When patients present with persistent bodily complaints that cannot be explained by a symptom-linked organic pathology (medically unexplained symptoms), they are diagnosed with ‘functional’ somatic syndromes (FSS). Despite their prevalence, the management of FSS is notoriously challenging in clinical practice. This may be because FSS are heterogeneous disorders in terms of etiopathogenesis. They include patients with primarily peripheral dysfunction, primarily centrally driven somatic symptoms, and a mix of both. Brain-imaging studies, particularly data-driven pattern recognition methods using machine learning algorithms, could provide brain-based biomarkers for these clinical conditions. In this review, we provide an overview of our brain imaging data on brain-body interactions in one of the most well-known FSS, irritable bowel syndrome (IBS), and discuss the possible development of a brain-based biomarker for FSS. Anticipation of unpredictable pain, which commonly elicits fear in FSS patients, induced increased activity in brain areas associated with hypervigilance during rectal distention and non-distention conditions in IBS. This was coupled with dysfunctional inhibitory influence of the medial prefrontal cortex (mPFC) and pregenual anterior cingulate cortex (pACC) on stress regulation systems, resulting in the activated autonomic nervous system (ANS) and neuroendocrine system stimulated by corticotropin-releasing hormone (CRH). IBS subjects with higher alexithymia, a risk factor for FSS, showed stronger activity in the insula during rectal distention but reduced subjective sensitivity. Reduced top-down regulation of the ANS and CRH system by mPFC and pACC, discordance between the insula response to stimulation and subjective sensation of pain, and stronger threat responses in hypervigilance-related areas may be a candidate brain-based biomarker.
Recently, biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionized the treatment of rheumatoid arthritis (RA) and provided patients with a higher chance of achieving clinical remission. Among them, abatacept (ABT), which selectively inhibits T cell activation through blocking costimulation signal, has been reported efficacious in controlling disease activity. Previous studies have shown that ABT has a high retention rate of up to three years with tolerable adverse events; however, it remains unclear whether this is maintained in the longer term. Here we conducted a retrospective five-year follow-up study to explore prognostic factors concerning better retention. In total, 98 patients who were treated with ABT from May 2011 to July 2019 in Osaki Citizen Hospital were enrolled, including 73 female patients (74.5%). The Kaplan-Meier method was used to estimate the retention rate of ABT. The mean age of ABT initiation was 72.1 years. Concomitant methotrexate was prescribed for 39 patients, and ABT was used as the first-line bDMARD for 65 patients. Rheumatoid factor (RF) was positive in 79 patients. One-, three-, and five-year retention rates of ABT were 83.3%, 66.2%, and 62.7%, respectively. Approximately two-thirds of discontinuation resulted from an inadequate response. Multivariate logistic regression analysis revealed that positive RF was associated with better drug retention. Receiver operating characteristics analysis showed that patients with high RF (≥ 45 IU/mL) had better retention rate of ABT. In conclusion, ABT shows high retention rate among patients with positive RF. The present study may provide better insights when selecting bDMARDs.
Labor arrest is the most common indication for emergency cesarean section (ECS). Increased biparietal diameter (BPD) has been reported as a risk factor for ECS due to labor arrest in different countries, but it is unclear whether this relationship is relevant in Japan. Considering the difference in maternal physique according to race and ethnicity, we retrospectively evaluated the association between ECS due to labor arrest and BPD, measured by ultrasonography < 7 days before term deliveries in Japanese women. BPD is routinely measured in Japan for estimating fetal weight. Information was extracted from obstetric records at the National Hospital Organization Kofu National Hospital between January 2012 and November 2019. Patients with multiple pregnancies, instrumental (forceps or vacuum) delivery, elective cesarean sections, and ECS due to reasons other than labor arrest were excluded. Thus, 2,695 women were included (age, 31.3 ± 6.2 years; pre-pregnancy body mass index, 20.9 ± 3.2 kg/m2), and 1,319 (48.9%) were nulliparous. The incidence of ECS due to labor arrest was 2.4% (64/2,695). Multivariable analysis indicated that BPD was significantly associated with ECS due to labor arrest (adjusted odds ratio, 1.12; 95% confidence interval, 1.04-1.20). The optimal BPD cut-off value for predicting ECS due to labor arrest was 94 mm (area under the curve, 0.61; sensitivity, 53.1%; specificity, 65.1%). Despite the significant association with ECS, BPD is not useful to predict ECS due to labor arrest. Thus, mothers should be encouraged for attempting vaginal deliveries, even in the case of having babies with large fetal BPD.
Abusive head trauma (AHT), commonly known as shaken baby syndrome, is a cranial injury of infants and young children. AHT is an important cause of morbidity and mortality in young children, particularly those younger than 12 months of age. We describe two patients who developed West syndrome, which is a severe epilepsy syndrome composed of the triad of infantile spasms, hypsarrhythmia on electroencephalography, and developmental arrest or regression, possibly attributable to AHT. Case 1 was a 5-month-old boy presented with generalized convulsive status epilepticus when a babysitter had cared for him. Brain magnetic resonance imaging (MRI) exhibited a subdural hemorrhage with diffuse brain edema and a midline shift highly suggestive of AHT. He developed West syndrome at the age of 10 months. Case 2 was a 6-month-old girl presented infantile spasms and diagnosed with West syndrome. Although she had poor weight gain due to inadequate care by her mother, there were no history of trauma, no cutaneous finding, and no developmental delay. Brain MRI performed when West syndrome was diagnosed revealed contusional tears highly suggestive of AHT. The MRI finding indicated that contusional tears had occurred 1~2 months before the development of West syndrome. There are no reports of West syndrome due to contusional tears. AHT may be an important risk factor for postnatal West syndrome. It is noteworthy that evidence of AHT was found only after West syndrome onset, as in Case 2. The onset of West syndrome may contribute to the finding that AHT had occurred earlier.
Common bile duct (CBD) stone is a relatively common but potentially life‐threatening disease. Endoscopic sphincterotomy (EST) has been performed as standard therapy for CBD stones, but the rate of recurrence of CBD stones is high. Risk factors have been poorly defined, and no effective means for the prevention of the recurrence of CBD stones have been established so far. We aimed to identify significant risk factors for the recurrence of bile duct stones. This study included 477 patients (231 women; mean age, 80.5 years) who underwent EST and cleared CBD stones on cholangiography. A retrospective analysis was performed for the consecutively collected data. During the follow-up period of 6-75 months, the recurrence of CBD stones was observed in 99 patients (20.8%). The median time to the recurrence was 19.0 months (range 4-72 months). Multivariate analysis identified the need for mechanical lithotripsy, which was used for stone fragmentation, as a risk factor. Mechanical lithotripsy caused cholangiography-negative small residua. Notably, saline solution irrigation of the bile duct reduced the recurrence of CBD stones. These results demonstrate that subsequent biliary irrigation after stone removal may prevent the recurrence of CBD stones by clearing small residual fragments.
Varicella zoster virus (VZV) causes a life-threatening infection in immunocompromised hosts. The immune response to VZV of healthy subjects has been rigorously assessed, but little is known about that of immunocompromised individuals. This study aimed to clarify the primary response to VZV infection in immunocompromised children. This prospective study enrolled six immunocompromised children (median age, 33 months; range, 20-62) receiving steroids or immunosuppressants, and 10 immunocompetent children (median age, 32 months; range, 15-81) with varicella. The immunocompromised children were three patients with acute lymphoblastic leukemia, two recipients with liver transplantation and one patient with juvenile idiopathic arthritis. Interferon-γ-producing CD69+T-cells produced by VZV stimulation (VZV-specific T-cells) were studied during the acute or convalescent phase. To further address the direct effect of immunosuppressants, we analyzed the number of VZV-specific T-cells after stimulating peripheral blood mononuclear cells obtained from healthy adults with live-attenuated VZV with or without prednisolone, cyclosporine-A, or tacrolimus. The circulating numbers of lymphocytes in the convalescent stage but not acute stage were lower in immunocompromised children compared with immunocompetent children. In the acute stage, immunocompromised patients showed lower VZV-specific CD8+T-cell counts than immunocompetent subjects. In contrast, in the convalescent phase, immunocompromised patients had lower VZV-specific CD4+T-cell counts than immunocompetent hosts. The in vitro culture of activated lymphocytes with prednisolone or immunosuppressants significantly decreased the proportion of VZV-specific CD4+T-cells. In conclusion, the decreased numbers of VZV-specific CD8+T-cells during the acute phase and VZV-specific CD4+T-cells during the convalescent phase of disease may account for severe varicella in immunocompromised children.