Intractable Nocardial mycetoma with possible colonisation by Candida species.

A Japanese male in his 30s with no underlying medical condition presented with painless nodules after being bitten by a dog during a stay in Bali, Indonesia, 7 years earlier. He was referred to our department with multiple ulcers, nodules, and masses on the right leg. The final diagnosis was mycetoma caused by Nocardia vulneris, which may have been exacerbated by colonization of Candida parapsilosis and C. tropicalis as these yeasts were isolated by culture from the tissue. Treatment with minocycline hydrochloride and sulfamethoxazole trimethoprim showed partial efficacy, but the addition of posaconazole achieved significant efficacy. This suggests that the surmised coexistence of pathogenic yeasts of lower virulency may have made mycetoma in this case intractable.

Impacts of fluid retention on prognostic abilities of cachexia diagnostic criteria in cancer patients with refractory cachexia.

BACKGROUND & AIMS: The international cancer cachexia criteria with a cutoff of 5% weight loss (WL) was proposed in Western patients. The Asian Working Group for Cachexia (AWGC) developed new criteria in Asian patients. The AWGC criteria are not cancer-specific and employ a cutoff of 2% WL. However, it is unclear whether both criteria are useful in patients with very advanced cancer because WL can be underestimated owing to fluid retention. Therefore, this study aimed to investigate the impacts of fluid retention on the prognostic abilities of both criteria in cancer patients with weeks of survival. METHODS: This study involved a secondary analysis of a prospective cohort study. The inclusion criteria constrained the study to adult patients with advanced cancer. Patients were divided into Non-cachexia and Cachexia groups using the international criteria and AWGC criteria. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: A total of 402 patients were included in the analysis. Using the international criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.55 and 0.18, respectively. Using the AWGC criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.38 and 0.12, respectively. Without considering the impacts of fluid retention, no significant differences were observed between the Non-cachexia and Cachexia groups for both criteria. After adjusting for the status of fluid retention, significantly higher risks of mortality were not observed in the Cox proportional hazard model for the Cachexia group compared with the Non-cachexia group, for both criteria. However, significant associations were observed between fluid retention and overall survival. CONCLUSIONS: The international criteria and AWGC criteria lost their prognostic abilities in cancer patients with weeks of survival. Since measurements of %WL were significantly confounded by fluid retention, fluid retention-adjusted criteria for cachexia need to be developed for cancer patients with refractory cachexia.

Fluid retention and weight loss in refractory cancer cachexia.

OBJECTIVES: It is unknown to what extent the fluid retention (FR) status disrupts the detection of weight loss rate (WLR) in adult patients with advanced cancer. This study aimed to determine the association of FR status with WLR. METHODS: This study was a secondary analysis of a prospective cohort study. FR was evaluated as follows: oedema (0, no; 1, yes), pleural effusion (0, no; 1, yes but asymptomatic; 2, symptomatic) and ascites (0, no; 1, yes but asymptomatic; 2, symptomatic). Patients were divided into three groups according to their FR scores: no-FR (0), moderate-FR (1-2) and high-FR (3-5). Multiple regression analysis was performed. RESULTS: Four hundred and twenty patients were categorised: no-FR group (n=164), moderate-FR group (n=158) and high-FR group (n=98). The prevalence of oedema, pleural effusion and ascites was 63.9%, 27.8% and 36.7% in the moderate-FR group, and 93.9%, 61.3% and 82.6% in high-FR group. The means of WLR were 9.2, 8.4 and 3.8 in the groups. The high-FR group and the FR score of 5 were correlated with WLR (estimate -4.71, 95% CI -7.84 to -1.58; estimate -10.29, 95% CI -17.84 to -2.74). CONCLUSIONS: The coexistence of FR was significantly correlated with WLR.

Malignancy-related ascites in palliative care units: prognostic factor analysis.

OBJECTIVES: The prognostic factors in patients with malignancy-related ascites (MA) have been poorly investigated. This study aimed to evaluate both the prognostic impact of MA on terminally ill patients with cancer and the prognostic factors in those with MA. METHODS: This was a post hoc analysis of a multicentre, prospective cohort study. Patients with advanced cancer admitted to palliative care units at 23 institutions and aged≥18 years were enrolled between January and December 2017. Overall survival (OS) was compared according to MA. A multivariate analysis was conducted to explore prognostic factors in patients with MA. RESULTS: Of 1896 eligible patients, gastrointestinal and hepatobiliary pancreatic cancers accounted for 42.5%. 568 (30.0%) of the total had MA. Patients with MA had significantly shorter OS than those without MA (median, 14 vs 22 days, respectively; HR, 1.55; 95% CI, 1.39 to 1.72; p<0.01). A multivariate analysis showed that MA was a poor prognostic factor (HR, 1.30; 95% CI, 1.13 to 1.50; p<0.01) and that among patients with MA, significant poor prognostic factors were liver metastasis, moderately to severely reduced oral intake, delirium, oedema, gastric cancer, high serum creatinine, high serum C reactive protein, high serum total bilirubin, dyspnoea and fatigue, while significant good prognostic factors were female sex, good performance status, high serum albumin and colorectal cancer. CONCLUSIONS: MA had a negative impact on survival in terminally ill patients with cancer. A multivariate analysis revealed several prognostic factors in patients with terminal cancer and MA.

Low serum creatinine as a prognostic marker in advanced cancer.

OBJECTIVES: To evaluate whether low serum creatinine levels are associated with poor outcomes in patients with advanced cancer. METHODS: This is a secondary analysis of a prospective cohort study. Patients were divided into three groups according to their baseline serum creatinine levels. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: 809 males were divided: male-low group (n=192), male-normal group (n=403) and male-high group (n=214). 808 females were divided: female-low group (n=239), female-normal group (n=389) and female-high group (n=180). Significant differences were observed in survival rates between the high and normal groups in the males and females (both log-rank p<0.001). Significantly higher risks of mortality were observed in the Cox proportional hazard model for the high group than for the normal group in both sexes (adjusted HR 1.292, 95% CI 1.082 to 1.542; adjusted HR 1.316, 95% CI 1.094 to 1.583, respectively). High serum creatinine was associated with shorter survival than normal creatinine, while low serum creatinine was not. CONCLUSIONS: Low serum creatinine levels did not have prognostic abilities in this population.

Comparison of the Effects of Bathing and the Dry Technique on the Skin Condition of Early Neonates: A Prospective Observational Study.

BACKGROUND: In Japan, neonates have typically been bathed in a bathtub immediately after birth because bathing is a custom for cleansing impurities. However, dry technique has been introduced into many institutions since 2000. There is little scientific evidence on the benefit or harmfulness of either method to neonatal skin, and consequently, opinion remains split on which method is superior. OBJECTIVE: The purpose of the present study was to determine whether bathing or the dry technique of cleaning is better in maintaining skin health in the early neonatal period. METHODS: Transepidermal water loss (TEWL) and skin pH, considered an index of skin barrier function, were measured in each group. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, which are inflammatory cytokines released by keratinocytes, were measured by skin blotting. RESULTS: TEWL and skin pH of neonates were lower with the dry technique than with bathing. The expression level of IL-6 and TNF-α in chest skin of neonates was higher with bathing than with the dry technique. CONCLUSION: These results suggest that the dry technique may maintain skin health better than bathing in the early neonatal period.

"Outside-to-inside," "inside-to-outside," and "intrinsic" endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations.

Permeability barrier disruption has been shown to induce immunological alterations (i.e., an "outside-to-inside" pathogenic mechanism). Conversely, several inflammatory and immunological mechanisms reportedly interrupt permeability barrier homeostasis (i.e., an "inside-to-outside" pathogenic mechanism). It is now widely recognized that alterations of even a single molecule in keratinocytes can lead to not only permeability barrier dysfunction but also to immunological alterations. Such a simultaneous, bidirectional functional change by keratinocytes is herein named an "intrinsic" pathogenic mechanism. Molecules and/or pathways involved in this mechanism could be important not only as factors in disease pathogenesis but also as potential therapeutic targets for inflammatory cutaneous diseases, such as atopic dermatitis, psoriasis, and prurigo nodularis. Elevation of skin surface pH following permeability barrier abrogation comprises one of the key pathogenic phenomena of the "outside-to-inside" mechanism. Not only type 2 cytokines (e.g., IL-4, IL-13, IL-31) but also type 1 (e.g. IFN-γ), and type 3 (e.g., IL-17, IL-22) as well as several other inflammatory factors (e.g. histamine) can disrupt permeability barrier homeostasis and are all considered part of the "inside-to-outside" mechanism. Finally, examples of molecules relevant to the "intrinsic" pathogenic mechanism include keratin 1, filaggrin, and peroxisome proliferator-activated receptor-α (PPARα).

Continuous Deep Sedation for Psycho-Existential Suffering: A Multicenter Nationwide Study.

Background: There is ongoing debate on whether continuous deep sedation (CDS) for psycho-existential suffering is appropriate. Objective: We aimed to (1) clarify clinical practice of CDS for psycho-existential suffering and (2) assess its impact on patients' survival. Methods: Advanced cancer patients admitted to 23 palliative care units in 2017 were consecutively enrolled. We compared patients' characteristics, CDS practices, and survival between those receiving CDS for psycho-existential suffering ± physical symptoms and only for physical symptoms. Results: Of 164 patients analyzed, 14 (8.5%) received CDS for psycho-existential suffering ± physical symptoms and only one of them (0.6%) solely for psycho-existential suffering. Patients receiving CDS for psycho-existential suffering, compared with those only for physical symptoms, were likely to have no specific religion (p = 0.025), and desired (78.6% vs. 22.0%, respectively; p < 0.001) and requested a hastened death more frequently (57.1% vs. 10.0%, respectively; p < 0.001). All of them had a poor physical condition with limited estimated survival, and mostly (71%) received intermittent sedation before CDS. CDS for psycho-existential suffering caused greater physicians' discomfort (p = 0.037), and lasted for longer (p = 0.029). Dependency, loss of autonomy, and hopelessness were common reasons for psycho-existential suffering that required CDS. The survival time after CDS initiation was longer in patients receiving it for psycho-existential suffering (log-rank, p = 0.021). Conclusion: CDS was applied to patients who suffered from psycho-existential suffering, which often associated with desire or request for a hastened death. Further studies and debate are warranted to develop feasible treatment strategies for psycho-existential suffering.

Comparison of Symptom Severity and Progression in Advanced Cancer Patients Among Different Care Settings: A Secondary Analysis.

Background: Most people in Japan wish to spend their final days at home, but the majority fail to do so; earlier studies indicated a more pronounced worsening of symptoms if treated at home. Objectives: This study compared the prevalence of symptom worsening and explored associated factors between patients with advanced cancer receiving palliative care in palliative care units (PCUs) and at home. Design: We conducted a secondary analysis of two multicenter, prospective cohort studies involving patients with advanced cancer receiving palliative care in PCUs or at home. Setting/Subjects: One study was conducted at 23 PCUs (January to December 2017) and the other on 45 palliative home care services (July to December 2017) in Japan. Measurements: Symptom changes were categorized as stable, improved, or worse. Results: Of the 2998 registered patients, 2877 were analyzed. Among them, 1890 patients received palliative care in PCUs, and 987 at home. Patients receiving palliative care at home were more likely to have worsening of pain (17.1% vs. 3.8%; p < 0.001) and drowsiness (32.6% vs. 22.2%; p < 0.001) than those in PCUs. By multivariate logistic regression analysis, palliative care at home was significantly associated with worsening of the Palliative Prognostic Index dyspnea subscale in the unadjusted model (odds ratio, 1.42 [95% confidence interval, 1.08-1.88]; p = 0.014) but not for any symptoms in the adjusted model. Conclusions: After adjusting for patient background, the prevalence of symptom worsening was not different between patients with advanced cancer receiving palliative care at home and in PCUs.

Survival rates of systemic interventions for psoriasis in the Western Japan Psoriasis Registry: A multicenter retrospective study.

Psoriasis affects approximately 0.3% of the Japanese population. Recently, various effective systemic drugs have become available, and the continuation of a given treatment has become critical because of the chronic nature of psoriasis. Factors affecting drug survival (the time until treatment discontinuation) in psoriasis treatment include efficacy, safety, ease of use, and patient preference. In the present study, the authors retrospectively surveyed a multifacility patient registry to determine the real-world evidence of the survival rate of systemic interventions for psoriasis treatment. Patients with psoriasis who visited 20 facilities in the Western Japan area between January 2019 and May 2020 and gave written consent were registered as study participants, and their medical history of systemic interventions for psoriasis (starting from 2010) was retrospectively collected and analyzed. The drugs investigated were adalimumab, infliximab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, cyclosporine, and apremilast. When drugs were discontinued, the reasons were also recorded. A total of 1003 patients with psoriasis including 268 with psoriatic arthritis (PsA) were enrolled. In biologics, more recently released drugs such as interleukin 17 inhibitors showed a numerically higher survival rate in the overall (post-2010) analysis. However, in the subset of patients who began treatment after 2017, the difference in the survival rate among the drugs was smaller. The reasons for discontinuing drugs varied, but a loss of efficacy against dermatological or joint symptoms were relatively frequently seen with some biologics and cyclosporine. The stratification of drug survival rates based on patient characteristics such as bio-naive or experienced, normal weight or obese, and with or without PsA, revealed that bio-experienced, obese, and PsA groups had poorer survival rates for most drugs. No notable safety issues were identified in this study. Overall, the present study revealed that the biologics show differences in their tendency to develop a loss of efficacy, and the factors that negatively impact the survival rate of biologics include the previous use of biologics, obesity, and PsA.

Clinical characteristics of patients with psoriasis with family history: A multicenter observational study.

Previous studies on family history of psoriasis showed that patients with a family history have an earlier onset of the disease, but such studies in Japan are still limited. To elucidate the characteristics of patients with familial psoriasis, we studied the family history of patients with psoriasis using the West Japan Psoriasis Registry, a multi-institutional registry operated by 26 facilities in the western part of Japan, including university hospitals, community hospitals, and clinics. This study enrolled 1847 patients registered between September 2019 and December 2021, with 199 (10.8%) having a family history of psoriasis. Patients with a family history of psoriasis had significantly earlier onset of the disease than those without a family history. Furthermore, patients with a family history of psoriasis had significantly longer disease duration. Psoriatic arthritis (PsA) was significantly more common in patients with a family history (69/199, 34.7%) than in those without a family history (439/1648, 26.6%) (adjusted P = 0.023). A subanalysis of patients with PsA revealed a significant difference in the patient global assessment (PaGA) score in Fisher's exact test and adjusted test. The numbers of patients with PaGA 0/1 were 29 (43.3%) and 172 (39.9%) in patients with PsA with and without family history of psoriasis, respectively, whereas the numbers of patients with PaGA 3/4 were 13 (19.4%) and 145 (33.6%) in patients with PsA with and without family history of psoriasis, respectively. Other disease severity variables did not show a difference between the two groups. Our findings suggest that genetics play a larger role in the development of PsA than in the development of psoriasis vulgaris. Most cases of PsA occur in patients who already have psoriasis, therefore dermatologists should pay attention to joint symptoms, especially in patients with psoriasis who have a family history of psoriasis.

Thromboembolism and bleeding in patients with autoimmune blistering disease.

The prevention and early detection of venous thromboembolism (VTE), including pulmonary embolism (PE), is essential in daily medical practice. We previously reported the risk of VTE in patients with autoimmune blistering disease (AIBD). We have also experienced multiple cases of pemphigus or pemphigoid that developed severe complications related to abnormal blood coagulation other than VTE. This study summarizes and discusses those cases. Nine patients with AIBD developed thromboembolism and/or bleeding; these included (some patients overlapped) six patients with VTE, including five patients with PE; three patients with severe bleeding; one patient with sudden critical limb ischaemia resulting in thigh amputation; and one patient with cerebral infarction. Although five patients developed PE, only one had apparent respiratory symptoms with PE, and a second developed severe bleeding during the treatment for PE. Clinicians should be aware of the systemic complications related to abnormal blood coagulation when treating patients with AIBD.