Reliability and validity of the Japanese version of the Chemotherapy-induced Alopecia Distress Scale.

BACKGROUND: The Chemotherapy-induced Alopecia Distress Scale (CADS) is a patient-reported outcome measure for assessing distress associated with Chemotherapy-induced alopecia (CIA). This study aimed to confirm the psychometric validity of the Japanese version of the CADS (CADS-J). METHODS: A total of 132 patients with breast cancer who developed CIA were asked to complete the CADS-J twice at 2 week intervals to confirm test-retest reliability. The body image domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) breast cancer-specific module, the self-esteem scale from the Rosenberg Self-Esteem Scale, and the emotional domain of the EORTC QLQ Core 30 were used to confirm the convergent validity of the CADS-J. The overall quality of life and physical domains of the EORTC QLQ Core 30 were used to confirm the discriminant validity of the CADS-J. RESULTS: In total, 125 participants provided valid responses. The mean age was 52.2 years. The overall Cronbach's alpha for the CADS-J was 0.903. The intraclass correlation coefficients of the first and second responses were r = 0.874, r = 0.952, r = 0.911, and r = 0.959 for the physical domain, emotional domain, activity domain, and relationship domain, respectively. In terms of convergent validity, the total CADS-J score was moderately correlated with body image (r = - 0.63), self-esteem (r = - 0.48), and the emotional domain (r = - 0.61). Regarding discriminant validity, the total CADS-J score was weakly correlated with the overall quality of life (r = - 0.34) and physical domain (r = - 0.24). CONCLUSIONS: The CADS-J is psychometrically reliable and valid for evaluating the distress caused by CIA. It is expected to be used in daily practice and as an endpoint in various studies.

De-differentiation in cultures of organoids from luminal-type breast cancer is restored by inhibition of NOTCH signaling.

Estrogen receptor (ER) expression in breast cancer can change during progression and the treatment, but the mechanism has not been well studied. In this study, we successfully prepared organoids from samples obtained from 33 luminal-type breast cancer patients and studied their ER expression. The expression status was well maintained in primary organoids, whereas it decreased after passaging in most of the cases. In fact, the studied organoid lines were classified into those that retained a high level of ER expression (9%), those that completely lost it (9%), and those that repressed it to varying degrees (82%). In some cases, the ER expression was suddenly and drastically decreased after passaging. Marker protein immunohistochemistry revealed that after passaging, the differentiation status shifted from a luminal- to a basal-like status. Differentially expressed genes suggested the activation of NOTCH signaling in the passaged organoids, wherein a NOTCH inhibitor was able to substantially rescue the decreased ER expression and alter the differentiation status. Our findings suggest that the differentiation status of luminal-type cancer cells is quite flexible, and that by inhibiting the NOTCH signaling we can preserve the differentiation status of luminal-type breast cancer organoids.

Dramatic Recovery of Vision after Trastuzumab Deruxtecan Treatment of HER2-Positive Breast Cancer with Pituitary Metastasis.

In recent years, both the number of patients with breast cancer and those with associated brain metastases (BMs) have increased. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer has a high BM frequency. The prognosis of BM from breast cancer is poor, and establishing effective treatment for this disease is essential. We report a HER2-positive patient with multiple BM and right-eye blindness due to pituitary metastasis. She responded promptly to trastuzumab deruxtecan (T-DXd) in the 5th line of treatment, which shrunk the tumors and restored vision. Although the Graded Prognostic Assessment (GPA) predicted survival of 13 months, the patient recovered well after treatment and continued T-DXd use with no progression, including vision loss at 22 months after treatment initiation. This case demonstrates the successful action of T-DXd in the face of multiple BM and poorly predicted outcomes.

Isolation and characterization of indigo-reducing bacteria and analysis of microbiota from indigo fermentation suspensions.

In natural indigo dyeing, the water-insoluble indigo included in the composted indigo leaves called sukumo is converted to water-soluble leuco-indigo through the reduction activities of microorganisms under alkaline conditions. To understand the relationship between indigo reduction and microorganisms in indigo-fermentation suspensions, we isolated and identified the microorganisms that reduce indigo and analyzed the microbiota in indigo-fermentation suspensions. Indigo-reducing microorganisms, which were not isolated by means of a conventional indigo carmine-reduction assay method, were isolated by using indigo as a direct substrate and further identified and characterized. We succeeded in isolating bacteria closely related to Corynebacterium glutamicum, Chryseomicrobium aureum, and Enterococcus sp. for the first time. Anthraquinone was found to be an effective mediator that facilitated the indigo-reduction activity of the isolated strains. On analysis of the microbiota in indigo-fermentation suspensions, the ratio of indigo-reducing bacteria and others was found to be important for maintaining the indigo-reduction activity.

Voltammetric in-situ monitoring of leuco-indigo in indigo-fermenting suspensions.

Cyclic voltammetry was successfully applied to in-vivo monitoring of leuco-indigo in indigo-fermenting suspensions under quiescent conditions without deoxygenation; the working and counter electrodes were kept on the surface of each suspension by a polyethylene vinyl alcohol tube holder. The anodic peak current was used as a measure of the leuco-indigo concentration. The voltammetric wave shape suggested partial solubilization of the indigo with some macromolecules in the fermenting suspensions, which lead to an in-situ method without any electrode surface pretreatment. The anodic peak current well reflected the dyeing activity of a suspensions. The results obtained for laboratory-level fermentation systems clarified the number of days required for dye fermentation, the effectiveness of addition of old suspension as an additive for preparing fresh fermenting suspensions, and the importance of addition of a nitrogen-based nutrient as well as a glucose-based one to recover the indigo-reducing activity. The method can also be applied to determine the amounts of indigo in used dye suspensions and extracts of fermented indigo leaves (sukumo) by adding a chemical reduction pretreatment.

Delirium is independently associated with early mortality in elderly patients starting hemodialysis.

BACKGROUND: Delirium is an independent predictor of death in patients undergoing dialysis for end-stage renal disease (ESRD). However, it is unknown whether delirium during hospitalization at the start of hemodialysis (HD) in elderly populations is associated with early mortality. METHODS: We conducted a retrospective cohort study to investigate the association between delirium and early mortality in the elderly after starting HD. The cohort consisted of patients ≥ 75 years who started dialysis for ESRD at the National Center for Global Health and Medicine from 2010 to 2017 and at Yokosuka Kyosai Hospital from 2007 to 2011. Delirium was defined as patients who showed new symptoms of transient confused thinking and reduced awareness of their environment and were prescribed antipsychotic medications. The primary outcome was death within 1 year. Data were analyzed using Cox proportional hazard models with adjustments for baseline characteristics. A multinomial logistic regression was used to identify the determinants of patients developing delirium. RESULTS: We enrolled 259 patients (males, 60%); 33 patients were diagnosed with delirium. The primary outcome was observed in 19 patients with delirium (58%) and 24 patients without delirium (11%) (p < 0.01). Delirium was independently associated with all-cause mortality within 1 year after starting HD (hazard ratio 7.82, 95% confidence interval 4.26-14.3; adjusted hazard ratio 7.16, 95% confidence interval 3.49-14.7). Delirium was positively correlated with "cognitive impairment" as well as "the use of steroids." CONCLUSION: Delirium is independently associated with early mortality in the elderly after starting HD.

Fatal Fulminant Legionnaires' Disease in a Patient on Maintenance Hemodialysis.

We herein report a case of fulminant Legionnaires' disease with autopsy findings in a patient on maintenance hemodialysis (HD). Chronic kidney disease is a strong risk factor for Legionnaires' disease, although there have been only a few reports in HD patients. Because most patients on HD are anuric, the use of rapid assay kits to detect antigens in urine samples for the diagnosis of Legionnaires' disease is not always feasible. We suggest the use of clinical predictive tools or the loop-mediated isothermal amplification (LAMP) method, which can be applied for anuric patients, such as those on HD, with pneumonia.

A Case of Frequently Relapsing Minimal-Change Nephrotic Syndrome with Steroid-Induced Psychiatric Syndrome Treated by Low-Dose, Short-Term Steroid Therapy in Combination with Cyclosporine.

Adults with minimal-change nephrotic syndrome (MCNS) generally receive oral prednisolone (PSL) at an initial dosage of 1.0 mg/kg/day for a minimum of 4 weeks, with 80% of patients achieving clinical remission. However, relapses are frequent, necessitating repeated treatment with high-dose PSL. Long-term treatment with high-dose steroids increases the risk of steroid toxicities, such as diabetes mellitus, gastric complications, infections, osteoporosis, and steroid-induced psychiatric syndrome (SIPS), which may compromise the patient's quality of life. Strategies are therefore needed to reduce the dosage and duration of steroid therapy for frequently relapsing MCNS (FRNS). Here, we suggest a new combination therapy of low-dose and short-term steroid with cyclosporine (CsA). We encountered an adult patient who developed recurrence of FRNS with depression arising from SIPS and was treated using low-dose, short-term PSL combined with CsA. He was successfully treated with PSL at an initial dosage of 0.3 mg/kg/day (20 mg/day) for just 2 weeks combined with CsA, allowing earlier induction of complete remission. We then promptly reduced the dose of PSL to below a physiological dosage (5 mg/day) over 3 weeks without relapse after episodes of SIPS and quickly resolved psychiatric symptoms. CsA in combination with PSL can reduce the initial dosage of PSL, shorten the time to remission, and easily maintain clinical remission. This protocol appears clinically useful and potentially applicable as a future treatment strategy for FRNS troubled by SIPS.

Anion gap predicts early mortality after starting hemodialysis in the elderly.

BACKGROUND: Serum anion gap (AG) has recently been proven to represent a biomarker for predicting prognosis in patients with end-stage renal disease (ESRD). However, whether change in AG (ΔAG) at the time of starting hemodialysis predicts mortality after starting hemodialysis in elderly patients with ESRD remains unknown. METHODS: This retrospective cohort investigated the association between ΔAG and mortality after starting hemodialysis in the elderly. The cohort comprised patients ≥ 75 years old who started hemodialysis for ESRD at National Center for Global Health and Medicine between 2010 and 2017 and at Yokosuka Kyosai Hospital between 2007 and 2011. Patients were stratified into three groups (G1-3) based on ΔAG, calculated according to the equation: ΔAG = sodium - (chloride + bicarbonate) - 12. The primary outcome was death within 1 year of starting hemodialysis. Data were analyzed using Cox proportional hazard models with adjustments for baseline characteristics. RESULTS: We enrolled 254 patients (59% male). Median ΔAG was 2.6 (G1: > 3, n = 111; G2: 0-3, n = 103; G3: < 0, n = 40). The primary outcome was observed in 43 patients. Hazard ratios (HRs) were significantly higher for G1 and G3 than for G2 (G1: HR 2.47, 95% confidence interval 1.13-5.37; G3: HR 3.86, 95% confidence interval 1.62-9.16). Adjusted HRs (aHRs) were significantly higher for G1 and G3 than for G2 (G1: aHR 3.06, 95% confidence interval 1.23-7.62; G3: aHR 3.12, 95% confidence interval 1.10-8.78). CONCLUSIONS: A J-curve phenomenon is evident between ΔAG and early mortality after starting hemodialysis in the elderly.

Risk Factors for Skin Flap Necrosis in Breast Cancer Patients Treated with Mastectomy Followed by Immediate Breast Reconstruction.

BACKGROUND: Skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) are the standard techniques for achieving a cosmetic outcome, but necrosis of a cutaneous flap including the nipple-areolar complex (NAC) is a serious complication. To analyze the risk factors for skin flap necrosis, we retrospectively evaluated a clinical database of breast cancer patients treated with mastectomy followed by immediate breast reconstruction. METHODS: Four hundred and twelve cases were consecutively recorded between 2006 and 2016. Body weight (BW), body mass index (BMI), distance from NAC to referent tumor, distance from overlying skin to the tumor and weight of breast resection (WBR) as measured in the operating theater were included in the statistical analysis. RESULTS: NSM, SSM and total mastectomy were performed in 123 (30%), 96 (23%) and 193 cases (47%), respectively. A tissue expander was used in 379 cases (92%), a silicone implant in 8 (2%) and autologous breast reconstruction in 25 (6%). Skin flap necrosis was found in 7% of all cases and NAC necrosis in 13% of NSM cases. In a univariate analysis, BW, NSM and WBR were risk factors for skin flap necrosis, and BW, BMI and WBR were risk factors for NAC necrosis. In a multivariate analysis, NSM and WBR remained significant risk factors for skin flap necrosis, and WBR was a significant risk factor for NAC necrosis. CONCLUSIONS: WBR is an important risk factor for skin flap necrosis. Especially, NAC necrosis should be considered for patients with large-volume breasts who undergo NSM and immediate breast reconstruction.

[Locally Advanced Breast Cancer Treated with Mohs' Paste and Neoadjuvant Chemotherapy-A Case Report].

Cutaneous infiltration by breast cancer significantly reduces patient quality of life(QOL)due to bleeding, exudate, and pain. We report a case of combined treatment using Mohs' paste and neoadjuvant chemotherapy for locally advanced breast cancer. Mohs' paste decreased bleeding and exudate from the tumor and neoadjuvant chemotherapy combined with bevacizumab down-staged a large tumor to a volume that permitted mastectomy. Good local control using Mohs' paste and neoadjuvant chemotherapy can improve patient QOL and reduce the physical burden.

Progesterone receptor expression in proliferating cancer cells of hormone-receptor-positive breast cancer.

Breast cancer has been suggested to have two distinct driving mechanisms: the hormone receptor and the growth factor receptor pathways. We hypothesized that each driving system produces a different expression pattern of estrogen-regulated genes, such as progesterone receptor, in proliferating cells. Progesterone receptor and Ki67 expressions were assessed by dual-fluorescence immunohistochemistry in estrogen-receptor-positive breast cancer tissues. Two distinct proliferating cell populations were observed: progesterone-receptor-positive and progesterone-receptor-negative. In the training cohort, tissues with progesterone-receptor-positive proliferating cells were associated with lower grade and better disease-free survival (p = 0.0055 and 0.0026, respectively). These associations were confirmed in the validation cohort from the neoadjuvant endocrine trial JFMC34 (p = 0.033 and 0.0003, respectively). In the validation cohort, patients with progesterone-receptor-positive proliferating cells responded better to endocrine therapy and had a lower Oncotype DX Recurrence Score. In the multivariate analysis, progesterone receptor status of proliferating cells, but not progesterone receptor or Ki67 alone, was an independent predictor of disease-free survival in both cohorts (p = 0.0043 and 0.0026). In conclusion, the progesterone receptor status of proliferating cancer cells was associated with histological grade and Recurrence Score, and a potent prognostic factor in estrogen-receptor-positive breast cancers. Results suggest that different driving systems generate different expression patterns of progesterone receptor in proliferating cancer cells. Further studies are warranted to validate the findings.

Non-uniform Progression of Chronic Tubulointerstitial Nephritis and Widespread Nephrocalcification in a Patient with Anorexia Nervosa.

Although patients with anorexia nervosa (anorexia) are known to show tubulointerstitial nephritis (TIN), the pathophysiology of its progression is not fully understood. We herein report a 31-year-old woman with anorexia who showed acute exacerbation of chronic kidney disease. Renal biopsy showed non-uniform chronic TIN; some areas were obsolete lesions and other areas were active lesions. In addition, many calcium-containing crystals were widely deposited in the distal tubules. The results suggest that chronic TIN in the setting of anorexia does not uniformly progress and that not only TIN but also widespread calcification of distal tubules might aggravate the renal function of anorexia patients.

An adult case of severe steroid-resistant Henoch-Schönlein purpura nephritis treated with intravenous cyclophosphamide and tonsillectomy.

A previously healthy 37-year-old Canadian man living in Japan visited a hospital in Thailand while traveling because of edematous legs, purpura, arthralgia, bloody stool, and fever after an insect bite. Henoch-Schönlein purpura (HSP) was suspected. His creatinine level was 5.2 mg/dL. He was treated with oral prednisolone (PSL) and oral cyclophosphamide (CPA); after treatment, his creatinine level improved to 2.4 mg/dL. Upon returning to Japan, he was admitted to the National Center for Global Health and Medicine Hospital in Tokyo. A kidney biopsy was performed, and HSP nephritis (HSPN) was diagnosed. Renal dysfunction and proteinuria persisted despite 4 administrations of steroid-pulse therapy and 3 sessions of plasma exchange. Finally, he was treated with intravenous cyclophosphamide (IVCY). His creatinine level and proteinuria markedly improved. His microscopic hematuria disappeared after he underwent tonsillectomy. There have been only a few case reports describing patients with adult-onset HSPN necessitating IVCY. We present here a rare case of steroid-resistant HSPN treated with IVCY and tonsillectomy, with reference to some recent findings.

Clinical remission of IgA nephropathy in an HIV-positive patient after combined treatment with tonsillectomy and steroid pulse therapy.

Various renal diseases other than human immunodeficiency virus (HIV)-associated nephropathy, including IgA nephropathy (IgAN), have been recently reported to cause chronic kidney disease and end-stage renal disease in HIV-infected patients. The case of a 37-year-old HIV-infected male diagnosed as having IgAN with proteinuria and microscopic hematuria that was successfully treated with tonsillectomy and steroid pulse therapy in combination, resulting in disappearance of urinary abnormalities (clinical remission), is reported, the first such case in the literature. A renal biopsy revealed mesangial proliferation associated with mesangial deposition of IgA and C3, consistent with IgAN. Antiretroviral therapy and angiotensin receptor blocker therapy did not improve his proteinuria. Therefore, he underwent tonsillectomy and steroid pulse therapy, and clinical remission was successfully achieved with no opportunistic infections. Clinical remission has continued for more than 3 years even after discontinuation of steroid therapy. It appears that combined treatment with tonsillectomy and steroid pulse therapy can be a good choice in managing HIV-infected patients with IgAN as long as secondary infection is strictly and continuously monitored.

A case of acute interstitial nephritis and granulomatous hepatitis induced by ingesting quinine.

Quinine is used for the treatment of malarial infection, though not in common use. It is especially valuable for the parenteral treatment of severe illness owing to drug-resistant strains of Plasmodium falciparum. Quinine is also known to occasionally cause acute renal failure (ARF). Although quinine is listed in some reviews as a cause of acute interstitial nephritis, most cases of quinine-associated acute renal failure have been attributed to the hemolytic-uremic syndrome (HUS). Only two cases of acute renal failure due to acute interstitial nephritis associated with quinine have been reported [1, 2]. To our knowledge, there have been 6 reported cases of quinine-induced hepatic granuloma [3-8]. We report a case of quinine-induced acute interstitial nephritis (AIN) along with granulomatous hepatitis, both of which were confirmed on biopsy. A 50-year-old Nigerian man was admitted to the hospital with complaints of fever and general fatigue. He had been prescribed quinine as an antimalarial drug in a Nigerian hospital. The patient was febrile and showed nonoliguric ARF and liver dysfunction. In this case, liver injury showed gradual and spontaneous resolution after discontinuing quinine, and ARF resolved after treatment with oral prednisolone.

[Case of serious HIV-associated nephropathy resulting in the introduction of hemodialysis].

A previously healthy 46-year-old black man visited the other hospital because of fever, appetite loss and nausea. Renal dysfunction, liver injury, and a highly markedly elevated LDH level were found. Abdominal CT demonstrated enlarged liver, spleen, kidney and lymph nodes. Human immunodeficiency virus (HIV) was serologically positive. His serum BUN, creatinine and potassium were 74.9 mg/dL, 11.78 mg/dL, and 5.6 mEq/L, respectively. After admission, anuria persisted and the progression of renal failure continued despite various treatment methods, necessitating the introduction of maintenance hemodialysis(HD). A kidney biopsy was performed to confirm classical HIV-associated nephropathy (HIVAN). Antiretroviral therapy (ART) was started. Although urine was transiently excreted, HD could not be discontinued. It has been reported that HIVAN is too difficult to treat and that kidney dysfunction seldom recovers. HIVAN is well-known to occur frequently in black HIV-infected patients. However, in Japan, there have been only a few reports describing patients with serious HIVAN and renal failure necessitating HD. We present here a very rare case with HIVAN, with reference to some recent findings.

Thrombotic microangiopathy associated with tuberculous infection.

A 32-year-old man was diagnosed as having thrombotic microangiopathy (TMA) and treated by plasma exchange (PE). During the course of admission, he was also newly diagnosed with pulmonary tuberculosis, tuberculous peritonitis and pleuritis, which was thought to be the cause of the TMA. There are only a few previous reports on TMA associated with tuberculous infection. Although its pathogenetic mechanism is not well understood, it would be valuable to recognize that this worldwide infectious disease could cause TMA.

Factors associated with recovery of renal function in patients with multiple myeloma who were treated with hemodialysis.

BACKGROUND: The presence of renal failure in patients with multiple myeloma (MM) has been considered an ominous prognostic factor associated with a significantly decreased life expectancy. The prognostic factors have seldom been analyzed to predict discontinuation of hemodialysis (HD) therapy in MM patients with renal failure after HD initiation. It is clinically very important to predict whether HD can be discontinued after introducing HD in such patients. METHODS: All medical and HD records were reviewed in MM patients who underwent HD in the National Center for Global Health and Medicine Hospital between January 1995 and May 2009. Thirty-two patients with MM had undergone HD. The clinical features and the factors that might be associated with recovery of renal function leading to discontinuation of HD in MM patients with severe renal failure were examined. RESULTS: The factors associated with recovery of renal function and discontinuation of HD were: low International Staging System (ISS) score (p = 0.0034); high response to chemotherapy (p = 0.036); low serum Ca (p = 0.006); low Cr (p = 0.019), and low serum ß2-microglobulin (sß2M) (p = 0.002). On multivariate analysis, low serum Ca and sß2M were significantly associated with HD discontinuation. Moreover, discontinuing HD was the significant factor associated with improved overall survival in MM patients who required HD at least once. CONCLUSION: sß2M and Ca were the laboratory parameters that were significant, independent prognostic factors for predicting the probability of recovery from severe renal failure and discontinuation of HD in MM patients who needed HD at least once.

Antiepoetin antibody-related pure red cell aplasia: successful remission with cessation of recombinant erythropoietin alone.

An elderly patient with pure red cell aplasia (PRCA) with antierythropoietin (anti-EPO) antibodies is described. PRCA due to alloimmunization is a rare and severe complication of recombinant human erythropoietin (rHu-EPO) therapy. Most reported patients with PRCA were cured primarily by immunosuppressive drug therapy. The patient in this case, however, did not want to receive any immunosuppressive drugs. Therefore, rHu-EPO injection was simply discontinued, the severe anemia gradually improved, and the hemoglobin approached normal range. This case is very rare and significant in that there have been few such elderly patients with rHu-EPO-induced PRCA in whom PRCA remission was achieved, with decreasing antibody titers, after cessation of rHu-EPO alone. Further cases are needed to assess how PRCA should be treated in patients with anti-EPO antibodies.