole-body positron emission tomography/CT (WB-PET/CT) scans between patients positioned with their arms-raised and those with their arms-lowered during the scan on a large population. METHODS: The retrospective study involved 785 oncology patients who underwent WB-PET/CT scans with 18F-FDG between January and June 2019. Exclusion criteria were applied, resulting in a final analysis of data from 732 adult patients. All of the patients were measured height and weight, and the ED from CT in WB-PET/CT was estimated using the dose length product value and a conversion factor. Statistical analyses were conducted to explore relationships between factors and the ED. Linear regression analysis was performed to investigate connections between weight and ED, and height and ED. Multiple linear regression was used to predict ED based on sex, weight, and arm position. RESULTS: The arm-lowered group had a higher ED than the arm-raised group, and the median dose was 1.1 times higher in the arm-lowered group. The difference in ED between the two groups was found to be greater with higher body weight. Arm-position (ß = 0.460), sex (ß = -0.190), and weight (ß = 0.057) were significant predictors of ED. CONCLUSION: This study demonstrated that arm position, sex, and weight were significant factors influencing the ED from CT scans in WB-PET/CT. IMPLICATIONS FOR PRACTICE: The research underscores the importance of considering these factors when evaluating radiation exposure in clinical practice, particularly for patients undergoing WB-CT imaging. These findings contribute to a better understanding of the radiation dosimetry associated with different patient positions during WB-PET/CT scans.

In vitro fertilization: an unexpected finding in a cohort of patients with biliary atresia

In biliary atresia (BA), efforts to prevent premature liver transplantation (LT) are aimed at early diagnosis, timing of Kasai-portoenterostomy (KPE), and centralization of care. This report presents the clinical picture, treatment strategies, and outcomes of BA patients with no previous treatment. A retrospective cohort study (Jan/2001 to Jan/2021) was conducted to evaluate the outcome of patients with BA referred to a single team. Study groups were: 1) Kasai-only group (K-only) n=9), 2) LT-only group (n=7), and 3) Kasai+LT group (K+LT) (n=23). Survival with native liver and overall survival were 22.9 and 94.8%, respectively, at 120 months of follow-up. There was no difference in age at KPE in the K-only group (46.8±21.8 days) vs K+LT (52.1±22 days), P=0.4. Ten (25.6%) patients were babies conceived through in vitro fertilization (IVF). Four IVF patients (40%) presented associated congenital heart disease vs 5 patients (17%) in the remaining group (P=0.14). Two of the IVF patients were premature (<37 weeks). Median maternal age at birth was 35 years (33 to 41 years). Excellent patient survival is expected for patients with BA with the available treatment strategies. IVF+BA was an unexpected prevalent association in this cohort, and further studies are required to better understand these findings.

Successful domino liver transplantation in maple syrup urine disease using a related living donor

Maple syrup urine disease (MSUD) is an autosomal recessive disease associated with high levels of branched-chain amino acids. Children with MSUD can present severe neurological damage, but liver transplantation (LT) allows the patient to resume a normal diet and avoid further neurological damage. The use of living related donors has been controversial because parents are obligatory heterozygotes. We report a case of a 2-year-old child with MSUD who underwent a living donor LT. The donor was the patient's mother, and his liver was then used as a domino graft. The postoperative course was uneventful in all three subjects. DNA analysis performed after the transplantation (sequencing of the coding regions of BCKDHA, BCKDHB, and DBT genes) showed that the MSUD patient was heterozygous for a pathogenic mutation in the BCKDHB gene. This mutation was not found in his mother, who is an obligatory carrier for MSUD according to the family history and, as expected, presented both normal clinical phenotype and levels of branched-chain amino acids. In conclusion, our data suggest that the use of a related donor in LT for MSUD was effective, and the liver of the MSUD patient was successfully used in domino transplantation. Routine donor genotyping may not be feasible, because the test is not widely available, and, most importantly, the disease is associated with both the presence of allelic and locus heterogeneity. Further studies with this population of patients are required to expand the use of related donors in MSUD.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87 percent accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100 percent), but with reduction in diagnostic sensitivity (64 percent). When compared with the criteria of Ratziu et al. [Gastroenterology (2000) 118: 1117-1123] for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70 percent). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

Papiloma de células escamosas do esôfago: apresentaçäo de 3 casos; aspectos diagnósticos / Esophageal squamous cell papilloma: report of 3 cases; diagnostic aspects

Pacientes com papiloma escamoso de esôfago podem apresentar disfagia, porém há casos cujo diagnóstico é decorrente de mero achado de exame. OBJETIVO. Os autores apresentam três casos de papiloma de células escamosas de esôfago, discutindo seu diagnóstico e a associaçao ou nao com o papilomavírus humano. CASUISTICA. Trata-se de dois pacientes do sexo masculino e uma do feminino. Todos os pacientes foram submetidos a endoscopia digestiva alta: em um dos casos o tumor era maior do que normalmente relatado e, em todos, estava localizado no esôfago médio ou distal. Em um dos casos, utilizou-se cromoscopia e a lesao náo foi corada. Empregando testes de hibridizaçao de DNA, nao se conseguiu identificar papilomavírus humanos em nenhum dos casos. É feita revisao da literatura e os resultados dos autores sao semelhantes aos publicados. RESULTADO. De acordo com levantamento bibliográfico computadorizado, este é o primeiro relato de caso em nosso país, e o primeiro a utilizar cromoscopia para melhor identificaçao da lesao. CONCLUSAO. Nos casos deste trabalho, nao foi identificada correlaçao entre o papiloma vírus e papiloma escamoso de esôfago.

Analise da concentracao do cortisol no liquido amniotico de gestantes isoimunizadas ao fator Rh (D) em zona 2 do grafico prognostico de Liley / Analysis of cortisol concentration in the amniotic fluid of pregnant women with Rh isoimmunization with DDO in Liley's zone 2

No presente estudo analisamos a concentracao de cortisol no LA de 67 amostras coletadas de 31 gestantes isoimunizadas ao fator Rh(D) com DDO na segunda zona de Liley, entre a 20ª e a 38ª semana de gestacao. Notou-se uma elevacao da concentracao do cortisol e para melhor caracterizar este comportamento construimos uma curva que mostra tendencia quadratica nesta elevacao. Ao comparar-se esta curva com outra construida para o grupo controle, notou-se concentracao mais elevada entre as gestantes isoimunizadas, mostrando uma producao aumentada neste grupo. Especulamos que o cortisol esta aumentado nestes fetos devido a uma hipoxia cronica e estresse fetal.